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Background Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). Methods and findings Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. Conclusions Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. Trial registration HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710)., Author(s): Zoe Moodie 1,*, Erica Andersen-Nissen 1,2, Nicole Grunenberg 1, One B. Dintwe 1,2, Faatima Laher Omar 2, Jia J. Kee 1, Linda-Gail Bekker 3, Fatima Laher 4, Nivashnee Naicker [...]

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. [ABSTRACT FROM AUTHOR]

Objective: To guide animal experiments, we investigated the similarities and differences between humans and mice in aging and Alzheimer's disease (AD) at the single-nucleus RNA sequencing (snRNA-seq) or single-cell RNA sequencing (scRNA-seq) level., Methods: Microglia cells were extracted from dataset GSE198323 of human post-mortem hippocampus. The distributions and proportions of microglia subpopulation cell numbers related to AD or age were compared. This comparison was done between GSE198323 for humans and GSE127892 for mice, respectively. The Seurat R package and harmony R package were used for data analysis and batch effect correction. Differentially expressed genes (DEGs) were identified by FindMarkers function with MAST test. Comparative analyses were conducted on shared genes in DEGs associated with age and AD. The analyses were done between human and mouse using various bioinformatics techniques. The analysis of genes in DEGs related to age was conducted. Similarly, the analysis of genes in DEGs related to AD was performed. Cross-species analyses were conducted using orthologous genes. Comparative analyses of pseudotime between humans and mice were performed using Monocle2., Results: (1) Similarities: The proportion of microglial subpopulation Cell_APOE/Apoe shows consistent trends, whether in AD or normal control (NC) groups in both humans and mice. The proportion of Cell_CX3CR1/Cx3cr1, representing homeostatic microglia, remains stable with age in NC groups across species. Tuberculosis and Fc gamma R-mediated phagocytosis pathways are shared in microglia responses to age and AD across species, respectively. (2) Differences: IL1RAPL1 and SPP1 as marker genes are more identifiable in human microglia compared to their mouse counterparts. Most genes of DEGs associated with age or AD exhibit different trends between humans and mice. Pseudotime analyses demonstrate varying cell density trends in microglial subpopulations, depending on age or AD across species., Conclusions: Mouse Apoe and Cell_Apoe maybe serve as proxies for studying human AD, while Cx3cr1 and Cell_Cx3cr1 are suitable for human aging studies. However, AD mouse models (App_NL_G_F) have limitations in studying human genes like IL1RAPL1 and SPP1 related to AD. Thus, mouse models cannot fully replace human samples for AD and aging research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Osteoarthritis (OA) is a degenerative joint disease prevalent in the elderly. Currently, the relationship between the senescence inhibitor Klotho and OA remains unclear. This study investigated the relationship between serum soluble Klotho (S-Klotho) and OA., Methods: This cross-sectional study was based on the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Three multifactorial logistic regression models were constructed to assess the association between serum Klotho and OA. Restricted cubic spline (RCS) curves were further used to assess whether there was a nonlinear relationship between serum Klotho and OA. Finally, stratified analyses and interaction tests were used to evaluate the association's stability. To further investigate the relationship between serum Klotho and OA, we recruited 107 patients for analysis at the First Affiliated Hospital of Guangxi Medical University., Results: The final 8,918 participants included in this study comprised 50.55% females and 49.45% males, with 18.10% of participants suffering from OA and a mean S-Klotho level of 846.41 (5.61) pg/ml. All three logistic regression models observed a negative association between continuous S-Klotho and OA risk. When S-Klotho was categorized into tertiles, the fully adjusted model showed that participants in the third tertile had a 17% lower risk of OA than those in the first tertile (OR = 0.83, 95% CI: 0.70, 0.99, P = 0.035). The RCS curves showed a linear negative association between S-Klotho and the incidence of OA (P for overall = 0.025; P for non-linearity = 0.667). Further subgroup analyses and interaction tests suggested that the negative association between S-Klotho and OA remained stable in different conditions. Research conducted in China has shown that the negative correlation between serum Klotho levels and the prevalence of OA remains evident among Chinese individuals (OR: 0.77, 95% CI: 0.66, 0.90, P<0.001)., Conclusion: Our study suggests that elevated levels of the senescence inhibitor S-Klotho may be a potential protective factor for OA, which may provide new insights into the diagnosis and treatment of OA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Diabetic peripheral neuropathy (DPN), a prevalent complication among individuals diagnosed with type 2 diabetes, has a significant impact on both the well-being of patients and their financial situation. Acupuncture has been employed for thousands of years within China and is regarded as one of the primary characteristic therapies of traditional Chinese medicine. Research has indicated that acupuncture has the potential to enhance microcirculation, decrease the generation of free radicals, and augment nerve conduction velocity. There had been several meta-analyses of acupuncture on DPN. Nevertheless, there has been inadequate attention given to the assessment of blood glucose control, and scores related to quality of life. Hence, we get additional evidence by enhancing the quantity and quality of studies to draw more distinct findings., Methods: We will conduct a comprehensive search for reports published from the beginning until June 2023 using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and Chinese Biomedical Literature database. Only randomized controlled trials will be considered, with no exclusion of quasi-randomized control trials. Articles in both English and Chinese will be taken into account without any limitations on publication dates. The data will be extracted, managed, and analyzed by two researchers working independently. The primary outcomes will include improvement of symptom scores, change of nerve conduction velocity, and quality of life scores. Additional outcomes will encompass blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with acupuncture. We plan to use the RevMan V.5.4 application and the random-effects model for conducting the meta-analysis. The assessment of potential prejudice can be conducted by Cochrane's 'risk of bias' 2 (RoB 2) tool. Registration: PROSPERO (registration number: CRD42023425203)., Discussion: Our goal is to perform a meta-analysis that offers an unbiased approach to treating individuals with type 2 DPN. At the same time, it also provides doctors with more choices in the treatment of diabetes peripheral neuropathy., Competing Interests: The researchers affirm that the study was carried out without any business or financial affiliations that can be interpreted as a possible clash of interests., (Copyright: © 2024 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: G.D.T. was a recipient of a research subcontract through Duke University from GSK for work unrelated to this study., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vegetative soybean (maodou or edamame) serves as a nutrient-rich food source with significant potential for mitigating global nutritional deficiencies. This study undertook a thorough examination of the nutritional profiles and transcriptomic landscapes of six soybean cultivars, including three common cultivars (Heinong551, Heinong562, and Heinong63) and three fresh maodou cultivars (Heinong527, HeinongXS4, and HeinongXS5). Nutrient analysis of the seeds disclosed notable differences in the levels of protein, fat, soluble sugars, vitamin E, calcium, potassium, magnesium, manganese, iron, and zinc across the cultivars. Through comparative transcriptome profiling and RNA sequencing, distinct variations in differentially expressed genes (DEGs) were identified between fresh and traditional maodou cultivars. Functional enrichment analyses underscored the involvement of DEGs in critical biological processes, such as nutrient biosynthesis, seed development, and stress responses. Additionally, association studies demonstrated robust correlations between specific DEG expression patterns and seed nutrient compositions across the different cultivars. Sankey diagrams illustrated that DEGs are strongly linked with seed quality traits, revealing potential molecular determinants that govern variations in nutritional content. The identified DEGs and their relationships with nutritional profiles offer valuable insights for breeding programs focused on developing cultivars with improved nutritional quality, tailored to specific dietary needs or industrial applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Narrative medicine was introduced in China in 2011 and has been applied as a tool for humane medical practice. The prominent problem in the narrative medicine is the lack of adequate attention and devotion. This study aimed to investigate Chinese medical staffs' narrative competence and the influencing factors, confirming whether the level of narrative competence is different in different hospital settings., Methods: A cross-sectional survey was conducted among 1003 medical staffs, including 201 from Children's hospital and 802 from the General hospital. The participants were scored based on the Chinese narrative competence scale, a brief Chinese version of the resilience scale, and a Chinese version of the self-efficacy scale. Data were analyzed using IBM SPSS version 25.0., Results: A total of 1003 medical staff from Children's hospital and General hospital participated in the survey, with a response rate of 94.36%. Our results showed that the score of narrative competence of General hospital and Children's hospital was 149.45±26.22 and 147.10±18.87, respectively, both of which were in intermediate level. Resilience, familiarity with narrative medicine were influencing factors of narrative competence in 2 kinds of hospitals, and whether having written parallel charts before were the influencing factors of narrative competence in General hospital. Besides, our study found that the level of narrative competence (χ2 = 13.672, p≤0.001), resilience score (personal ability dimension, t = 3.439, p≤0.001) and self-efficacy (t = 1.976, p<0.005) are different between General and Children's hospital., Conclusions: Narrative competence is different between General hospital and Children's hospital. Medical staff in General hospital are more familiar with narrative medicine. The competence of medical staff in China needs to be improved., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, from the perspective of image processing, we propose the iDNA-ITLM model, using a novel data enhance strategy by continuously self-replicating a short DNA sequence into a longer DNA sequence and then embedding it into a high-dimensional matrix to enlarge the receptive field, for identifying DNA methylation sites. Our model consistently outperforms the current state-of-the-art sequence-based DNA methylation site recognition methods when evaluated on 17 benchmark datasets that cover multiple species and include three DNA methylation modifications (4mC, 5hmC, and 6mA). The experimental results demonstrate the robustness and superior performance of our model across these datasets. In addition, our model can transfer learning to RNA methylation sequences and produce good results without modifying the hyperparameters in the model. The proposed iDNA-ITLM model can be considered a universal predictor across DNA and RNA methylation species., Competing Interests: The authors declare no competing interests., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although faster and powerful, polymerase chain reaction (PCR) often failed to amplify targets efficiently. Numerous PCR enhancers have been used to increase the amplification efficiency of difficult DNA targets. However, there is no systematic comparison of their effects in normal and difficult PCR conditions. In this paper, we have selected nine different PCR enhancers that can promote the PCR amplification efficiency. We have compared their effect in Taq DNA polymerase thermostability, inhibitor resistance, and amplification of various DNA targets. Although the PCR enhancers more or less reduced the amplification efficiency of DNA fragments with moderate GC-content, they were able to improve the amplification efficiency and specificity of GC-rich fragments. Betaine outperformed the other enhancers in amplification of GC-rich DNA fragments, thermostabilizing Taq DNA polymerase, and inhibitor tolerance. Sucrose and trehalose showed similar effect in thermostabilizing Taq DNA polymerase and inhibitor tolerance, while they showed mildest inhibitory effect on normal PCR. For GC-rich region-containing long DNA fragment amplification, 1 M betaine, 0.5 M betaine + 0.2 M sucrose, or 1 M betaine + 0.1 M sucrose can be used to effectively promote the amplification, while keep their negative effect in amplification of normal fragment to a minimal level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Atomic magnetometer (AM) is utilized to non-invasively detect event-related magnetic fields (ERMFs) evoked by visual stimuli in rats. The aim of this study was to investigate the relationship between N2-like amplitude and visual attention. To achieve this, we combined the AM with a visual stimulation system and employed the passive single-stimulus paradigm. By measuring the ERMFs at various inter-stimulus intervals (ISIs) with a sensitivity of 20 fT/[Formula: see text], we analyzed the effects of the ISI and the 'habituation' resulting from repeated stimuli on the N2-like amplitude. Our method serves as a valuable reference for studying the passive single-stimulus paradigm and the time course of mammalian attention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The effective elimination of nitrogen and phosphorus in urban sewage treatment was always hindered by the deficiency of organic carbon in the low C/N ratio wastewater. To overcome this organic-dependent barrier and investigate community changes after sulfur electron addition. In this study, we conducted a simulated urban wastewater treatment plant (WWTP) bioreactor by using sodium sulfate as an electron acceptor to explore the removal efficiency of characteristic pollutants before and after the addition of sulfur electron acceptor. In the actual operation of 90 days, the removal rate of sulfur electrons' chemical oxygen demand (COD), ammonia nitrogen, and total phosphorus (TP) with sulfur electrons increased to 94.0%, 92.1% and 74%, respectively, compared with before the addition of sulfur electron acceptor. Compared with no added sulfur(phase I), the reactor after adding sulfur electron acceptor(phase II) was demonstrated more robust in nitrogen removal in the case of low C/N influent. the effluent ammonia nitrogen concentration of the aerobic reactor in Pahse II was kept lower than 1.844 mg N / L after day 40 and the overall concentration of total phosphorus in phase II (0.35 mg P/L) was lower than that of phase I(0.76 mg P/L). The microbial community analysis indicates that Rhodanobacter, Bacteroidetes, and Thiobacillus, which were the predominant bacteria in the reactor, may play a crucial role in inorganic nitrogen removal, complex organic degradation, and autotrophic denitrification under the stress of low carbon and nitrogen ratios. This leads to the formation of a distinctive microbial community structure influenced by the sulfur electron receptor and its composition. This study contributes to further development of urban low-carbon-nitrogen ratio wastewater efficient and low-cost wastewater treatment technology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vascular endothelial damage due to ionizing radiation is the main pathological process of radiation injury and the main cause of damage to various organs in nuclear accidents. Ferroptosis plays an important role in ionizing radiation-induced cell death. We have previously reported that luteolin is highly resistant to ferroptosis. In the present study, body weight, microvessel count, H&E, and Masson staining results showed that luteolin rescued radial vascular injury in vivo. Cell Counting Kit 8 (CCK8), Giemsa staining clarified the anti-ferroptosis ability of luteolin with low toxicity. Malondialdehyde (MDA), superoxide dismutase (SOD), NADP+/NADPH, Fe2+ staining, dihydroethidium (DHE) and MitoTracker assays for ferroptosis-related metrics, we found that luteolin enhances human umbilical vein endothelial cells (HUVECs) antioxidant damage capacity. Drug affinity responsive target stability (DARTS), surface plasmon resonance (SPR), computer simulated docking and western blot showed that heat shock protein beta-1 (HSPB1) is one of the targets of luteolin action. Luteolin inhibits ferroptosis by promoting the protein expression of HSPB1/solute carrier family 7 member 11 (SLC7A11)/ glutathione peroxidase 4 (GPX4). In conclusion, we have preliminarily elucidated the antioxidant damage ferroptosis ability and the target of action of luteolin to provide a theoretical basis for the application of luteolin in radiation injury diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner. Bortezomib potently induced the expression of Noxa, a pro-apoptotic initiator and when combined with venetoclax, inhibited Mcl-1 and Bcl-2 simultaneously. Bortezomib prevented LMP-1 induced proteasomal degradation of IκBα leading to the suppression of the NF-κB signaling pathway. Bortezomib also rescued Bcl-6 from EBNA-3C mediated proteasomal degradation thus maintaining the repression of cyclin D1 and Bcl-2 causing G1-S arrest and apoptosis. Concurrently, venetoclax inhibited Bcl-2 upregulated by either LMP-1 or EBNA-3C. Bort/venetoclax decreased the expression of phosphorylated p65 and Bcl-2 at serine 70 thereby suppressing the NF-κB signaling pathway and promoting apoptosis, respectively. These data corroborated the marked suppression of the growth of xenograft of sLCL in SCID mice (p<0.001). Taken together, the combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in spontaneous lymphoblastoid cell lines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To investigate the response of blueberry photosynthetic physiology to different light intensities during different stages of fruit development. In this study, four light intensity treatments (25%, 50%, 75% and 100% of full light) were set up to study the change rule of photosynthetic pigment content and photosynthetic characteristics of 'O'Neal' southern highbush blueberry leaves during the white fruiting stage (S1), purple fruiting stage (S2) and blue fruiting stage (S3) under different light intensity environments, and to explore the light demand and light adaptability of blueberry during different developmental stages of the fruit. The results showed that the chlorophyll and carotenoid contents of blueberry leaves showed an increasing trend with decreasing light intensity at all three stages of fruit development. The total chlorophyll content of blueberry leaves at 25% light intensity increased by 76.4% compared with CK during the blue fruiting stage; the maximum net photosynthetic rate (Pmax), light compensation point (LCP), light saturation point (LSP), rate of dark respirations (Rd), inter-cellular CO2 concentration (Ci), stomatal conductance (Gs), transpiration rate (Tr), net photosynthesis rate (Pn), and chlorophyll a/b showed a decreasing trend with decreasing light intensity. The Pn of blueberry leaves was highest under full light conditions at all three stages, and the Pn at 25% light intensity decreased by 68.5% compared with CK during the white fruiting stage Reflecting the fact that blueberries can adapt to low-light environments through increases in chlorophyll and carotenoids, but reduced light intensity significantly inhibited their photosynthesis. The photosynthetic physiology of blueberry showed a consistent pattern at all three stages, but there were some differences in the changes of photosynthetic parameters at different stages. The results of the study can provide theoretical references for the selection of sites and density regulation in blueberry production., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Long et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Rheumatoid arthritis is a common rheumatic disease, and its onset is closely related to genetic and environmental factors, however, the relationship between air pollution and RA is still hotly debated. Further investigation of the relationship between air pollution and rheumatoid arthritis is conducive to a comprehensive understanding of the risk factors of the disease, providing certain value for the clinical prevention and treatment of RA., Methods: We used a Two-Sample Mendelian Randomization approach, integrating the large-scale public genomewide association study, to assess the genetically predicted causal effect of air pollution (including: PM2.5, PM2.5-10, PM10, nitrogen dioxide, nitrogen oxides) on RA in European and European East Asian populations, respectively. Indicators related to air pollution (2,505 individuals to 423,796 individuals), including European and East Asian populations were obtained from the Integrative Epidemiology Unit open GWAS project. Published East Asian RA data were also obtained from the IEU open GWAS project (212,453 individuals), while large-scale publicly available European RA data were obtained from finngen R10 (13,621 cases and 262,844 controls). Inverse variance weighting was used as the primary analytical method, complemented by MR-egger, Weighed median, and Weighted mode results. Cochran Q tested for heterogeneity, and MR-Egger regression analyses were performed to test for multiplicity. leave-one-out analysis allowed for the robustness and reliability were assessed., Results: No statistically significant effects of PM2.5, PM2.5-10, PM10, nitrogen dioxide, nitrogen oxides and RA were observed in either European or East Asian populations. Results from European data: PM2.5 (IVW OR: 0.71; 95% CI: 0.27-1.91; p = 0.498; number of SNPs: 5), PM2.5-10 (IVW OR: 1.20; 95% CI: 0.61-2.40; p = 0.596; number of SNPs: 15), PM10 (IVW OR: 1.69; 95% CI: 0.84-3.39; p = 0.142; number of SNPs: 9), nitrogen dioxide (IVW OR: 3.88; 95% CI: 0.19-77.77; p = 0.375; number of SNPs: 2), nitrogen oxides (IVW OR: 0.51; 95% CI: 0.16-1.67; p = 0.268; number of SNPs: 4). East Asian data results: PM2.5 (IVW OR: 1.16; 95% CI: 0.98-1.38; p = 0.086; number of SNPs: 4), PM2.5-10 (IVW OR: 1.14; 95% CI: 0.95-1.38; p = 0.166; number of SNPs: 2), PM10 (IVW OR: 0.95; 95% CI: 0.81-1.11; p = 0.503; number of SNPs: 3), nitrogen dioxide (IVW OR: 0.87; 95% CI: 0.76-1.00; p = 0.051; number of SNPs: 6), nitrogen oxides (IVW OR: 0.96; 95% CI: 0.82-1.14; p = 0.671; number of SNPs: 3). No signs of pleiotropy or heterogeneity were observed in the MR-Egger intercept, MR-PRESSO and Cochrane's Q (p>0.05). In addition, no outliers were found in the MR-PRESSO analysis. The results were further validated by leave-one-out tests, confirming the robustness of the findings., Conclusions: We performed transethnic MR analysis suggesting that there may not be a genetically predicted causal relationship between air pollution and RA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (β = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Diabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown., Objective: This study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats., Methods: Diabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 μg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 μg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson's trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling., Results: The average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E., Conclusion: Maggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its genetic and geographical origins remain unclear, resulting in suspicions about its natural origin. In one of our previous studies, we reported the presence of a furin cleavage site RRAR in the junction region between S1 and S2 subunits of the spike protein, which was discovered as the first crucial clue for the origin tracing of SARS-CoV-2. In the present study, we conducted an integrative analysis of new genome data from bat Sarbecovirus strains reported after the COVID-19 outbreak. The primary results included the identification of BANAL-20-52, Rp22DB159, and S18CXBatR24 as three close relatives of SARS-CoV-2 and the successful detection of seven out of nine key genomic features (designated as RC0-7 and ORF8) observed in wild types of SARS-CoV-2 in the three close relatives from Laos, Vietnam, and Yunnan province of China, respectively. The most significant contribution of the present study lies in the detection of RC1 in wild genotype in a bat Sarbecovirus population BANAL-20-52 belonging to. Encoding a segment of the NSP3 protein, RC1 was discovered as the second crucial clue for the origin tracing of SARS-CoV-2. Although RC0, encoding the junction furin cleavage site, remains undetected outside of the SARS-CoV-2 genome, Feuang of Laos is the sole place where eight of the nine wild-type features (RC1-7 and ORF8) have been detected., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: It still needs to be determined if platelet-rich plasma (PRP) has any added advantage over Minoxidil in treating androgenetic alopecia. We reviewed randomized controlled trials (RCTs) comparing scalp injections of PRP plus Minoxidil vs Minoxidil alone for managing androgenetic alopecia., Methods: All RCTs published on Embase, Cochrane Library, and PubMed comparing PRP plus Minoxidil vs. Minoxidil alone were eligible. The literature search was completed on 5 March 2024. The review was registered on PROSPERO (CRD42024509826)., Results: Of five included RCTs, three had a high risk of bias, while one had some concerns. A systematic review of the studies showed that all trials reported better outcomes with PRP plus Minoxidil than with Minoxidil alone. Meta-analysis showed that hair density at one month (MD: 11.07 95% CI: 1.20, 20.94 I2 = 0%), three months (MD: 21.81 95% CI: 10.64, 33.00 I2 = 57%) and 5/6 months (MD: 17.80 95% CI: 7.91, 27.69 I2 = 80%) of follow-up was significantly better in the PRP plus Minoxidil vs the Minoxidil alone group. Meta-analysis of adverse events showed that the risk of adverse events was comparable in both groups (OR: 0.55 95% CI: 0.22, 1.36 I2 = 0%). The certainty of evidence on the GRADE assessment was "low to very low.", Conclusion: Very low-quality evidence shows that the addition of injectable PRP to topical Minoxidil may improve outcomes in patients with androgenetic alopecia. The addition of PRP was found to improve hair density and patient satisfaction significantly. However, the small number of studies with a high risk of bias and heterogeneity in PRP preparation methods are significant limitations of current evidence. Further studies with larger sample sizes and uniform PRP preparation protocols are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Diabetic peripheral neuropathy (DPN), a widely prevalent complication in patients with type 2 diabetes, exerts a significant influence on patients' overall health and financial circumstances. Photobiomodulation therapy is one of the means of physical therapy for DPN. Although preliminary findings suggest the efficacy of photobiomodulation therapy in alleviating peripheral neuropathy, the existing literature lacks substantial evidence regarding its safety and effectiveness specifically in the context of diabetes-related peripheral neuropathy. Therefore, we plan to arrive at more distinct findings through systematic evaluation and meta-analysis., Methods: We will conduct a comprehensive search for studies published from the beginning until October 1, 2023, using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and the Chinese Biomedical Literature database. Simultaneously, we will also search for the WHO International Clinical Trial Registration Platform, China Clinical Trial Registration Platform, and Clinical Trials.gov. Gray literature will be retrieved using Google Scholar and opengrey.edu. Only randomized controlled trials in Chinese and English were included, with no restrictions on publication status. The primary outcomes will include change of symptom scores, change of nerve conduction velocity. Additional outcomes will encompass quality of life, change in pain, blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with photobiomodulation therapy. Reman V.5.4 and R language will be used for the meta-analysis. Assessment of potential bias will be conducted through Cochrane risk of bias 2 tool (RoB 2.0) and Physiotherapy Evidence Database (PEDro) scale. Registration: PROSPERO (registration number: CRD42023466586)., Discussion: This meta-analysis aims to assess the efficacy and safety of photobiomodulation therapy as a potential treatment for diabetic peripheral neuropathy (DPN), and providing a straightforward and convenient therapeutic for patients. Additionally, it expands the range of treatment alternatives available to healthcare professionals managing DPN., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed. Here, we describe a novel allosteric CXCR4 antagonist TIQ-15 which inhibits CXCR4-tropic HIV-1 infection of primary and transformed CD4 T cells. TIQ-15 blocks HIV entry with an IC50 of 13 nM. TIQ-15 also inhibits SDF-1α/CXCR4-mediated cAMP production, cofilin activation, and chemotactic signaling. In addition, TIQ-15 induces CXCR4 receptor internalization without affecting the levels of the CD4 receptor, suggesting that TIQ-15 may act through a novel allosteric site on CXCR4 for blocking HIV entry. Furthermore, TIQ-15 did not inhibit VSV-G pseudotyped HIV-1 infection, demonstrating its specificity in blocking CXCR4-tropic virus entry, but not CXCR4-independent endocytosis or post-entry steps. When tested against a panel of clinical isolates, TIQ-15 showed potent inhibition against CXCR4-tropic and dual-tropic viruses, and moderate inhibition against CCR5-tropic isolates. This observation was followed by a co-dosing study with maraviroc, and TIQ-15 demonstrated synergistic activity. In summary, here we describe a novel HIV-1 entry inhibitor, TIQ-15, which potently inhibits CXCR4-tropic viruses while possessing low-level synergistic activities against CCR5-tropic viruses. TIQ-15 could potentially be co-dosed with the CCR5 inhibitor maraviroc to block viruses of mixed tropisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the increasing demand for building acoustic performance, accurately evaluating the acoustic performance of building walls has become an important research topic. However, existing research has mostly focused on general building materials such as concrete, iron and steel, and glass. For wooden structure wall, due to the sound absorption performance of the materials themselves and the complexity of structural design, the analysis of their acoustic performance is still relatively weak. Moreover, there is a lack of quantitative description of their spectral characteristics and acoustic impedance. To analyze the acoustic performance of wooden structure building walls, Building Information Model (BIM) and impedance tube method were integrated to construct a building wall performance testing system with BIM technology. The impedance tube method was applied and testing functions for sound absorption and insulation performance were designed. The outcomes indicated that in the error test, the error range between the experimental group and the control group was [0.01, 0.18], indicating a high reliability of the experimental results. In the calculation of sound insulation of different specimens at different sound frequencies, when the frequency was 1600Hz, the sound insulation of the control group and experimental group was 65.30dB and 70.14dB, proving the effectiveness of the design method. The above results demonstrate the practicality of integrating BIM technology and impedance tube method in the acoustic performance analysis of wooden structure building walls. This study provides strong technical support for reducing the indoor environment of wooden buildings and improving the comfort of people's living environment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yin, Ai. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients., Methods: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0., Results: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45-2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42-2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup., Conclusions: TBS may be an efficient prognostic index in HCC patients., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chlamydia psittaci-a zoonotic pathogen in birds-may be transmitted to humans, causing severe respiratory disease. Individuals working in or living near poultry farms are highly susceptible to C. psittaci infection. In this study, we assessed the prevalence and genotypes of C. psittaci in poultries and humans in three cities of China by collecting fecal samples from different poultry species and throat swab samples and serum samples from workers in poultry farms and zoos. These samples were screened by real-time fluorescence quantitative PCR (qPCR) targeting C. psittaci ompA. The positive samples were subjected to PCR amplification and sequencing of ompA. The strains detected in the samples were genotyped on the basis of the phylogenetic analysis of ompA sequences. In total, 3.13% (40/1278) poultry fecal samples were positive in the qPCR assay, whereas 3.82% (6/157) of throat swab samples and 42.59% (46/108) of serum samples from the workers were positive in the qPCR and indirect fluorescent antibody assays, respectively. The strains detected in the 32 poultry samples and 6 human samples were genotyped as type A, indicating that the workers were infected with C. psittaci that originated in poultry birds in farms. Additionally, eight peacocks showed strains with the genotype CPX0308, which was identified in China for the first time. Elucidating the distribution of C. psittaci in animals and poultry-related workers may provide valuable insights for reducing the risk of C. psittaci infection within a population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Museums increasingly rely on cutting-edge digital technologies to attract visitors. Understanding the intricate factors influencing user acceptance of these technologies is, however, crucial for their effective use. This study therefore proposes a model, grounded in the technology acceptance model, to investigate user acceptance of online virtual reality (VR) museum exhibitions. Leveraging the online VR exhibition at Liangzhu Museum as a case study, data were collected from 313 participants and analyzed using partial least squares structural equation modeling (PLS-SEM) with Smart PLS. Semi-structured interviews with 15 individuals were conducted to complement the quantitative findings. The results reveal that factors such as interactivity, immersion, and presence positively influenced users' intrinsic technological beliefs (perceived ease of use, perceived enjoyment, and perceived usefulness), ultimately affecting their willingness to use and intention to visit on-site. Notably, immersion had a direct positive effect on perceived usefulness. There is a pressing need to leverage digital and web technologies to cater to the increasingly complex and diverse needs of online visitors, and emphasizing navigational performance in online VR exhibitions is also paramount for enhancing the overall user experience., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li, Lv. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Using the sample of Chinese A-share listed firms from 2010 to 2020, this study examines the impact of non-controlling large shareholders (NCLSs) on corporate capital structure adjustment. The results show that NCLSs significantly increase the dynamic capital structure adjustment speed and reduce capital structure deviation. NCLSs have an asymmetric influence on capital structure adjustment speed for different deviation directions, i.e. compared to the speed of upward adjustment after a downward deviation of the capital structure, the effect of NCLSs on the speed of downward adjustment of the capital structure after an upward deviation is stronger. Whether in state-owned enterprises (SOEs) or non-state-owned enterprises (NSOEs), NCLSs significantly increase the dynamic capital structure adjustment speed. However, compared with SOEs, NCLSs in NSOEs have a more significant positive impact on the dynamic capital structure adjustment speed. The mechanism analysis suggests that reducing agency costs and mitigating financing constraints serve as the important channels through which NCLSs influence the dynamic adjustment of capital structure. This paper not only enriches and improves the theoretical basis of dynamic capital structure adjustment, but also helps to deepen the understanding of dynamic capital structure adjustment of Chinese listed firms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Due to the heterogeneity of cancer, precision medicine has been a major challenge for cancer treatment. Determining medication regimens based on patient genotypes has become a research hotspot in cancer genomics. In this study, we aim to identify key biomarkers for targeted therapies based on single nucleotide variants (SNVs) and copy number variants (CNVs) of genes. The experiment is carried out on 7 cancers on the Encyclopedia of Cancer Cell Lines (CCLE) dataset. Considering the high mutability of driver genes which result in abundant mutated samples, the effect of data sparsity can be eliminated to a large extent. Therefore, we focus on discovering the relationship between driver mutation patterns and three measures of drug response, namely area under the curve (AUC), half maximal effective concentration (EC50), and log2-fold change (LFC). First, multiple statistical methods are applied to assess the significance of difference in drug response between sample groups. Next, for each driver gene, we analyze the extent to which its mutations can affect drug response. Based on the results of multiple hypothesis tests and correlation analyses, our main findings include the validation of several known drug response biomarkers such as BRAF, NRAS, MAP2K1, MAP2K2, and CDKN2A, as well as genes with huge potential to infer drug responses. It is worth emphasizing that we identify a list of genes including SALL4, B2M, BAP1, CCDC6, ERBB4, FOXA1, GRIN2A, and PTPRT, whose impact on drug response spans multiple cancers and should be prioritized as key biomarkers for targeted therapies. Furthermore, based on the statistical p-values and correlation coefficients, we construct gene-drug sensitivity maps for cancer drug recommendation. In this work, we show that driver mutation patterns could be used to tailor therapeutics for precision medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis., Methods: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias., Results: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance., Conclusions: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the increasing burden of professional burnout in physicians, attention is being paid to optimizing sleep health, starting in training. The multiple dimensions of physicians' sleep are not well described due to obstacles to easily and reliably measuring sleep. This pilot study tested the feasibility of using commercial wearable devices and completing manual sleep logs to describe sleep patterns of medical students and residents. Prospective pilot study of 50 resident physicians and medical students during a single year of training. Participants completed a manual sleep log while concurrently wearing the Fitbit Inspire device for 14-consecutive days over three clinical rotations of varying work schedules: light, medium, and heavy clinical rotations. Study completion was achieved in 24/50 (48%) participants. Overall correlation coefficients between the sleep log and Fitbit were statistically low; however, the discrepancies were acceptable, i.e., Fitbit underestimated time in bed and total sleep time by 4.3 and 2.7 minutes, respectively. Sleep onset time and waketime were within 8 minutes, with good agreement. Treatment of sleep episodes during the day led to variance in the data. Average missingness of collected data did not vary between medical students or residents or by rotation type. When comparing the light to heavy rotations, hours slept went from 7.7 (±0.64) to 6.7 (±0.88), quality-of-life and sleep health decreased and stress, burnout, and medical errors increased. Burnout was significantly associated with worse sleep health, hours worked, and quality-of-life. Prospective data collection of sleep patterns using both sleep logs and commercial wearable devices is burdensome for physicians-in-training. Using commercial wearable devices may increase study success as long as attention is paid to daytime sleep. In future studies investigating the sleep of physicians, the timing of data collection should account for rotation type., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hassinger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear., Methods: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods., Results: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922-0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972-0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002-1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972-0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037-0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983-0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies., Conclusions: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Babesia is a tick-transmitted parasite that infects wild and domestic animals, causes babesiosis in humans, and is an increasing public health concern. Here, we investigated the prevalence and molecular characteristics of Babesia infections in the rodents in Southeastern Shanxi, China. Small rodents were captured, and the liver and spleen tissues were used for Babesia detection using traditional PCR and sequencing of the partial 18S rRNA gene. The analysis revealed that 27 of 252 small rodents were positive for Babesia, with an infection rate of 10.71%. The infection rates in different sexes and rodent tissues were not statistically different, but those in different rodent species, habitats, and sampling sites were statistically different. The highest risk of Babesia infection was observed in Niviventer confucianus captured from the forests in Huguan County. Forty-three sequences from 27 small rodents positive for Babesia infection were identified as Babesia microti, including 42 sequences from 26 N. confucianus, and one sequence from Apodemus agrarius. Phylogenetic analysis showed that all sequences were clustered together and had the closest genetic relationship with Babesia microti strains isolated from Rattus losea and N. confucianus in China, and belonged to the Kobe-type, which is pathogenic to humans. Compared to other Kobe-type strains based on the nearly complete 18S rRNA gene, the sequences obtained in this study showed the difference by 1-3 bp. Overall, a high prevalence of Babesia microti infection was observed in small rodents in Southeastern Shanxi, China, which could benefit us to take the implementation of relevant prevention and control measures in this area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms., Methods: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing., Results: AS-IV decreased the levels of TNF-α, IL-6, and IL-1β in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria., Conclusion: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins. Consequently, an appealing approach for TBI treatment involves using drug delivery systems that utilize targeting antibodies and nanocarriers to help restore BBB integrity. In our investigation of this strategy, we examined the efficacy of free antibodies and nanocarriers targeting a specific endothelial surface marker called vascular cell adhesion molecule-1 (VCAM-1), which is known to be upregulated during inflammation. In a mouse model of TBI utilizing central fluid percussion injury, free VCAM-1 antibody did not demonstrate superior targeting when comparing sham vs. TBI brain. However, the administration of VCAM-1-targeted nanocarriers (liposomes) exhibited a 10-fold higher targeting specificity in TBI brain than in sham control. Flow cytometry and confocal microscopy analysis confirmed that VCAM-1 liposomes were primarily taken up by brain endothelial cells post-TBI. Consequently, VCAM-1 liposomes represent a promising platform for the targeted delivery of therapeutics to the brain following traumatic brain injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Omo-Lamai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage., Methods: The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group., Results: A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342)., Conclusions: Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To identify the predictive role of sarcopenia in long-term survival among rectal cancer patients who underwent surgery based on available evidence., Methods: The Medline, EMBASE and Web of Science databases were searched up to October 20, 2023, for relevant studies. Overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) were the endpoints. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the association between sarcopenia and survival., Results: Fifteen studies with 4283 patients were included. The pooled results demonstrated that preoperative sarcopenia significantly predicted poorer OS (HR = 2.07, 95% CI = 1.67-2.57, P<0.001), DFS (HR = 1.85, 95% CI = 1.39-2.48, P<0.001) and CSS (HR = 1.83, 95% CI = 1.31-2.56, P<0.001). Furthermore, subgroup analysis based on neoadjuvant therapy indicated that sarcopenia was a risk factor for worse OS and DFS in patients who received (OS: HR = 2.44, P<0.001; DFS: HR = 2.16, P<0.001) but not in those who did not receive (OS: HR = 2.44, P<0.001; DDFS: HR = 1.86, P = 0.002) neoadjuvant chemoradiotherapy. In addition, subgroup analysis based on sample size and ethnicity showed similar results., Conclusion: Preoperative sarcopenia is significantly related to poor survival in surgical rectal cancer patients and could serve as a novel and valuable predictor of long-term prognosis in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su, Shen. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tumor microenvironment (TME) is a complex dynamic system with many tumor-interacting components including tumor-infiltrating leukocytes (TILs), cancer associated fibroblasts, blood vessels, and other stromal constituents. It intrinsically affects tumor development and pharmacology of oncology therapeutics, particularly immune-oncology (IO) treatments. Accurate measurement of TME is therefore of great importance for understanding the tumor immunity, identifying IO treatment mechanisms, developing predictive biomarkers, and ultimately, improving the treatment of cancer. Here, we introduce a mouse-IO NGS-based (NGSmIO) assay for accurately detecting and quantifying the mRNA expression of 1080 TME related genes in mouse tumor models. The NGSmIO panel was shown to be superior to the commonly used microarray approach by hosting 300 more relevant genes to better characterize various lineage of immune cells, exhibits improved mRNA and protein expression correlation to flow cytometry, shows stronger correlation with mRNA expression than RNAseq with 10x higher sequencing depth, and demonstrates higher sensitivity in measuring low-expressed genes. We describe two studies; firstly, detecting the pharmacodynamic change of interferon-γ expression levels upon anti-PD-1: anti-CD4 combination treatment in MC38 and Hepa 1-6 tumors; and secondly, benchmarking baseline TILs in 14 syngeneic tumors using transcript level expression of lineage specific genes, which demonstrate effective and robust applications of the NGSmIO panel., Competing Interests: All authors are/were paid employees of Crown Bioscience. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Light as a source of information regulates morphological and physiological processes of fungi, including development, primary and secondary metabolism, or the circadian rhythm. Light signaling in fungi depends on photoreceptors and downstream components that amplify the signal to govern the expression of an array of genes. Here, we investigated the effects of red and far-red light in the mycoparasite Trichoderma guizhouense on its mycoparasitic potential. We show that the invasion strategy of T. guizhouense depends on the attacked species and that red and far-red light increased aerial hyphal growth and led to faster overgrowth or invasion of the colonies. Molecular experiments and transcriptome analyses revealed that red and far-red light are sensed by phytochrome FPH1 and further transmitted by the downstream MAPK HOG pathway and the bZIP transcription factor ATF1. Overexpression of the red- and far-red light-induced fluffy gene fluG in the dark resulted in abundant aerial hyphae formation and thereby improvement of its antagonistic ability against phytopathogenic fungi. Hence, light-induced fluG expression is important for the mycoparasitic interaction. The increased aggressiveness of fluG-overexpressing strains was phenocopied by four random mutants obtained after UV mutagenesis. Therefore, aerial hyphae formation appears to be a trait for the antagonistic potential of T. guizhouense., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Increasing yield is an important goal of barley breeding. In this study, 54 papers published from 2001-2022 on QTL mapping for yield and yield-related traits in barley were collected, which contained 1080 QTLs mapped to the barley high-density consensus map for QTL meta-analysis. These initial QTLs were integrated into 85 meta-QTLs (MQTL) with a mean confidence interval (CI) of 2.76 cM, which was 7.86-fold narrower than the CI of the initial QTL. Among these 85 MQTLs, 68 MQTLs were validated in GWAS studies, and 25 breeder's MQTLs were screened from them. Seventeen barley orthologs of yield-related genes in rice and maize were identified within the hcMQTL region based on comparative genomics strategy and were presumed to be reliable candidates for controlling yield-related traits. The results of this study provide useful information for molecular marker-assisted breeding and candidate gene mining of yield-related traits in barley., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In response to increasingly complex social emergencies, this study realizes the optimization of logistics information flow and resource allocation by constructing the Emergency logistics information Traceability model (ELITM-CBT) based on alliance blockchain technology. Using the decentralized, data immutable and transparent characteristics of alliance blockchain technology, this research breaks through the limitations of traditional emergency logistics models and improves the accuracy and efficiency of information management. Combined with the hybrid genetic simulated Annealing algorithm (HGASA), the improved model shows significant advantages in emergency logistics scenarios, especially in terms of total transportation time, total cost, and fairness of resource allocation. The simulation results verify the high efficiency of the model in terms of timeliness of emergency response and accuracy of resource allocation, and provide innovative theoretical support and practical scheme for the field of emergency logistics. Future research will explore more efficient consensus mechanisms, and combine big data and artificial intelligence technology to further improve the performance and adaptability of emergency logistics systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fibrotic remodeling is the primary driver of functional loss in chronic kidney disease, with no specific anti-fibrotic agent available for clinical use. Transglutaminase 2 (TG2), a wound response enzyme that irreversibly crosslinks extracellular matrix proteins causing dysregulation of extracellular matrix turnover, is a well-characterized anti-fibrotic target in the kidney. We describe the humanization and characterization of two anti-TG2 monoclonal antibodies (zampilimab [hDC1/UCB7858] and BB7) that inhibit crosslinking by TG2 in human in vitro and rabbit/cynomolgus monkey in vivo models of chronic kidney disease. Determination of zampilimab half-maximal inhibitory concentration (IC50) against recombinant human TG2 was undertaken using the KxD assay and determination of dissociation constant (Kd) by surface plasmon resonance. Efficacy in vitro was established using a primary human renal epithelial cell model of tubulointerstitial fibrosis, to assess mature deposited extracellular matrix proteins. Proof of concept in vivo used a cynomolgus monkey unilateral ureteral obstruction model of chronic kidney disease. Zampilimab inhibited TG2 crosslinking transamidation activity with an IC50 of 0.25 nM and Kd of <50 pM. In cell culture, zampilimab inhibited extracellular TG2 activity (IC50 119 nM) and dramatically reduced transforming growth factor-β1-driven accumulation of multiple extracellular matrix proteins including collagens I, III, IV, V, and fibronectin. Intravenous administration of BB7 in rabbits resulted in a 68% reduction in fibrotic index at Day 25 post-unilateral ureteral obstruction. Weekly intravenous administration of zampilimab in cynomolgus monkeys with unilateral ureteral obstruction reduced fibrosis at 4 weeks by >50%, with no safety signals. Our data support the clinical investigation of zampilimab for the treatment of kidney fibrosis., Competing Interests: T. S. Johnson, P. F. Watson, and D. Matthews are inventors on patent WO 2013/175229 A1 (Anti-transglutaminase 2 antibodies) relating to the discovery and humanization of zampilimab. C. Kettleborough and D. Matthews are/were employees of LifeArc who hold rights to patent WO 2013/175229 and may therefore benefit from its development. Z. Song is the CEO of Prisys Biotechnologies who developed and ran the cynomolgus UUO model. J. Ni was an employee of Prisys Biotechnologies at the time the study was conducted. L. Huang, J. Atkinson, K. Cain, J. Kennedy, B. Twomey, H. Bon, and T. S. Johnson are/were employees of UCB Pharma who in-licensed zampilimab from LifeArc and may hold/have access to stock options., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Miscanthus lutarioriparia is a promising energy crop that is used for abandoned mine soil phytoremediation because of its high biomass yield and strong tolerance to heavy metals. However, the biological mechanism of heavy metal resistance is limited, especially for applications in the soil restoration of mining areas. Here, through the investigation of soil cadmium(Cd) in different mining areas and soil potted under Cd stress, the adsorption capacity of Miscanthus lutarioriparia was analyzed. The physiological and transcriptional effects of Cd stress on M. lutarioriparia leaves and roots under hydroponic conditions were analyzed. The results showed that M. lutarioriparia could reduce the Cd content in mining soil by 29.82%. Moreover, different Cd varieties have different Cd adsorption capacities in soils with higher Cd concentration. The highest cadmium concentrations in the aboveground and belowground parts of the plants were 185.65 mg/kg and 186.8 mg/kg, respectively. The total chlorophyll content, superoxide dismutase and catalase activities all showed a trend of increasing first and then decreasing. In total, 24,372 differentially expressed genes were obtained, including 7735 unique to leaves, 7725 unique to roots, and 8912 unique to leaves and roots, which showed differences in gene expression between leaves and roots. These genes were predominantly involved in plant hormone signal transduction, glutathione metabolism, flavonoid biosynthesis, ABC transporters, photosynthesis and the metal ion transport pathway. In addition, the number of upregulated genes was greater than the number of downregulated genes at different stress intervals, which indicated that M. lutarioriparia adapted to Cd stress mainly through positive regulation. These results lay a solid foundation for breeding excellent Cd resistant M. lutarioriparia and other plants. The results also have an important theoretical significance for further understanding the detoxification mechanism of Cd stress and the remediation of heavy metal pollution in mining soil., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Immune checkpoint inhibitor pneumonitis (CIP) is a prevalent form of immunotherapy-induced pulmonary toxicity, ranking among the leading causes of mortality associated with immune checkpoint inhibitors (ICIs). Despite its significance, the risk stratification of CIP in advanced non-small cell lung cancer (NSCLC) remains uncertain. In this study, we conducted a comprehensive analysis, comparing various factors such as histological types, treatment regimens, PD-L1 expression levels, and EGFR/ALK negativity in advanced NSCLC. Our investigation extends to evaluating the relative risk of developing CIP based on previous treatment history. This analysis aims to provide valuable insights for the identification of specific patient subgroups at higher risk, facilitating more effective risk management and precision therapy approaches., Methods: PubMed, Embase, and Cochrane databases were systematically searched up to February 16, 2023. We conducted a screening of randomized controlled trials (RCTs) that compared ICI monotherapy or its combination with chemotherapy in advanced NSCLC. The trials were categorized based on histological type, treatment regimen, PD-L1 expression level, EGFR/ALK-negative status, and prior treatment history. Subsequently, the data were stratified into five subgroups, and the occurrences of all-grades (1-5) and high-grades (3-5) pneumonia events were extracted. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were then calculated for further analysis., Results: Twenty-two RCTs, encompassing 13,725 patients with advanced NSCLC, were included in this analysis. Regardless of histology (OR = 2.47, 95% CI 1.41-4.33, P = 0.002; OR = 1.84, 95% CI 1.10-3.09, P = 0.02), treatment regimen (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.91, 95% CI 1.98-4.27, P < 0.00001), PD-L1 expression level (OR = 5.11, 95% CI 2.58-10.12, P < 0.00001; OR = 5.15, 95% CI 2.48-10.70, P < 0.0001), negative EGFR/ALK expression (OR = 4.32, 95% CI 2.22-8.41, P < 0.0001; OR = 3.6, 95% CI 1.56-8.28, P = 0.003), whether there is a history of treatment (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.74, 95% CI 1.75-4.29, P < 0.0001), ICI use was associated with a higher risk of all-grade (1-5) and high-grade (3-5) pneumonia compared to chemotherapy. Subgroup analysis revealed that the squamous group, the ICI vs. combination chemotherapy (CT) group, the PD-L1 > 50% group, and the previously untreated group had a higher risk of developing all-grade and grade 3-5 CIP (P < 0.05)., Conclusions: In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural disasters such as landslides often occur on soil slopes in seasonally frozen areas that undergo freeze‒thaw cycling. Ecological slope protection is an effective way to prevent such disasters. To explore the change in the mechanical properties of soil under the influence of both root reinforcement and freeze‒thaw cycles and its influence on slope stability, the Baijiabao landslide in the Three Gorges Reservoir area was taken as an example. The mechanical properties of soil under different confining pressures, vegetation coverages (VCs) and numbers of freeze‒thaw cycles were studied via mechanical tests, such as triaxial compression tests, wave velocity tests and FLAC3D simulations. The results show that the shear strength of a root-soil composite increases with increasing confining pressure and VC and decreases with increasing number of freeze‒thaw cycles. Bermuda grass roots and confining pressure jointly improve the durability of soil under freeze‒thaw conditions. However, with an increase in the number of freeze‒thaw cycles, the resistance of root reinforcement to freeze‒thaw action gradually decreases. The observed effect of freeze‒thaw cycles on soil degradation was divided into three stages: a significant decrease in strength, a slight decrease in strength and strength stability. Freeze‒thaw cycles and VC mainly affect the cohesion of the soil and have little effect on the internal friction angle. Compared with that of a bare soil slope, the safety factor of a slope covered with plants is larger, the maximum displacement of a landslide is smaller, and it is less affected by freezing and thawing. These findings can provide a reference for research on ecological slope protection technology., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. Statement: we confirm that all the experiments/ protocols were performed with relevant institutional, national, and international guidelines and legislation, (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Parkinson's disease (PD) is the second most common worldwide age-related neurodegenerative disorder without effective treatments. Cuproptosis is a newly proposed conception of cell death extensively studied in oncological diseases. Currently, whether cuproptosis contributes to PD remains largely unclear., Methods: The dataset GSE22491 was studied as the training dataset, and GSE100054 was the validation dataset. According to the expression levels of cuproptosis-related genes (CRGs) and differentially expressed genes (DEGs) between PD patients and normal samples, we obtained the differentially expressed CRGs. The protein-protein interaction (PPI) network was achieved through the Search Tool for the Retrieval of Interacting Genes. Meanwhile, the disease-associated module genes were screened from the weighted gene co-expression network analysis (WGCNA). Afterward, the intersection genes of WGCNA and PPI were obtained and enriched using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the key genes were identified from the datasets. The receiver operating characteristic curves were plotted and a PPI network was constructed, and the PD-related miRNAs and key genes-related miRNAs were intersected and enriched. Finally, the 2 hub genes were verified via qRT-PCR in the cell model of the PD and the control group., Results: 525 DEGs in the dataset GSE22491 were identified, including 128 upregulated genes and 397 downregulated genes. Based on the PPI network, 41 genes were obtained. Additionally, the dataset was integrated into 34 modules by WGCNA. 36 intersection genes found from WGCNA and PPI were significantly abundant in 7 pathways. The expression levels of the genes were validated, and 2 key genes were obtained, namely peptidase inhibitor 3 (PI3) and neuroserpin family I member 1 (SERPINI1). PD-related miRNAs and key genes-related miRNAs were intersected into 29 miRNAs including hsa-miR-30c-2-3p. At last, the qRT-PCR results of 2 hub genes showed that the expressions of mRNA were up-regulated in PD., Conclusion: Taken together, this study demonstrates the coordination of cuproptosis in PD. The key genes and miRNAs offer novel perspectives in the pathogenesis and molecular targeting treatment for PD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The primary treatment method for eradicating Helicobacter pylori (H. pylori) infection involves the use of antibiotic-based therapies. Due to the growing antibiotic resistance of H. pylori, there has been a surge of interest in exploring alternative therapies. Cetylpyridinium chloride (CPC) is a water-soluble and nonvolatile quaternary ammonium compound with exceptional broad-spectrum antibacterial properties. To date, there is no documented or described specific antibacterial action of CPC against H. pylori. Therefore, this study aimed to explore the in vitro activity of CPC against H. pylori and its potential antibacterial mechanism. CPC exhibited significant in vitro activity against H. pylori, with MICs ranging from 0.16 to 0.62 μg/mL and MBCs ranging from 0.31 to 1.24 μg/mL. CPC could result in morphological and physiological modifications in H. pylori, leading to the suppression of virulence and adherence genes expression, including flaA, flaB, babB, alpA, alpB, ureE, and ureF, and inhibition of urease activity. CPC has demonstrated in vitro activity against H. pylori by inhibiting its growth, inducing damage to the bacterial structure, reducing virulence and adherence factors expression, and inhibiting urease activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics., Methods: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction., Results: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably., Conclusion: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multiple myeloma (MM) is the second most prevalent hematologic malignancy which remains uncurable. Numerous drugs have been discovered to inhibit MM cells. Indisulam, an aryl sulfonamide, has a potent anti-myeloma activity in vitro and in vivo. This study aims to explore the new mechanism of indisulam and investigate its potential use in combination with melphalan. We examined DNA damage in MM cells through various methods such as western blotting (WB), immunofluorescence, and comet assay. We also identified the role of topoisomerase IIα (TOP2A) using bioinformatic analyses. The impact of indisulam on the RNA and protein levels of TOP2A was investigated through qPCR and WB. Cell proliferation and apoptosis were assessed using CCK-8 assays, Annexin V/PI assays and WB. We predicted the synergistic effect of the combination treatment based on calculations performed on a website, and further explored the effect of indisulam in combination with melphalan on MM cell lines and xenografts. RNA sequencing data and basic experiments indicated that indisulam caused DNA damage and inhibited TOP2A expression by decreasing transcription and promoting degradation via the proteasome pathway. Functional experiments revealed that silencing TOP2A inhibited cell proliferation and induced apoptosis and DNA damage. Finally, Indisulam/melphalan combination treatment demonstrated a strong synergistic anti-tumor effect compared to single-agent treatments in vitro and in vivo. These findings suggest that combination therapies incorporating indisulam and melphalan have the potential to enhance treatment outcomes for MM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Compared with visible light images, thermal infrared images have poor resolution, low contrast, signal-to-noise ratio, blurred visual effects, and less information. Thermal infrared sports target detection methods relying on traditional convolutional networks capture the rich semantics in high-level features but blur the spatial details. The differences in physical information content and spatial distribution of high and low features are ignored, resulting in a mismatch between the region of interest and the target. To address these issues, we propose a local attention-guided Swin-transformer thermal infrared sports object detection method (LAGSwin) to encode sports objects' spatial transformation and orientation information. On the one hand, Swin-transformer guided by local attention is adopted to enrich the semantic knowledge of low-level features by embedding local focus from high-level features and generating high-quality anchors while increasing the embedding of contextual information. On the other hand, an active rotation filter is employed to encode orientation information, resulting in orientation-sensitive and invariant features to reduce the inconsistency between classification and localization regression. A bidirectional criss-cross fusion strategy is adopted in the feature fusion stage to enable better interaction and embedding features of different resolutions. At last, the evaluation and verification of multiple open-source sports target datasets prove that the proposed LAGSwin detection framework has good robustness and generalization ability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)