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Abstract Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, gastrointestinal bleeding, iron deficiency anemia, and arteriovenous malformations (AVMs) affecting the lungs, liver, and brain. Owing to its rarity and diagnostic challenges, early identification is often elusive. Underdiagnosis and prolonged diagnostic delays are prevalent. Here, we present the case of a 63-year-old male who presented with chest pain and was diagnosed with an ST-elevation myocardial infarction (STEMI). Subsequently, he underwent placement of a drug-eluting stent in the right coronary artery (RCA). However, recurrent postoperative epistaxis resulted in severe anemia, prompting further investigation leading to the diagnosis of hereditary hemorrhagic telangiectasia through comprehensive medical history and genetic testing. Future studies are warranted to evaluate reperfusion strategies in HHT patients presenting with myocardial infarction.

Predicting the Cooling Load (CL) of a building’s energy consumption is paramount in optimizing energy usage and mitigating environmental impacts. This study implemented a Decision Tree (DT) model to forecast the CL, aiming to optimize energy efficiency in building operations. To refine the predictive accuracy and generalization capability of the DT model, two advanced metaheuristic optimization algorithms were employed: the Giant Trevally Optimizer (GTO) and the Equilibrium Slime Mould Algorithm (ESMA). The algorithms were pivotal in hyperparameter tuning and model optimization, leading to enhanced performance metrics and more robust predictive outcomes. In this article, the models are evaluated using several metrics, including the Scatter Index (SI), Correlation Coefficient (R²), Mean Absolute Error (MAE), BIAS, and Root Mean Square Error (RMSE), where strong algorithm performance is determined by a high R² value and reduced model error is preferred with lower RMSE and MAE values. The findings yielded promising outcomes. The DTGT model, incorporating the GTO optimizer, exhibited remarkable performance, boasting an exceptional R2 value of 0.996, indicating a near-perfect alignment with the dataset. Moreover, the Root Mean Square Error (RMSE) value of 0.604 underscored the model’s exceptional precision in making predictions, with an impressively low error margin. These results underscore the resilience of the DTGT model as a useful instrument for exceptionally precise CL forecasts. Effective prediction of the CL leads to enhancing energy efficiency, reducing operational costs, and supporting smart building technologies by providing accurate.

Abstract Background Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi. Methods Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes. Results DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection. Conclusions DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium. Graphical Abstract

Background/purpose: Rho GTPase activating protein 11A (ARHGAP11A) can facilitate GTP hydrolysis in RhoA. The functions of ARHGAP11A in oral squamous cell carcinoma (OSCC) have not yet been explored. This study aimed to investigate the expression profile of ARHGAP11A in OSCC, its correlation with patient prognosis, its effect on cell-cycle progression, and the mechanisms by which it is dysregulated. Materials and methods: Bioinformatics analysis was conducted using data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC). Lentiviruses carrying ARHGAP11A shRNAs were employed to determine the effects of ARHGAP11A knockdown on tumor cell proliferation and cell-cycle progression. Dual-luciferase reporter assays were utilized to examine how FOXM1 transcriptionally regulates ARHGAP11A expression. Results: ARHGAP11A upregulation was associated with unfavorable overall survival (OS) in patients with TSCC (HR: 2.142, 95%CI: 1.224–3.749, P = 0.007), but not in patients with OSCC of sites other than the tongue. ARHGAP11A knockdown inhibited the proliferation of TSCC cells in vitro and in vivo, and induced G1 phase arrest. ARHGAP11A knockdown increased GTP-RhoA but decreased p-RB levels, while it did not affect the total expression of RhoA and RB. ARHGAP11A knockdown increased p27 and decreased cyclin E1 expression. ARHGAP11A is transcriptionally activated by FOXM1 via multiple FOXM1 binding sites in the promoter regions in TSCC cells. Conclusion: This study revealed the oncogenic role of ARHGAP11A in TSCC, highlighting its impact on cell-cycle control and tumor proliferation. Furthermore, the regulatory relationship between FOXM1 and ARHGAP11A provides new insights into the transcriptional networks in TSCC.

Abstract Purpose The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. Patients and methods From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. Results Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. Conclusion Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.

Abstract Fuel cell vehicles are a reliable solution to address energy shortages. However, when the road conditions are complex, the system distributes power unevenly between fuel cells and lithium batteries, and cannot effectively absorb the energy generated by braking. In response to this issue, an adaptive control strategy is adopted to allocate the required power of the car to two types of batteries in real time. Fuzzy logic is used to continuously optimize the relevant parameters of the controller based on the vehicle state, and a multi-island genetic algorithm is used to optimize the control strategy, enhancing the global search ability of the control strategy and increasing the vehicle’s ability to absorb and reuse the energy generated by braking. The experiment findings denote that the optimized control strategy increases the remaining capacity of lithium batteries by an average of 1.67%, increases energy recovery by an average of 135 W, increases the overall energy recovery rate by an average of 2.8%, and reduces vehicle fuel consumption by an average of 0.24 L/100 Km. It can be concluded that the optimized adaptive fuzzy control strategy can reduce the probability of over-charging and discharging of lithium batteries and improve the battery life. Meanwhile, the optimized strategy can improve the energy reuse rate, reduce vehicle fuel consumption, lower usage costs. The optimized strategy provides a reference for subsequent research on energy management of fuel cell vehicles.

Abstract Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms. Graphical Abstract

Recent studies have uncovered intriguing connections between Parkinson’s disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise. This has sparked our interest in exploring common molecular mechanisms and genetic factors that may be involved in the relationship between neurodegenerative diseases and tumorigenesis. The Gene4PD database was used to retrieve PD differentially expressed genes (DEGs), the biological functions of differential expression disulfidptosis-related genes (DEDRGs) were analyzed, the ROCs of DEDRGs were analyzed using the GEO database, and the expression of DEDRGs was verified by an MPTP-induced PD mouse model in vivo. Then, the DEDRGs in more than 9000 samples of more than 30 cancers were comprehensively and systematically characterized by using multi-omics analysis data. In PD, we obtained a total of four DEDRGs, including ACTB, ACTN4, INF2, and MYL6. The enriched biological functions include the regulation of the NF-κB signaling pathway, mitochondrial function, apoptosis, and tumor necrosis factor, and these genes are rich in different brain regions. In the MPTP-induced PD mouse model, the expression of ACTB was decreased, while the expression of ACTN4, INF2, and MYL6 was increased. In pan-cancer, the high expression of ACTB, ACTN4, and MYL6 in GBMLGG, LGG, MESO, and LAML had a poor prognosis, and the high expression of INF2 in LIHC, LUAD, UVM, HNSC, GBM, LAML, and KIPAN had a poor prognosis. Our study showed that these genes were more highly infiltrated in Macrophages, NK cells, Neutrophils, Eosinophils, CD8 T cells, T cells, T helper cells, B cells, dendritic cells, and mast cells in pan-cancer patients. Most substitution mutations were G-to-A transitions and C-to-T transitions. We also found that miR-4298, miR-296-3p, miR-150-3p, miR-493-5p, and miR-6742-5p play important roles in cancer and PD. Cyclophosphamide and ethinyl estradiol may be potential drugs affected by DEDRGs for future research. This study found that ACTB, ACTN4, INF2, and MYL6 are closely related to PD and pan-cancer and can be used as candidate genes for the diagnosis, prognosis, and therapeutic biomarkers of neurodegenerative diseases and cancers.

Abstract The stress hyperglycemia ratio (SHR) is established as a reliable marker for assessing the severity of stress-induced hyperglycemia. While its effectiveness in managing patients with Acute Ischemic Stroke (AIS) remains to be fully understood. We aim to explore the relationship between SHR and clinical prognosis in AIS patients and to assess how diabetes status influences this relationship. In this study, we analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, selecting patients with AIS who required ICU admission. These patients were categorized into tertiles based on their SHR levels. We applied Cox hazard regression models and used restricted cubic spline (RCS) curves to investigate relationships between outcomes and SHR. The study enrolled a total of 2029 patients. Cox regression demonstrated that a strong correlation was found between increasing SHR levels and higher all-cause mortality. Patients in the higher two tertiles of SHR experienced significantly elevated 30-day and 90-day mortality rates compared to those in the lowest tertile. This pattern remained consistent regardless of diabetes status. Further, RCS analysis confirmed a progressively increasing risk of all-cause mortality with higher SHR levels. The findings indicate that SHR is association with increased 30-day and 90-day mortality among AIS patients, underscoring its potential value in risk stratification. Although the presence of diabetes may weaken this association, significant correlations persist in diabetic patients.

Abstract This study improves the Logistic chaotic system and combines it with the hyperchaotic Chen system to create a dual chaotic system. The algorithm encrypts images in three stages. In the first stage, a plaintext-related key generation scheme is designed to generate the parameters and initial values of the dual chaotic system. In the second stage, the chaotic sequences generated by the dual chaotic system are used for dynamic DNA encoding and computation. In the third stage, the chaotic sequences generated by the improved Logistic chaotic system are used to perform row-column permutations, completing the scrambling. The security analysis of the encrypted images shows that the algorithm described in this paper is robust and secure, capable of resisting most known attacks. The algorithm is fast in encryption, provides high-quality image reconstruction, and is suitable for scenarios with high comprehensive performance and image quality requirements.

Abstract Contrast-enhanced magnetic resonance neurography (CE-MRN) holds promise for diagnosing brachial plexopathy by enhancing nerve visualization and revealing additional imaging features in various lesions. This study aims to validate CE-MRN’s efficacy in improving brachial plexus (BP) imaging across different patient cohorts. Seventy-one subjects, including 19 volunteers and 52 patients with BP compression/entrapment, injury, and neoplasms, underwent both CE-MRN and plain MRN. Two radiologists assessed nerve visibility, with inter-reader agreement evaluated. Quantitative parameters such as signal intensity (SI), contrast-to-noise ratio (CNR), and contrast ratio (CR) of the C7 nerve were measured. Both qualitative scoring and quantitative metrics were compared between CE-MRN and plain MRN within each patient group. Patient classification followed the Neuropathy Score Reporting and Data System (NS-RADS), summarizing additional imaging features for each brachial plexopathy type. Inter-reader agreement for qualitative assessment was strong. CE-MRN significantly enhanced BP visualization and nerve-tissue contrast across all cohorts, particularly in volunteers and patients with injuries. It also uncovered additional imaging features such as hypointense signals in ganglia, compressed nerve sites, and neoplastic enhancements. CE-MRN effectively mitigated muscle edema and vascular contamination, enabling precise classification of BP injuries. Overall, CE-MRN consistently enhances BP visualization and provides valuable imaging features for accurate diagnosis.

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery remains a standard of care for resectable esophageal cancer (EC), and definitive chemoradiotherapy (dCRT) is an alternative for unresectable diseases. However, it is controversial for the use of the two aggressive regimens in elderly patients. Methods We systematically searched multiple databases for studies comparing overall survival (OS) and/or progression-free survival (PFS) between dCRT and surgery (nCRT + surgery or surgery alone) or between dCRT and radiotherapy (RT) alone in elderly patients (age ≥ 65 years) until March 28, 2024. Statistical analysis was performed using random-effects model. Results Fourty-five studies with 33,729 patients were included. dCRT significantly prolonged OS (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.58–0.70) and PFS (HR = 0.67, 95% CI: 0.60–0.76) compared to RT alone for unresectable EC, and resulted in a worse OS compared to surgery for resectable cases (HR = 1.34, 95% CI: 1.23–1.45). Similar results of OS were also observed when the multivariate-adjusted HRs were used as the measure of effect (dCRT vs. RT alone: HR = 0.65, 95% CI: 0.58–0.73; dCRT vs. surgery: HR = 1.49, 95% CI: 1.28–1.74). Subgroup analyses according to age group (≥ 70, ≥ 75, or ≥ 80 years), study design, study region, histological type, radiation field, chemotherapy regimen revealed comparable results. Conclusions nCRT + surgery is likely a preferred strategy for elderly patients with good physiological conditions; and dCRT is a better alternative for unresectable cases. Advanced age alone does not appear to be a key predictor for the tolerability of the two aggressive treatments.

Objective: To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective target. Methods: The Nup50 gene was knocked down in HUVEC cells using lentiviruses. Colony formation, CCK-8, and flow cytometry were performed to determine the viability, proliferation and apoptosis of HUVEC cells treated with γ-rays，respectively. The extent of DNA damage was evaluated by using comet assay and immunofluorescence staining against γ-H2AX. In addition, we explored the role of Nup50 in DNA damage response (DDR) pathways through western blotting assay. Finally, nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 knockdown. Results: Nup50 knockdown increased the cellular resistance to ionizing radiation. The CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation (t ​= ​4.23, P ​

ObjectiveTo analyze the effects of dapagliflozin on blood glucose levels, renal function, and the levels of miR-21-5p and miR-423-5p in patients with diabetic nephropathy. Methods A total of 98 patients with diabetic nephropathy admitted in The Second People's Hospital of Hefei from February 2022 to October 2023 were selected and divided into the control group (n=49) and the observation group (n=49) according to the random number table method. The control group was treated with metformin, and the observation group was treated with a combination of metformin and dapagliflozin. Blood glucose levels, renal function, expression levels of miR-21-5p, miR-423-5p and serum proinflammatory factors before and after treatment were compared between the two groups, and the incidence of adverse reactions was recorded. Results The levels of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (Cys-C) in both groups decreased after 3 months of treatment, and the above indexes in the observation group were lower than those in the control group (P0.05). Conclusion Daglipzin can help improve the blood sugar level and renal function of patients with diabetes nephropathy, reduce the expression of miR-21-5p, miR-423-5p and the level of serum proinflammatory factors, with good safety.

Background Hypertension is a common chronic disease that seriously endangers the health of the population. The primary-care doctors are the main force in the management of hypertension. However, the doctor-induced therapeutic of inertia greatly affects the achievement of primary-care hypertension control. Objective The aim of this study is to investigate the current status of therapeutic inertia among primary healthcare providers in the diagnosis and treatment process of hypertension, and analyze the causes of therapeutic inertia, providing a reference basis for improving hypertension control rates in China. Methods A simple random sampling method was used to distribute questionnaires to primary healthcare providers in 32 primary healthcare institutions in Tianjin from July to August 2023. The therapeutic inertia in the diagnosis and treatment process of hypertension was evaluated from three dimensions: "soft reasons" and "overestimation of treatment efficacy" as well as "medical insurance policies". Binary Logistic regression analysis was employed to explore the influencing factors of therapeutic inertia. Results A total of 407 questionnaires were distributed in this study, and 386 valid questionnaires were collected, yielding an effective response rate of 94.84%. The average score for primary healthcare providers' knowledge of hypertension diagnosis and treatment was 6 (0.5), with a scoring rate of 61.11% (5.50/9.00). The total score for therapeutic inertia in hypertension management was 48 (7.0), with a scoring rate of 56.55% (45.24/80.00). The scores for the "soft reasons" dimension, "overestimation of treatment efficacy" dimension, and "medical insurance policies" dimension were 26 (4.8), 10 (2.0), and 6 (2.5) respectively, with scoring rates of 51.92% (25.96/50.00), 65.40% (9.81/15.00), and 46.40% (6.96/15.00) respectively. When comparing the average scores of the three dimensions of therapeutic inertia, the "overestimation of treatment efficacy" dimension had the highest score compared to the other two groups (P

Abstract Background Patients with severe infection often require careful fluid management. Intravenous linezolid can increase the fluid volume, whereas oral linezolid can effectively limit the fluid volume. However, the differences in the treatment effect and incidence of thrombocytopenia between oral and intravenous linezolid in patients with severe infection remain unclear. Methods Patients who received linezolid in the intensive care unit of PLA General Hospital from December 2010 to December 2020 were divided into an oral group and intravenous group according to the route of administration, and we further established the PO group and PO-match group by propensity score matching. The anti-infection effect of linezolid and incidence of thrombocytopenia were compared between the two groups. Results In total, 177 patients were enrolled in the study (59 in PO group and 118 in PO-match group). The microbial clearance rate and clinical cure rate were similar between the two groups (70.0% vs. 79.3%, P = 0.293; 72.9% vs. 83.9%, P = 0.213). The 30-day mortality rate was slightly higher in the PO group than in the PO-match group, but the difference was not statistically significant (13.6% vs. 6.8%, P = 0.138). There was no difference in the incidence of thrombocytopenia between the two groups (62.7% vs. 65.3%, P = 0.739). Conclusions There were no significant differences in the treatment effect or incidence of thrombocytopenia between oral and intravenous administration of linezolid in patients with severe infection.

Abstract The transformation and upgrading of traditional supply chain models through digital technology receive widespread attention from the fields of circular economy, manufacturing, and sustainable development. Enterprises need to choose a digital supply chain partner (DSCP) during the process of digital transformation in uncertain and sustainable environments. Thus, the research constructs an innovative decision methodology for selecting the optimal DSCP to achieve digital transformation. The proposed methodology is propounded based upon the entropy measure, generalized Dombi operators, integrated weight-determination model, and complex proportional assessment (COPRAS) method under spherical fuzzy circumstances. Specifically, a novel entropy measure is proposed for measuring the fuzziness of spherical fuzzy (SF) sets, while generalized Dombi operators are presented for fusing SF information. The related worthwhile properties of these operators are discussed. Further, an integrated criteria weight-determination model is presented by incorporating objective weights obtained from the SF entropy-based method and subjective weights from the SF best worst method. Afterward, an improvement of the COPRAS method is proposed based on the presented generalized Dombi operators with SF information. Lastly, the practicability and validity of the proposed methodology are verified by an empirical study that selects an appropriate DSCP for a new energy vehicle enterprise to finish the goal of digital transformation. The sensitivity and comparative analysis are carried out to illustrate the stability, reliability, and superiority of the propounded methodology from multiple perspectives. The results and conclusions indicate that the propounded method affords a synthetic and systematic uncertain decision-making framework for identifying the optimal DSCP with incomplete weight information.

Abstract Soils around bedrock outcrops, even if they are protected by vegetation to some extent after ecological restoration, are prone to being washed away by rock surface flow (RSF) derived from these outcrops in rocky desertification land. However, the extent of the scouring scale and sorting effect of RSF on the soils around outcrops remains unknown. To solve this problem, a series of soils around bedrock outcrops exposed in sloping farmland (SF, without RSF), abandoned land (AL, 1 year of RSF) and shrub–grassland (SG, 5 years of RSF) were examined by the laser diffraction method in a natural ecological restoration area of rocky desertification, where the duration of the RSF is also the time for ecological restoration. It was found that the RSF had a limited effect on the particle size distribution of the soils, only having a significant scouring effect on the soils at the rock–soil interface within a horizontal distance of 2 cm from the outcrops and an insignificant effect on the soils far away from the outcrops in terms of horizontal distance (10 cm and 20 cm). The particle size distributions of the soil around the outcrops were related to erosion caused by the RSF, but mainly benefited from ecological restoration. Compared with SF, the fine particle content in the soils around the outcrops significantly decreased in AL, but significantly increased in SG. Within a short period (1 year) after natural recovery, the RSF had a reduced effect on the fine particles of the soil around the outcrops; however, this did not occur after a long period (5 years). The results of this study further explain the influence of the RSF on soil erosion and leakage loss in karst areas.

Abstract Neoadjuvant therapy (NAT) is an important treatment for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), but neoadjuvant resistance affects the overall treatment outcome. Therefore, it is particularly important to accurately screen the population for NAT and explore the mechanism of resistance. Usually, different chemotherapy regimens cause different drug resistance mechanisms. Prior to combining immunotherapy with chemotherapy, extensive research has been conducted on previous drug resistance mechanisms. Currently, the mainstream NAT for ESCC involves chemotherapy combined with immunotherapy. We have witnessed the remarkable effect of this combination therapy; however, there are still a considerable number of patients whose tumor tissues show no change or even progress after NAT, and their drug resistance mechanisms remain unclear. Hence, we aim to identify relevant evidence that can distinguish and predict the effectiveness of NAT from a clinical perspective in order to provide a clinical basis for future screening of suitable populations for NAT and discovery of drug resistance mechanisms. This study is based in China's high incidence area of esophageal cancer, where enrolled patients all receive the current mainstream NAT regimen resulting in more reliable outcomes.

Abstract Cochlear implants can directly activate the auditory system’s primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration. Graphical Abstract

Free formaldehyde is released due to the addition of aldehyde-based adhesives during the production of fiberboard. This is harmful to human health and pollutes the environment, and for that reason binderless fiberboard has become a research hotspot. There have been reports about pretreatments with white-rot fungi or lignocellulase to produce binderless fiberboard, but there have been no such reports about optimizing the bio-pretreatment conditions. In this study, poplar wood shavings were used for fiberboard production, and the bio-pretreatment conditions with Coriolus versicolor were studied using response surface methodology. After single-factor optimization, the central levels of bran, molasses, and magnesium sulfate were obtained. Further optimization was carried out using Box-Behnken design to study the influence of the factors. A second-order polynomial equation was obtained, and the low p-value (0.001) implied that the model was highly significant. The optimized bio-pretreatment conditions for modulus of rupture (MOR) of the fiberboard were obtained by ridge analysis as 3.021 g of bran, 8.907 g of molasses, and 0.27 g of magnesium sulfate. Under the optimized conditions, MOR of fiberboard reached 27.21±0.64 MPa, which was 2.2 times that of the control fiberboard. Bio-pretreatment with C. versicolor should be a good choice to produce a high-strength binderless fiberboard.

Abstract Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine’s antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.

Abstract Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10−6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.

Abstract Non-iatrogenic trauma of the iliac artery is rarely reported but is always life-threatening. In this report, we describe the case of a child with complete transection and partial disappearance of the iliac artery caused by bicycle handlebar impalement. He experienced catastrophic hemorrhage, malignant arrhythmia, and difficulty in exploring transected vessel stumps. Aggressive infusion, blood transfusion in time, and pediatric vascular characteristics help delay the deterioration during anesthesia induction. Eventually he was successfully rescued by performing interventional balloon occlusion and open revascularization after more than 7 h post-trauma. A series of interventions and precautionary methods may benefit such severely injured patients; thus, these methods should be highlighted.

Abstract Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

Abstract Background Neuroblastoma, a prevalent solid tumor in children, often manifests with hidden onset sites, rapid growth, and high metastatic potential. The prognosis for children with high-risk neuroblastoma remains poor, highlighting the urgent need for novel prognostic models and therapeutic avenues. In recent years, puerarin, as a kind of small molecule drug extracted from Chinese medicine Pueraria lobata, has demonstrated significant anticancer effects on various cancer cell types. In this study, through bioinformatics analysis and in vitro experiments, the potential and mechanism of puerarin in the treatment of neuroblastoma were investigated, and a prognostic model was established. Methods A total of 9 drug-disease related targets were observed by constructing a database of drug targets and disease genes. Besides, GO and KEGG enrichment analysis was performed to explore the potential mechanism of its therapeutic effect. To construct the prognostic model, risk regression analysis and LASSO analysis were carried out for validation. Finally, the prognostic genes were identified. Parachute test and immunofluorescence staining were performed to verify the potential mechanism of puerarin in neuroblastoma treatment. Results Three prognostic genes, i.e., BIRC5, TIMP2 and CASP9, were identified. In vitro studies verified puerarin's impact on BIRC5, TIMP2, and CASP9 expression, inhibiting proliferation in neuroblastoma SH-SY5Y cells. Puerarin disrupts the cytoskeleton, boosts gap junctional communication, curtailing invasion and migration, and induces mitochondrial damage in SH-SY5Y cells. Conclusions Based on network pharmacology and bioinformatics analysis, combined with in vitro experimental verification, puerarin was hereby observed to enhance GJIC in neuroblastoma, destroy cytoskeleton and thus inhibit cell invasion and migration, cause mitochondrial damage of tumor cells, and inhibit cell proliferation. Overall, puerarin, as a natural medicinal compound, does hold potential as a novel therapy for neuroblastoma.

Abstract Background Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. Methods Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16 S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. Results PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p

Abstract Background Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys. Methods Differential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes’ functions in WiT-49 cells. Results The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients’ prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells. Conclusions EMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Abstract Background Early prediction of survival of hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is vital. We aimed to establish a nomogram to predict the survival probability of AECOPD patients. Methods Retrospectively collected data of 4601 patients hospitalized for AECOPD. These patients were randomly divided into a training and a validation cohort at a 6:4 ratio. In the training cohort, LASSO-Cox regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of AECOPD patients. A model was established based on 3 variables and visualized by nomogram. The performance of the model was assesed by AUC, C-index, calibration curve, decision curve analysis in both cohorts. Results Coexisting arrhythmia, invasive mechanical ventilation (IMV) usage and lower serum albumin values were found to be significantly associated with lower survival probability of AECOPD patients, and these 3 predictors were further used to establish a prediction nomogram. The C-indexes of the nomogram were 0.816 in the training cohort and 0.814 in the validation cohort. The AUC in the training cohort was 0.825 for 7-day, 0.807 for 14-day and 0.825 for 21-day survival probability, in the validation cohort this were 0.796 for 7-day, 0.831 for 14-day and 0.841 for 21-day. The calibration of the nomogram showed a good goodness-of-fit and decision curve analysis showed the net clinical benefits achievable at different risk thresholds were excellent. Conclusion We established a nomogram based on 3 variables for predicting the survival probability of AECOPD patients. The nomogram showed good performance and was clinically useful.

Abstract The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB–IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

Coating modification is an important way to enhance the reactivity of aluminum powder. In this paper, ammonium perchlorate and aluminum powder were assembled into energetic microunits by liquid deposition method. Spherical particles with AP as shell and ultrafine aluminum powder as the core (Al@AP) were gained. The micromorphology results show that the coated particles are about 5 μm, and the coating layer is evenly distributed on the outer surface of aluminum powder, indicating a complete coating. The energetic microunits were implanted into the nitrate ester plasticizing adhesive system (NEPE) as solid phase fillers. The effect of filler on the rheological properties, safety, mechanical properties, thermal reaction and energy properties of the system was analyzed by comparing with the raw aluminum filler. The test results show that the rheological properties, mechanical properties and pressure index of NEPE containing system Al@AP meets the requirements of solid propellant charging. Compared with Al based propellant, the mechanical sensitivity and thermal sensitivity are decreased, the safety is better, and the explosion heat of the propellant is increased by 7.8%. The engine test shows that the specific impulse is increased by 1.2 s. Al@AP can improve the energy output and safety of NEPE propellant, and has potential application prospects in high-energy propellants.

Abstract Background Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. Methods We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. Results From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8–14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. Conclusions Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. Trial registration ChiCTR2100046811; 28/05/2021.

Abstract Background Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. Objective This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. Methods Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People’s Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. Result The NSE levels in the MP + group were 17.86 (14.29–22.54) ng/mL, while those in the MP- group were 17.89 (14.10–21.66) ng/mL, both of which were higher than the control group’s NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95–34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27–21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. Conclusion Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia.

Abstract This study aims to investigate the potential impact of high-dose radiotherapy (RT) on brain structure, cognitive impairment, and the psychological status of patients undergoing brain tumor treatment. We recruited and grouped 144 RT-treated patients with brain tumors into the Low dose group (N = 72) and the High dose group (N = 72) according to the RT dose applied. Patient data were collected by using the HADS and QLQ-BN20 system for subsequent analysis and comparison. Our analysis showed no significant correlation between the RT doses and the clinicopathological characteristics. We found that a high dose of RT could aggravate cognitive impairment and deteriorate patient role functioning, indicated by a higher MMSE and worsened role functioning in the High dose group. However, the depression status, social functioning, and global health status were comparable between the High dose group and the Low dose group at Month 0 and Month 1, while being worsened in the High dose group at Month 3, indicating the potential long-term deterioration of depression status in brain tumor patients induced by high-dose RT. By comparing patient data at Month 0, Month 1, Month 3, Month 6, and Month 9 after RT, we found that during RT treatment, RT at a high dose could aggravate cognitive impairment in the short term and lead to worsened patient role functioning, and even deteriorate the overall psychological health status of patients in the long term.

Background International Mission on Prognosis and Analysis of Clinical Trial (IMPACT) and Corticosteroid Randomisation after Significant Head Injury (CRASH) are internationally influential prognostic models for traumatic brain injury (TBI), which need to be continuously developed, improved and continuously verified externally to ensure generalizability to different settings. Objective To verify and compare the prognostic evaluation values of IMPACT and CRASH simultaneously in TBI population in China. Methods A total of 210 TBI patients treated in Zhengzhou Central Hospital Affiliated to Zhengzhou University from 2017 to 2019 were retrospectively selected as the study objects, and the basic information of the included patients was collected. The 14-day survival and 6-month Glasgow prognostic score (GOS) of the patients were followed up until June 2021, with a termination event of loss of follow-up. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive efficacy of IMPACT and CRASH models in TBI patients, and the area under ROC curve (AUC) was calculated. Brier score was used to evaluate the calibration degree of the model. Results The average age of the patients was (54.0±17.4) years. The ROC curves of the IMPACT model and CRASH model to predict the prognosis of TBI patients were plotted, respectively, and the results showed that the AUCs of IMPACT core model, CT model and laboratory model to predict the poor prognosis of GOS in TBI patients at 6 months was 0.807 (95%CI=0.747-0.866, P

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

The WRKY transcription factors comprise one of the most extensive gene families and serve as pivotal regulators of plant responses to heavy metal stress. They contribute significantly to maintaining plant growth and development by enhancing plant tolerance. However, research on the role of WRKY genes in response to cadmium (Cd) stress in mustard is minimal. In this study, we conducted a genome-wide analysis of the mustard WRKY gene family using bioinformatics. The results revealed that 291 WRKY putative genes (BjuWRKYs) were identified in the mustard genome. These genes were categorized into seven subgroups (I, IIa-e and III) through phylogenetic analysis, with differences in motif composition between each subgroup. Homology analysis indicated that 31.62% of the genes originated from tandem duplication events. Promoter analysis revealed an abundance of abiotic stress-related elements and hormone-related elements within the BjuWRKY genes. Transcriptome analysis demonstrated that most BjuWRKY genes exhibited differential expression patterns at different Cd treatment stages in mustard. Furthermore, 10 BjuWRKY genes were confirmed to respond to Cd stress through the construction of a BjuWRKY protein interaction network, prediction of hub genes, and real-time fluorescence quantitative PCR analysis, indicating their potential involvement in Cd stress. Our findings provide a comprehensive insight into the WRKY gene family in mustard and establish a foundation for further studies of the functional roles of BjuWRKY genes in Cd stress response.

Tree-tree interactions are fundamental in shaping forest community dynamics, driven by factors such as nutrient availability and species composition. While recent research underscores the role of functional traits in influencing tree sensitivity to neighborhood interactions, a clear consensus is lacking on how these traits interact with biotic and abiotic factors. Based on a multi-level modeling approach, this study examines how specific leaf area (SLA), potential maximum tree height (Hmax), and wood density (WD) mediate the combined effects of soil nutrients and neighborhood biotic factors on net tree interactions among 4,210 individual stems for 13 species in a 30-ha temperate forest in northeastern China. The findings indicate that while functional traits independently account for a small portion of the variation in net tree interaction intensity (NIntC), they significantly mediate the effects of neighborhood crowding, neighborhood structure, and soil nutrients on NIntC. Specifically, only the response of growth NIntC of species with low-Hmax to available phosphorus (AP) was consistent with the stress gradient hypothesis. Conspecific neighborhood crowding consistently increases competitive NIntC, whereas heterospecific neighborhood crowding significantly facilitates survival NIntC. Moreover, the positive impact of heterospecific crowding on survival NIntC is significantly greater for high-Hmax species compared to low-Hmax species. Neighborhoods with higher tree species diversity, greater size heterogeneity, and more uniform distribution increase the facilitative NIntC of high-SLA or high-WD species but intensify the competitive NIntC of low-SLA or low-WD species. Our results also indicate that the relative importance of neighborhood structure exceeds that of soil nutrients in explaining variation in NIntC. When environmental conditions are difficult to change, adjusting the forest stand structure may be a more efficient way to regulate the intensity of interactions between trees and improve forest productivity.

Summary: Background: Which cell populations that determine the fate of bacteria in infectious granulomas remain unclear. Leprosy, a granulomatous disease with a strong genetic predisposition, caused by Mycobacterium leprae infection, exhibits distinct sub-types with varying bacterial load and is considered an outstanding disease model for studying host–pathogen interactions. Methods: We performed single-cell RNA and immune repertoire sequencing on 11 healthy controls and 20 patients with leprosy, and integrated single-cell data with genome-wide genetic data on leprosy. Multiplex immunohistochemistry, and in vitro and in vivo infection experiments were conducted to confirm the multimodal omics findings. Findings: Lepromatous leprosy (L-LEP) granulomas with high bacterial burden were characterised by exhausted CD8+ T cells, and high RGS1 expression in CD8+ T cells was associated with L-LEP. By contrast, tuberculoid leprosy (T-LEP) granulomas with low bacterial burden displayed enrichment in resident memory IFNG+ CD8+ T cells (CD8+ Trm) with high GNLY expression. This enrichment was potentially attributable to the communication between IL1B macrophages and CD8+ Trm via CXCL10-CXCR3 signalling. Additionally, IL1B macrophages in L-LEP exhibited anti-inflammatory phenotype, with high APOE expression contributing to high bacterial burden. Conversely, IL1B macrophages in T-LEP were distinguished by interferon-γ induced GBP family genes. Interpretation: The state of IL1B macrophages and functional CD8+ T cells, as well as the relationship between them, is crucial for controlling bacterial persistence within granulomas. These insights may indicate potential targets for host-directed immunotherapy in granulomatous diseases caused by mycobacteria and other intracellular bacteria. Funding: The Key research and development program of Shandong Province (2021LCZX07), Natural Science Foundation of Shandong Province (ZR2023MH046), Youth Science Foundation Cultivation Funding Plan of Shandong First Medical University (Shandong Academy of Medical Sciences) (202201-123), National Natural Science Foundation of China (82471800, 82230107, 82273545, 82304039), the China Postdoctoral Science Foundation (2023M742162), Shandong Province Taishan Scholar Project (tspd20230608), Joint Innovation Team for Clinical & Basic Research (202410), Central guidance for local scientific and technological development projects of Shandong Province (YDZX2023058).

In this study, active and intelligent films were fabricated using M. esculenta starch (MES), gum ghatti (GG) and R. nigrum extract (RNE) and their functionality, physicochemical properties and practical application were assessed. Incorporation of GG decreased water vapor permeability (WVP) (9.73 to 8.91 × 10-11 g m−1 s−1 Pa−1), increased tensile strength (TS) (16.63 to 44.45 MPa) and elongation at break (EAB) (4.47 to 6.82%) of MES film. Incorporation of RNE decreased WVP (8.91 to 7.87 × 10−11 g m−1 s−1 Pa−1) and TS (44.45 to 26.33 MPa) of MES-GG film. MES-GG-RNE films showed enhanced thermal stability, light barrier performance, excellent pH and ammonia sensitivities, strong antioxidant activity, and significant visible color change when monitoring beef freshness. Findings supported the application of this strategy in fabrication of MES-GG-RNE films for active and intelligent packaging. Further study on stability, sustainability and consumer acceptability of films is in progress.

BackgroundLinarine is a natural chemical component widely found in Buddleja officinalis Maxim., Chrysanthemum indicum L., Mentha canadensis L., and other medicinal plants. Modern pharmacological studies have shown that linarine with good anti-inflammatory and antioxidant activities can inhibit the proliferation and induce apoptosis of many kinds of tumor cells. Moreover, linarine showed protective effect on the liver, kidneys, and other organs.MethodsInflammation model of human corneal epithelial cell (HCEC) was constructed using NaCl induction, and cytotoxicity was detected by the CCK8 assay. The levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were measured using Enzyme-linked immunoassay (ELISA). Chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops in a desiccator established a mouse model of dry eye disease (DED). The following parameters were recorded: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. The levels of inflammatory factors mitogen activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), c-Jun N-terminal kinase (JNK), IL-1β, Interleukin 18(IL-18), A2A, A3, P2X4, P2X7, P2Y1 were measured by using immunofluorescence (IF) staining.ResultsLinarine can inhibit the secreation of TNF-α, and IL-1β in HCECs. Linarine prolonged tear film rupture time, promoted tear secretion, repaired corneal damage, and reduced the levels of inflammatory factors of MAPK, NF-kB, JNK, IL-1β, IL-18, and modulated the levels of the purinergic receptor.ConclusionsLinarine is effective in treating dry eye in mice by inhibiting purinergic receptors-mediated inflammatory response.

Abstract Solid polymer electrolytes (SPEs) are pivotal in advancing the practical implementation of all‐solid‐state batteries. Poly(1,3‐dioxane) (PDOL)‐based electrolytes have attracted significant attention due to the pseudo‐high conductivity achieved through sophisticated in situ polymerization methods; however, such PDOL‐based electrolytes present challenges of crystallization over time and monomers residual during processing. In this study, integrating LiTFSI and LiDFOB as a universal copolymerization strategy for developing high‐performance PDOL electrolytes with a wide range of epoxy crosslinkers is proposed. It is discovered that this approach leverages the protective effects of TFSI anions on the boron active center and catalyzes polymer chain growth via crosslinking. The homogenously crosslinked (benzene‐centered) PDOL electrolyte exhibits remarkable thermo‐mechanical stability (up to 100 °C), high ion migration number (tLi+ = 0.42), a wide electrochemical window (≈5.0 V vs Li+/Li), and high ionic conductivity (4.5×10−4 S cm−1). Notably, the crosslinked PDOL electrolyte is in the all‐solid‐state with minimal monomer/oligomer residual, exhibiting no crystallization during relaxation, delivering a robust performance in all‐solid‐state lithium metal batteries.

The depletion of fossil fuels has fueled an increased interest in biomass resources usage for heat and electricity generation. As an important biomass resource, Chinese medicine residues have great potential in substituting fossil fuels. However, that is basically limited by its poor properties, including low bulk density, high moisture content, and inhomogeneous structure. Herein, a safe and sustainable strategy was reported to prepare a high-quality densified pellet derived from Chinese medicine residues to address these worries. In this process, mixed and simple size materials were densified under various moisture content and pressure using a laboratory electronic tablet press machine equipped a single pellet mold. Results showed that higher pressure, ideal moisture content (∼6.5 %), and mixed particle size could densify better quality pellets. These findings pave the way for the safely and efficient resource utilization of Chinese medicine residues, as well as providing theoretical guidance and technical support for the household heating.

BackgroundMost studies have indicated that peripheral insulin-like growth levels factor-1 (IGF-1) is valuable in diagnosing heart failure, although the results have been inconsistent. To help solve the debate, we performed a meta-analysis to explore the relationship between IGF-1 and heart failure (HF).MethodsWe conducted an extensive search across various databases such as Embase, Cochrane Library, Pubmed, Medline, and Web of Science on May 30, 2023. From the extensive pool of studies, we selected 16 relevant articles, encompassing a total of 1,380 cases and 1,153 controls, to conduct a rigorous meta-analysis.ResultsThe total results indicated that there is an association between lower IGF-1 level and HF. The random-effects model yielded a pooled standardized mean difference (SMD) of −0.598 (95% CI: −1.081 to −0.116, P = 0.015). Further subgroup analysis also showed that IGF-1 levels were associated with HF in the age difference ≥5 years subgroup and body mass index difference >1 subgroup. Additionally, significant association between IGF-1 levels and HF were detected in the “serum” samples and “Europe” subgroups. Importantly, we observed IGF-1 showed significant lower levels in patients with reduced ejection fraction (HFrEF) compared to the controls, not in patients with preserved ejection fraction (HFpEF). The Begg’s and Egger’s tests revealed no indication of publication bias.ConclusionsOur meta-analysis has provided evidence suggesting a substantial correlation between reduced levels of IGF-1 and the occurrence of HF. Further prospective studies are necessary to ascertain the use of IGF-1 as a reliable biomarker for diagnosing HF, especially for HFrEF. But the diagnosis of HFpEF should be cautious.

BackgroundCommunity-acquired pneumonia (CAP) is a common infectious disease characterized by inflammation of the lung parenchyma in individuals who have not recently been hospitalized. It remains a significant cause of morbidity and mortality worldwide. Aspirin is a widely used drug, often administered to CAP patients. However, the benefits of aspirin remain controversial.ObjectiveWe sought to determine whether aspirin treatment has a protective effect on the outcomes of CAP patients.MethodsWe selected patients with CAP from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) balanced baseline differences. A multivariate Cox regression model assessed the relationship between aspirin treatment and 28-day mortality.ResultsA total of 3,595 patients were included, with 2,261 receiving aspirin and 1,334 not. After PSM, 1,219 pairs were matched. The 28-day mortality rate for aspirin users was 20.46%, lower than non-users. Multivariate Cox regression indicated aspirin use was associated with decreased 28-day mortality (HR 0.75, 95% CI 0.63–0.88, p < 0.001). No significant differences were found between 325 mg/day and 81 mg/day aspirin treatments in terms of 28-day mortality, hospital mortality, 90-day mortality, gastrointestinal hemorrhage, and thrombocytopenia. However, intensive care unit (ICU) stay was longer for the 325 mg/day group compared to the 81 mg/day group (4.22 vs. 3.57 days, p = 0.031).ConclusionAspirin is associated with reduced 28-day mortality in CAP patients. However, 325 mg/day aspirin does not provide extra benefits over 81 mg/day and may lead to longer ICU stays.

Statins are widely used in the treatment of hyperlipidemia disease, which are refractory in the municipal sewage treatment plant. The photocatalytic degradation of statins by the Z-scheme heterostructured photocatalyst is confirmed, but the degradation mechanism of statins needs to be further revealed. In this study, the effects of photocatalyst dosage, solution pH and humic acid (HA) on the photocatalysis of fluvastatin by ZnIn2S4/Bi2WO6 Z-scheme heterostructured photocatalyst (ZIS/BWO photocatalyst) were investigated and the degradation mechanism was proposed. Results showed that adsorption of fluvastatin was improved with the increase of photocatalyst dosage, but photoinduced desorption and light scattering resulted in the decrease of the removal of fluvastatin with high dosage. 0.2[Formula: see text]g/L of the ZIS/BWO photocatalyst was optimal dosage. 65.21% of fluvastatin was removed at pH=9, because high concentration of OH− was conducive to produce ⋅OH. The change of pH, competition of photons and active sites, and trapping of reactive oxygen species (ROS) by carboxyl group of HA combined to inhibit the photocatalysis of fluvastatin in the presence of HA. The C–C, C[Formula: see text]C and C–N bonds of fluvastatin were attacked by a variety of ROS to generate degradable intermediates that were easily mineralized to H2O and CO2.

Atherosclerosis is a chronic inflammatory disease characterized by innate and adaptive immune responses, which seriously threatens human life and health. It is a primary cause of coronary heart disease, myocardial infarction, and peripheral vascular disease. Research has demonstrated that immune cells are fundamental to the development of atherosclerosis and chronic inflammation. Therefore, it is anticipated that immunotherapy targeting immune cells will be a novel technique in the management of atherosclerosis. This article reviews the growth of research on the regulatory role of immune cells in atherosclerosis and targeted therapy approaches. The purpose is to offer new therapeutic approaches for the control and treatment of cardiovascular illnesses caused by atherosclerosis.

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer.