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AIM: To explore the DNA methylation of COL4A1 in ultraviolet-B (UVB)-induced age-related cataract (ARC) models in vitro and in vivo. METHODS: Human lens epithelium B3 (HLEB3) cells and Sprague Dawley rats were exposure to UVB respectively. The MTT assay was utilized to evaluate cell proliferation. Flow cytometry was employed for analysis of cell apoptosis and cell cycle. COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence. The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR (BSP). DNMTs and TETs mRNA levels was examined by RT-PCR. RESULTS: UVB exposure decreased HLEB3 cells proliferation, while increased the apoptosis rate and cells were arrested in G0/G1 phase. COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls. Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure. Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls, while expressions of TETs including TET1/2/3 showed the opposite trend. Results from the UVB treated rat model further confirmed the decreased expression of COL4A1, hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/ in UVB exposure group. CONCLUSION: DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

Abstract Background Previous research has discovered that surfactant protein A (SP-A) is involved in the pathophysiology processes of certain lung illnesses. However, no definitive clinical studies have delved into the function of SP-A in individuals afflicted with community-acquired pneumonia (CAP). A prospective cohort study was used to investigate the relationships between blood SP-A levels and the severity and prognosis among CAP patients. Materials and methods This study included 260 patients with CAP. Clinical traits and demographic data were examined during hospitalization. The concentrations of serum SP-A and serum interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). In addition, to evaluate the severity of CAP, a variety of scores, including the CURB-65, PSI, SMART-COP, and APACHE II, were employed. Results The serum levels of SP-A at admission exhibited a gradual decline as the severity scores of CAP increased. Through Spearman correlation analysis, we observed an association between serum SP-A and some clinical indicators among CAP patients. Furthermore, results from a multiple linear regression model suggested changes in PSI scores (-17.868 scores, 95% CI: -32.743, -2.993) affect serum SP-A more than CURB-65 (-0.547 scores, 95% CI: -0.964, -0.131), SMART-COP (-1.097 scores, 95% CI: -1.889, -0.304) and APACHE II (-3.475 scores, 95% CI: -5.874, -1.075) with age, hypertension, diabetes mellitus, cerebral infarction, coronary heart disease, and bronchitis adjusted. In addition, the prognosis in CAP patients was monitored. Throughout their hospital stay, higher serum levels of SP-A decreased the risks of mechanical ventilation (RR: 0.315; 95% CI: 0.106, 0.937), vasoactive agents (RR: 0.165; 95% CI: 0.034, 0.790), intensive care unit (ICU) admissions (RR: 0.218; 95% CI: 0.066, 0.717) and longer hospital stays (RR: 0.397; 95% CI: 0.167, 0.945). Conclusion In CAP patients, inverse dose-response correlations exist between serum SP-A levels with severity scores as well as prognosis at admission, suggesting that SP-A may take part in the CAP pathophysiological processes. Moreover, lower serum SP-A on admission is associated with an elevated prognostic risk of mechanical ventilation, the use of vasoactive agents, longer hospital stays, ICU admission, and mortality. Therefore, as a biomarker, SP-A may have the potential to predict the severity and poor prognosis of CAP patients.

Wicker home products, handcrafted from sustainable materials such as willow, vine, and bamboo, embody principles of sustainable development. However, they face a lack of clear appeal among young consumers in the Chinese market. This study utilizes the AHP-CRITIC-TOPSIS method to examine user preferences for Funan Wicker home products to enhance the original products based on young users’ choices in the contemporary era. Using the AHP method, 14 evaluation indicators were selected across three key factors and determined subjective weights. Objective weights were calculated using the CRITIC method to establish a comprehensive ranking. Subsequently, the TOPSIS method was employed to evaluate and order the nine design alternatives. The findings highlight a strong emphasis on emotional criteria in the evaluation process, with variables such as Weaving Fineness, Stress Release, Pleasure, and Cultural Value significantly influencing user preference. According to the calculations, the program IX with the highest proximity emerged as the optimal choice. Based on these results, the study refines design focus and quantitative indexes for willow home product designers, proposing innovative design methods that offer theoretical support and practical guidance for the development of willow products in Funan, China.

The development of conductive coatings has significant implications for microelectronics and electrochemistry. However, conductive coatings may exhibit different electrochemical properties when prepared on different substrate materials. This research explores the comparative performance of graphene, graphene oxide (GO), and silver nanoparticle (Ag NP) composites as conductive coatings on diverse substrate materials, including polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), and glass. The study employed various preparation methods, such as mixing conductive materials with substrate materials and preparing copolymer composite materials. The conductive coating approach was found to be the most straightforward and convenient, with broader development prospects and fewer restrictive conditions. The results indicate that the distinct surface characteristics of the substrate materials influence the conductive properties of coating materials. Consequently, results show that graphene exhibits the highest conductivity on all three substrates, while GO is more conductive than Ag NPs on PMMA and PDMS but less conductive than Ag NPs on glass. That offers valuable insights into the selection of substrate materials and coating materials for the preparation of conductive materials.

Abstract Healthcare-associated infections (HAIs) represent a major global health burden, which necessitate effective frameworks to identify potential risk factors and estimate the corresponding direct economic disease burden. In this article, we proposed a framework designed to address these needs through a case study conducted in a Tuberculosis (TB) hospital in Hubei Province, China, using data from 2018 to 2019. A comprehensive multistep procedure was developed, including ethical application, participant inclusion, risk factor identification, and direct economic disease burden estimation. In the case study, ethical approval was obtained, and patient data were anonymized to ensure privacy. All TB hospitalized patients over the study period were included and classified into groups with and without HAIs after screening the inclusion and exclusion criteria. Key risk factors, including gender, age, and invasive procedure were identified through univariate and multivariate analyses. Then, propensity score matching was employed to select the balanced groups with similar characteristics. Comparisons of medical expenditures (total medical expenditure, medicine expenditure, and antibiotics expenditure) and hospitalization days between the balanced groups were calculated as the additional direct economic disease burden measures caused by HAIs. This framework can serve as a tool for not only hospital management and policy-making, but also implementation of targeted infection prevention and control measures. Moreover, it has the potential to be applied in various healthcare settings at local, regional, national, and international levels to identify high-risk areas, optimize resource allocation, and improve hospital management and governance, as well as inter-organizational learning. Challenges to implement the framework are also raised, such as data quality, regulatory compliance, considerations on unique nature of communicable diseases and other diseases, and training need for professionals.

Abstract Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.

Abstract Background An increased risk of diabetes mellitus (DM) after COVID-19 has been reported in the United States, Europe, and Asia. The burden of COVID-related DM has yet to be described in Africa, where the overall risk of DM has been increasing rapidly. Our objective was to compare the prevalence of pre-DM and DM in Nigerian individuals with a history of COVID-19 to individuals without known COVID-19 infection. Methods We undertook a retrospective cohort study with 256 individuals with a past medical history of COVID-19 with no history of pre-DM or DM and 256 individuals without a history of COVID-19 or pre-DM/DM. Participants were categorized as pre-DM (fasting capillary glucose 100–125 mg/dL) or DM (fasting capillary glucose ≥ 126 mg/dL). We employed univariate and multivariable logistic regression to identify key predictors and adjust for confounders related to hyperglycaemia risk factors. Additionally, we used multinomial logistic regression to analyze the relationship between COVID-19 history and diabetes status, distinguishing between normal, pre-diabetic, and diabetic glucose levels. All models were adjusted for age, gender, hypertension, physical activity, central adiposity, and family history of DM. Results Compared to the control group, those with a history of COVID-19 had a similar median age (38 vs. 40 years, p = 0.84), had a higher proportion of men (63% vs. 49%), and had a lower prevalence of central adiposity (waist: hip ratio ≥ 0.90 for males and WHR ≥ 0.85 for females) (48% vs. 56.3%, p = 0.06). Of the 256 with a history of COVID-19, 44 (17%) required in-patient care. The median (interquartile range) time interval between COVID-19 diagnosis and the glycaemic assessment was 19 (IQR: 14, 24) months. Pre-DM prevalence was 27% in the post-COVID-19 group and 4% in the control group, whereas the prevalence of DM was 7% in the post-COVID-19 group and 2% in the control group. After multivariable adjustment, the odds of pre-DM were 8.12 (95% confidence interval (CI): 3.98, 16.58; p

Abstract. Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Abstract Growing evidence suggests a potential link between the gut microbiome and schizophrenia. However, it is unclear whether the gut microbiome is causally associated with schizophrenia. We performed two-sample bidirectional Mendelian randomization to detect bidirectional causal relationships between gut microbiome and schizophrenia. Summary genome-wide association study (GWAS) datasets of the gut microbiome from the MiBioGen consortium (n = 18,340) and schizophrenia (n = 130,644) were utilized in our study. Then a cohort of sensitive analyses was followed to validate the robustness of MR results. We identified nine taxa that exerted positive causal effects on schizophrenia (OR: 1.08–1.16) and six taxa that conferred negative causal effects on schizophrenia (OR: 0.88–0.94). On the other hand, the reverse MR analysis showed that schizophrenia may increase the abundance of nine taxa (OR: 1.03–1.08) and reduce the abundance of two taxa (OR: 0.94). Our study unveiled mutual causal relationships between gut microbiome and schizophrenia. The findings may provide evidence for the treatment potential of gut microbiomes in schizophrenia.

Objective: Based on the inhibitory effect of bacillomycin D (BD) and chitosan (CTS) on Penicillium digitatum, the effect of BD and CTS combination on post-harvest disease control and freshness preservation of sugar oranges was investigated. Method: Sugar oranges as the research object, mold strains were screened in the moldy sugar oranges for identification, and the minimum inhibitory concentration and FIC index of BD and CTS against P. digitatum were determined by the checkerboard microdilution method. Finally, treated sugar oranges with BD and CTS were stored and preserved under the conditions of 28 ℃ and 90% relative humidity, and the changes of morbidity, weight loss, hardness, soluble solids, enzyme activity and other indicators were determined. Result: The isolated and purified fungus from the sugar orange was identified as P. digitatum and named P. digitatum strain L6. The minimum inhibitory concentrations of BD and CTS for P. digitatum were 42.19 and 62.5 mg/L, respectively, and the FIC index was 0.75, indicating that the inhibition of BD and CTS on P. digitatum was cumulative. The storage and preservation results showed that after 15 days of storage, the weight loss rates of BD, CTS, and BD+CTS treated sugar oranges were 0.99%, 1.62%, and 1.09%, respectively, which were 66.44%, 45.08%, and 63.05% lower compared to the control groups. In addition, the results of changes in titratable acidity, soluble solids, ascorbic acid, and plant-related enzyme activities also indicated that BD, CTS, and BD+CTS combination treatments had good preservation effects on sugar oranges, with the BD+CTS combination treatment group having the best results. Conclusion: Both BD and CTS had significant inhibition effect on P. digitatum, which could be used for storage and preservation of sugar orange to extend the shelf life. The combination of the two could not only enhance the preservation effect, but also the low price of CTS could reduce the use of BD and save the cost.

Background: Cancer is the most common cause of death and is still a serious public health problem. Alkaloids, a class of bioactive compounds widely diffused in plants, especially Chinese herbs, are used as functional ingredients, precursors, and lead compounds in food and clinical applications. Among them, aporphine alkaloids (AAs), as an important class of isoquinoline alkaloids, exert a strong anticancer effect on multiple cancer types. Aim of review: This review aims to comprehensively summarize the phytochemistry, pharmacokinetics, and bioavailability of seven subtypes of AAs and their derivatives from various plants and highlight their anticancer bioactivities and mechanisms of action.Key Scientific Concepts of Review.The chemical structures and botanical diversity of AAs are elucidated, and promising results are highlighted regarding the potent anticancer activities of AAs and their derivatives, contributing to their pharmacological benefits. This work provides a better understanding of AAs and combinational anticancer therapies involving them, thereby improving the development of functional food containing plant-derived AA and the clinical application of AAs.

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor β (TGFβ) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFβ inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1 (as those levels found in patients’ synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the “PLGA-PFD + HA” strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Abstract SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial–mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration.

AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

Abstract Background Adverse birth outcomes, including preterm birth, low birth weight, and stillbirth, remain a major global health challenge, particularly in developing regions. Understanding the possible risk factors is crucial for designing effective interventions for birth outcomes. Accordingly, this study aimed to develop a predictive model for adverse birth outcomes among childbearing women in Sub-Saharan Africa using advanced machine learning techniques. Additionally, this study aimed to employ a novel data science interpretability techniques to identify the key risk factors and quantify the impact of each feature on the model prediction. Methods The study population involved women of childbearing age from 26 Sub-Saharan African countries who had given birth within five years before the data collection, totaling 139,659 participants. Our data source was a recent Demographic Health Survey (DHS). We utilized various data balancing techniques. Ten advanced machine learning algorithms were employed, with the dataset split into 80% training and 20% testing sets. Model evaluation was conducted using various performance metrics, along with hyperparameter optimization. Association rule mining and SHAP analysis were employed to enhance model interpretability. Results Based on our findings, about 28.59% (95% CI: 28.36, 28.83) of childbearing women in Sub-Saharan Africa experienced adverse birth outcomes. After repeated experimentation and evaluation, the random forest model emerged as the top-performing machine learning algorithm, with an AUC of 0.95 and an accuracy of 88.0%. The key risk factors identified were home deliveries, lack of prenatal iron supplementation, fewer than four antenatal care (ANC) visits, short and long delivery intervals, unwanted pregnancy, primiparous mothers, and geographic location in the West African region. Conclusion The region continues to face persistent adverse birth outcomes, emphasizing the urgent need for increased attention and action. Encouragingly, advanced machine learning methods, particularly the random forest algorithm, have uncovered crucial insights that can guide targeted actions. Specifically, the analysis identifies risky groups, including first-time mothers, women with short or long birth intervals, and those with unwanted pregnancies. To address the needs of these high-risk women, the researchers recommend immediately providing iron supplements, scheduling comprehensive prenatal care, and strongly encouraging facility-based deliveries or skilled birth attendance.

Abstract Many DNA viruses develop various strategies to inhibit cell death to facilitate their replication. However, whether influenza A virus (IAV), a fast-replicating RNA virus, attenuates cell death remains unknown. Here, we report that IAV infection induces TAK1 phosphorylation in a murine alveolar epithelial cell line (LET1) and a murine fibroblastoma cell line (L929). The TAK1-specific inhibitor 5Z-7-Oxzeneonal (5Z) and TAK1 knockout significantly enhance IAV-induced apoptosis, as evidenced by increased PARP, caspase-8, and caspase-3 cleavage. TAK1 inhibition also increases necroptosis as evidenced by increased RIPK1S166, RIPK3T231/S232, and MLKLS345 phosphorylation. Mechanistically, TAK1 activates IKK, which phosphorylates RIPK1S25 and inhibits its activation. TAK1 also activates p38 and its downstream kinase MK2, which phosphorylates RIPK1S321 but does not affect RIPK1 activation. Further investigation revealed that the RIPK1 inhibitor Nec-1 and RIPK1 knockout abrogate IAV-induced apoptosis and necroptosis; re-expression of wild-type but not kinase-dead (KD)-RIPK1 restores IAV-induced cell death. ZBP1 knockout abrogates IAV-induced cell death, whereas RIPK3 knockout inhibits IAV-induced necroptosis but not apoptosis. 5Z treatment enhances IAV-induced cell death and slightly reduces the inflammatory response in the lungs of H1N1 virus-infected mice and prolongs the survival of IAV-infected mice. Our study provides evidence that IAV activates TAK1 to suppress RIPK1-dependent apoptosis and necroptosis, and that RIPK3 is required for IAV-induced necroptosis but not apoptosis in epithelial cells.

Abstract Objective To investigate the accuracy and consistency of MDCT and TEE in the preoperative assessment of aortic root surgery. Methods From January 2021 to September 2022, 118 patients who underwent aortic root surgery were included in this study. All patients underwent high-quality preoperative MDCT and TEE examinations, and the examination results were independently measured and assessed by two senior radiologists or ultrasound specialists. Bland–Altman analysis and Pearson correlation testing were employed to assess the correlation and consistency between MDCT and TEE. These analyses were then compared with actual intraoperative measurement data. Results Among all the patients, 73 (61.86%) had tricuspid aortic valve (TAV), and 45 (38.14%) had bicuspid aortic valve (BAV). A comparison between the TEE and MDCT measurements showed that for the annulus diameter, the area-derived diameter had the best correlation and agreement. For the sinus of Valsalva diameter, the circumference-derived diameter was optimal. However, for the STJ diameter, the minimum cross-sectional diameter showed the best agreement with TEE. In contrast, measurements of geometric height showed a weaker correlation and agreement. Conclusion Contrast-enhanced MDCT can be a valuable tool for perioperative evaluation in aortic root surgery, with good correlation, consistency, and feasibility when compared to TEE. The choice of MDCT measurement methodology, specifically area-derived and circumference-derived diameter, proved to be more accurate than other methods. Further research is required to enhance the understanding of aortic valve repair and associated imaging techniques.

Abstract The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Abstract Background This systematic review aims to assist clinical decision-making in selecting appropriate preoperative prediction methods for difficult tracheal intubation by identifying and synthesizing literature on these methods in adult patients undergoing all types of surgery. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive electronic searches across multiple databases were completed on March 28, 2023. Two researchers independently screened, selected studies, and extracted data. A total of 227 articles representing 526 studies were included and evaluated for bias using the QUADAS-2 tool. Meta-Disc software computed pooled sensitivity (SEN), specificity (SPC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was assessed using the Spearman correlation coefficient, Cochran’s-Q, and I2 index, with meta-regression exploring sources of heterogeneity. Publication bias was evaluated using Deeks’ funnel plot. Results Out of 2906 articles retrieved, 227 met the inclusion criteria, encompassing a total of 686,089 patients. The review examined 11 methods for predicting difficult tracheal intubation, categorized into physical examination, multivariate scoring system, and imaging test. The modified Mallampati test (MMT) showed a SEN of 0.39 and SPC of 0.86, while the thyromental distance (TMD) had a SEN of 0.38 and SPC of 0.83. The upper lip bite test (ULBT) presented a SEN of 0.52 and SPC of 0.84. Multivariate scoring systems like LEMON and Wilson’s risk score demonstrated moderate sensitivity and specificity. Imaging tests, particularly ultrasound-based methods such as the distance from the skin to the epiglottis (US-DSE), exhibited higher sensitivity (0.80) and specificity (0.77). Significant heterogeneity was identified across studies, influenced by factors such as sample size and study design. Conclusion No single preoperative prediction method shows clear superiority for predicting difficult tracheal intubation. The evidence supports a combined approach using multiple methods tailored to specific patient demographics and clinical contexts. Future research should focus on integrating advanced technologies like artificial intelligence and deep learning to improve predictive models. Standardizing testing procedures and establishing clear cut-off values are essential for enhancing prediction reliability and accuracy. Implementing a multi-modal predictive approach may reduce unanticipated difficult intubations, improving patient safety and outcomes.

Abstract The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Abstract Background Tooth loss is a common problem that affects many people worldwide. Exploring knowledge, attitude, and practice (KAP) among patients can identify barriers and challenges in following recommended practices, providing valuable insights for dental healthcare providers, policymakers, and researchers. This study aimed to explore the KAP of patients with dental arch deficiencies regarding tooth loss and dentures. Methods This web-based, cross-sectional study was conducted among patients with dental arch deficiencies using a self-designed questionnaire. Result 3166 valid questionnaires were included. Participants’ mean KAP scores were 6.84 ± 2.27 (possible range: 0 ~ 12), 39.4 ± 3.72 (possible range: 9 ~ 45), and 27.7 ± 4.36 (possible range: 8 ~ 40), respectively. Multivariable logistic regression analysis showed that knowledge (OR = 1.383), employed (OR = 1.805), family history (OR = 2.158), and treatment (OR = 1.683) were independently associated with attitude. Moreover, knowledge (OR = 1.239), attitude (OR = 1.250), female (OR = 0.619), age (OR = 0.967), college/bachelor (OR = 0.373), and master and above degree (OR = 0.418), employed (OR = 0.554) or student (OR = 0.434), with 10,001–20,000 Yuan household income per month (OR = 0.492), have been married (OR = 0.609), smoking (OR = 0.595), drinking (OR = 0.397), disease duration (OR = 0.972), with family history (OR = 1.676), and with treatment (OR = 3.492) were independently associated with practice (all P

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

Abstract Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

Plant anatomy is patterned early during leaf development which suggests studying the spatial–temporal transcriptomes of primordia will help identify critical regulative and functional genes. We successfully isolated the leaf primordia tissues from the C3 grass rice and the C4 grass foxtail millet by laser capture microdissection (LCM) and studied the gene expression throughout leaf developmental stages. Our data analysis uncovered the conserved expression patterns of certain gene clusters both in rice and foxtail millet during leaf development. We revealed genes and transcription factors involved in vein formation, stomatal development, and suberin accumulation. We identified 79 candidate genes associated with functional regulation of C4 anatomy formation. Screening phenotype of the candidate genes revealed that knock-out of a putative polar auxin transport related gene NAL1 resulted significantly reduced veinal space in rice leaf. Our present work provides a foundation for future analyses of genes with novel functions in grasses and their role in leaf development, in particular the role in leaves with a contrasting C3 vs. C4 biosynthetic pathway.

Abstract Background The relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function. Methods This study recruited 1111 participants aged 25–83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function. Results Compared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta = − 0.25, 95% confidence interval [CI] − 0.39 to − 0.11 and beta = − 0.15, 95% CI − 0.29 to − 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta = − 0.24, 95% CI − 0.38 to − 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta = − 0.18, 95% CI − 0.32 to − 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline. Conclusions It is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.

Abstract Background Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have led to groundbreaking advancements in life sciences. To develop bioinformatics tools for scRNA-seq and SRT data and perform unbiased benchmarks, data simulation has been widely adopted by providing explicit ground truth and generating customized datasets. However, the performance of simulation methods under multiple scenarios has not been comprehensively assessed, making it challenging to choose suitable methods without practical guidelines. Results We systematically evaluated 49 simulation methods developed for scRNA-seq and/or SRT data in terms of accuracy, functionality, scalability, and usability using 152 reference datasets derived from 24 platforms. SRTsim, scDesign3, ZINB-WaVE, and scDesign2 have the best accuracy performance across various platforms. Unexpectedly, some methods tailored to scRNA-seq data have potential compatibility for simulating SRT data. Lun, SPARSim, and scDesign3-tree outperform other methods under corresponding simulation scenarios. Phenopath, Lun, Simple, and MFA yield high scalability scores but they cannot generate realistic simulated data. Users should consider the trade-offs between method accuracy and scalability (or functionality) when making decisions. Additionally, execution errors are mainly caused by failed parameter estimations and appearance of missing or infinite values in calculations. We provide practical guidelines for method selection, a standard pipeline Simpipe ( https://github.com/duohongrui/simpipe ; https://doi.org/10.5281/zenodo.11178409 ), and an online tool Simsite ( https://www.ciblab.net/software/simshiny/ ) for data simulation. Conclusions No method performs best on all criteria, thus a good-yet-not-the-best method is recommended if it solves problems effectively and reasonably. Our comprehensive work provides crucial insights for developers on modeling gene expression data and fosters the simulation process for users.

Abstract Assessing the hypoxic status within the tumor microenvironment (TME) is crucial for its significant clinical relevance in evaluating drug resistance and tailoring individualized strategies. In this study, we proposed a robust pan-cancer hypoxic quantification method utilizing multiple public databases, diverse bioinformatics, and statistical methods. All tumor samples were classified into four subtypes: non-hypoxic/TMEhigh (C1), hypoxic/TMEhigh (C2), non-hypoxic/TMElow (C3), and hypoxic/TMElow (C4). We systematically analyzed multi-omics data and single-cell RNA-sequencing (scRNA-seq) data to reveal distinct immune landscape patterns and genomic characteristics among the four subtypes across pan-cancer. Furthermore, we employed multiple machine learning approaches to construct a hypoxic-TME model to enhance the predictive accuracy of immunotherapy response. Additionally, drug repositioning was implemented for cancer patients predicted as non-responders to immunotherapy. A pan-cancer analysis identified PDK1 as a hub gene linking tumor hypoxia, glycolysis, and immunotherapy resistance. In vivo experimental validation further confirmed that targeting PDK1 could improve the response to immunotherapy. Overall, our study may offer valuable insights for integrating hypoxic-TME classification into tumor staging and providing personalized strategies for cancer patients.

Abstract Background Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. Methods Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. Results We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. Conclusions These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P

Objective: The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China. Methods: An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED. Results: A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists. Only 36.7% of participants claimed there was an MDT clinical pattern for TED in their institutions. The coverage of biological agents was around 10% or lower. These were distinctly lower than in Western countries. About 62.6% of participants believed the incidence of TED has increased in recent years. Imaging techniques were used widely to assist in the diagnosis of TED. However, there was still controversy regarding the definition of proptosis in the Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.4%) were inclined to recommend therapy for hyperthyroidism alone, while ophthalmologists (43.6%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.8%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.6%). Conclusion: The study documented the consistency and differences between current clinical practices in the management of TED in China and the recently updated guidelines. There was a remarkable difference between ophthalmology and endocrinology departments, warranting management optimization.

Abstract Mitochondria are crucial organelles closely associated with cellular metabolism and function. Mitochondrial DNA (mtDNA) encodes a variety of transcripts and proteins essential for cellular function. However, the interaction between the inner membrane (IM) and mtDNA remains elusive due to the limitations in spatiotemporal resolution offered by conventional microscopy and the absence of suitable in vivo probes specifically targeting the IM. Here, we have developed a novel fluorescence probe called HBmito Crimson, characterized by exceptional photostability, fluorogenicity within lipid membranes, and low saturation power. We successfully achieved over 500 frames of low-power stimulated emission depletion microscopy (STED) imaging to visualize the IM dynamics, with a spatial resolution of 40 nm. By utilizing dual-color imaging of the IM and mtDNA, it has been uncovered that mtDNA tends to habitat at mitochondrial tips or branch points, exhibiting an overall spatially uniform distribution. Notably, the dynamics of mitochondria are intricately associated with the positioning of mtDNA, and fusion consistently occurs in close proximity to mtDNA to minimize pressure during cristae remodeling. In healthy cells, >66% of the mitochondria are Class III (i.e., mitochondria >5 μm or with >12 cristae), while it dropped to

Abstract Logistics distribution is one of the main sources of carbon dioxide emissions at present, and there are also such distribution problems in the shipbuilding process. With the increasing attention paid to environmental problems, how to effectively reduce the energy consumption of block transportation and improve the utilization rate of resources in the factory is the key problem that China’s shipbuilding industry needs to solve at present. This article considers the time windows for block transportation tasks, as well as the self-loading constraints of different types of flat cars, and establishes an optimization model that minimizes the empty transport time and energy consumption of the flat cars as the optimization objective. Then, an Improved Genetic Whale Optimization Algorithm is designed, which combines the cross and mutation ideas of genetic algorithms and proposes a whale individual position updating mechanism under a mixed strategy. Furthermore, the performance and computational efficiency of the algorithm are verified through comparative analysis with other classical optimization algorithms on standard test examples. Finally, the shipyard’s block transportation example proves that the energy-saving ship block transportation scheduling method can effectively improve the efficiency of shipbuilding enterprise’s block transportation and reduce the energy consumption in the block transportation process. It proves the engineering practicality of the green dispatching method proposed in this paper, which can further provide a decision-making method for shipyard managers.

Abstract The emerging wearable skin-like electronics require the ultra-flexible organic transistor to operate at low voltage for electrical safety and energy efficiency and simultaneously enable high field-effect mobility to ensure the carrier migration ability and the switching speed of circuits. However, the currently reported low-voltage organic transistors generally present low mobility, originating from the trade-off between molecular polarity and surface polarity of the dielectrics. In this work, the orientation polarization of the dielectric is enhanced by introducing a flexible quaternary ammonium side chain, and the surface polarity is weakened by the shielding effect of the nonpolar methyl groups on the polar nitrogen atom. The resulting antisolvent QPSU dielectric enables the high-dielectric constant up to 18.8 and the low surface polarity with the polar component of surface energy only at 2.09 mJ/m2. Such a synergistic polarization engineering between orientation polarization and surface polarity makes the solution-processed ultraflexible transistors present the ultralow operational voltage down to −3 V, the ultrahigh charge-carrier mobility up to 8.28 cm2 V−1 s−1 at 1 Hz, excellent cyclic operational stability and long-term air stability. These results combined with the ultrathin thickness of transistor as low as 135 nm, the ultralight mass of 0.5 g/m2, the conformal adherence capability on human skin and 1-μm blade edge, and the strong mechanical robustness with stable electrical properties for 30,000 bending cycles, open up an available strategy to successfully realize low-voltage high-mobility solution-processed organic transistor, and presents the potential application of QPSU dielectric for the next-generation wearable imperceptible skin-like electronics.

In this work, the phase transition process of β-Ga2O3 thin films under heating and (or) electron irradiation condition was investigated by in-situ transmission electron microscopy. It is found that only under the high temperature, β-Ga2O3 did not undergo phase transition even when the temperature was up to 1000 °C. When under electron irradiation condition, the unconventional phase transition from β-Ga2O3 to δ-Ga2O3 occurred with a slow rate. When electron irradiation was coupled with a thermal field, the initial temperature of phase transition decreased, and the speed of phase transition also greatly accelerated. The new phase maintains crystallography relationship with the β-Ga2O3 parent phase as following: [010]β//[011‾]δ, (200)β//(2‾11)δ, and (402‾)β//(411)δ. The results reveal that electron irradiation can trigger the phase transition process from β-Ga2O3 to δ-Ga2O3, and the high temperature obviously accelerates the rate of phase transition process.

Metastasis is the main cause of death in cancer patients, the lung is one of the most common metastatic organs of malignant solid tumors. Before tumor cells metastasize to the lungs, they interact with immunosuppressive cells, alveolar epithelial cells, and lung fibroblasts to form a pre-metastatic niche. The pre-metastatic niche is a key factor leading to tumor cell metastasis to the lungs. Research has found that traditional Chinese medicine and its components can inhibit the formation of pre-metastatic niche. Therefore, this article reviewed the research progress on the formation of lung pre-metastatic niche and the intervention of traditional Chinese medicine in pulmonary PMN, in order to provide new Chinese medicine prescriptions and research ideas for further clinical prevention and treatment of tumor metastasis to the lung.

Abstract Background We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment. Methods For this prospective multicenter clinical study, HER2‐positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan–Meier method was used to generate survival curves. The log‐rank test was used to compare progression‐free survival (PFS) between the two groups. Results A total of 59 HER2‐positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively. Conclusions For metastatic HER2‐positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway‐activated metastatic HER2‐positive breast cancer patients.

The universal contamination of arable land with potentially toxic elements (PTEs) poses a severe threat to food security and jeopardizes worldwide efforts to meet the United Nations Sustainable Development Goals (SDGs). How to obtain more reliable concentrations of PTEs in regional agricultural soils is a priority problem to be solved. Multispectral satellite remote sensing, with its advantages of high spatial and temporal resolution, broad coverage, and low cost, offers the potential to acquire spatial distribution of PTEs in agricultural soils over large areas. However, owing to the complexity of soil environments and the insufficiency of spectral information, the mechanism for retrieving concentrations of PTEs in agricultural soils via multispectral satellites is not yet clear, and the accuracy needs to be improved. In this study, we aimed to assess whether employing a fusion of spectral information and environmental covariates, results in more accurate retrievals of PTEs, specifically chromium (Cr) and mercury (Hg), in croplands than does employing spectral information alone. Three machine learning algorithms—kernel-based support vector machine (SVM), neural network-based back propagation neural network (BPNN), and tree-based extreme gradient boosting (XGBoost)—were developed to retrieve Cr and Hg concentrations in agricultural soils. The results showed that the fusion of spectral information and environmental covariates combined with the XGBoost model performed best in retrieving both Cr and Hg concentrations in agricultural soils with coefficient of determination (R2) values of 0.73 and 0.74, respectively. Environmental covariates were important variables for determining Cr and Hg concentrations in agricultural soils, but the ability to retrieve these element concentrations by utilizing spectral information alone was limited. High Cr concentrations occurred in central towns and southern hilly mountains. High Hg concentrations were detected in the northwestern region and southern hilly mountains. The potential of fusing spectral information and environmental covariates to precisely retrieve PTE concentrations in agricultural soils can serve as a reference for agricultural soil health information monitoring worldwide.

At present, chemotherapy combined with photodynamic therapy is exerting satisfactory therapeutic effects in the treatment of tumors. Chlorin e6 (Ce6) is a photosensitizer with high efficiency and low dark toxicity. At the same time, elemene (ELE) contains high-efficiency and low-toxicity anti-cancer active ingredients, which can effectively penetrate tumor tissue and inhibit its recovery and proliferation. Due to the poor water solubility of these two drugs, we prepared ELE/Ce6 co-loaded liposomes (Lipo-ELE/Ce6) to improve their water solubility, thereby enhancing the anti-tumor effect. The characterization of Lipo-ELE/Ce6 showed that Lipo-ELE/Ce6 had suitable encapsulation efficiency (EE), particle size, polydispersity (PDI), zeta potential, and good photo-controlled release properties. In vitro, Lipo-ELE/Ce6 effectively inhibited the growth of T24 cells and induced apoptosis, and more importantly, in vivo experiments showed that Lipo-ELE/Ce6 had significant anti-tumor effects, which was significantly better than free drugs. The above results suggest that Lipo-ELE/Ce6 can significantly enhance the induction of apoptosis of non-muscle invasive bladder cancer (NMIBC) by light-controlled release and ROS response.

Abstract Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence‐related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3‐rich extracellular vesicles to NPCs, thereby alleviating aging‐associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane‐bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2‐TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia‐induced BMSC exosomes deliver BNIP3‐rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Mass cytometry is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level, advancing clinical research in immune monitoring. Nevertheless, the vast data generated by cytometry by time-of-flight (CyTOF) poses a significant analytical challenge. To address this, we describe ImmCellTyper (https://github.com/JingAnyaSun/ImmCellTyper), a novel toolkit for CyTOF data analysis. This framework incorporates BinaryClust, an in-house developed semi-supervised clustering tool that automatically identifies main cell types. BinaryClust outperforms existing clustering tools in accuracy and speed, as shown in benchmarks with two datasets of approximately 4 million cells, matching the precision of manual gating by human experts. Furthermore, ImmCellTyper offers various visualisation and analytical tools, spanning from quality control to differential analysis, tailored to users’ specific needs for a comprehensive CyTOF data analysis solution. The workflow includes five key steps: (1) batch effect evaluation and correction, (2) data quality control and pre-processing, (3) main cell lineage characterisation and quantification, (4) in-depth investigation of specific cell types; and (5) differential analysis of cell abundance and functional marker expression across study groups. Overall, ImmCellTyper combines expert biological knowledge in a semi-supervised approach to accurately deconvolute well-defined main cell lineages, while maintaining the potential of unsupervised methods to discover novel cell subsets, thus facilitating high-dimensional immune profiling.

Microalgae biofilm has garnered significant attention from researchers in the field of sewage treatment due to its advantages such as ease of collection and stable sewage treatment capabilities. Using agricultural waste as biofilm carriers has become a hotspot in reducing costs for this method. This study first combined Tetradesmus obliquus with loofah to form a microalgae biofilm for the study of periodic nitrogen and phosphorus removal from municipal wastewater. The biofilm could stably treat 7 batches of wastewater within one month. The removal rate of TP almost reached 100 %, while the removal rates of NH4+ and TN both reached or exceeded 80 %. The average biomass yield over 25 days was 102.04 mg/L/day. The polysaccharide content increased from 8.61 % to 16.98 % during the cyclic cultivation. The lipid content gradually decreased from 40.91 to 26.1 %. The protein content increased from 32.93 % in the initial stage to 41.18 % and then decreased to 36.31 % in the later stage. During the mid-stage of culturing, the richness of anaerobic bacteria decreased, while the richness of aerobic and facultative bacteria increased, which was conducive to the construction of the microalgae-bacteria symbiotic system and steadily improved the effect of nitrogen and phosphorus removal. As the culturing progressed, the Rotifers that emerged during the mid-stage gradually damaged the biofilm over time, leading to a decline in the effectiveness of sewage treatment in the later stages. This study offers technical support for carrier selection in microalgae biofilm methods and for the periodic removal of nitrogen and phosphorus from wastewater.

Hyperuricemia (HUA), recognized as the fourth “high” condition following hypertension, hyperlipidemia, and hyperglycemia, is a metabolic disorder that severely impairs renal function. Spike lavender essential oil (SLEO) exhibits substantial anti-inflammatory and antioxidant activities and can inhibit xanthine oxidase (XOD), suggesting its potential therapeutic potential against HUA. This of this study aimed to analyze the chemical constituents of SLEO with potential efficacy in treating HUA and to explore their mechanisms of action. Gas chromatography-mass spectrometry (GC–MS) combined with a greedy algorithm identified linalool, β-pinene, and β-caryophyllene as key active components of SLEO. Through network pharmacology “weight coefficient” method, the NOD-like signaling pathway emerged as a significant mechanism for SLEO in treating HUA. Investigating an in vitro uric acid (UA)-induced HK-2 cell model revealed that SLEO effectively inhibited the production of IL-1β and IL-18 in the supernatant of HK-2 cells compared to the NLRP3 (antagonist MCC950). Additionally, a HUA rat model demonstrated that SLEO administration significantly reduced hyperuricemia pathological indicators, such as UA, XOD, and blood urea nitrogen (BUN) levels, with renal histopathological sections showing a marked reduction in following SLEO treatment. Metabolomics and transcriptomics analyses further highlighted significant changes in differential metabolites such as arachidonic acid and glycine, as well as the regulation of differential genes such as pycard and PTGS2 in rats.Immunohistochemistry, Western blotting, molecular docking and in vitro XOD activity inhibition assays elucidated the active components mechanisms of SLEO in treating HUA and associated renal inflammation. The findings concluded that SLEO mitigates HUA and renal inflammation by modulating the arachidonic acid metabolic pathway and the NF-κB signaling pathway. Moreover, linalool, β-pinene and β-caryophyllene in SLEO were shown to reduce UA production and lower UA levels in vivo by inhibiting the TLR4/NF-κB/NLRP3 pathway, thereby alleviating HUA-induced renal injury.

Coronary heart disease is a prevalent cardiovascular ailment globally, with myocardial infarction (MI) being one of its most severe manifestations. The morbidity and mortality of MI are escalating, showing an increasing trend among younger, highly educated individuals, thereby posing a serious threat to public health. Currently, thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting are the primary clinical treatments for MI. Although these methods significantly reduce patient mortality, complications often result in poor prognoses. Due to limitations in chemical synthetic drug research, the focus has shifted towards developing herbs based on natural substances. Natural medicines represent a novel approach for safer and more effective MI management and treatment. They can control multiple pathogenic variables by targeting various pathways and systems. This paper investigates the molecular mechanisms of MI and evaluates the application of natural products and medicinal plants in MI treatment over the past 5 years, demonstrating their specific good therapeutic potential and superior tolerance. These natural therapies have been shown to mitigate myocardial cell damage caused by MI through mechanisms such as oxidative stress, inflammation, apoptosis, angiogenesis, myocardial fibrosis, autophagy, endoplasmic reticulum stress, mitophagy, and pyroptosis. This review offers the latest insights into the application of natural products and medicinal plants in MI treatment, elucidating their mechanisms of action and serving as an important reference for MI prevention.

ABSTRACT Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

Summary: Cellular cholesterol plays an important role in influenza A virus (IAV) endocytosis and replication. However, how IAV infection regulates cholesterol biosynthesis remains poorly understood. Here, we report that IAV infection activates SREBP2 and induces the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis pathway. SREBP2 deficiency suppresses IAV-induced HMGCR expression and virus replication. Mechanistically, IAV infection activates JAK2 and STAT3, inhibition of JAK2 and STAT3 activity by their inhibitors or by gene knockout downregulates IAV-induced SREBP2 and HMGCR expression and IAV replication, reduces the content of cellular cholesterol and virus binding to host cells. Exogenous cholesterol reverses the inhibitory effect of S3I-201 and STAT3 deficiency on virus replication. STAT3 or JAK2 overexpression increases the expression of SREBP2 and its downstream target genes, leading to increased IAV replication. These observations collectively suggest that STAT3 activation facilitates IAV replication by inducing SREBP2 expression and increasing cholesterol biosynthesis.

When a curling rock slides on an ice sheet with an initial rotation, a lateral movement occurs, which is known as the curling phenomenon. The force of friction between the curling rock and the ice sheet changes continually with changes in the environment; thus, the sport of curling requires great skill and experience. The throwing of the curling rock is a great challenge in robot design and control, and existing curling robots usually adopt a combination scheme of a wheel chassis and gripper that differs significantly from human throwing movements. A hexapod curling robot that imitates human kicking, sliding, pushing, and curling rock rotating was designed and manufactured by our group, and completed a perfect show during the Beijing 2022 Winter Olympics Games. Smooth switching between the walking and throwing tasks is realized by the robot’s morphology transformation based on leg configuration switching. The robot’s controlling parameters, which include the kicking velocity vk, pushing velocity vp, orientation angle θc, and rotation velocity ω, are determined by aiming and sliding models according to the estimated equivalent friction coefficient μequ and ratio e of the front and back frictions. The stable errors between the target and actual stopping points converge to 0.2 and 1.105 m in the simulations and experiments, respectively, and the error shown in the experiments is close to that of a well-trained wheelchair curling athlete. This robot holds promise for helping ice-makers rectify ice sheet friction or assisting in athlete training.

Abstract Photo thermal power generation, as a renewable energy technology, has broad development prospects. However, the operation and scheduling of photo thermal power plants rarely consider their internal structure and energy flow characteristics. Therefore, this study explains the structure of a solar thermal power plant with a thermal storage system and analyzes its main energy flow modes to establish a self-operation and low-carbon scheduling optimization model for the solar thermal power plant. The simulation results of the example showed that for the self-operating model oriented towards power generation planning and peak valley electricity prices, the existence of a thermal storage system could improve the power generation capacity and revenue of the photovoltaic power plant. For example, when the capacity of the thermal storage system was greater than 6 h, the penalty for insufficient power generation in the simulation result was 0 $, and the maximum increase in revenue reached 84.9% as the capacity of the thermal storage system increased. In addition, when the capacity of the thermal storage system increased from 0 to 8 h, the comprehensive operating cost decreased from 1635.2 k $ to 1224.6 k $, and the carbon emissions decreased from 26.4 × 103 ton to 22.1 × 103 ton. Compared with the existing literature, this study provides a more comprehensive and systematic solution through detailed energy flow analysis and optimization model. The research has practical and far-reaching significance for promoting the development of clean energy technology, improving the sustainable utilization of renewable energy, and optimizing the overall performance of the energy system.