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Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 μM. It also reduced the syntheses of viral antigens at concentrations of 2.5 μM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.

The regulation of aircraft engine NO x emissions was introduced to improve local air quality and reduce NO x emissions at altitude. Here, the authors find that greater fuel efficiency of aircrafts, and therefore lower CO2 emissions, could be preferable to reducing NO x emissions in terms of the aviation industries future climate impacts.

Abstract This study explored relationships between students’ attitudes toward science and their preferred versus actual experience of cooperative, constructivist-oriented, or direct instruction. The sample consisted of 1334 Chinese middle school students in physics and chemistry classrooms. Results showed that students report experiencing more direct instruction, very little constructivist-oriented instruction, and a moderate amount of cooperative instruction. Attitudes toward science were positively related to cooperative teaching strategies like group work in class or developing small-group projects. There was no significant effect of constructivist-oriented instruction or of direct instruction on students’ attitudes. Whereas previous studies demonstrated positive impacts of constructivist teaching on student understanding of science concepts, student attitude toward school science appears to be more related to social interaction or cooperation. Lack of any statistically significant differential effect from constructivist-oriented instruction might also be related to the overall low incidence of such instruction experienced by our sample.

Three global chemistry-transport models (CTM) are used to quantify the radiative forcing (RF) from aviation NOx emissions, and the resultant reductions in RF from coupling NOx to aerosols via heterogeneous chemistry. One of the models calculates the changes due to aviation black carbon (BC) and sulphate aerosols and their direct RF, as well as the BC indirect effect on cirrus cloudiness. The surface area density of sulphate aerosols is then passed to the other models to compare the resulting photochemical perturbations on NOx through heterogeneous chemical reactions. The perturbation on O3 and CH4 (via OH) is finally evaluated, considering both short- and long-term O3 responses. Ozone RF is calculated using the monthly averaged output of the three CTMs in two independent radiative transfer codes. According to the models, column ozone and CH4 lifetime changes due to coupled NOx/aerosol emissions are, on average, +0.56 Dobson Units (DU) and −1.1 months, respectively, for atmospheric conditions and aviation emissions representative of the year 2006, with an RF of +16.4 and −10.2 mW/m2 for O3 and CH4, respectively. Sulphate aerosol induced changes on ozone column and CH4 lifetime account for −0.028 DU and +0.04 months, respectively, with corresponding RFs of −0.63 and +0.36 mW/m2. Soot-cirrus forcing is calculated to be 4.9 mW/m2.

Plastic pollution poses a serious threat to marine ecosystems; yet quantifying the mass concentrations of nano- and microplastics (NMPs) in saltmarsh sediments at the ocean-land interface remains a critical research gap. Here, the study employed reliable and efficient analytical techniques, namely pressurized liquid extraction and the double-shot model of thermal desorption/pyrolysis-gas chromatography-mass spectrometry, to quantify six different types of NMPs in the sediment of a multi-species saltmarsh, providing the first comprehensive assessment of NMP mass concentration and burial in this saltmarsh environment. The results demonstrate that polyethylene, polyvinyl chloride, and polypropylene dominated the NMP composition in sediments, constituting 72.6%, 17.3%, and 4.5% of the total NMPs, respectively. The measured NMPs represent an anthropogenic intrusion, constituting 0.10%-0.23% of the carbon storage in the saltmarsh. By examining the vertical concentration profiles, this study unveiled the influence of saltmarsh vegetation on NMP deposition in sediments, establishing a connection with local sedimentation patterns and the historical zonation of plant species such as Scirpus mariqueter, Phragmites australis and Spartina alterniflora. These findings underscore the crucial role of saltmarsh vegetation in facilitating NMP settling and retention, highlighting the necessity of considering vegetation dynamics in examining the emerging NMP pollution in coastal wetlands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Purpose: Activation of AMP-activated protein kinase (AMPK) is essential in maintaining the epithelial tight junction (TJ) barrier. Berberine, a phytochemical AMPK agonist, has been widely reported to ameliorate colitis. Berberine or AMPK activation inhibits cytoskeletal contraction induced by myosin light chain kinase (MLCK), thereby ameliorating TJ barrier defects. We previously found that swiprosin-1, an actin-binding protein, affects MLCK expression. Here, we aimed to reveal the role of swiprosin-1 in the regulation of AMPK/MLCK by berberine., Methods: Caco-2 monolayer transfected with AMPKα1 (or swiprosin-1) siRNA was treated with berberine after being stimulated with TNFα/IFNγ to assess the effect on the TJ barrier. Intestinal epithelial conditional knockout mice for AMPKα1 (or swiprosin-1) were treated with berberine after experimental colitis to evaluate the effect on the TJ barrier. TJ integrity was evaluated by immunoblotting and immunofluorescence for ZO-1 and Occludin., Results: The protection of berberine against TJ barrier damage was blocked by AMPK inhibitor or knockout of AMPKα1 in epithelial cells. Swiprosin-1 was distributed in colonic epithelial cells and upregulated in colitis. Knockout of swiprosin-1 in intestinal epithelial cells ameliorated TJ barrier damage and abolished the protective effect of berberine. Impaired assembly of TJ caused by overexpression of swiprosin-1 was alleviated by MLCK inhibitor, and inhibition of the MLCK pathway by berberine also required the presence of swiprosin-1. In addition, berberine downregulated swiprosin-1 expression in an AMPK-dependent manner., Conclusion: Swiprosin-1 may be a key intermediate molecule in the regulation of the AMPK/MLCK pathway by berberine to attenuate colitis-induced TJ barrier damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction and Aims: As an experimental teaching method, emerging learning methods including problem-based learning (PBL), case-based learning, team-based learning and flipped classroom (FC) have been widely applied in dental education. This study aims to evaluate the effect of these teaching methods on dental education performance compared to traditional lecture-based learning (LBL)., Methods: The search was carried out in April 2024 in PubMed, EMBASE, Web of Science, and Cochrane Library. All randomized controlled trials were included and the methodological quality assessment was based on the guidelines described in the Cochrane Handbook for Systematic Reviews, followed by a meta-analysis using Stata 14.0 software. Using standard mean deviation (SMD) and 95% confidence interval (95% CI) to determine the effectiveness of emerging teaching methods and LBL in all dental disciplines. Meta-regression was used to analyse sources of heterogeneity. Sensitivity analysis was performed to determine the stability, and Begg's analysis was used to determine whether there is publication bias., Results: A total of 29 randomized controlled trials including 3502 students were included. The results indicate that emerging educational methods have a significantly positive effect on achieving higher scores (SMD = 0.48, 95% CI = 0.34-0.62, P < .001), whether it was theoretical scores (SMD = 0.52, 95% CI = 0.32-0.72, P < .001) or skill scores (SMD = 0.45, 95% CI = 0.15-0.76, P < .001). Compared to LBL, PBL (SMD = 0.33, 95% CI = 0.01-0.65, P = .045) and FC (SMD = 0.50, 95% CI = 0.31-0.69, P < .001) can both significantly improve students' academic performance., Conclusion: Compared to LBL, emerging educational methods (PBL, case-based learning, and FC) have significantly improved the learning effectiveness of dental students. These emerging educational methods can be advocated and popularized as routine teaching methods., Clinical Relevance: This study is the first meta-analysis of the effects of emerging teaching methods in dental education which shows great impact of emerging teaching methods on students' development., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Effective postoperative pain management is critical for pediatric craniotomies. Scalp nerve block (SNB) interventions present a potential solution, yet their comparative benefits in preoperative and postoperative settings remain unclear. This study investigated the analgesic effects of SNB in pediatric craniotomy patients by comparing preoperative versus postoperative administration., Methods: This randomized trial included 180 children (1-12 years) who underwent elective craniotomy and were assigned to the preoperative, postoperative, or nonblocking control group. The outcomes included cumulative sufentanil use, pain scores (1, 2, 4, 24, 48 h postoperation), rescue medicine utilization, postoperative complications (24, 48 h), and hospitalization length. The primary outcome was total sufentanil use within 24 h postsurgery., Results: Total sufentanil use (µg·kg - 1 ) in the postoperative block group was significantly lower than that in the nonblocking control group at 1 h (P < 0.001, 95% CI [-0.024 to -0.006]), 2 h (P < 0.001, 95% CI [-0.054 to -0.020]), 4 h (P < 0.001, 95% CI [-0.089 to -0.032]), 24 h (P < 0.001, 95% CI [-0.192 to -0.047]), and 48 h (P = 0.010, 95% CI [-0.208 to -0.022]) postoperation. Additionally, sufentanil use in the preoperative block group was significantly lower than that in the nonblocking control group at 1 h (P = 0.004, 95% CI [-0.021 to -0.003]), 2 h (P < 0.001, 95% CI [-0.043 to -0.010]), and 4 h (P = 0.002, 95% CI [-0.069 to -0.013]). Within 24 h postoperation, the use of sufentanil in the postoperative block group was significantly lower than that in the preoperative block group (P = 0.014, 95% CI [-0.157 to -0.013])., Conclusion: Compared with preoperative SNB or nonblocking, postoperative SNB significantly reduces postoperative sufentanil use within 24 h for pediatric patients undergoing craniotomy, highlighting its potential as an effective analgesic intervention in this population., Trial Registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR1800017386) on 27/07/2018, under the title "A study of scalp nerve block for neurosurgical analgesia in children with craniotomy.", Competing Interests: Declarations. Ethics approval and consent to participate: This single-center, prospective, double-blinded, randomized controlled trial received approval from the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (IRB No. KY 2018-078-02; August 23, 2018). The study period spanned from September 2018 to October 2020, with the first patient recruited on September 13, 2018. All children obtained written informed consent from their guardians, and school-aged children aged 7 years and older also provided their own informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) has exhibited escalating contagion and resistance to immunity, resulting in a surge in infections and severe cases. This study endeavors to formulate two nomogram predictive models aimed at discerning patients at heightened risk of severe and fatal outcomes upon hospital admission. The primary objective is to enhance clinical management protocols and mitigate the incidence of severe illness and mortality associated with COVID-19., Methods: 1600 patients diagnosed with COVID-19 and discharged from Fujian Provincial Hospital were chosen as the subjects of this study. These patients were categorized into three groups: mild group (n = 940), severe group (n = 433), and fatal group (n = 227). The patients were randomly divided into training and validation cohorts in a 7:3 ratio. COVID-19 symptoms were treated as dependent variables, and univariate regression analysis was conducted for the laboratory indicators. Risk factors with p-values greater than 0.05 in the univariate regression analysis were eliminated. The remaining risk factors were then analyzed using direct multiple regression analysis to establish an unadjusted model. Subsequently, risk factors with p-values greater than 0.05 were further removed. Clinical characteristics were added to the model as adjustment factors, and the method of multiple stepwise regression analysis was employed to derive the final fully adjusted model. The severe and fatal COVID-19 models were converted into nomograms, respectively. Receiver operating characteristic (ROC) curves were utilized to evaluate the discrimination of the nomogram models. Calibration was assessed using the Hosmer-Lemeshow test and calibration curves. Clinical benefit was evaluated by decision curve analysis., Results: Compared to the mild group, individuals in the severe COVID-19 group exhibited significant increases in age, neutrophil (NEU), and lactate dehydrogenase (LDH) levels, alongside notable decreases in lymphocyte (LYM) and albumin (ALB) levels. Nomogram model incorporating age, NEU, LDH, LYM, and ALB demonstrated efficacy in predicting the onset of severe COVID-19 (AUC = 0.771). Furthermore, history of cerebral infarction and cancer, LDH and ALB as risk factors for fatal COVID-19 cases compared to the severe group. The nomogram model comprising these factors was capable of early identification of COVID-19 fatalities (AUC = 0.748)., Conclusions: Elevated age, NEU, and LDH levels, along with decreased LYM and albumin (ALB) levels, are risk factors for severe illness in hospitalized patients with COVID-19. A history of cerebral infarction and tumors, along with elevated LDH and decreased ALB levels, are risk factors for death in critically ill patients. The nomogram model based on these factors can effectively predict the risk of severe or fatal illness from COVID-19, thereby assisting clinicians in timely interventions to reduce the rates of severe illness and mortality among hospitalized patients. However, the model faces challenges in processing longitudinal data and specific points in time, indicating that there is room for improvement., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Fujian Provincial Hospital. The data used in this study were anonymized before use. Informed consent: was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Purpose: Both Ku80 and Ku70 are promising drug targets for hepatocellular carcinoma (HCC) and crucial for immune regulation. However, their correlation with HCC immune signatures has not yet been investigated. Therefore, we aimed to investigate the relationship between Ku80, Ku70, and immune signatures in HCC and validate their significance in cytotoxic lymphocyte (CTL) immunotherapy., Patients and Methods: Analyses of Ku70, Ku80, and immune signatures in public datasets was performed using R software, an online Kaplan-Meier plotter, g:Profiler, GeneTrail, and Metascape. Uniform manifold approximation and projection, correlation chord diagrams, Pearson's correlation tests, and Spearman correlation tests were used to describe various correlation levels. HCC mRNA sequencing data (n=373 tumor samples and n=50 para-tumor samples) were drawn from The Cancer Genome Atlas (TCGA) public database. Immunofluorescent staining was used to validate Ku70/Ku80 and CD8 + CTL expression in 120 HCC patients from our center. Survival analysis was performed using the Kaplan-Meier survival analysis with the Log rank test and was adopted to analyze immunotherapy outcomes correlated with Ku70/Ku80 expression in various solid tumors. Multivariate analysis of HCC patient data from our center was performed using a Cox proportional hazards model., Results: Increased Ku70/Ku80 expression positively correlated with more enriched immune microenvironment signatures, indicating increased immune infiltration in HCC. Upregulation of Ku70/Ku80 indicated better anti-PD1 and anti-PDL1 treatment outcomes in various solid tumors. Higher Ku70/Ku80 expression with lower CD8 + CTL signatures indicated worse survival outcomes, whereas lower Ku70/Ku80 expression with higher CD8 + CTL signatures indicated the best prognosis., Conclusion: Higher Ku70/Ku80 expression indicated an immune-hot infiltration signature in HCC. Patients with increased Ku70/Ku80 expression and high CD8 + CTL signatures may potentially benefit from CTL-centered immunotherapies., Competing Interests: All authors declare no conflicts of interests., (© 2024 Yang et al.)

Background: Multiple brands of immune checkpoint inhibitors (ICIs), including domestic and imported agents, have been approved as front-line therapy in China. However, little is known about the difference in efficacy and safety of these agents of different origins. This study aims to systematically compare the difference between National Medical Products Administration (NMPA) approved domestic and imported ICIs regarding their efficacy, safety, and price., Methods: We systematically searched PubMed, Embase, and Cochrane Central, from inception to July 1st, 2023, for phase III trials evaluating ICIs as first- or second-line settings that have available hazard ratio (HR) for Asians or non-Asians. Studies of domestic and imported ICIs were screened and paired by the matching clinical characteristics as mirror groups. The primary endpoint was to assess the difference in efficacy between domestic and imported ICIs regarding overall survival. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Heterogeneity was assessed by I 2 statistics. Monthly treatment costs for each drug were calculated based on dosing information on National Medical Products Administration (NMPA) label and prices extracted from INSIGHT database. The difference in monthly treatment costs was compared by unpaired T-test. The protocol is registered on PROSPERO, CRD42024580753., Results: Overall, domestic ICIs exhibited better efficacy regarding overall survival (HR, 0.87; 95 % CI, 0.79-0.97; P < 0.05; I 2 = 0) compared with imported agents. No difference was observed regarding benefits in progression free survival (HR, 0.95; 95 % CI, 0.82-1.09; P > 0.05; I 2 = 0). Consistent results were obtained through frequentists and Bayesian approaches. The differences in safety; measured by relative risk of treatment-related adverse events (TARE) of any grade, TARE of grade 3 or higher, immune-related adverse events(irAE) of any grade, irAE of grade 3 or higher, discontinuation due to treatment, and death due to treatment; were also similar between domestic and imported ICIs. Moreover, in current Chinese market, the monthly treatment prices of domestic ICIs was statistically lower than that of imported ICIs (P < 0.01)., Conclusions: Our research provides an essential reference of cost-effectiveness of ICIs manufactured in China for clinicians in routine practice of cancer care as well as public health authorities for decision making process., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The ability to lubricate and resist wear at temperatures above 600 °C in an oxidative environment remains a significant challenge for metals due to their high-temperature softening, oxidation, and rapid degradation of traditional solid lubricants. Herein, we demonstrate that high-temperature lubricity can be achieved with coefficients of friction (COF) as low as 0.10-0.32 at 600-900 °C by tailoring surface oxidation in additively-manufactured Inconel superalloy. By integrating high-temperature tribological testing, advanced materials characterization, and computations, we show that the formation of spinel-based oxide layers on superalloy promotes sustained self-lubrication due to their lower shear strength and more negative formation and cohesive energy compared to other surface oxides. A reversible phase transformation between the cubic and tetragonal/monoclinic spinel was driven by stress and temperature during high temperature wear. To span Ni- and Cr-based ternary oxide compositional spaces for which little high-temperature COF data exist, we develop a computational design method to predict the lubricity of oxides, incorporating thermodynamics and density functional theory computations. Our finding demonstrates that spinel oxide can exhibit low COF values at temperatures much higher than conventional solid lubricants with 2D layered or Magnéli structures, suggesting a promising design strategy for self-lubricating high-temperature alloys., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Melanoma, recognized as the most aggressive type of skin cancer, has experienced a notable increase in cases, especially within populations with fair skin. This highly aggressive cancer is largely driven by UV radiation exposure, resulting in the uncontrolled growth and malignant transformation of melanocytes. The cGAS-STING pathway, an immune signaling mechanism responsible for detecting double-stranded DNA in the cytoplasm, is essential for mediating the immune response against melanoma. This pathway serves a dual purpose: it enhances antitumor immunity by activating immune cells, but it can also promote tumor growth when chronically activated by creating an immunosuppressive environment. This review comprehensively examines the multifaceted implication of the cGAS-STING pathway in melanoma pathogenesis and treatment. We explore its molecular mechanisms, including epigenetic regulation, interaction with signaling pathways such as AR signaling, and modulation by various cellular effectors like TG2 and activin-A. The therapeutic potential of modulating the cGAS-STING pathway is highlighted, with promising results from STING agonists, combination therapies with immune checkpoint inhibitors, and novel drug delivery systems, including nanoparticles and synthetic drugs. Our findings underscore the importance of the cGAS-STING pathway in melanoma, presenting it as a critical target for enhancing anti-tumor immunity. By leveraging this pathway, future therapeutic strategies can potentially convert 'cold' tumors into 'hot' tumors, making them more susceptible to immune responses., Competing Interests: Declarations Ethics approval and consent to participate Not applicable (Review Study). Informed consent to consent for publication Not applicable (Review Study). Declaration of generative AI and AI-assisted technologies in the writing process During the preparation of this work, the authors used ChatGPT by OpenAI to improve paper readability. After using this tool/service, the authors reviewed and edited the content as needed and took full responsibility for the publication’s content. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway., Methods: The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6's role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1's pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference's inhibitory effect on CC proliferation in vivo., Results: Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments., Conclusion: Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment., Competing Interests: Declarations Ethics statement Our study was approved by Ethics Review Board of the First Affiliated Hospital of the Nanchang University and Jiangxi Maternal and Child Health Hospital. Competing interests The authors declare no competing interests. Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Predicting the bioconcentration of chemical compounds plays a crucial role in assessing environmental risks and toxicological impacts. This study presents a robust multitask deep learning model for predicting the bioconcentration potential. The model can predict the bioconcentration of compounds in multiple categories, including non-bioconcentrative (non-BC), weakly bioconcentrative (weak-BC), and strongly bioconcentrative (strong-BC). We also employed the SHapley Additive exPlanations (SHAP) technology for the model interpretation. The binary classification models (non-BC vs BC and weak-BC vs strong-BC) showed good predictive performance, which achieved accuracy values over 90% and area under the curve (AUC) values with 0.95. The final ternary classification model provided an overall accuracy with 91.11%. Comparative analysis of molecular physicochemical properties showed that the importance of molecular weight, polar surface area, solubility, and hydrogen bonding are important for chemical bioconcentration. Besides, we identified eight structural alerts responsible for chemical bioconcentration. We made the model available as an online tool named BCdpi-predictor, which is accessible at http://bcdpi.sapredictor.cn/. Users can predict the bioconcentration potential of chemical compounds freely. The model has significant implications for environmental policy and regulatory frameworks, such as REACH, by providing a more accurate and interpretable method for assessing chemical risks. We hope that the results of this study can provide helpful tools and meaningful information for chemical bioconcentration prediction in environmental risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cephalanthera nanchuanica is a terrestrial orchid species and has been red listed as a second-grade protected plant due to its limited distributions in China. Initially classified within a monotypic genus Tangtsinia, this species was later reassigned to Cephalanthera based on morphological and molecular data. However, previous phylogenetic analyses of Cephalanthera using several segment sequences exhibited a low discriminatory power in delineating its relationships., Results: In this study, we characterized and comparatively analyzed the complete chloroplast (cp) genome of C. nanchuanica with those of six previously reported Cephalanthera species. Our findings revealed that the cp genome of C. nanchuanica had the typical quadripartite structure, with a size of 161,365 bp and a GC content of 37.27%. A total of 113 unique genes were annotated, among which nearly half of protein-encoding genes (RSCU > 1) showed a preference in codon usage. No structural rearrangements were observed among the cp genomes of Cephalanthera species, except for C. humilis, which displayed structural alterations due to gene loss, relocation, and inverted repeat (IR) expansion/contraction. The cp genomes of Cephalanthera species were highly conserved, with only a small number of SSRs detected, most of which preferred A/T bases. Comparative analysis of cp genomes indicated that IR and coding regions were less divergent than single copy and non-coding regions and eight mutational hotspots were identified. Phylogenetic analysis suggested that the tribe Neottieae was a monophyletic group, divided into five clades. Palmorchis was the earliest-diverging lineage, followed by Cephalanthera. Diplandrorchis was deeply nested within Neottia, forming a clade. Aphyllorchis and Limodorum formed another clade, sister to Epipactis. Within the Cephalanthera clade, C. nanchuanica was sister to C. falcata with a strong support., Conclusions: This study demonstrated that the cp genome characters of C. nanchuanica are highly similar to those of other Cephalanthera species, except for the mycoheterotrophic species C. humilis. Although the cp genomes of Cephalanthera species (excluding C. humilis) exhibited conservation in genome structure and sequence, SSR repeats and mutational hotspots were identified, which could potentially serve as as molecular markers for distinguishing Cephalanthera species. The phylogenetic analysis based on the protein-coding genes provided high-resolution support for the infrageneric classification. Therefore, cp genome data will be instrumental in resolving the phylogeny of the genus Cephalanthera., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction and Importance: Congenital iris and choroidal coloboma is a congenital ocular developmental anomaly, most occur in both eyes, which may exist in isolation or be accompanied by systemic developmental abnormalities. Herein, we report a case of congenital bilateral coloboma of iris and choroid accompanied by unilateral multiple primary pigmented iris cysts. The selection of treatment methods for iris cysts has always been a challenge for ophthalmologists. Especially for primary iris pigment epithelial cysts without clinical symptoms, no particular intervention measures are required. Which in turn helps ophthalmologists to make clinical decisions in real-world practice., Case Presentation: A 16-year-old boy presented to the ophthalmology clinic with a history of poor eyesight in both eyes since childhood. The pupils of both eyes were pear shaped, and there was a pigmented iris cyst about 1.5 mm × 2 mm at 6-7 o'clock pupillary margin of the left eye on slit-lamp examination. A large fan-shaped coloboma of choroid in both eyes respectively, involving the optic nerve and macular area on fundus examination. Ultrasound biomicroscopy revealed three cysts with hyperreflective walls and clear hyporeflective lumen in the left eye, one located on the anterior surface of the iris and the other two located on the posterior surface of the iris. Above all, he had no history of surgery, trauma, infection, tumor or medication. Therefore, primary pigmented iris epithelial cysts were diagnosed. Given that the patient was asymptomatic, with no impact on visual function, his cysts were monitored. After 2 years follow-up, the cysts remained stable., Clinical Discussion: Iris cysts, whether primary or secondary, are a diagnostic and a treatment challenge. Primary iris cysts are mostly present in the iridociliary sulcus and the ciliary crown, often asymptomatic, with a few located forward or larger, manifested as local protrusions around the iris. This patient had no history of ocular surgery or trauma, therefore, combining clinical manifestations and imaging examination results, primary pigmented iris epithelial cysts were diagnosed. For this patient, on the one hand, the surgical risk was high, and iris cysts probably recur after surgery, and there might be no improvement in postoperative visual acuity. On the other hand, the patient's fundus was poor and his family's economic conditions were not good. In addition, the iris cysts of this patient remained stable after 2 years of observation, therefore, no treatment was taken., Conclusion: Ophthalmologists should be aware of this rare but distinctive presentation, especially in patients without symptoms. Prompt diagnosis and treatment are pivotal in ensuring favorable outcomes and preventing further ocular complications in individuals affected by these uveal anomalies., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coleoptile length, in wheat, is a significant agronomic trait impacting yield by facilitating the successful establishment of seedlings. In arid regions, varieties possessing longer coleoptile can evade harsh conditions by deep sowing, paving the way for improved yield. However, the study of genes involved in coleoptile development is insufficient. In this study, a high-density 660 K SNP array was used for genome-wide association study (GWAS) on coleoptile length in 150 wheat varieties. The findings revealed the detection of 353 significantly associated SNPs across all environments. The integration of linkage disequilibrium analysis and haplotype analysis mined 23 core QTLs capable responsible for the stable regulating coleoptile length in wheat. In wheat varieties characterized by extended coleoptile length, 6,600, 11,524, and 6,059 genes were found to be differentially expressed at three distinct developmental stages within the coleoptile, respectively. Through GWAS, gene expression levels, and functional annotation, we concluded the identification of two candidate genes ( TraesCS2B02G423500 , TraesCS2B02G449200 ) regulating wheat coleoptile length. By employing WGCNA and protein interactions prediction, discovered that the 19 genes were found to interact with candidate genes and participate in plant hormone metabolism and signaling, cell elongation or proliferation, which collectively contributing to coleoptile elongation. Additionally, two KASP markers were developed which can be used in breeding. These results offer a basis for understanding the genetic regulatory network responsible for wheat coleoptile length formation. The QTLs and candidate genes identified in this study can be further utilized for genetic improvement of wheat coleoptile length., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01520-6., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

For the first time, we constructed a band-matched ZnO/NiO staggered p-n heterojunction photoelectrochemical (PEC) catalyst with superior charge separation and transfer efficiency to optimize the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics demands of a photo-enhanced zinc-air battery (PZAB). The ingenious design of heterojunction architecture effectively stimulates an internal self-built electric field (BEF), thus accelerating charge separation and migration during PEC catalysis. Upon illumination, the photocathode not only endows a promoted PEC catalytic competence to drive ORR and OER, but also reduces the charge-discharge voltage gap of PZAB. Density functional theory (DFT) calculations further disentangled the PEC catalysis activity origins by substantiating the strongly decreased Gibbs free energy potently for generating the essential intermediates *OH and *OOH during ORR and OER, respectively, and visualized the charge densities in photocathode to illustrate the authentic separation of photogenerated carriers. Remarkably, our work experimentally and theoretically sheds lights on engineering innovative and efficient bifunctional PEC catalysts to drive PZABs with photo-enhancement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM., Methods: Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1., Results: Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis., Conclusion: Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications., (© 2024. The Author(s).)

Objectives: Technology-related prescribing errors curtail the positive impacts of computerised provider order entry (CPOE) on medication safety. Understanding how technology-related errors (TREs) occur can inform CPOE optimisation. Previously, we developed a classification of the underlying mechanisms of TREs using prescribing error data from two adult hospitals. Our objective was to update the classification using paediatric prescribing error data and to assess the reliability with which reviewers could independently apply the classification., Materials and Methods: Using data on 1696 prescribing errors identified by chart review in 2016 and 2017 at a tertiary paediatric hospital, we identified errors that were technology-related. These errors were investigated to classify their underlying mechanisms using our previously developed classification, and new categories were added based on the data. A two-step process was used to identify and classify TREs involving a review of the error in the CPOE and simulating the error in the CPOE testing environment., Results: The technology-related error mechanism (TREM) classification comprises six mechanism categories, one contributing factor and 19 subcategories. The categories are as follows: (1) incorrect system configuration or system malfunction, (2) opening or using the wrong patient record, (3) selection errors, (4) construction errors, (5) editing errors, (6) errors that occur when using workflows that differ from a paper-based system (7) contributing factor: use of hybrid systems., Conclusion: TREs remain a critical issue for CPOE. The updated TREM classification provides a systematic means of assessing and monitoring TREs to inform and prioritise system improvements and has now been updated for the paediatric setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

A typical industrial park in the upper reaches of the Yangtze River Economic Belt, which is 70 km from the Chongqing urban center, was used to investigate the occurrence and exposure of harmful volatile organic compounds (VOCs). An exposure risk method and a risk-oriented source apportionment approach were performed to assess the inhalation risks and apportion VOC sources, respectively. The quantitative relationships between risk factors and pollution sources were established, identifying key pathogenic and odorous VOCs. The quantitative emission reduction strategies were developed based on risk thresholds. Residents within the industrial parks face potential health risks due to pathogenic VOCs and nuisance odors, and workers in specific sectors experience two to six times higher risks than those in residential areas. Six risk sources were identified in the industrial park, ranked according to their contribution to VOC concentrations as follows: industrial sewage treatment (IST) (32.59 %), natural gas chemical industry (NGCI) (27.77 %), diesel vehicle exhaust (DVE) (12.04 %), pharmaceutical manufacturing industry (PMI) (11.14 %), chemical raw materials manufacturing (CRMM) (9.96 %), and iron and steel industry (ISI) (6.5 %). Among these, NGCI, IST, and CRMM were the top contributors to pathogenic risks, with contributions of 32.13 %, 29.71 %, and 21.71 % to non-carcinogenic risks, and 18.15 %, 19.87 %, and 27.99 % to carcinogenic risks, respectively. DVE produced significantly higher odor pollution compared to other sources, with intensities that were 3 to 10 times greater. The key pathogenic and odorous VOCs differ by source, resulting in varying control priorities for different VOC species. Reducing emissions from these six sources for 20 high-risk species (e.g., acrolein, 2-chlorotoluene, 1,2-dibromoethane, dichloromethane, and p-diethylbenzene) will simultaneously lower pathogenic and odor risks, with cumulative reduction rates ranging from 4.11 % to 93.75 %. This study provides quantitative control targets for VOCs from a health risk perspective, offering valuable guidance for developing risk management policies in industrial parks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aβ) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored., Methods: Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age., Results: Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aβ load. Single nucleus RNA sequencing analysis revealed that in the absence of Trem2, microglia were activated but trapped in transition to the fully reactive state, with distinct responses of vascular cells., Discussion: Our study provides the first evidence that TREM2 differentially modulates parenchymal and vascular Aβ pathologies, offering significant implications for both TREM2- and Aβ-targeting therapies for AD., Highlights: Triggering receptor expressed on myeloid cells 2 (TREM2) differentially modulates brain parenchymal and vascular amyloidosis. Loss of Trem2 markedly reduces cerebral amyloid angiopathy despite an overall increase of amyloid beta load in Tg-SwDI mice. Microglia are trapped in transition to the fully reactive state without Trem2. Perivascular macrophages and other vascular cells have distinct responses to Trem2 deficiency. Balanced TREM2-targeting therapies may be required for optimal outcomes., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

De novo lipogenesis (DNL), a hallmark of cancer, facilitates tumor growth and metastasis. Therapeutic drugs targeting DNL are being developed. However, how DNL is directly regulated in cancer remains largely unknown. Here, transcription factor sine oculis homeobox 1 (SIX1) is shown to directly increase the expression of DNL-related genes, including ATP citrate lyase (ACLY), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), via histone acetyltransferases amplified in breast cancer 1 (AIB1) and lysine acetyltransferase 7 （HBO1/KAT7）, thus promoting lipogenesis. SIX1 expression is regulated by insulin/lncRNA DGUOK-AS1/microRNA-145-5p axis, which also modulates DNL-related gene expression as well as DNL. The DGUOK-AS1/microRNA-145-5p/SIX1 axis regulates liver cancer cell proliferation, invasion, and metastasis in vitro and in vivo. In patients with liver cancer, SIX1 expression is positively correlated with DGUOK-AS1 and SCD1 expression and is negatively correlated with microRNA-145-5p expression. DGUOK-AS1 is a good predictor of prognosis. Thus, the DGUOK-AS1/microRNA-145-5p/SIX1 axis strongly links DNL to tumor growth and metastasis and may become an avenue for liver cancer therapeutic intervention., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Herein, a composite of N-doped carbon coated phosphating cobalt hollow nanofibers (N/C@CoP-HNFs) was synthesized by electrospinning, phosphating, and carbon coating processes. When employed as multifunctional electrode materials for potassium-ion batteries (PIBs) and lithium-sulfur (Li-S) batteries, the N/C@CoP-HNFs demonstrated notable electrochemical properties. Specifically, it delivered an initial specific capacity of 420.4 mA h g -1 at a current density of 100 mA g -1 , with a sustained capacity of 190.8 mA h g -1 after 200 cycles in PIBs, and a specific capacity of 1448 mA h g -1 at a current density of 0.5C in Li-S batteries, which is considered relatively high for these types of battery technology. This good performance may due to the combination of the carbon nitrogen layer and cobalt phosphide bilayer hollow tube structure, which is conducive to telescoping the diffusion length of ions and electrons and buffer volume variation, and effectively inhibits the shuttle effect. Density functional theory (DFT) calculations were also used to explore the energy storage mechanism of the material. The possible adsorption sites and corresponding adsorption energy of K + were analyzed, and the advantages of the material were explored by calculating the diffusion barrier and state density. The theoretical simulations further validated the strong adsorption capability of CoP for polysulfides. This work is expected to provide new ideas for new energy storage materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The angioedema risk may vary among stroke patients receiving different thrombolytic agents. This study aimed to investigate the angioedema risk associated with different thrombolytic agents and to identify associated risk factors. We conducted a large-scale retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. Stroke patients receiving thrombolytic therapy (i.e., alteplase or tenecteplase) were identified, and the associations with angioedema were explored using disproportionality analysis and time-to-onset analysis. Additionally, we used adapted Bradford Hill criteria to confirm these associations. Risk factors for angioedema were explored using stepwise logistic regression. A total of 17,776 stroke patients were included, with 2973 receiving alteplase and 278 receiving tenecteplase. Disproportionality analysis revealed that angioedema might be associated with alteplase (adjusted ROR [aROR] 5.13 [95 ​% CI, 4.55-5.79]) or tenecteplase (aROR 2.72 [95 ​% CI, 1.98-3.67]). The adapted Bradford Hill criteria suggested a probable causal relationship between alteplase and angioedema, whereas there was insufficient evidence of a probable causal relationship with tenecteplase. Multivariate analysis revealed that ACE-inhibitors use (aROR 9.73 [95 ​% CI, 7.29-12.98]), female sex (aROR 1.38 [95 ​% CI, 1.13-1.67]) and hypertension (aROR 2.11 [95 ​% CI, 1.52-2.92]) were significant risk factors for angioedema among alteplase-treated stroke patients. Our study suggested that alteplase is associated with a greater risk of angioedema among stroke patients, but there is insufficient evidence to support an association between tenecteplase and angioedema. Clinicians should be vigilant for this potentially life-threatening complication, particularly in patients with identified risk factors. It is also prudent to consider tenecteplase as an alternative, if available., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plants are important ecological factors and food resources, which can significantly affect the occurrence and distribution of insects. The metabolites in host plants can affect the feeding, spawning, and avoidance behaviors of herbivorous insects. Galeruca daurica (Joannis) is a phytophagous pest that has seriously occurred in the desert steppe of Inner Mongolia in recent years, only infesting the leaves of Allium plants. In order to clarify the effects of plant metabolites on the gene expression in G. daurica larvae at the transcriptome level, we fed the larvae of G. daurica with Allium tuberosum leaves soaked in 10% DMSO solutions containing d-galactose, β-d-glucopyranose, l-rhamnose, isoquercitrin, isoflavone, and rutin, respectively, used the larvae fed on A. tuberosum leaves soaked in a 10% DMSO solution as the control, and screened out the differentially expressed genes (DEGs) by performing high-throughput transcriptome sequencing. The results showed that a total of 291 DEGs were identified compared to the solvent control (DMSO), including 130, 34, 29, 21, 72, and 97 in the isoquercitrin, isoflavone, rutin, d-galactose, β-d-glucopyranose, and l-rhamnose treatment groups, respectively. GO and KEGG enrichment analysis showed that most DEGs were enriched in various metabolic pathways, implying that these six main primary and secondary metabolites in Allium plants may affect various metabolic processes in the larvae of G. daurica .

Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis , including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps , exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris . Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation., Competing Interests: The authors state that there are no conflicts of interest.

Variable thickness plates are relatively common structure in large-scale transportation equipment such as aerospace and ships. Due to their high running speed and large structural dimensions, such structures are usually induced high-frequency severe vibrations, which likely lead to structural damage. Therefore, it is crucial to accurately predict the high-frequency dynamic response characteristics during the structural design phase. The energy finite element method (EFEM) is a powerful tool for predicting high-frequency dynamic response. But, in recent EFEM for variable thickness plates, an approximate method (AEFEM) using a large number of constant thickness plate elements to approximate variable thickness plates is used. Due to that AEFEM is based on the constitutive equation for constant thickness plate, it will be imprecise and time-consuming. Aiming at power-law variable thickness plates, the constitutive equation based on energy density is derived and the finite element discrete scheme of the constitutive equation was studied. In this way, the precise new EFEM (NEFEM) for variable thickness plates was established. In addition, the dynamic response of a variable thickness plate was predicted by NEFEM presented and finite element method (FEM) respectively. The results are consistent. It is shown that the constitutive model presented is reliable and time-saving. Comparison of the results from AEFEM, the NEFEM can get more accurate results with fewer elements. The NEFEM based on the constitutive model presented can be used to predict precisely the high-frequency dynamic response for power-law variable thickness plates., (© 2024. The Author(s).)

Background: Hypoparathyroidism (HP) is a rare endocrine disorder, while situs inversus totalis (SIT) is a rare condition in which the internal organs are positioned in a mirrored pattern compared to their usual positions. This case illustrates some potential shared mechanisms between HP and SIT, highlighting the importance of accurate identification and prompt first emergency, offering insights for future research., Case Summary: This report discusses a case of a middle-aged patient with adolescent-onset HP with concurrent SIT. The patient experienced recurrent episodes of increased neuromuscular excitability (manifesting as spasms in the hands and feet and laryngospasms) and even periods of unconsciousness. Initially, these symptoms led to a misdiagnosis of epilepsy. Nevertheless, upon thorough examination and treatment in the general medicine ward, the correct diagnosis was established. Corresponding treatment resulted in improved management of the patient's symptoms., Conclusion: Co-occurrence of HP and SIT may be associated with genetic mutations, chromosomal anomalies, or hereditary factors, as may other similar conditions., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients., Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as "hospitalization" or "home management"; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423-7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity ( p = 0.292) or MECI incidence ( p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed.

As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment., (© 2024. The Author(s).)

Salt stress has become a major environmental problem affecting plant growth and development. Some WRKY transcription factors have been reported to be involved in the salt stress response in plants. However, there are few studies on the involvement of WRKYs in the salt stress response in Rosa rugosa . In this study, we isolated a salt tolerance gene, RrWRKY1 , from R. rugosa . RrWRKY1 was found to belong to Group I of the WRKY family, and it was specifically expressed in leaves and petals. RrWRKY1 expression was upregulated under NaCl stress in rose leaves. After silencing RrWRKY1 in R. rugosa , transgenic plants showed dry leaves and black and brown veins, indicating sensitivity to salt stress. At the same time, the transcription levels of the salt tolerance-related genes RrNHX1 , RrABF2 , RrRD22 , RrNCED1 , and RrHKT1 also changed significantly. The superoxide dismutase (SOD) and peroxidase (POD) activities decreased, the proline content decreased, and the malondialdehyde (MDA) content in the gene-silenced plants increased, indicating that RrWRKY1 regulates the salt tolerance of R. rugosa. In addition, the overexpression of RrWRKY1 in Arabidopsis thaliana improved the germination rate and the average of the main root and lateral root lengths, and the transgenic plants had a larger number of lateral roots than the WT plants under salt stress. This study provides candidate gene resources for salinity tolerance breeding and a theoretical basis for analyzing the salinity tolerance mechanism of the WRKY gene.

As a critical component of a welded structure, the integrity of the welded joint significantly affects the safety and reliability of the structure in service. Therefore, it is essential to investigate the integrity of welded joints. However, given the harshness of standard measurements renders them unsuitable for application to small volume zones, welded structures or in-service structures. In this study, the fracture properties of a Q235 steel butt-welded joint was evaluated by boundary effect modelling (BEM) method and the ball indentation (BI) method. The results demonstrate that the fracture toughness distribution obtained by the two methods are consistent, with the highest fracture toughness in the weld metal, followed by the heat-affected zone and the base metal, and the lowest fracture toughness in the fusion zone, which is in agreement with the results of the metallographic testing. Furthermore, the relative errors of the zones obtained by the ball indentation method and the boundary effect modelling method ranging from 10.16 to 19.05%, which indicates safety margin ought to be considered for employing the BI method to determine fracture properties of in-service structures., (© 2024. The Author(s).)

Background: Axial symptoms (AS) represent one of the primary complications after cervical spondylotic myelopathy (CSM) surgery. Traditional Chinese Medicine (TCM), as a complementary and alternative therapy, is widely used in the treatment of postoperative AS in CSM. However, it lacks standardised treatment protocols, uniform therapeutic criteria, assessment methods and a sufficiently in-depth understanding of its mechanisms of action. These shortcomings impact the credibility of TCM treatment in clinical practice., Methods and Analysis: We will conduct comprehensive searches, both manual and electronic, on literature published up to 31 July 2024, and database searches will commence after the publication of this agreement, with an estimated commencement date of 1 October 2024 and the end date of 31 March 2025, without language restrictions. Key databases such as MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, WHO International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wanfang Database will be explored. In addition, we will include resources such as library journals and conference abstracts. After identifying and screening all randomised controlled trials focused on TCM for postoperative AS of CSM, the two investigators will conduct a meta-analysis of the included studies. The results will be summarised as the risk ratio for binary data and the standardised or weighted average difference for continuous data., Ethics and Dissemination: Ethical approval is not required since this review does not involve individual patient data. The review's findings will provide clinicians with evidence on using TCM treatment for AS post-CSM surgery, disseminated through peer-reviewed publications or conferences., Prospero Registration Number: CRD42024505160., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Steatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF)., Materials and Methods: The UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland-Altman., Results: One hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICC intra-observer  = 0.96, ICC inter-observer  = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, -0.24 ± 1.44), and the results of both S5 (mean difference: -0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF., Conclusion: UDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach., Critical Relevance Statement: UDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting)., Trial Registration: The research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 ( http://www.chictr.org.cn/ ). The registration number is ChiCTR 2300076457., Key Points: There is a lack of non-invasive quantitative measurement options for hepatic steatosis. UDFF demonstrated excellent reproducibility in measuring hepatic steatosis. S8, end-expiratory, supine, and fasting may be the more stable measuring condition. Training could improve the operators' measurement stability. Variable measurement state affects the repeatability of the UDFF values (Cov)., (© 2024. The Author(s).)

Asymmetric seasonal warming trends are evident across terrestrial ecosystems, with winter temperatures rising more than summer ones. Yet, the impact of such asymmetric seasonal warming on soil microbial carbon metabolism and growth remains poorly understood. Using 18 O isotope labeling, we examined the effects of a decade-long experimental seasonal warming on microbial carbon use efficiency (CUE) and growth in alpine grassland ecosystems. Moreover, the quantitative stable isotope probing with 18 O-H 2 O was employed to evaluate taxon-specific bacterial growth in these ecosystems. Results show that symmetric year-round warming decreased microbial growth rate by 31% and CUE by 22%. Asymmetric winter warming resulted in a further decrease in microbial growth rate of 27% and microbial CUE of 59% compared to symmetric year-round warming. Long-term warming increased microbial carbon limitations, especially under asymmetric winter warming. Long-term warming suppressed the growth rates of most bacterial genera, with asymmetric winter warming having a stronger inhibition on the growth rates of specific genera (e.g., Gp10 , Actinomarinicola , Bosea , Acidibacter , and Gemmata ) compared to symmetric year-round warming. Bacterial growth was phylogenetically conserved, but this conservation diminished under warming conditions, primarily due to shifts in bacterial physiological states rather than the number of bacterial species and community composition. Overall, long-term warming escalated microbial carbon limitations, decreased microbial growth and CUE, with asymmetric winter warming having a more pronounced effect. Understanding these impacts is crucial for predicting soil carbon cycling as global warming progresses., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: COVID-19 viral infection results in dysregulation of the complement system and a decrease in cortisol and adrenocorticotropin hormone (ACTH) levels. This study aimed to explore the complement system, as well as cortisol and ACTH responses in patients with post-COVID-19 conditions (PCC) and type 2 diabetes mellitus (T2DM)., Patients and Methods: This study recruited 31 patients with PCC and T2DM (PCC-T2DM), 19 patients with PCC (PCC), 10 patients with T2DM (T2DM), and 10 healthy participants (control). Cortisol and ACTH in the PCC and PCC-T2DM groups were assessed using the insulin tolerance test. In the fasting state, serum samples were collected for proteomic analyses. Spearman correlation analysis was performed between proteins and cortisol, as well as between proteins and ACTH., Results: Cortisol and ACTH levels were consistently decreased in the PCC and PCC-T2DM groups. Proteomic analyses revealed that most of the differentially abundant proteins (DAPs) in the PCC vs control and PCC-T2DM vs T2DM were involved in the coagulation and complement cascade, and the essential complement C3 was significantly upregulated in the PCC and PCC-T2DM groups when compared to their controls. Additionally, complement-related DAPs in the PCC vs control and PCC-T2DM vs T2DM were significantly correlated with cortisol and ACTH levels. In comparing PCC-T2DM samples with PCC samples, we found that upregulated DAPs were linked to the complement system and other immune system, and most DAPs were negatively correlated with cortisol and ACTH., Conclusion: Our study revealed that T2DM exacerbated dysregulation of the complement system in patients with PCC, and significant correlations were present between complement protein levels and those of cortisol and ACTH. These results provide novel insights into the dysregulation of complement and endocrine hormones in patients with PCC and T2DM., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ji et al.)

Objectives: To explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE)., Methods: This study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF)., Results: Compared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p  < 0.05) and lower values of mean DTI-ALPS index (1.491 ± 0.142 vs. 1.642 ± 0.123, p  < 0.001). Significantly lower DTI-ALPS index values were observed in the ipsilateral hemisphere than in the contralateral hemisphere (1.466 ± 0.129 vs. 1.517 ± 0.175, p  = 0.013) for patients with unilateral TLE. Correlation analyses found that SVF performance was significantly or borderline significantly associated with glymphatic function ( FDR-corrected p  < 0.05 for all DTI-ALPS index and FDR-corrected p  = 0.057 for CPV) in TLE patients. Linear regression analyses showed that increased CPV and decreased DTI-ALPS index were independent risk factors for semantic fluency impairment (all p  < 0.05). Furthermore, mediation analyses found the mediator role of the mean DTI-ALPS index in the relationship between choroid plexus enlargement and semantic fluency impairment (indirect effect: β  = -0.182, 95%CI  = -0.486 to -0.037)., Conclusion: These findings reveal the important role of the DTI-ALPS index and CPV in SVF performance in unilateral TLE. Decreased DTI-ALPS index and increased CPV are the independent risk factors for semantic fluency impairment. The DTI-ALPS index may fully mediate the relationship between CP enlargement and SVF performance. These insights provide a radiological foundation for further investigations into the mechanism of the glymphatic system in TLE pathophysiology., Competing Interests: FS and YW were employed by Shanghai United Imaging Intelligence Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Xia, Zhang, Ma, Shi, Wei, Li and Meng.)

Background: Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings., Methods: Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP)., Results: The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029)., Conclusion: The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants' outcomes by facilitating timely clinical decisions., (© 2024. The Author(s).)

Background: Hypertension continues to increase in prevalence, and it has become a major cause of increased mortality globally. Physical activity (PA) has been shown to be a first-line treatment for controlling blood pressure. However, participation rates in PA are still poor. Therefore, it's imperative to explore the factors that affect patient PA adherence., Methods: A synthesis of qualitative research of the PA experience of patients with hypertension was conducted. We systematically searched for qualitative studies published in English from inception to May 2023 in the databases of PubMed, Embase, Web of Science, CINAHL, PsycINFO, and Cochrane Library. The Joanna Briggs Institute tool was used to extract data, and the Capability, Opportunity, Motivation-Behaviour model was used to synthesize data., Results: This qualitative research included 17 studies, identified 85 findings, summarized 9 categories, and finally meta-aggregated 3 synthesized findings, including capabilities of patients with hypertension, PA opportunities and PA motivators. The capabilities included age, other health problems, and PA knowledge and skills. Opportunities included time constraints, environmental factors, physical activity resources, and social support. Motivators included self-efficacy, pursuing physical health, and experience from PA., Conclusion: The available evidence contributes to a comprehensive understanding of the barriers and facilitators of PA in patients with hypertension. Most of these barriers can be addressed and improved. When designing and implementing physical activity programs for patients with hypertension, an individualized PA program should first be designed, tailored to the patient's capacity. Secondly, patients should be provided with additional PA resources and enhanced social support. Lastly, patients' motivation can be increased by enhancing their PA experience., (© 2024. The Author(s).)

Hyaluronic acid (HA) has been approved to be added to milk and other dairy products, it has highly water-binding ability which can combine with a large number of water molecules through intramolecular hydrogen bonding to form high viscous gels. In addition, HA is one of the prebiotics, can provide health benefits like anti-aging, anti-inflammatory, angiogenic, is a potential additive for enhancing the quality of yogurt. Therefore, the aim of this study was to evaluate the effect of 0%, 0.02%, 0.05%, 0.1%, 0.25% and 0.5% HA on rheological properties, functional properties, thermal stability, protein stability, protein structure and protein fractions of yogurt. The addition of HA, storage modulus (G') is always larger than loss modulus (G'') in all the samples, which is a typical characteristic of gel networks, and the microstructures of the yogurt samples showed a continuous and more homogeneous spatial network structure. Overall, the higher concentration (0.5%) had positive effect on the yogurt characteristics, like higher WHC, foam stability, microstructure, and texture. In contrast, the 0.1% concentration HA lead to a very abnormal results, it had a negative effect on yogurt including water-holding capacity, texture, and protein stability, suggesting structural destabilization and disruption of inter-aggregation before protein. These findings provide a valuable fundamental data for commercialized HA adding yogurt development and quality control processes., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Digital health literacy (DHL) is pivotal for individuals to access trustworthy health information and make informed decisions, closely intertwined with health behaviors and psychological resilience-these factors collectively shape an individual's approach to health management. Despite extensive research on digital health literacy in broader populations, the specific dynamics of digital health literacy in relation to health behaviors and psychological resilience among undergraduate nursing students in China remain understudied, highlighting a gap that this research endeavors to address. This study aims to assess the levels of digital health literacy among undergraduate nursing students in China, and to explore its association with health lifestyles and psychological resilience, which are considered influential factors., Methods: Employing a descriptive cross-sectional research design, eligible Chinese nursing undergraduates were surveyed from June to October 2023. This study recruited a total of 418 undergraduate nursing students. After excluding 11 students on leave, 407 students participated in questionnaire completion and submission. The College Students' Digital Health Literacy Scale, Healthy Lifestyle Assessment Scale and The Psychological Resilience Scale were used in this study., Results: The mean scores for digital health literacy, health lifestyles, and psychological resilience were 74.78 ± 8.44, 127.14 ± 11.22, and 79.21 ± 11.02, respectively. Pearson correlation analysis results indicated that the correlations between digital health literacy and both health lifestyles (r = 0.707, P < 0.01) and psychological resilience (r = 0.638, P < 0.01) were statistically significant and positive. The multiple linear regression analysis revealed that volunteer activity experience, academic performance, physical fitness, psychological traits, health lifestyle, and psychological resilience significantly predicted digital health literacy (F = 58.091, P < 0.001, R² = 0.678, adjusted R² = 0.666). Specifically, excellent academic performance (β = 0.210, P < 0.001) and good physical fitness (β = 0.188, P = 0.002) were the strongest predictors of higher digital health literacy., Conclusions: There is a correlation between the digital health literacy of nursing undergraduates and their health lifestyles and psychological resilience. Future research should consider interventions in digital health literacy for undergraduate nursing students in China from the perspectives of health lifestyles and psychological resilience., (© 2024. The Author(s).)

Acute lung injury (ALI) is a severe pulmonary disorder of sepsis with high clinical incidence and mortality. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-cysteinyl aspartate specific proteinase 1-gasdermin D (GSDMD)-dependent pyroptosis of alveolar epithelial cells (AECs) has emerged as a crucial contributor to ALI during sepsis. Phillyrin (PHI), a natural lignan isolated from the traditional Chinese herbal medicine Forsythia suspensa , has been shown to have anti-inflammatory, antioxidant and antiviral properties. However, little is known about the protective role and potential mechanism of PHI in sepsis-induced ALI, and it is uncertain whether the protective effect of PHI in sepsis-induced ALI is connected to pyroptosis. This study aims to examine the preventive effects of PHI on sepsis-induced ALI via the inhibition of NLRP3/caspase-1/GSDMD-mediated pyroptosis in AECs. Our findings demonstrate that preadministration of PHI successfully reduces sepsis-induced pulmonary edema, systemic/pulmonary inflammation, and pulmonary histological damage in lung tissues, bronchoalveolar lavage fluid, and the serum of septic mice. Intriguingly, PHI preadministration suppresses sepsis-induced protein expressions of pyroptosis-specific markers, especially their active forms. In vitro assays show that PHI pretreatment also protects type II AECs (MLE-12) from lipopolysaccharide-induced pyroptosis by preventing the activation of the pyroptosis signaling pathway. The results from molecular docking and surface plasmon resonance reveal that PHI has a significant affinity for direct binding to the GSDMD protein, suggesting that GSDMD is a potential pharmacological target for PHI. In conclusion, PHI can prevent sepsis-triggered ALI by effectively suppressing the activation of the canonical pyroptosis signaling pathway and pyroptosis of AECs.

Competing Interests: None.