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Background: The primary cause of subarachnoid hemorrhage (SAH) is the rupture of intracranial aneurysms. Over-activation of microglia following SAH is a primary driving force in early brain injury (EBI), which is a leading cause of poor outcomes. Silybin is a flavonoid compound extracted from Silybum marianum, a plant belonging to the Asteraceae family. Its anti-inflammatory and antioxidant properties could provide neuroprotective effects. The mechanism of silybin on EBI after SAH is unclear., Purpose: To determine the therapeutic effect of silybin on SAH and its underlying mechanisms., Methods: We used a prechiasmatic autologous arterial blood injection in vivo and hemoglobin in vitro to establish experimental SAH model. Dexamethasone was used as a positive control drug. We evaluated the neuroprotective effect of silybin on the in vivo SAH model by neurological function scores, rotarod test, and open field test, and explored the protective effect of silybin on neuroinflammation and apoptosis after SAH by quantitative polymerase chain reaction (qPCR), western blot (WB), Immunofluorescence (IF) and TUNEL staining. IF staining of CD86 and CD206 was used to assess microglial phenotype polarization. Then we used WB and IF labeling of STING to explore the effect of silybin on the STING pathway after SAH, and used a combination of transcriptomics and non-targeted metabolomics to study the potential mechanism of silybin in detail, and verified the essential genes by qPCR. We also extracted cerebrospinal fluid from SAH patients and detected the expression level of STING in cerebrospinal fluid by enzyme-linked immunosorbent assay (ELISA) to clarify the association between STING and neural function., Results: Results showed that silybin ameliorated neuronal damage and improved short-term neurological function, and reduced inflammatory damage and neuronal apoptosis in SAH mice. Silybin inhibited the expression levels of TNF-α, IL-1β and NLRP3, and promoted the expression levels of CD206, Arg1 and IL-10. Notably, Silybin promoted M2 microglia polarization. Further studies found that silybin reduced the mRNA and protein levels of the stimulator of interferon genes (STING) in microglia. And the use of a specific activator of STING (CMA) disrupted the protective effect of silybin. A total of 358 differential expression genes were identified using transcriptomics, and 150 different metabolites abundance were identified using metabolomic screening. Analysis of the effects of STING on transcriptomics and metabolomics revealed that STING might impact metabolic pathways, including linoleic acid metabolism. The qPCR results confirmed the decreased expression of essential proteins involved in the pathway. Finally, we found that increased STING expression in the cerebrospinal fluid of SAH patients was associated with decreased neurological function scores and poor prognosis., Conclusion: Silybin had a therapeutic effect on SAH. The underlying mechanism involves linoleic acid metabolism, which is associated with the differential genes and metabolites detected in the study. This study presented a pharmacological rationale for using silybin to treat SAH., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Schisandra chinensis (Turcz.) Baill, which is frequently used in health products and drinks, is recognized for its high content of essential oils that could have protective effects against PD, despite the lack of complete understanding of its pharmacological mechanisms. This research aims to examine how ESC can affect autophagy signaling pathways and activate the Nrf2/HO-1 pathway to effectively decrease oxidative damage, thus shedding light on the possible anti-PD effects of this treatment. The results demonstrated that ESC significantly reduced behavioral issues linked to Parkinson's disease in a mouse model that was induced by MPTP and safeguarded dopaminergic neurons that expressed tyrosine hydroxylase. Moreover, ESC boosted the antioxidant capability of Nrf2, assisted with autophagy processes, and finally decreased protein expression levels of Keap1, HO-1, MAPK, mTOR, and ERK. According to in vitro studies, ESC treatment had a significant reduction in H 2 O 2 -induced cytotoxicity and oxidative stress levels, which suggests that Nrf2 targets ESC after treatment. The activation of both autophagy and Nrf2 antioxidant pathways was assessed using western blotting. In conclusion, ESC exhibits the potential to suppress oxidative stress by activating Nrf2 in response to autophagy, which is positioned as a promising pharmaceutical candidate, especially for the management and treatment of PD and related disorders., 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 © 2025 Elsevier Inc. All rights reserved.)

RNA granules are liquid-liquid-phase-separated condensates comprising RNA and proteins. Despite growing insights into their biological functions, studies have predominantly relied on biological methodologies lacking adequate chemical tools. Here, we introduce ICP-CHARGINGS, a concept for efficiently identifying chemical probes to characterize RNA granules of interest among nucleic acid-targeting agents. Focusing on mitochondrial RNA granules (MRGs), whose functions remain elusive, we developed a methodology within this framework and identified NATA , a new fluorescent molecule that, following mechanistic studies, was found to bind to the mitoribosome, enabling MRG labeling and recognition. Using NATA to reveal the potential buffering roles of MRGs, we demonstrated a close correlation between MRG maintenance and assembly and cellular survival and proliferation under cold shock and hypoxic stress. Overall, the introduction and implementation of the ICP-CHARGINGS strategy provide a specialized chemical tool for advancing our comprehension of MRG biology and establish a paradigm for elucidating RNA structures within RNA granules that can be targeted by small molecules, paving the way for developing tailored chemical probes for diverse RNA granules in future research.

Congenital Zika virus (ZIKV) infection significantly affects neurological development in infants and subsequently induces neurodevelopmental abnormality symptoms; however, the potential mechanism is still unknown. Therefore, in order to effectively intervene in neurodevelopmental abnormalities in infected infants, it is necessary to identify the main brain regions affected by congenital infection. In this study, we constructed a congenital ZIKV-infected murine model using immunocompetent human STAT2 knock-in mice, which presented long-term neurodevelopmental abnormalities with abnormal neurodevelopmental symptoms. We found that the hippocampus, which regulates cognitive behavior and processes spatial information and navigation, was the main brain region affected by congenital infection and that hippocampal cells were more prone to autophagy during the growth period of these mice at the transcriptional and pathological levels. These findings highlighted that congenital ZIKV infection could interrupt hippocampal function by activating autophagy, thus providing a theoretical basis for the clinical treatment of congenital ZIKV-infected infants.

Twenty constituents, three new terpenes named Paeoniterpene A-C (1-3), and three new fatty glycosides named Paeoniglycoside A-C (4-6) were isolated from the leaves of Paeonia lactiflora Pall. The structures of compounds 1-6 were identified using extensive spectroscopic methods, such as NMR, MS, CD, IR, and UV. Compounds 4-6 were characterized through quantum chemical calculations and DP4 + probability analysis, and ECD definitively confirmed their structures. Additionally, all compounds were assessed for their neuroprotective effects against H 2 O 2 -induced damage in PC 12 cells. Compounds 1-3, 7, 8, 11, and 12 could significantly improve H 2 O 2 -induced PC 12 injury., Competing Interests: Declaration of competing interest Xin-Yu Min and Jia-Tong Wu have contributed equally to this work. The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Ardisia Crispae Radix et Rhizoma comprises three primary source plants: Ardisia crenata Sims, Ardisia crispa (Thunb.) A. DC., and Ardisia crenata Sims var. bicolor (Walk) C. Y. Wu et C. Chen. These species are prevalent in mid-to-low-latitude regions and are traditionally utilized as herbal medicines in East Asia and India. They have demonstrated notable efficacy in anti-inflammatory properties and possess potential anti-tumor, antimicrobial, antioxidant, and anti-angiogenic activities., Aim: This review systematically evaluated the botany, traditional uses, phytochemistry, pharmacology, and toxicity of Ardisia Crispae Radix et Rhizoma to assist future innovative research and facilitate the development of new therapeutic agents., Materials and Methods: Literature was sourced from both library and electronic databases, including Web of Science, PubMed, Elsevier, Google Scholar, and CNKI. The review focuses on phytochemistry, pharmacological research, and toxicity studies related to Ardisia Crispae Radix et Rhizoma., Results: Ardisia Crispae Radix et Rhizoma is traditionally used to treat inflammation and injuries. Current pharmacological studies suggest its potential anti-tumor, anti-inflammatory, antimicrobial, antioxidant, and anti-angiogenic activities. This review identified approximately 161 compounds in Ardisia Crispae Radix et Rhizoma, such as saponins, flavonoids, coumarins, essential oils, lignans, and terpenes., Conclusions: Ardisia Crispae Radix et Rhizoma is a promising medicinal plant resource with a diverse range of specialized metabolites. However, existing research predominately addresses phytochemistry and pharmacological activities, with limited exploration of underlying mechanisms. Further systematic evaluations of its efficacy and clinical safety are required., 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 B.V. All rights reserved.)

Two new compounds ( 1 - 2 ), together with six known ones ( 3-8 ), were isolated from the roots of Paeonia lactiflora Pall. The structures of two new compounds were elucidated based on HR-ESI-MS, UV, and NMR spectroscopic data analysis. Moreover, the anti-inflammatory activities of compounds 1-8 were determined using LPS-induced RAW 264.7 cells. Compounds 2, 6, and 8 showed the most potent inhibitory activities on NO production with IC 50 values of 17.34 ± 1.5, 27.22 ± 1.3, and 14.79 ± 1.7 μM, respectively. Compounds 4 and 7 showed moderate inhibitory activities. Compounds 3 and 5 showed relatively weak inhibitory activities.

Aim: The aim of this study is to explore and integrate educational measures and teaching methods designed to enhance ethical sensitivity, with the goal of developing a cohesive and practical reference framework for nursing administrators and educators., Background: In recent years, ethical sensitivity has garnered increasing attention. While many intervention studies addressing ethical sensitivity have been conducted, there is currently no systematic review that consolidates and integrates the various intervention strategies and teaching methods., Design: This study is a systematic review., Method: In this systematic review, relevant studies were retrieved from the PubMed, EBSCO, Cochrane, Embase, Scopus and Web of Science databases, covering the period from the inception of these databases through December 2024. The quality of the quasi-experimental studies and randomized controlled trials were assessed the Joanna Briggs Institute's (JBI) Critical Evaluation Checklist. Finally, the findings were synthesized through qualitative analysis to identify key themes., Results: A total of 25 studies were included in this study. Three themes were identified: theoretical foundations of ethics, clinical ethics, cultural ethics. In terms of teaching methodologies, the findings suggest that student-centered approaches are more effective than traditional teaching methods in enhancing ethical sensitivity., Conclusion: Currently, the content of ethical sensitivity education remains fragmented. It is recommended that future curricula incorporate two additional topics: the ethics of science and technology and the ethics of public health. Furthermore, adopting a collaborative, team-based approach and integrating new teaching technologies are proposed as effective strategies to enhance ethical sensitivity., Competing Interests: Declaration of Competing Interest There's no conflict of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objective: Hyperuricemia is a risk factor for cardiovascular disease complications in patients with chronic kidney disease. The impact of febuxostat on cardiovascular disease in advanced chronic kidney disease remains unclear. This study aimed to explore the cardiovascular benefits of xanthine oxidase inhibitors, particularly febuxostat and allopurinol, in patients with advanced chronic kidney disease., Methods: A retrospective population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD) (2012-2020). The TriNetX dataset served as an external validation dataset. The study involved 13,187 patients with advanced chronic kidney disease treated with febuxostat or allopurinol. After propensity score matching, a balanced cohort of 976 patients (488 in each arm) was created. Hazard ratios (HRs) were calculated for all-cause mortality and hospitalizations, utilizing the competing risk regression model., Results: Febuxostat was associated with lower all-cause mortality (HR, 0.79; 95% confidence interval [CI], 0.64-0.98) and fewer hospitalizations (HR, 0.53; 95% CI, 0.44-0.63) than allopurinol. After adjustments, febuxostat also reduced hospitalizations for heart failure (HR, 0.59; 95% CI, 0.43-0.80) and infection (HR, 0.65; 95% CI, 0.52-0.82). This cardiovascular benefit of febuxostat was consistently observed in the TriNetX dataset. Moreover, subgroup analysis revealed that febuxostat was better in reducing death and heart failure events than allopurinol across most of the subgroups., Conclusions: Febuxostat may confer cardioprotective effects in patients with advanced chronic kidney disease compared with allopurinol, thereby making it potentially useful in reducing cardiovascular risks in this high-risk population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The conformational dynamics and activation mechanisms of KRAS proteins are of great importance for targeted cancer therapy. However, the detailed molecular mechanics of KRAS activation induced by GTP binding remains unclear. In this study, we systematically investigated how GTP/GDP exchange affects the thermodynamic and kinetic properties of KRAS and explored the activation mechanism using molecular dynamics (MD) simulations, Markov state models (MSMs), and neural relational inference (NRI) models. Our MD simulation results show that GTP binding significantly enhances the conformational flexibility of KRAS, and thus promotes its transition to an active conformation with more open switch I and II regions. MSMs analyses show that KRAS in the GTP-bound state can be transitioned to the active state more efficiently during the simulation than in the GDP-bound state. In addition, NRI model calculations showed that GTP binding enhanced residue-residue interactions within the KRAS protein, especially when the long-range interactions were significantly enhanced. Furthermore, the allosteric signaling pathways from the P-loop to switch I and II as well as the key amino acid sites along the pathways were obtained using a graph-based shortest path analysis. Our results can contribute to a deeper understanding of the mechanism of KRAS allosteric activation and provide a foundation for the development of targeted therapeutic drugs to regulate KRAS activity., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: To explore the association between gamma-glutamyltransferase (GGT) and in-hospital heart failure (HF) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)., Methods: A total of 412 patients diagnosed with STEMI and treated with primary PCI were included in our study. Univariate and multivariate logistic regression models were used to evaluate the association between GGT and the risk of in-hospital HF in STEMI patients. The receiver operating characteristic (ROC) curve was used to assess the accuracy of GGT in predicting in-hospital HF., Results: The incidence of HF after STEMI increased significantly with increasing GGT tertiles (the first, second, and third tertile groups were 7.97%, 14.49%, and 18.38%, respectively; p = 0.039). Multivariate logistic regression analysis revealed that the risk of HF in the second and third GGT tertile groups was 2.51 times greater (95% CI, 1.06-5.96) and 2.77 times greater (95% CI, 1.13-6.81), respectively, than that in the first GGT tertile group. Each 1-unit increase in the lnGGT level was related to a 1.88-fold increased risk of HF (odds ratio, OR, 1.88; 95% CI, 1.19-2.96; p = 0.007). Restricted cubic splines suggested a linear relationship between GGT and in-hospital HF ( p for nonlinearity = 0.158). The area under the curve was 0.607 (95% CI, 0.558-0.654; p = 0.007) when GGT was used to predict in-hospital HF, with a sensitivity of 57.14% and a specificity of 64.04%. Moreover, the incidence of HF significantly increased in-hospital death risk (OR, 7.75; 95% CI, 1.87-32.12; p = 0.005)., Conclusions: GGT is positively associated with in-hospital HF and is an independent risk factor for in-hospital HF in STEMI patients., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2025 The Author(s). Published by IMR Press.)

On-site or in-sensor biosignal transduction and amplification can offer several benefits such as improved signal quality, reduced redundant data transmission, and enhanced system integration. Ambipolar organic electrochemical transistors (OECTs) are promising for this purpose due to their high transconductance, low operating voltage, biocompatibility, and suitability for miniaturized amplifier design. However, limitations in material performance and stability have hindered their application in biosignal amplification. Here, we propose using high-spin, hydrophilic conjugated polymers and a computational screening approach to address this challenge. We designed a high-spin polymer, namely P(TII-2FT), which exhibits satisfactory, stable, and balanced ambipolar OECT performance. The figure-of-merits achieved by the P(TII-2FT) devices surpass those of the current leading materials by 5 to 20 times, resulting in remarkable voltage gains while maintaining a compact form factor. Based on this amplifier, we have successfully achieved on-site capture and amplification of various electrophysiological signals with greatly enhanced signal quality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Patients with type 2 diabetes mellitus (T2DM) have higher pancreatic cancer (PC) risk. While aspirin has chemopreventive effects on digestive cancers, its effect on PC among patients with T2DM is unclear., Methods: This retrospective cohort study identified newly diagnosed adult patients with T2DM in Hong Kong between 2001 and 2015 from a territory-wide healthcare registry. Exclusion criteria were history of PC, pancreatic cyst, IgG4 disease, or pancreatectomy. To address reverse causality between PC and T2DM, we excluded patients with PC diagnosed within 1 year of T2DM. We also excluded patients with less than 1 year of observation. Primary outcome was PC, and secondary outcomes were PC-related and all-cause mortality. Aspirin use was treated as time-varying variable (≥180 day-use/year) to address immortal-time bias, and multivariable Cox regression model was employed to derive adjusted HR (aHR). Propensity-score (PS) matching was used as secondary analysis., Results: Among 343 966 newly diagnosed patients with T2DM (median follow-up: 10.5 years; IQR: 7.7-14.5 years), 1224 (0.36%) developed PC. There were 51 151 (14.9%) deaths from any cause, and 787 (0.2%) died from PC. Aspirin use was associated with lower PC risk in both time-dependent (aHR: 0.58; 95% CI 0.49 to 0.69) and PS matching analysis (aHR: 0.61; 95% CI 0.48 to 0.77). An inverse relationship was observed with increasing dose and duration of aspirin use ( P trend <0.001). Aspirin was also associated with a lower risk of PC-related mortality (aHR: 0.43; 95% CI 0.34 to 0.53) and all-cause mortality (aHR: 0.78; 95% CI 0.76 to 0.80)., Conclusion: Aspirin use may be an oncopreventive strategy to reduce PC risk in patients with T2DM. Further studies are warranted to validate the study findings., Competing Interests: Competing interests: WKS received speaker’s fees from AstraZeneca, is an advisory board member and received speaker’s fees of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The slaughtering environment is crucial for the food hygiene and safety of poultry products. Despite the global dominance of industrial processing, live bird slaughtering in wet markets persists due to cultural, religious, and economic reasons. This study aims to reveal the correlation between hygiene scales in wet markets and bacterial contamination levels on broiler carcasses, with a particular focus on pathobiont transmission risks and microbiome characteristics. Wet markets were categorized based on home-made ratings and the Hygiene and Biosecurity Assessment Tool (HABT). The study assessed total aerobic bacterial (TAB) levels, food spoilage and hygiene indicators (Pseudomonas and E. coli), foodborne pathogen Salmonella, and the microbiome of broiler carcasses, intestinal contents, and slaughtering facilities. Comparative analyses were conducted between market and industrial processing environments. TAB levels on broiler carcasses showed a significant negative correlation with hygiene scores, indicating that both HABT and home-made rating tools effectively assess and improve processing hygiene. Industrial processing consistently reduced bacterial contamination compared to wet markets. Although Salmonella spp. prevalence was lower in market-processed carcasses, the study identified significant cross-transmission of pathobionts and variations in bacterial composition with hygiene improvements. Notably, the microbiome analysis revealed overlaps in amplicon sequence variants (ASVs) between carcasses and contamination vectors, highlighting pathobiont transmission risks. The present study confirmed the scales of hygiene standards among wet markets reflect bacterial contamination on broiler carcasses. Enhancing slaughter practices to meet industrial hygiene standards is essential for reducing the transmission of foodborne pathogens and pathobionts, and improving food safety., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Species of Seuratascaris Sprent, 1985 are a rarely reported group of ascaridoid nematodes, parasitising various frogs and toads. In the present study, a new subspecies of Seuratascaris, S. physalis bazhaiensis n. subsp. was described using integrated taxonomic methods, based on specimens collected from Odorrana graminea (Anura: Ranidae) in Guangxi Zhuang Autonomous Region, China. Results of the Assemble Species by Automatic Partitioning (ASAP) and Bayesian inference based on the mitochondrial cox1, cox2 and rrnS data all supported S. physalis bazhaiensis representing a distinct taxon from the nominate subspecies S. physalis physalis. Supplementary morphometric and genetic data of S. phy. physalis are presented based on newly collected material from Odorrana tiannanensis (Anura: Ranidae) and Rhacophorus sp. (Anura: Rhacophoridae) in Yunnan Province, China. A key to species of Seuratascaris is provided. The complete mitochondrial genome of S. physalis bazhaiensis was sequenced and annotated, and represents the first mitogenomic data for the genus Seuratascaris. This mitogenome has only 13,628 bp (including 12 protein-coding genes, 22 tRNA genes, 2 ribosomal RNAs, and only 1 non-coding region), and is the smallest of the reported ascaridoid mitogenomes so far., (© X. Gu et al., published by EDP Sciences, 2025.)

Acetylcholinesterase (AChE) is one of the most successful targets for the treatment of Alzheimer's disease (AD). Inhibition of AChE can result in preventing AD. In this context, the machine-learning (ML) model, molecular docking, and molecular dynamics calculations were employed to characterize the potential inhibitors for AChE from MedChemExpress (MCE) database. The trained ML model was initially employed for estimating the inhibitory of MCE compounds. Atomistic simulations including molecular docking and molecular dynamics simulations were then used to confirm ML outcomes. In particular, the physical insights into the ligand binding to AChE were clarified over the calculations. Two compounds, PubChem ID of 130467298 and 132020434, were indicated that they can inhibit AChE., 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., (Published by Elsevier Inc.)

Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages. Here, we found that L-malate exerts anti-inflammatory effect via BiP-IRF2BP2 signaling, which is a sensor of cytosolic pH in macrophages. First, L-malate, a TCA intermediate upregulated in pro-inflammatory macrophages, was identified as a potent anti-inflammatory metabolite through initial screening. Subsequent screening with DARTS and MS led to the isolation of L-malate-BiP binding. Further screening through protein‒protein interaction microarrays identified a L-malate-restrained coupling of BiP with IRF2BP2, a known anti-inflammatory protein. Interestingly, pH reduction, which promotes carboxyl protonation of L-malate, facilitates L-malate and carboxylate analogues such as succinate to bind BiP, and disrupt BiP-IRF2BP2 interaction in a carboxyl-dependent manner. Both L-malate and acidification inhibit BiP-IRF2BP2 interaction, and protect IRF2BP2 from BiP-driven degradation in macrophages. Furthermore, both in vitro and in vivo, BiP-IRF2BP2 signal is required for effects of both L-malate and pH on inflammatory responses. These findings reveal a previously unrecognized, proton/carboxylate dual sensing pathway wherein pH and L-malate regulate inflammatory responses, indicating the role of certain carboxylate metabolites as adaptors in the proton biosensing by interactions between macromolecules., Competing Interests: Conflict of interest: Hongming Miao is the editorial board member of Signal Transduction and Targeted Therapy, but he has not been involved in the process of the manuscript handling. Other authors declare no competing interest., (© 2024. The Author(s).)

Coronary atherosclerosis (or coronary heart disease [CHD]) is a common cardiovascular disease that seriously damages human health. Percutaneous coronary stent implantation represents the primary treatment option for severe CHD in clinical practice; meanwhile, dual antiplatelet therapy (DAPT) is widely used to reduce the risk of postoperative thrombosis. Although the mechanisms of action of the two most commonly used antiplatelet drugs, aspirin and clopidogrel, remain unclear, clinical studies have shown that some patients are susceptible to stent thrombosis-antiplatelet resistance (high on-treatment platelet reactivity [HTPR])-despite using these drugs. Therefore, screening for HTPR and formulating personalized antiplatelet therapies is necessary. Ticagrelor, indobufen, and rivaroxaban are the most common and safe antiplatelet drugs used in clinical practice, with broad application prospects. This review summarizes the mechanisms of action of existing antiplatelet drugs, reasons for personalized treatment, screening of antiplatelet reactions, and development of novel antiplatelet drugs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Objective: The objective of this study was to evaluate the short-term outcomes of single-port thoracoscopic rib fracture reduction and internal fixation for the treatment of multiple rib fractures., Methods: This study included 149 patients with multiple rib fractures admitted to the Second People's Hospital Affiliated with Fujian University of Chinese Medicine between June 2021 and April 2024. The patients were divided into two groups based on the surgical method. The study group, consisting of 84 cases, underwent rib fracture reduction using a single-port thoracoscopy and internal fixation with a memory alloy reverse rib embrace device. The control group, consisting of 65 cases, underwent traditional open surgery for rib fracture internal fixation. Perioperative and follow-up data were collected and analyzed to assess incision length, total operation time, intraoperative blood loss, number of memory alloy embrasures placed, placement success rate, drainage tube placement time, time to mobilization, total hospitalization duration, total cost, preoperative and postoperative pain levels, postoperative complications, and rib CT results three months postoperatively., Results: There was no statistically significant difference in general conditions between the study group and the control group. All 149 patients successfully completed the surgery, with 3 to 10 intrathoracic memory alloy embrace devices placed in each patient, achieving a 100% success rate. Compared to the control group, the study group showed significant improvements in incision length (3.5 ± 0.6 vs. 6.5±1.6 cm), intraoperative blood loss (92.5 ± 15.1 vs. 113 ± 18.2 ml), drainage tube placement time (75.4 ± 13.1 vs. 90.6 ± 15.4 h), mobilization time (2.9 ± 1.1 vs. 3.3 ± 1.3 days), and hospital stay (10.8 ± 2.7 vs. 12 ± 3.5 days), with differences being statistically significant (P < 0.05). In terms of preoperative Visual Analogue Scale (VAS) pain scores, the study group had a significantly lower score on the first postoperative day compared to the control group (3.9 ± 1.1 vs. 4.5 ± 1.4, P < 0.05). A follow-up CT and 3D reconstruction at 3 months post-surgery showed that all patients had securely fixed plates, with the study group demonstrating a higher rate of excellent fracture healing (94% vs. 83.1%), which was statistically significant (P < 0.05)., Conclusion: The use of a memory alloy reverse rib embrasure device for intrathoracic rib fracture fixation via single-port thoracoscopic surgery is safe and reliable. This method demonstrates a high success rate of internal fixation, excellent clinical fracture healing, and advantages such as minimal trauma, rapid recovery, and the simultaneous treatment of other intrathoracic conditions. It significantly reduces postoperative pain and enhances the quality of life., Competing Interests: Declarations. Conflict of interests: The authors declare that they have no competing interests. Ethical approval: This study was approved by the Ethics Committee of The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Patients were consented by an informed consent process that was reviewed by the Ethics Committee of The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki., (© 2024. The Author(s).)

Purpose: To assess the correlation of body mass index (BMI), diet and lifestyle with allergic conjunctivitis (AC) in children., Methods: This prospective case-control study included 105 children with AC and 105 age- and sex-matched children with no AC. Clinical data were collected, including BMI, dietary habits, physical activity, and sleep time. Multivariate regression analysis was used to analyze the risk factors for AC., Results: Dietary habits including vitamin A supplement use (χ2 = 0.00; P = 1.00), the consumption of sweet food (χ2 = 6.70; P = 0.08), fast food (χ2 = 3.74; P = 0.29), beverages (χ2 = 1.17; P = 0.76), and seafood and fish (χ2 = 6.15; P = 0.10) and snacking before sleep (χ2 = 2.23; P = 0.53), were not associated with AC. There were significant differences in physical activity (χ2 = 12.64; P < 0.01) between the children with AC and healthy children. Physical activity of less than 1 h per day is more found among AC and more than 2 h of exercise per day is more found in healthy children. There were no differences in sleep duration (χ2 = 5.39; P = 0.07). Multivariate regression analysis revealed that a high BMI (overweight and obesity) (OR = 3.05; 95% CI: 1.30-7.20; P = 0.01) was a significant risk factor for AC. The consumption of fish oil supplements (OR = 0.38; 95% CI: 0.17-0.81; P = 0.01) and having been breastfed (OR = 0.34; 95% CI: 0.16-0.72; p = 0.005) were protective factors against AC., Conclusion: A high BMI (overweight and obesity) can increase the incidence of AC. Breastfeeding and dietary supplementation with fish oil are recommended for children susceptible to AC., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving research study participants were approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University, Chongqing, China (NO.2022 − 486). Verbal informed consent was obtained from legal guardian of all subjects/patients. Verbal consent was witnessed and formally recorded. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Schisandra chinensis (Turcz.) Baill (S. chinensis), a member of the Magnoliaceae family, is renowned for its distinctive medicinal attributes and is commonly employed in the treatment of disorders affecting the CNS., Purpose: The potential therapeutic effects of a lignan-enriched extract derived from Schisandra chinensis (Turcz.) Baill (LSC) on PD is assessed, which focuses on its mechanisms of action in addressing neuroinflammation., Methods: The LSC has been obtained by purifying the ethyl alcohol extract of S. chinensis. The Orbitrap-MS method has been employed to analyze the chemical composition of the LSC. In LPS-induced BV2 cells, LSC-induced changes in M1/M2 type inflammatory cytokines have been examined using the Griess reaction, Elisa, JC-1, flow cytometry, IF, and WB methods. A model of PD has been established by treatment of MPTP in C57BL/6 mice. The effect of LSC on behavioral changes, inflammatory factor levels, expression of TH and IBA-1, and production of autophagy in the midbrain has been investigated by TEM, immunohistochemistry, Elisa, and WB., Results: LSC has relieved sports injuries and pathological damage, and targeted the TRPV1-AMPK-NLRP3 signaling pathway, which affected neuroinflammation and autophagy in vivo. Furthermore, in vitro investigations demonstrated that LSC has activated M1/M2 transformation, its related inflammatory factors, and protein expressions of the NLRP3-Caspase1 signaling pathway in LPS-BV2 cells. The research notably demonstrated that the LSC promoted autophagy and suppressed inflammation through targeting TRPV1., Conclusion: In the investigation, LSC focused on TRPV1 and controlled neuroinflammation-autophagy by regulating AMPK-NLRP3, which has been proven for the first time. The study has presented molecular data supporting the use of LSC in treating PD and offers references for developing drugs. Remarkably, LSC has the potential to be utilized as a therapeutic or health medication that could significantly decrease PD., Competing Interests: Declaration of competing interest The authors affirm that they have no known competing financial interests or personal relationships that could have potentially influenced the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4 + monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4 + monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

Polymyxin B is a viable option for treating antibiotic-resistant infections; however, current data on its pharmacokinetics, particularly in patients with renal insufficiency, remain inconclusive and necessitates further investigation. To address this gap, we conducted an open-label, single-center, single-dose, parallel-group pharmacokinetic study. Participants received an intravenous dose of 0.75 mg/kg of polymyxin B and were categorized based on their renal function: those with normal function (creatinine clearance [CLcr] ≥ 90 mL/min), mild renal insufficiency (CLcr 60-89 mL/min), and end-stage kidney disease patients on intermittent hemodialysis (IHD) (CLcr < 10 mL/min). The pharmacokinetic parameters assessed included the area under the curve (AUC), maximum concentration (C max ), clearance rate (CL), volume of distribution (Vz), and half-life (t 1/2 ). Results indicated that subjects with mild renal insufficiency exhibited pharmacokinetic profiles similar to healthy individuals. Nevertheless, in patients undergoing long-term IHD, we observed significant differences: the AUC was 58% higher, C max was 29% lower, CL was 42% lower, Vz was 60% larger, and t 1/2 was extended by 10 h compared to healthy controls. Secondary outcomes revealed good tolerability of polymyxin B across all groups, with no serious adverse effects related to renal function. In summary, while kidney function may have a slight impact on the pharmacokinetic of polymyxin B, it does not compromise the drug's therapeutic effectiveness., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Wheat growth process has been experiencing severe challenges arising from the adverse environment. Notably, the incidence of Fusarium crown rot (FCR), a severe soil-borne disease caused by Fusarium pseudograminearum (Fp), has significantly intensified in various wheat-growing regions, resulting in a decline in grain yield. However, the identification of wheat varieties and the exploration of effective gene resources resistant to FCR have not yet been accomplished. Here, we screened and identified the tryptophan metabolism pathway to participate in wheat resistance to FCR by correlation analysis between transcriptome and metabolome, and found that indole-3-acetaldehyde (IAAld) and melatonin, two key metabolites in the tryptophan metabolic pathway, were significantly accumulated in Fp-induced wheat stem bases. Interestingly, exogenous application of these two metabolites could significantly enhance wheat resistance against Fp. Additionally, we observed that the activity of TaALDHase, a crucial enzyme responsible for catalyzing IAAld to produce indole-3-acetic acid (IAA), was inhibited. Conversely, the activity of TaMTase, a rate-limiting involved in melatonin biosynthesis, was enhanced in the Fp-induced wheat transcriptome. Further analysis showed that TaWRKY24 could regulate IAA and melatonin biosynthesis by inhibiting the expression of TaALDHase and enhancing the transcription of TaMTase, respectively. Silencing of TaALDHase could significantly increase wheat resistance to FCR. However, interference with TaWRKY24 or TaMTase could decrease wheat resistance to FCR. Collectively, our findings demonstrate the crucial role of the tryptophan metabolism pathway in conferring resistance against FCR in wheat, thereby expanding its repertoire of biological functions within the plant system., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) especially in children. The majority of EV-A71 cases are mild, however, severe cases have exhibited an array of neurological complications which often lead to death. In a screening campaign to discover hits against EV-A71, we identified six 2,4-diaryl-substituted thiophene compounds that were previously reported as Dyrk1A inhibitors. From these, compound S43 (EC 50  = 4.4 μM; CC 50  = 12.8 μM and SI = 2.9) was selected for an optimization campaign. Our SAR study revealed that the terminal pyridine could be removed without loss of the antiviral activity, which led to the new lead compound 23, maintaining anti-EV-A71 activity (EC 50  = 4.3 μM; CC 50  = 75.7 μM and SI = 17.6) while the cytotoxicity was 6-fold lower. Importantly, this modification also eliminated Dyrk1A inhibitory activity, avoiding further potential side effects related to inhibition of this kinase. Further results using harmine, a structurally distinct Dyrk1A inhibitor, ruled out Dyrk1A as a target in the observed antiviral effect against EV-A71. Mechanistically, our compounds act on the post-entry stage of the viral infection. When tested against a panel of related viruses, the compounds exhibited a broad spectrum against the enterovirus genus but could not inhibit the influenza virus. Additionally, S43 showed potent inhibition against herpes simplex virus (HSV). Altogether, we discovered 2-aryl thiophenes as a new class of antiviral compounds, which might be developed further into therapeutics against enterovirus infections., 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 © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and Aim: We aimed to investigate whether gut microbiota could predict the treatment response to pharmacological agents among metabolic dysfunction-associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM), as data are lacking., Methods: We prospectively followed up non-diabetic MASLD patients who used empagliflozin. Clinical, anthropometric, laboratory assessments and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were performed from baseline to week 52 (EOT). Baseline stool samples were collected, and shotgun DNA metagenomic sequencing was performed to profile microbiome. The primary outcome was treatment response to empagliflozin at EOT, defined as MRI-PDFF decline ≥ 30% at EOT from baseline. Linear discriminant analysis [LDA] effect size was used to identify putative bacterial species. Multivariable logistic regression was used to derive adjusted odds ratio (aOR) of outcome with bacterial species by adjusting for clinical factors., Results: Twenty-two (48.9%) of 45 patients (median age: 56.9 years [IQR: 51.0-63.2]; male: 23 [51.1%]) achieved treatment response at EOT. There was difference in alpha diversity (Shannon index: p < 0.001; Simpson index: p = 0.001) and beta diversity (p = 0.048) in baseline microbiome between treatment response and non-response groups. Faecalibacterium prausnitzii (log 10 LDAscore = 4.27), Lachnospira pectinoschiza (log 10 LDAscore = 3.99), Anaerostipes hadrus (log 10 LDAscore = 3.98), Roseburia faecis (log 10 LDAscore = 3.97), Roseburia inulinivorans (log 10 LDAscore = 3.58) and Agathobaculum butyriciproducens (log 10 LDAscore = 2.77) were enriched in the treatment response group. L. pectinoschiza (aOR: 34.1; p = 0.015), A. hadrus (aOR:35.0; p = 0.032) and A. butyriciproducens (aOR:22.3; p = 0.023) independently predicted treatment response but not clinical factors. These three species collectively predicted treatment response with AUROC of 0.89 (95% CI: 0.80-0.99)., Conclusions: Certain gut bacterial species, particularly the combination of A. hadrus, L. pectinoschiza and A. butyriciproducens, may predict treatment response to empagliflozin in MAFLD patients without DM., (© 2025 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Leigh syndrome is a common mitochondrial disorder caused by gene mutations in the nucleus and mitochondria. When building mitochondrial complex I, the main subunit ND1 combines with the Q module to form a 273 kDa complex, which then adds Ndufa3, Ndufa8, and Ndufa13 to create an intermediate product of about 283 kDa called Q/Pp-a. Although Ndufa8 and Ndufa13 have been linked to mitochondrial diseases, the role of Ndufa3 in disease development is still not fully understood., Methods: A family suspected of having Leigh syndrome was examined. Subjects (two brothers and a sister) underwent brain imaging, and their clinical symptoms were evaluated. Also, whole exome sequencing and minigene testing were performed by examining peripheral blood samples (2 ml) collected from the proband, his parents, and brothers., Results: Three affected children showed early-onset symptoms, including abnormalities in muscle tone and delayed motor and language development. Symptoms were relatively mild. The second child of the second pregnancy experienced worsened muscle tone abnormalities after injury, slow wound healing, and sustained increased muscle tone up to a year after wound closure. His brain scans revealed lesions in the basal ganglia and brainstem, consistent with Leigh syndrome diagnosis. Genetic analysis identified compound heterozygous mutations in the Ndufa3 gene in all affected family members., Conclusion: This is the first report of a family affected by Leigh syndrome associated with mutations in the Ndufa3 gene. Our analyses of clinical symptoms, radiological scans, and genetic investigations broaden our understanding of Ndufa3 gene mutations and their role in the development of Leigh syndrome., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval (2021 − 152) was obtained by the Ethics Committee of Children’s Hospital of Hebei Province l. All patients signed the informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Influenza A and B viruses spread out worldwide, causing several global concerns. Discovering neuraminidase inhibitors to prevent influenza A and B viruses is thus of great interest. In this work, a machine learning model was trained and tested to evaluate the ligand-binding affinity to neuraminidase. The model was then used to predict the binding affinity of compounds from the CHEMBL database, which is a manually curated database of bioactive molecules with drug-like properties. The physical insights into the binding process of ligands to neuraminidase were clarified via molecular docking and molecular dynamics simulations. Experimental investigation on enzymatic activity validated our computational results and suggested that 2 compounds were potential inhibitors of neuraminidase of the influenza A and B viruses., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

An unprecedented natural light promoted DMSO/O 2 -catalyzed N-acylation reaction of imidazoles/triazoles with cyclopropenones at room temperature under metal-free conditions has been developed. The remarkable advantages of this strategy include atomic economy and environmentally benign conditions (such as natural light promotion, DMSO/O 2 -catalysis, room temperature, and DMC as solvent), stereospecific (E)-olefins synthesis (N-acyl imidazoles and triazoles), wide functional group tolerance and high reaction yields. Furthermore, the typical products (1c and 1e) display good photocurrent and electrochemical property and are potentially applicable in biosensor materials fields., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Optimal glycaemic control has well-established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver-related outcomes., Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver-related mortality., Methods: In a population-based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3-year lead-in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver-related mortality., Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow-up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver-related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61-0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29-1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54-0.80), sex (SHR 0.68-0.69), BMI <25 or ≥25 kg/m 2 (SHR 0.63-0.75), smoking (SHR 0.61-0.72), hepatic steatosis (SHR 0.67-0.68) and aspirin/statin/metformin use (SHR 0.67-0.75). A lower risk of liver-related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61-0.80)., Conclusions: Glycaemic control is an independent risk factor for HCC and liver-related mortality, and should be incorporated into oncoprotective strategies in the general DM population., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

The purified neutral polysaccharide fraction, namely SBP-1, was isolated and characterized from Schisandra chinensis (Turcz.) Baill crude polysaccharides, which have anti-Parkinson's disease activity were investigated in vivo and in vitro. Experiments have shown that the main chain of SBP-1 was Glcp-(1→, →4)-Glcp-(1→ and →4,6)-Glcp-(1→. We also revealed the effect of SBP-1 on the PD mice model and the potential underlying molecular mechanism. The results showed that SBP-1 administration improved behavioral deficits, increased tyrosine hydroxylase-positive cells, attenuated loss of dopaminergic neurons in MPTP-exposed mice, and reduced cell death induced by MPP + . The MCL-1 was identified as the target of SBP-1 by the combination of docking-SPR-ITC, WB, and IF experiments. Subsequently, the study showed that SBP-1 could target MCL-1 to enhance autophagy with a change in the apoptotic response, which was further demonstrated by a change in LC3/P62, PI3K/AKT/mTOR, and possesses a change in the expression of BCL2/BAX/Caspase3. These results demonstrate that SBP-1 may protect neurons against MPP + or MPTP-induced damage in vitro and in vivo through enhancing autophagy. In summary, these findings indicate that SBP-1 and S. chinensis show potential as effective candidates for further investigation in the prevention and treatment of PD or associated illnesses, specifically through autophagy apoptotic-based mechanisms., 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 B.V. All rights reserved.)

Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research., (© 2024. Science China Press.)

Background and Aim: We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant., Methods: Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use., Results: One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131)., Conclusion: Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Competing Interests: The authors have no conflicts of interest to declare.

Six new highly oxidized seco -terpenoids, including three 3- nor -labdane type diterpenes, talaroterpenoids A-C ( 1 - 3 ), and three meroterpenoids containing an orthoester group, talaroterpenoids D-F ( 6 - 8 ), together with five known compounds ( 4 - 5 and 9 - 11 ), were isolated from the marine-derived fungus Talaromyces aurantiacus . Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J -based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20- γ -lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC 50 values of 11.47 and 11.32 μM, respectively. Talaroterpenoid C ( 3 ) showed moderate antifungal activity against A. alternata and P. theae Steyaert.

Studies on the piezoelectric materials capable of efficiently outputting high electrostrains at low electric fields are driven by the demand for precise actuation in a wide range of applications. Large electrostrains of piezoceramics in operation require high driving fields, which limits their practical application due to undesirable nonlinearities and high energy consumption. Herein, a strategy is developed to enhance the electrostrains of piezoceramics while maintaining low hysteresis by incorporating lead magnesium niobate relaxors into lead zirconate titanium at the morphotropic phase boundary. An ultrahigh inverse piezoelectric coefficient d 33 * of 1380 pm/V with a reduced hysteresis of 11.5% is achieved under a low electric field of 1 kV/mm, outperforming the major lead-based piezoelectric materials. In situ synchrotron X-ray diffraction and domain wall dynamics characterization with sub-microsecond temporal resolution reveal that the outstanding performances originate from facilitated domain wall movement, which in turn is due to reduced lattice distortion and miniaturized domain structures. These findings not only address the pending challenges of effective actuation under reduced driving conditions but also lay the foundation for a more systematic approach to exploring the origin of large electrostrains., (© 2024. The Author(s).)

Background and Introduction: In comparison to other physical assessment methods, the inconsistency in respiratory evaluations continues to pose a major issue and challenge., Objectives: This study aims to evaluate the difference in the identification ability of different breath sound., Methods/description: In this prospective study, breath sounds from the Formosa Archive of Breath Sound were labeled by five physicians. Six artificial intelligence (AI) breath sound interpretation models were developed based on all labeled data and the labels from the five physicians, respectively. After labeling by AIs and physicians, labels with discrepancy were considered doubtful and relabeled by two additional physicians. The final labels were determined by a majority vote among the physicians. The capability of breath sound identification for humans and AI was evaluated using sensitivity, specificity and the area under the receiver-operating characteristic curve (AUROC)., Results/outcome: A total of 11,532 breath sound files were labeled, with 579 doubtful labels identified. After relabeling and exclusion, there were 305 labels with gold standard. For wheezing, both human physicians and the AI model demonstrated good sensitivities (89.5% vs. 86.0%) and good specificities (96.4% vs. 95.2%). For crackles, both human physicians and the AI model showed good sensitivities (93.9% vs. 80.3%) but poor specificities (56.6% vs. 65.9%). Lower AUROC values were noted in crackles identification for both physicians and the AI model compared to wheezing., Conclusion: Even with the assistance of artificial intelligence tools, accurately identifying crackles compared to wheezing remains challenging. Consequently, crackles are unreliable for medical decision-making, and further examination is warranted., (© 2024. The Author(s).)

Intact autophagy-lysosomal pathway (ALP) in neuronal survival is crucial. However, it remains unclear whether ALP is intact after subarachnoid hemorrhage (SAH). Ten-eleven translocation (TET) 3 primarily regulates genes related to autophagy in neurons in neurodegenerative diseases. This study aims to investigate the role of TET3 in the ALP following SAH. The results indicate that the ALP is impaired after SAH, with suppressed autophagic flux and an increase in autophagosomes. This is accompanied by a decrease in TET3 expression. Activation of TET3 by α-KG can improve ALP function and neural function to some extent. Silencing TET3 in neurons significantly inhibited the ALP function and increased apoptosis. Inhibition of miR-93-5p, which is elevated after SAH, promotes TET3 expression. This suggests that the downregulation of TET3 after SAH is, at least in part, due to elevated miR-93-5p. This study clarifies the key role of TET3 in the functional impairment of the ALP after SAH. The preliminary exploration revealed that miR-93-5p could lead to the downregulation of TET3, which could be a new target for neuroprotective therapy after SAH., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown., Purpose: To investigate the mechanism by which Pae regulates ferroptosis after TBI., Methods: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI., Results: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53., Conclusion: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT., Methods: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal., Results: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube., Conclusions: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future., (© 2024. The Author(s).)

Background and Aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus., Approach and Results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05)., Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261)., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Osteoporotic fracture is a prevalent noncommunicable disease globally, causing significant mortality, morbidity, and disability. As the population ages, the healthcare and economic burden of osteoporotic fracture is expected to increase further. Due to its multifactorial features, the development of osteoporotic fracture involves a complex interplay of multiple risk factors, including genetic, environmental, and lifestyle factors. Helicobacter pylori, which infects approximately 43% of the world's population, has been associated with increased fracture risk due to hypochlorhydria from atrophic gastritis and systemic inflammation from elevated pro-inflammatory cytokines. However, the potential impact of H. pylori infection and eradication on fracture risk remains contentious among various studies due to the study design and inadequate adjustment of confounding factors including baseline gastritis phenotype. In this review, we provided a comprehensive evaluation of the current evidence focusing on the underlying mechanisms and clinical evidence of the association between H. pylori infection and osteoporotic fracture. We also discussed the potential benefits of H. pylori eradication on fracture risk., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B ( 1 and 2 ), and four known cytochalasan monomers ( 3 - 6 ), as well as four known macrolide derivatives ( 7 - 10 ), were obtained from the endophytic fungus Aspergillus spelaeus GDGJ-286. Sucurchalasins A and B ( 1 and 2 ) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1 and 2 exhibited cytotoxic effects on A2780 cells, with IC 50 values of 3.9 and 8.3 μM, respectively. They also showed antibacterial activities against E. faecalis and B. subtilis with MIC values of 3.1 and 6.3 μg/mL, respectively.

Background: Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis., Objective: This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model., Design: Animal study., Settings: Animal laboratory at China Medical University., Patients: Eight healthy pigs were included., Interventions: Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips., Main Outcome Measures: The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining., Results: End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention., Limitations: Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine., Conclusions: Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Colon and Rectal Surgeons.)

Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice., 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 B.V. All rights reserved.)