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Long-term PM2.5 data are essential for the atmospheric environment, human health, and climate change. PM2.5 measurements are sparsely distributed and of short duration. In this study, daily PM2.5 concentrations are estimated using a machine learning method for the period from 1959 to 2022 in the Northern Hemisphere based on near-surface atmospheric visibility. They are extracted from the Integrated Surface Database (ISD). Daily continuous monitored PM2.5 concentration is set as the target, and near-surface atmospheric visibility and other related variables are used as the inputs. A total of 80 % of the samples of each site are the training set, and 20 % are the testing set. The training result shows that the slope of linear regression with a 95 % confidence interval (CI) between the estimated PM2.5 concentration and the monitored PM2.5 concentration is 0.955 [0.955, 0.955], the coefficient of determination (R2) is 0.95, the root mean square error (RMSE) is 7.2 µg m−3, and the mean absolute error (MAE) is 3.2 µg m−3. The test result shows that the slope within a 95 % CI between the predicted PM2.5 concentration and the monitored PM2.5 concentration is 0.864 [0.863, 0.865], the R2 is 0.79, the RMSE is 14.8 µg m−3, and the MAE is 7.6 µg m−3. Compared with a global PM2.5 concentration dataset derived from a satellite aerosol optical depth product with 1 km resolution, the slopes of linear regression on the daily (monthly) scale are 0.817 (0.854) from 2000 to 2021, 0.758 (0.821) from 2000 to 2010, and 0.867 (0.879) from 2011 to 2022, indicating the accuracy of the model and the consistency of the estimated PM2.5 concentration on the temporal scale. The interannual trends and spatial patterns of PM2.5 concentration on the regional scale from 1959 to 2022 are analyzed using a generalized additive mixed model (GAMM), suitable for situations with an uneven spatial distribution of monitoring sites. The trend is the slope of the Theil–Sen estimator. In Canada, the trend is −0.10 µg m−3 per decade, and the PM2.5 concentration exhibits an east–high to west–low pattern. In the United States, the trend is −0.40 µg m−3 per decade, and PM2.5 concentration decreases significantly after 1992, with a trend of −1.39 µg m−3 per decade. The areas of high PM2.5 concentration are in the east and west, and the areas of low PM2.5 concentration are in the central and northern regions. In Europe, the trend is −1.55 µg m−3 per decade. High-concentration areas are distributed in eastern Europe, and the low-concentration areas are in northern and western Europe. In China, the trend is 2.09 µg m−3 per decade. High- concentration areas are distributed in northern China, and the low-concentration areas are distributed in southern China. The trend is 2.65 µg m−3 per decade up to 2011 and −22.23 µg m−3 per decade since 2012. In India, the trend is 0.92 µg m−3 per decade. The concentration exhibits a north–high to south–low pattern, with high-concentration areas distributed in northern India, such as the Ganges Plain and Thar Desert, and the low-concentration area in the Deccan Plateau. The trend is 1.41 µg m−3 per decade up to 2013 and −23.36 µg m−3 per decade from 2014. The variation in regional PM2.5 concentrations is closely related to the implementation of air quality laws and regulations. The daily site-scale PM2.5 concentration dataset from 1959 to 2022 in the Northern Hemisphere is available at the National Tibetan Plateau/Third Pole Environment Data Center (https://doi.org/10.11888/Atmos.tpdc.301127) (Hao et al., 2024).

Active faults serve as potential sources of destructive earthquakes. Studies and investigations of active faults are necessary for earthquake disaster prevention. This study presents a nation-scale database of active faults in China and its adjacent regions, in tandem with an associated web-based query system. This database is an updated version of the active faults data included in the Seismotectonic Map of China and its Adjacent Regions (1:4 000 000), which is one of the four essential maps of the mandatory Chinese standard GB 18306-2015 Seismic Ground Motion Parameter Zonation Maps of China. The data update and integration stem from regional-scale studies and surveys conducted over the past 2 decades (at reference scales from 1:250 000 to 1:50 000). The information amassed from these regional-scale studies and surveys encompasses geophysical probing, drill logging, measurement of offset landforms, sample dating, as well as geometric and kinematic parameters of exposed and blind faults, paleo-earthquake sequences, and recurrence intervals. These data have been acquired and analyzed utilizing a uniform technical standard framework and reviewed by expert panels in both field and laboratory settings. Our system hosts this nation-scale database accessible through a Web Geographic Information System (GIS) application, enabling browsing, querying, and downloading functionalities via a web browser. The system we built also publishes the Open Geospatial Consortium (OGC) Web Feature Service and the OGC Web Map Service of active faults data. Users can incorporate map layers and obtain fault data in OGC-compliant GIS software for further analysis through these services. The Chinese government, research institutions, and companies have widely used the active faults data from the previous versions of the database. The database is available at https://doi.org/10.12031/activefault.china.400.2023.db (Xu, 2023) and via the web system (https://data.activetectonics.cn/arcportal/apps/webappviewer/index.html?id=684737e8849c4170bbca14447608c451, CEFIS, 2023; http://data.activetectonics.cn/arcserver/services/Hosted/CAFD400_2022_WFS/MapServer/WFSServer, CAFD WFS, 2024).

Long-term and high spatial resolution aerosol optical depth (AOD) data are essential for climate change detection and attribution. Global ground-based AOD observations are sparsely distributed, and satellite AOD retrievals have a low temporal frequency as well low accuracy before 2000 over land. In this study, AOD at 550 nm is derived from visibility observations collected at more than 5000 meteorological stations over global land regions from 1959 to 2021. The AOD retrievals (550 nm) of the Moderate Resolution Imaging Spectroradiometer (MODIS) on board the Aqua Earth observation satellite are used to train the machine learning model, and the ERA5 reanalysis boundary layer height is used to convert the surface visibility to AOD. Comparisons with an independent dataset (AERONET ground-based observations) show that the predicted AOD has a correlation coefficient of 0.55 at the daily scale. The correlation coefficients are higher at monthly and annual scales, which are 0.61 and 0.65, respectively. The evaluation shows consistent predictive ability prior to 2000, with correlation coefficients of 0.54, 0.66, and 0.66 at the daily, monthly, and annual scales, respectively. Due to the small number and sparse visibility stations prior to 1980, the global and regional analysis in this study is from 1980 to 2021. From 1980 to 2021, the mean visibility-derived AOD values over global land areas, the Northern Hemisphere, and the Southern Hemisphere are 0.177, 0.178, and 0.175, with a trend of −0.0029 per 10 years, −0.0030 per 10 years, and −0.0021 per 10 years from 1980 to 2021. The regional means (trends) of AOD are 0.181 (−0.0096 per 10 years), 0.163 (−0.0026 per 10 years), 0.146 (−0.0017 per 10 years), 0.165 (−0.0027 per 10 years), 0.198 (−0.0075 per 10 years), 0.281 (−0.0062 per 10 years), 0.182 (−0.0016 per 10 years), 0.133 (−0.0028 per 10 years), 0.222 (0.0007 per 10 years), 0.244 (−0.0009 per 10 years), 0.241 (0.0130 per 10 years), and 0.254 (0.0119 per 10 years) in Eastern Europe, Western Europe, Western North America, Eastern North America, Central South America, Western Africa, Southern Africa, Australia, Southeast Asia, Northeast Asia, Eastern China, and India, respectively. However, the trends decrease significantly in Eastern China (−0.0572 per 10 years) and Northeast Asia (−0.0213 per 10 years) after 2014, with the larger increasing trend found after 2005 in India (0.0446 per 10 years). The visibility-derived daily AOD dataset at 5032 stations over global land from 1959 to 2021 is available from the National Tibetan Plateau/Third Pole Environment Data Center (https://doi.org/10.11888/Atmos.tpdc.300822) (Hao et al., 2023).

Molecular conformational diversity plays a crucial role in both polymorphic nucleation and cocrystal formation during the cocrystallization process. However, the relationship between molecular conformation and cocrystallization polymorphism is not well-explored. Herein, the impact of molecular conformational landscapes on cocrystallization outcomes was investigated using tizanidine (TZND) as model compound. Four coformers, namely maleic acid (MA), salicylic acid (SA), p-hydroxybenzoic acid (pHBA), and heptanedioic acid (HDA), were employed and five salt forms were developed for the first time. Compared with TZND, all five salts showed significantly improved water solubility and dissolution rate. The cocrystallization behavior of TZND varied with each coformer: MA exhibited solvent-dependent polymorphism, while SA, pHBA, and HDA showed solvent-independent monomorphism. Crystal structure and conformational analyses revealed the conformational variation of TZND across different cocrystallization outcomes. Molecular dynamics simulations and quantum chemical calculations demonstrated that the interplay between solvent effects and coformer interactions determines the dominant conformations of TZND. The cocrystallization nucleation process was also examined, and the molecular mechanism that explains both polymorphism and monomorphism in the cocrystallization of TZND was proposed., 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.)

Background: Preeclampsia (PE) is a complex multi-organ disorder characterized by systemic inflammation, endothelial dysfunction, and vasoconstriction, which manifests as hypertension, with or without proteinuria. Effective preventive strategies for PE are currently lacking in clinical practice, leading to significant morbidity and mortality among mothers and newborns., Objective: This study aims to investigate the impact of metformin (MET) on the l-NAME-induced PE rat model, focusing on the mechanisms through which MET may exert its effects., Methods: Thirty pregnant Sprague-Dawley (SD) rats were randomly assigned to three groups: Control, PE, and PE + MET, on gestational day 0 (GD0). Regularly measure blood pressure and 24-h proteinuria, and collect tissue samples on GD20. Enzyme-linked immunosorbent assay (ELISA) was used to analyze inflammatory factors, endothelial function biomarkers, angiogenic factors, and apoptosis-related factors in the rat plasma. Western blot, RT-qPCR, and immunohistochemistry techniques were employed to determine the expression levels of key apoptotic proteins in placental tissue., Results: The study findings demonstrate that MET administration improves blood pressure and 24-h proteinuria, alleviates fetal growth restriction, ameliorate inflammation cytokines, and restores the balance of angiogenic factors and endothelial function. Moreover, MET inhibits the expression levels of critical apoptotic proteins in the plasma and placental tissue of PE-like rats., Conclusion: The results suggest that MET shows promise in alleviating symptoms associated with l-NAME-induced PE in rats, preserving endothelial function, enhancing angiogenesis, reducing inflammation, inhibiting placental apoptosis, improving placental function, and promoting fetal growth. These findings highlight MET as a potential therapeutic agent for the prevention and treatment of preeclampsia., 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.)

Histone deacetylases (HDACs) have emerged as prominent therapeutic targets in drug discovery. Among the members of the HDAC family, HDAC8 exhibits distinct structural and physiological features from other members of the class Ⅰ HDACs. In addition to histones, numerous non-histone substrates such as structural maintenance of chromosomes 3 (SMC3), p53, estrogen-related receptor alpha (ERRα), etc., have been identified for HDAC8, suggesting the involvement of HDAC8 in diverse biological processes. Studies have demonstrated that HDAC8 plays essential roles in certain disease development, e.g., acute myeloid leukemia (AML), neuroblastoma, and X-Linked disorders. Despite several HDAC8 inhibitors have been discovered, only one compound has progressed to clinical studies. Recently, novel strategies targeting HDAC8 have emerged, including identifying innovative zinc-chelating groups (ZBG), developing multi-target drugs, and HDAC8 PROTACs. This review aims to summarize recent progress in developing new HDAC8 inhibitors that incorporate novel strategies and provide an overview of the clinical improvements associated with HDAC8 inhibitors., 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 Masson SAS. All rights reserved.)

Malnutrition is an important risk factor for multiple organ dysfunction syndrome in the elderly (MODSE) and seriously affects the occurrence, progression and prognosis of MODSE. Shenling Baizhu Power (SBP), a classic formula from traditional Chinese medicine (TCM), when integrated with enteral nutrition, has been proven to be an effective clinical strategy for treating the patients of MODSE with malnutrition. This study aimed to investigate the metabolic changes during disease occurrence and SBP treatment, and to discover potential metabolic biomarkers for the diagnosis and efficacy evaluation. An untargeted metabolomics strategy based on UHPLC-Q-Orbitrap-HRMS was performed to reveal the differential serum metabolites between MODSE patients with malnutrition (n=59) and healthy controls (n=33), and those between patients treated with enteral nutrition (n=31) and SBP combined with enteral nutrition (n=28). Significantly different metabolites were identified and mapped onto the network of metabolic pathways to explore the metabolic disorders caused by the disease and the metabolic regulatory mechanism of SBP. Additionally, the area under the curve (AUC) of the potential biomarkers was investigated for predicting the disease and the efficacy of SBP. Sixty differential metabolites were identified between the disease and control groups, which were mainly related to amino acid metabolism, energy metabolism and carbohydrate metabolism. In the same way, 50 differential metabolites associated with SBP treatment were identified, which improved metabolic abnormalities in vivo mainly by regulating the above-mentioned metabolic pathways. Finally, 13 differential metabolites in common were selected as the potential biomarkers and the AUC value of each biomarker was within the range of 0.8-1.0, indicating that these biomarkers had high prediction accuracy for the diagnosis and efficacy evaluation of MODSE with malnutrition. This study demonstrates that serum metabolomics approaches based on the UHPLC-Q-Orbitrap-HRMS platform can be applied as a tool to reveal the metabolic changes induced by MODSE with malnutrition and SBP can play an important role in the clinical application., 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.)

Developing novelplatinum (Pt)-based hydrogen evolution reaction (HER) catalysts with high activity and stability is significant for the ever-broader applications of hydrogen energy. However, achieving precise modulation of the ultrafine Pt nanoparticles coordination environment in conventional catalysts is challenging. In this work, we developed a unique "ring-shaped cavity induced" strategy to anchor the Pt x through the ring-shaped cavity of polyoxometalates (POMs) Na 33 H 7 P 8 W 48 O 184 (denoted as P 8 W 48 ). The Na y Pt x [P 8 W 48 O 184 ] (Pt x P 8 W 48 ) was in-situ converted into abundant Pt/WO 3-x heterostructure with Pt (∼2 nm) and highly depressed Pt-O-W heterointerfaces. Pt/WO 3-x nanoparticles supported on highly conductive rGO exhibit superior HER activity. The overpotentials of the catalyst are only 2.8 mV and 4.7 mV at 10 mA·cm -2 in acidic water and seawater, far superior to commercial 20 % Pt/C catalyst. Additionally, the catalyst can be stabilized at a current density of 30 mA·cm -2 for 180 h. This study provides a feasible strategy for rational design of Pt-based catalysts for renewable energy applications., 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.)

Accurate health risk prediction (HRP) is an effective means of reducing the hazards of heavy metal (HM) exposure. It can address the drawbacks of lag and passivity faced by health risk assessment. This study innovatively proposed an HRP method, MEL-HR, based on multilevel ensemble learning (MEL) technology and environment compatibility. We conducted point and interval prediction experiments on health risks using 490 sets of data covering 17 environment factors. The point prediction results indicated that when the model predicts HI and TCR, the R 2 values were 0.707 and 0.619, respectively. For P5, P50, and P95 in interval prediction, the R 2 values of the model were 0.706, 0.703, and 0.672 for HI, and that for TCR were 0.620, 0.607, and 0.616, respectively. The analysis of feature importance indicated that, in addition to HM factors, longitude, mining area coefficient, and soil organic matter were key environmental factors affecting the MEL-HR model. Comparative experiments showed that compared to soil HMs-based MEL-HR, environment compatibility-based MEL-HR has improved the accuracy for HI and TCR by 19.83 % and 40.36 % for the point prediction and 22.06 % and 40.01 % for interval prediction. This study can provide technical support for targeted and resilient prevention and control of health risks., 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.)

Background: To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT)., Methods: This retrospective observational study analyzed data from allograft LTs performed for various liver diseases., Results: The study included 22 males and 4 females with LT indications comprising cirrhosis ( n  = 9), hepatocellular carcinoma ( n  = 12), PVCT ( n  = 2), liver failure from fulminant hepatitis B ( n  = 1), dysfunction of transplanted liver ( n  = 1), and chronic rejection of transplanted liver ( n  = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1-C5). In total 16 simple operations were performed on C1-C3 cases and 9 complex operations on C4-C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively ( p  = 0.526)., Conclusion: The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Background and Purpose: Although a large collection of data has shown that ginsenosides, the major active ingredients from Ginseng, have neuroprotective and anti-depressant effect, the mechanism of action is incompletely understood. This study aims to elucidate the antidepressant mechanism of ginsenoside Rg1 (Rg1), a poorly absorbed ginsenoside, from the perspective of gut microbe to brain signaling., Methods: A mouse model of depression was induced by unpredictable mild stress (UMS). Behavioral and neurochemical tests were conducted to evaluate the effect and mechanism of Rg1 on depressive behavior. Non-target and target metabolomics were performed to identify the signaling metabolites underlying the antidepressant efficacy of Rg1. Gut microbial structure was analyzed by 16S rRNA sequencing and the potential functional strains associated with Rg1 action were investigated by in vitro bacterial culture. Chemical intervention was used to explore the mechanism of Rg1 and signaling metabolite., Results: Rg1 improved UMS-induced despair, anxiety-like and social avoidance behaviors in mice, which were accompanied by increased hypothalamic oxytocin secretion and restored neural proliferation in the hippocampus. Metabolomic analysis of the gut-brain axis revealed that Rg1 increased the concentration of serum and brain indole-3-acetic acid (IAA), a bacterial metabolite that was partially attributed to the enrichment of Lactobacillus murinus in the gut microbiome. Oral supplementation of IAA mimicked the anti-depressant action of Rg1, while oxytocin receptor antagonist abrogated the anti-depressant effects of both Rg1 and IAA., Conclusion: Our work provides a new gut-to-brain signaling mechanism for the antidepressant effects of Rg1. In particular, Rg1 enriches the abundance of Lactobacillus murinus, which in turn increases the level of brain IAA and potentiates hypothalamic oxytocin signal. These findings suggest a promising pathway for producing antidepressant effects through gut-brain crosstalk., 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.)

In this investigation, 396 endophytic bacterial strains from six indigenous medicinal plant species within the Xinjiang Tumor Peak National Nature Reserve were subjected to screening. The strain MR4 emerged as a noteworthy contender, demonstrating pronounced biocontrol capabilities coupled with exceptional cold tolerance. Through morphological scrutiny and comprehensive genomic sequencing, MR4 was identified as Bacillus amyloliquefaciens. Antagonistic assays revealed MR4's efficacy in suppressing the causative agents of cotton wilt and verticillium wilt, achieving inhibition rates surpassing 50%. Analyses, underpinned by PCR methodologies, indicated MR4's capacity to biosynthesize a minimum of eight distinct antimicrobial agents. The whole-genome sequencing data indicated that B. amyloliquefaciens MR4 had the genome size and GC content of 4,017,872 bp and 47.14%, respectively, and 4191 coding genes were identified. The genome consists of a single chromosome and one plasmid. Moreover, it was augmented by annotations from various databases, including GO, KEGG, and COG. The pathogenicity of MR4 undergoes evaluation, while predictions concerning MR4's secondary metabolites have disclosed gene clusters for 13 varieties of these compounds, with particular emphasis on surfactins and fengycin. Comparative analyses with four paradigmatic strains shed light on MR4's genomic composition and its phylogenetic lineage within the Bacillus genus. The genomic data pertaining to MR4 have been duly submitted to the NCBI GenBank, bearing the accession numbers CP146236 (Chr1) and CP146237 (plas1). This study endeavors to furnish potent microbial resources for the biocontrol and enhancement of plant growth, thereby providing a theoretical groundwork for MR4's agronomic utilization., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

The renin-angiotensin system (RAS) is a crucial factor in chronic kidney disease (CKD) progression, affecting renal function and contributing significantly to renal tissue inflammation and fibrosis. Activation of the classical ACE/Ang II/AT1 axis exacerbates renal damage, while the ACE2/Ang-(1-7)/Mas axis has shown promise in reducing CKD progression in numerous animal models. Recently, the ACE2/Ang-(1-7)/Mas axis has emerged as a promising target for CKD interventions. This review provides a comprehensive review of the pivotal role of this axis in CKD pathogenesis and systematically examines various molecules and pharmaceutical agents targeting this pathway. This review aims to elucidate potential strategies for delaying or halting CKD progression, offering patients more effective treatment options., 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.)

Self-powered photoelectrochemical (PEC) sensing is a novel sensing modality. The introduction of dual-mode sensing and photoelectrocatalysis in a self-powered system enables both detection and sterilization purposes. To this end, herein, a self-powered multifunctional platform for the photoelectrochemical-fluorescence (PEC-FL) detection and in-situ inactivation of Salmonella enteritidis (SE) was constructed. The platform utilized Bi 4 NbO 8 Cl/V 2 CT x /FTO as a photoanode and CuInS 2 /FTO as a photocathode and incubated quantum dot (QDs) signaling probes on the surface of the photocathode. During detection, the system drives the transfer of photogenerated electrons between the dual photoelectrodes through the Fermi energy level difference. The photoanode amplifies the photoelectric signal, while the photocathode is solely dedicated to the immune recognition process. QDs provide an additional fluorescence signal to the system. Under optimal experimental conditions, the multifunctional platform achieves detection limits of 3.2 and 5.3 CFU/mL in PEC and FL modes respectively, with a detection range of 2.91 × 10 2 to 2.91 × 10 8  CFU/mL. With the application of an external bias voltage, it further promotes electron transfer between the dual photoelectrodes, inhibits the recombination of photogenerated electrons and holes. It generates a significant amount of superoxide radicals (·O 2 - ) in the cathodic region, resulting in strong sterilization efficiency (99%). The constructed self-powered multifunctional platform exhibits high sensitivity and sterilization efficiency, it provides a feasible and effective strategy to enhance the comprehensive capability of self-powered sensors., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study examines the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and urinary stones in American adults., Methods: We conducted a cross-sectional study utilizing the 2007-2018 National Health and Nutrition Examination Survey (NHANES) data set. The prevalence of urinary stones was determined based on patient-reported experiences of renal colic. We converted NHHR to natural logarithm (ln-NHHR) to align it better with our statistical analyses. Our analysis methods included weighted multivariate logistic regression, generalized additive model (GAM), and application of smoothed curves to better elucidate the association between ln-NHHR and the prevalence of urinary stones. In addition, we conducted subgroup analyses and employed multiple imputation for sensitivity analyses., Results: This study involved a total of 30,903 participants, with a 9.97% prevalence of urinary stones and reported colic experience. Elevated ln-NHHR levels were linked with a higher likelihood of urinary stones (OR = 1.20, 95% CI 1.07-1.35). Smooth curve fitting revealed an inverted U-shaped relationship, pinpointing a significant increase in urinary stone risk at ln-NHHR levels below 1.43 (OR = 1.40, 95% CI 1.19-1.64, p < 0.001). Notably, this correlation was stronger among Non-Hispanic Whites and those married or living with a partner. Multiple imputation analyses strengthened the confidence in our results., Conclusions: Our findings suggest a reverse U-shaped association between urinary stone occurrence and NHHR level, with a positive association at ln-NHHR < 1.43. This correlation was more pronounced in the Non-Hispanic White population and among those married or living with a partner., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8 + T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment., Competing Interests: Declaration of Competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The cardiometabolic index (CMI), encompassing obesity and lipid metrics, is potentially linked to kidney stone prevalence in diabetic patients. However, studies on this association are sparse. This research evaluates CMI's impact on kidney stone occurrence in this group., Methods: Utilizing data from the 2007-2018 National Health and Nutrition Examination Survey, we explored the relationship between CMI and kidney stones in diabetic patients through multivariate logistic regression, generalized additive models, and smoothed curve fitting. Robustness checks included subgroup analyses and propensity score matching (PSM)., Results: This study comprised 2714 participants in total, where the prevalence of kidney stones was found to be 16.82%. Using weighted multivariate logistic regression and fully adjusted models, it was revealed that elevated CMI levels are positively associated with an increased likelihood of developing kidney stones (OR = 1.17, 95% CI: 1.06, 1.30). Smooth curve fitting demonstrated that there was no non-linear relationship between CMI and kidney stones (log-likelihood ratio test P = 0.236). Subgroup analyses and interactions indicated that the association between CMI and kidney stone prevalence was notably stronger in individuals who were living with a partner /married and had a poverty income ratio (PIR) of 1.5 to less than 3.5 (P for interaction < 0.05). propensity score matching (PSM) further verified the robustness of our results., Conclusion: Elevated CMI correlates with greater kidney stone prevalence in diabetic individuals, particularly those married or living with a partner and within certain economic statuses. This study supports the hypothesis linking CMI and kidney stones in U.S. diabetic population, suggesting a target demographic for preventive strategies., Competing Interests: Declarations. Ethical approval: The portions of this study involving human participants, human materials, or human data were conducted in accordance with the Declaration of Helsinki and were approved by the National Center for Health Statistics (NCHS) Ethics Review Board. The patients/participants provided their written informed consent to participate in this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a major cause of cancer deaths globally. Unlike traditional molecularly targeted drugs, magnetically controlled drug delivery to micro/nanorobots enhances precision in targeting tumors, improving drug efficiency and minimizing side effects. This study develops a dual-responsive, magnetically controlled drug delivery system using PEGylated paramagnetic nanoparticles conjugated with decoy receptor 3 (DCR3) antibodies. The clusters demonstrate capabilities for long-range, magnetically driven control and molecular chemotaxis. Paramagnetic PEGylated particles form vortex- and liquid-like drug moieties within a magnetically controlled system. Vortex-like nanoparticle clusters exhibit high controllability and countercurrent movement, while liquid-nanoparticle robot clusters display greater deformability. Upon loading with DCR3 antibodies, the particles navigate along DCR3-protein gradients in blood and tissue, effectively targeting liver tumor sites in vivo. Clusters of DCR3-coupled magnetic nanoparticles target cells that highly express DCR3, thereby effectively inhibiting tumor cell proliferation and migration. Compared with conventional nanomedicine, DCR3-coupled magnetic nanoparticle clusters are capable of delivering controlled drugs over long distances and responding in a molecular-targeting manner. This research is expected to significantly impact the field of precise tumor drug delivery., (© 2024 Wiley‐VCH GmbH.)

Boron neutron capture therapy (BNCT) is an advanced binary tumor-cell-selected heavy-particle radiotherapy used for treating invasive malignant tumors. However, its clinical applications have been impeded by the rapid metabolism and insufficient tumor-specific accumulation of boron agents. To tackle this issue, we develop a smart boron nanosensitizer (BATBN) capable of transforming its size in response to cancer biomarker for optimal balance between penetration and retention of boron-10 for BNCT. BATBN comprises an ultrasmall boron quantum dots (BQD) core (4 nm) conjugated with cell-penetrating peptides, which facilitates its cellular uptake and deep tumor penetration. In the tumor microenvironment, the tumor biomarker can specifically initiate a self-condensation reaction of BATBN, leading to the formation of larger-sized nanoaggregates. Due to such a specific intratumoral transformation, BATBN demonstrate a 2.4-fold increase in intratumoral boron concentration and a 5.0-fold increase in tumor retention time compared to the BQDs. Thus, the relative tumor volume of the BATBN-treatment group is 2.7-fold smaller than that of BQDs in preclinical tumor models after 21 days of neutron irradiation treatment. This study presents a supramolecular strategy to endow BNCT agents with the biomarker-activated size interconversion, permitting precise and efficient BNCT for cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Dynamic molecular crystals are an emerging class of smart engineering materials that possess unique ability to convert external energy into mechanical motion. Moreover, they have being considered as strong candidates for dynamic elements in applications such as flexible electronic devices, artificial muscles, sensors, and soft robots. However, the inherent defects of molecular crystals like brittleness, short-life and fatigue, have significantly impeded their practical applications. Inspired by the concept of "the whole is greater than the sum of its parts" in the field of biology, building stimuli-response composites materials can be regarded as one of the ways to break through the current limitations of dynamic molecular crystals. Moreover, the hybrid materials can exhibit new functionalities that cannot be achieved by a single object. In this review, the focus was placed on the analysis and discussion of various hybrid strategies and options, as well as the functionalities of hybrid dynamic molecular crystal materials and the important practical applications of composite materials, with the introduction of photomechanical molecular crystals and flexible molecular crystals as a starting point. Moreover, the efficiency, limitations, and advantages of different hybrid methods were compared and discussed., (© 2024 Wiley‐VCH GmbH.)

Structural-functional integrated polymer fibers with exciting properties are increasingly important for next-generation technologies. Herein, we report the structural-functional integrated graphene-skinned aramid fiber (GRAF) featuring high conductivity, high strength, and light weight, which is weaved for efficient electromagnetic interference (EMI) shielding. Graphene was self-assembled onto the surface of aramid fibers through a dip-coating strategy using an aramid polyanion (APA) as the binder and the etchant. The molecular dynamics (MD) simulation results show that the binding energy of the APA-modified aramid chain and graphene (1.3 J/m 2 ) is superior to that of the aramid chain and graphene (0.2 J/m 2 ). The APA has a higher surface energy (55.2 mJ/m 2 ) and can etch the fiber surface, forming grooves, which enables effective adsorption and self-assembly of graphene onto the fiber surface. The GRAF exhibits a high conductivity of 1062.04 ± 116.78 S/m, along with excellent strength (4.66 ± 0.16 GPa) and modulus (106.33 ± 8.21 GPa), outperforming most reported conductive composite fibers (e.g., natural fibers, polymer-based fibers, inorganic fibers, etc.). The weaved functional fabric using the structural-functional integrated GRAF shows an EMI shielding efficiency (SE) of up to 67.86 dB in the X-band and can rapidly heat up to 200 °C within 40 s at 12 V voltage. In addition, the GRAF fabric can maintain its electrical conductivity after a long-term washing, showing excellent washing resistance. This study demonstrates an effective method to fabricate structural-functional integrated materials and shows the promise of carbonene fibers for EMI shielding.

Background: The role of B cells in antitumor immunity remains controversial, with studies suggesting the protumor and antitumor activity. This controversy may be due to the heterogeneity in B cell populations, as the balance among the subtypes may impact tumor progression. The immunosuppressive regulatory B cells (Breg) release interleukin 10 (IL-10) but only represent a minor population. Additionally, tumor-specific antibodies (Abs) also exhibit antitumor and protumor functions dependent on the Ab isotype. Transcription factor c-Maf has been suggested to contribute to the regulation of IL-10 in Breg, but the role of B cell c-Maf signaling in antitumor immunity and regulating Ab responses remains unknown., Methods: Conditional B cell c-Maf knockout (KO) and control mice were used to establish a KPC pancreatic cancer model and B16.F10 melanoma model. Tumor progression was evaluated. B cell and T cell phenotypes were determined by flow cytometry, mass cytometry, and cytokine/chemokine profiling. Differentially expressed genes in B cells were examined by using RNA sequencing (RNA-seq). Peripheral blood samples were collected from healthy donors and patients with melanoma for B cell phenotyping., Results: Compared with B cells from the spleen and lymph nodes (LN), B cells in the pancreas exhibited significantly less follicular phenotype and higher IL-10 production in naïve mice. c-Maf deficiency resulted in a significant reduction of CD9 + IL-10-producing Breg in the pancreas. Pancreatic ductal adenocarcinoma (PDAC) progression resulted in the accumulation of circulating B cells with the follicular phenotype and less IL-10 production in the pancreas. Notably, B cell c-Maf deficiency delayed PDAC tumor progression and resulted in proinflammatory B cells. Further, tumor volume reduction and increased effective T cells in the tumor-draining LN were observed in B cell c-Maf KO mice in the B16.F10 melanoma model. RNA-seq analysis of isolated B cells revealed that B cell c-Maf signaling modulates immunoglobulin-associated genes and tumor-specific Ab production. We furthermore demonstrated c-Maf-positive B cell subsets and an increase of IL-10-producing B cells after incubation with IL-4 and CD40L in the peripheral blood of patients with melanoma., Conclusion: Our study highlights that B cell c-Maf signaling drives tumor progression through the modulation of Breg, inflammatory responses, and tumor-specific Ab responses., 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.)

Background: Annual influenza epidemics lead to substantial public health burden, and pregnant people are vulnerable to severe outcomes. Influenza during pregnancy is hypothesized to increase risk of adverse birth outcomes, but population-based epidemiologic evidence remains limited and inconsistent., Methods: We conducted a time-series analysis to estimate short-term associations between community-level seasonal influenza activity and daily counts of preterm births in Atlanta, United States from October 17th, 2010 to July 10th, 2017. We defined weekly influenza exposures four ways: (1) percent test-positive from virologic surveillance, (2) percent of patients with symptoms of influenza-like illness (ILI) in outpatient settings, (3) a composite measure of percent test-positive and ILI, and (4) influenza hospitalization rates. We used Poisson log-linear models to estimate associations, adjusting for time-varying confounders and ongoing at-risk pregnancies. We further examined associations by influenza type and exposure lags, and effect modification by maternal characteristics., Results: We studied a total of 316,253 births. We found consistent positive associations between influenza activity and preterm birth across different exposure measures and exposure lags. An interquartile range increase in composite measure of ILI activity and percent test-positive was associated with a 1.014 (95% confidence interval: 1.001, 1.027) increase in preterm birth during the same week. In stratified analyses, associations were more pronounced among married, non-Black, and Hispanic pregnant people., Conclusion: Periods of high influenza activity were associated with increased risk of preterm birth., Competing Interests: Conflicts of Interest: None Noted, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This research aimed to prepare and characterize acetylated starch/papain composites by encapsulating papain within acetylated cassava starch with a low degree of substitution (DS = 0.037) through a stepwise antisolvent precipitation method. The effects of starch concentrations, starch solution volumes, and surfactant types and concentrations were examined. An increase in starch concentration generally enhanced EE, but an excessive concentration led to a decrease in performance due to the aggregation of starch. Furthermore, LC decreased as the starch concentration increased, while the volume of the starch solution primarily influenced LC. Surfactants were employed to disperse the particles and prevent their aggregation during encapsulation, with higher concentrations, particularly of Tween 80, improving both EE and LC but reducing the activity of papain. Optimal results were achieved with a starch concentration of 30 mg mL -1 , solution volume of 7 mL, and 3% v/v Tween 80, resulting in an EE of 96.23% and LC of 12.40%. However, the residual papain activity under these conditions dropped to approximately 56%. In contrast, Tween 20 at 1% v/v preserved higher papain activity (87%), although it yielded a lower EE of 69.87% and LC of 9.32%. SEM images revealed that the resulting composite particles had rough, indistinct clusters with surfaces featuring clustered starch nanoparticles. Confirmatory analyses via fluorescence spectra and FTIR confirmed successful entrapment of papain within acetylated starch with a lower degree of substitution., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To address the issues of motion disturbance and low loading accuracy in electro-hydraulic load simulation systems, and to effectively mitigate the impact of uncertainty on system performance, this paper proposes a novel independent load port electro-hydraulic load simulation system. A nonlinear variable structure state equation is derived to describe the pressure working states of the left and right chambers of the servo valve and hydraulic cylinder under loading conditions. In light of the presence of substantial motion disturbances, an integrated sliding mode automatic disturbance rejection composite controller is proposed with a focus on fixed-time convergence. To mitigate system chattering and enhance system loading performance and disturbance immunity, a fixed-time integral sliding mode controller was developed within the framework of active disturbance rejection control. Stability analysis was also carried out. Simulation research demonstrates that the pressure control accuracy of the composite controller is 99.88%, 99.86%, and 99.83% respectively when the system step command is given with disturbance frequencies of 1 Hz, 3 Hz, and 5 Hz. Similarly, under the same disturbance frequencies, the pressure control accuracy is 99.88%, 99.86%, and 99.84% respectively when the system sine command is given. The simulation results demonstrate that the independent load port electro-hydraulic load simulation system exhibits a notable energy-saving effect. Specifically, energy savings of around 45% and 48% were achieved compared to the original system. The research and exploration conducted have laid a strong groundwork for future in-depth studies on the independent load port electro-hydraulic load simulation system., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

As society advances, the demand for high-performance crystal materials with versatile stimuli-responsive capabilities has increased. However, there remains a notable shortage of simple molecular crystals that exhibit stable and swift responses to various stimuli. In this study, we synthesized a novel acylhydrazone crystal by integrating benzene-fused heterocycles and halogens, achieving a crystal material with multiple stimuli-responsive behaviours. The crystal demonstrates good mechanical flexibility, capable of with standing a strain of 2.3% under applying mechanical force and recovering its original shape after force removal. Crystal structure analysis reveals this property is due to the strong and flexible intermolecular interactions. It also exhibits rapid photomechanical bending away from light source under UV irradiation, which could be attributed to the facile photoisomerization. Moreover, the crystal undergoes significant thermomechanical transitions, including cracking and jumping, upon heating. Additionally, the prepared crystal exhibits passive optical waveguide of red light at 850 nm, which, combining the photomechanical bending, can achieve controllable light output direction. These multi-stimuli-responsive behaviors make the acylhydrazone crystal a promising candidate for applications in multifunctional sensors, optoelectronic devices, and thermal switches. This work provides a helpful reference for the study of potential crystal material design and functionality of advanced responsive systems., (© 2024 Wiley‐VCH GmbH.)

Tomato harvesting in intelligent greenhouses is crucial for reducing costs and optimizing management. Agricultural robots, as an automated solution, require advanced visual perception. This study proposes a tomato detection and counting algorithm based on YOLOv8 (TCAttn-YOLOv8). To handle small, occluded tomato targets in images, a new detection layer (NDL) is added to the Neck and Head decoupled structure, improving small object recognition. The ColBlock, a dual-branch structure leveraging Transformer advantages, enhances feature extraction and fusion, focusing on densely targeted regions and minimizing small object feature loss in complex backgrounds. C2fGhost and GhostConv are integrated into the Neck network to reduce model parameters and floating-point operations, improving feature expression. The WIoU (Wise-IoU) loss function is adopted to accelerate convergence and increase regression accuracy. Experimental results show that TCAttn-YOLOv8 achieves an mAP@0.5 of 96.31%, with an FPS of 95 and a parameter size of 2.7 M, outperforming seven lightweight YOLO algorithms. For automated tomato counting, the R 2 between predicted and actual counts is 0.9282, indicating the algorithm's suitability for replacing manual counting. This method effectively supports tomato detection and counting in intelligent greenhouses, offering valuable insights for robotic harvesting and yield estimation research.

Protein lactylation is a novel post-translational modification (PTM) involved in many important physiological processes such as macrophage polarization, immune regulation, and tumor cell growth. However, traditional methodologies for studying lactylation have predominantly relied on peptide enrichment from whole-cell lysates, which tend to favor the detection of high-abundance peptides, thus limiting the identification of low-abundance lactylated peptides. To address this limitation, here, we employed subcellular fractionation to separate proteins and map lactylated peptides from each isolated subcellular fraction using a model cell line. In brief, we identified 1,217 lysine lactylation (Kla) sites on 553 proteins across four subcellular fractions. Subsequent pathway enrichment analysis revealed that Kla proteins participate in distinct pathways depending on the subcellular contexts. In addition, this subcellular fractionation method enabled the discovery of 36 previously unreported Kla proteins and 223 novel Kla sites, many of which are present in low abundance. Notably, several proteins contain multiple newly identified Kla sites, exemplified by the transcriptional regulator ATRX. Furthermore, our results indicate the possibility of PTM crosstalk between Kla and other PTMs such as ubiquitination and sumoylation. In conclusion, subcellular fractionation facilitates the identification of Kla proteins that have been previously uncovered and could be overlooked by affinity enrichment of whole-cell lysates.

During the loading process, significant external position disturbances occur in the electro-hydraulic load simulation system. To address these position disturbances and effectively mitigate the impact of uncertainty on system performance, this paper first treats model parameter uncertainty and external disturbances as lumped disturbances. The various states of the servo valve and the pressures within the hydraulic cylinder chambers are then examined. Building on this foundation, the paper proposes a nonlinear multi-mode variable structure independent load port electro-hydraulic load simulation system that is tailored for specific loading conditions. Secondly, in light of the significant motion disturbances present, this paper proposes an integral sliding mode active disturbance rejection composite control strategy that is based on fixed-time convergence. Based on the structure of the active disturbance rejection control framework, the fixed-time integral sliding mode and active disturbance rejection control algorithms are integrated. An extended state observer is designed to accurately estimate the lumped disturbance, effectively compensating for it to achieve precise loading of the independent load port electro-hydraulic load simulation system. The stability of the designed controller is also demonstrated. The results of the simulation research indicate that when the command input is a step signal, the pressure control accuracy under the composite control strategy is 99.94%, 99.86%, and 99.76% for disturbance frequencies of 1 Hz, 3 Hz, and 5 Hz, respectively. Conversely, when the command input is a sinusoidal signal, the pressure control accuracy remains high, measuring 99.94%, 99.8%, and 99.6% under the same disturbance frequencies. Furthermore, the simulation demonstrates that the influence of sensor random noise on the system remains within acceptable limits, highlighting the effective filtering capabilities of the extended state observer. This research establishes a solid foundation for the collaborative control of load ports and the engineering application of the independent load port electro-hydraulic load simulation system.

We aimed to elucidate the clinicopathological and imaging differences between pediatric and adult patients with anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase (anti-HMGCR) myopathy. A series of 111 patients with anti-HMGCR myopathy were divided into pediatric (33 patients, onset age < 18 years) and adult (78 patients, onset age ≥ 18 years) groups. Clinical, imaging, and pathological characteristics were compared between the groups. Overall median age at onset was 40 years. Median duration of disease was 12 months. The male:female ratio was 41:70. Prevalence of statin exposure was 0% in the pediatric group and 21% in the adult group (P < 0.001). The prevalence of severe weakness was significantly higher in the pediatric group (63.6% vs. 36.4%; P = 0.008). Myalgia was significantly more frequent in adults (49.3% vs. 20.8%; P = 0.03). The median serum creatine kinase (CK) concentration was significantly higher in the pediatric group (7263.0 vs. 3388.5U/L; P = 0.03). Magnetic resonance imaging of the thigh revealed muscle edema in 82.8% of patients and fatty infiltration in 60.9%. Muscle edema scores in the sartorius (P = 0.02) and gracilis (P = 0.03) were significantly higher in the pediatric group. Fatty infiltration score was significantly correlated with disease duration (r = 0.51; P < 0.001). Dystrophic pathology was significantly more frequent in pediatric patients (47% vs. 8%; P = 0.001). Regeneration score was significantly higher in pediatric group (P = 0.025). Sarcolemmal deposition of membrane attack complex (MAC) was significantly greater in pediatric patients (P = 0.010) and correlated significantly with manual muscle testing-8 score (r =  - 0.14; P = 0.04) and serum CK concentration (r = 0.36; P = 0.002). Pediatric patients presented with more severe weakness, higher CK concentration, higher muscle edema score in the sartorius and gracilis, more muscle regeneration, more sarcolemmal MAC deposition, and dystrophic pathology. Adult patients exhibited more myalgia and more minimal changes. Sarcolemmal MAC deposition is a biomarker for disease activity., Competing Interests: Declarations Disclosures None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The Nrf2/ARE pathway is considered the most important endogenous antioxidant signaling pathway in mammals, playing a crucial role in defending against external damage. This study investigated the functional characteristics of Nrf2 in the abalone, Haliotis discus hannai . The full-length cDNA sequence of the HdhNrf2 gene was cloned using rapid amplification of cDNA ends (RACE) technology and consists of 4568 base pairs encoding a protein of 694 amino acids. The predicted theoretical molecular weight was 77 kDa, with an isoelectric point of 4.72. Multiple sequence alignment analysis revealed the relative conservation of the HdhNrf2 amino acid sequence in H. discus hannai . The tissue expression pattern of the HdhNrf2 gene was analyzed using real-time fluorescence quantitative PCR, which showed the highest expression in the gills, followed by hemocytes, with the lowest levels in the foot and mantle. The inducible expression of HdhNrf2 and antioxidant genes in abalone under H 2 O 2 stress was investigated at various time points. Furthermore, an expression vector, pET-28a(+)-rHdhNrf2, was constructed, and the recombinant protein rHdhNrf2 was obtained through induced expression and purification. These findings indicated that HdhNrf2 plays a crucial role in the defense of abalones against oxidative stress.

Excessive autophagy has been implicated in the pathogenesis of necrotizing enterocolitis (NEC), yet the molecular underpinnings of the autophagy-lysosomal pathway (ALP) in NEC are not well characterized. This study aimed to elucidate alterations within the ALP in NEC by employing RNA sequencing on intestinal tissues obtained from affected infants. Concurrently, we established animal and cellular models of NEC to assess the therapeutic efficacy of itaconic acid (ITA). Our results indicate that the ALP is significantly disrupted in NEC. Notably, ITA was found to modulate the ALP, enhancing autophagic flux and lysosomal function, which consequently alleviated NEC symptoms. Further analysis revealed that ITA's beneficial effects are mediated through the promotion of TFEB nuclear translocation, thereby augmenting the ALP. These findings suggest that targeting the ALP with ITA to modulate TFEB activity may represent a viable therapeutic approach for NEC., 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. Published by Elsevier Inc.)

Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated the impact of G1 phase extension on resource allocation, metabolic functions, and the unfolded protein response (UPR) in yeast, along with the potential for enhancing the production of lipophilic compounds. In brief, the regulation of the G1 phase was achieved by deleting CLN3 (G1 cyclin) in various yeast strains. This modification resulted in a 83% increase in cell volume, a 76.9% increase in dry cell weight, a 82% increase in total protein content, a 41% increase in carotenoid production, and a 159% increase in fatty alcohol production. Transcriptomic analysis revealed significant upregulation of multiple metabolic pathways involved in acetyl-CoA (acetyl coenzyme A) synthesis, ensuring an ample supply of precursors for the synthesis of lipophilic products. Furthermore, we observed improved protein synthesis, attributed to UPR activation during the prolonged G1 phase. These findings not only enhanced our understanding and application of yeast's capacity to synthesize lipophilic compounds in applied biotechnology but also offered unique insights into cellular behavior during the modified G1 phase, particularly regarding the UPR response, for basic research. This study demonstrates the potential of G1 phase intervention to increase the yield of hydrophobic compounds in yeast, providing a promising direction for further research., Competing Interests: Competing interests statement:The authors declare no competing interest.

Antibiotic-induced inflammation involves the release of myeloperoxidase (MPO), an enzyme whose expression in tissues is associated with the inflammatory pathway. However, existing methods for detecting MPO in cells are limited. In this study, a DNAzyme nanorobot was developed using a scaffold of gold nanoparticles (AuNPs) decorated with functional DNAzyme strands and their fluorophore-labeled substrate strands. The DNAzyme remains inactive due to a self-assembled hairpin structure, with a phosphorothioate (PT) modification inserted into the stem domain. When MPO is present, it triggers a halogenation process that generates hypochlorous acid (HClO). HClO specifically catalyzes the cleavage of the PT-site, releasing free DNAzyme strands to cleave their substrates and generating an increasing fluorescent signal. The detection limit for MPO and its primary product, HClO, were determined to be 0.038 μg/mL and 0.013 μM, respectively. The DNAzyme nanorobot can be readily introduced into cells and function autonomously to differentiate increased MPO/HClO levels caused by antibiotics. This approach was applied to image RAW264.7 cells exposed to four prevalent antibiotics found in the environment (phorbol 12-myristate 13-acetate, erythromycin, penicillin, and tetracycline) as well as antibiotic production wastewater. This nanorobot offers novel strategies for monitoring inflammation to evaluate the health impacts of antibiotic exposure.

Background: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial., Methods: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy., Results: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels., Conclusions: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation., Competing Interests: Competing interests: XS and XZ are employees of Angecon Biotechnology Co, Ltd. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear., Method: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed., Results: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-beta NREM : r=0.9, p=0.0001, sleep fragmentation index (SFI)-beta NREM : r=0.6, p=0.0301; SFI-gamma NREM : r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPR NREM : r=-0.8, p=0.0053; ArI-LHPR REM : r=-0.6, p=0.0373; SFI-LHPR NREM : r=-0.7, p=0.0204; SFI-LHPR REM : r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (β=-0.24, p<0.001)., Conclusion: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction., Trial Registration Number: NCT02937727., Competing Interests: Competing interests: Luming Li and Hongwei Hao serve on the scientific advisory board for Beijing Pins Medical Co., Ltd and are listed as inventors in issued patents and patent applications on the deep brain stimulator used in this work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The aging of the central nervous system(CNS) is a primary contributor to neurodegenerative diseases in older individuals and significantly impacts their quality of life. Neuroinflammation, characterized by activation of microglia(MG) and release of cytokines, is closely associated with the onset of these neurodegenerative diseases. The activated status of MG is modulated by specifically programmed metabolic changes under various conditions. Succinylation, a novel post-translational modification(PTM) mainly involved in regulating mitochondrial energy metabolism pathways, remains unknown in its role in MG activation and aging. In the present study, we found that succinylation levels were significantly increased both during aging and upon lipopolysaccharide-induced(LPS-induced) MG activation undergoing metabolic reprogramming. Up-regulated succinylation induced by sirtuin 5 knockdown(Sirt5 KD) in microglial cell line BV2 resulted in significant up-regulation of aging-related genes, accompanied by impaired mitochondrial adaptability and a shift towards glycolysis as a major metabolic pathway. Furthermore, after LPS treatment, Sirt5 KD BV2 cells exhibited increased generation of reactive oxygen species(ROS), accumulation of lipid droplets, and elevated levels of lipid peroxidation. By employing immunoprecipitation, introducing point mutation to critical succinylation sites, and conducting enzyme activity assays for succinate dehydrogenase(SDH) and trifunctional enzyme subunit alpha(ECHA), we demonstrated that succinylation plays a regulatory role in modulating the activities of these mitochondrial enzymes. Finally, down-regulation the succinylation levels achieved through administration of succinyl phosphonate(SP) led to amelioration of MG senescence in vitro and neuroinflammation in vivo. To our knowledge, our data provide preliminary evidence indicating that up-regulated succinylation modifications elicit a senescence phenotype in MG through alterations in energy metabolism. Moreover, these findings suggest that manipulation of succinylation levels may offer valuable insights into the treatment of aging-related neuroinflammation., Competing Interests: Declarations Ethical approval All procedures were in accordance with the Dalian Medical University guidelines for the proper care and use of laboratory animals and were approved by the Laboratory Animal Care and Use Committee of Dalian Medical University. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Methylation of the DNA genome plays an important role in viral gene inactivation. However, the role of DNA methylation in human bocavirus (HBoV) remains unclear. In this study, the HBoV1 genomic DNA was found extensively methylated at the CHG and CHH sites. Inhibiting DNA methylation with 5-aza-2'-deoxycytidine (DAC) altered the methylation status and reduced viral DNA production, while enhanced the RNA splicing at D1 and D3 sites and the polyadenylation at the proximal polyadenylation site, (pA)p. Knockdown of DNA methyltransferase 1 (DNMT1) had the same effect on viral DNA synthesis and RNA processing as the DAC treatment, indicating that DNMT1 is the major host methyltransferase involved in viral DNA methylation. In addition, the nonstructural protein NS1 promoted DNMT1 degradation through the ubiquitin-proteasome pathway to regulate viral replication and RNA processing. Collectively, the results suggest that DNA methylation and DNMT1 facilitate HBoV replication and are essential for appropriate NS1 localization in the nucleus. DNMT1 degradation through NS1 promotes the virus RNA processing, leading to viral protein expression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

High-level liquid waste (HLLW) generated through nuclear reactions and spent fuel reprocessing contains the critical transuranic element neptunium (Np). Thus, the efficient recovery of Np from HLLW via the TRPO (trialkylphosphine oxide) process is not only beneficial for radioactive contamination remediation but also boosts the recycling of precious nuclear resources. However, this process including Np(V)-Np(IV) conversion is highly dependent on the components coexisting in HLLW, and its underlying mechanism is still not clear, restricting the recovery of Np in multiple scenarios. Herein, the effect of coexisting metal ions on the reduction and extraction of Np(V) was studied, and molybdenum (Mo) was identified to play a vital role in this course. Additionally, in combination with absorption spectral analysis, X-ray photoelectron spectroscopy and solvent extraction, the promotion of the extraction of Np by Mo was elucidated to be due to the catalytic reduction effect both in the aqueous phase and organic phase. This study can help researchers better understand the redox chemistry of Np in the treatment of HLLW.

Ocular surface diseases affect a significant portion of the population worldwide. Accurate segmentation and quantification of different ocular surface structures are crucial for the understanding of these diseases and clinical decision-making. However, the automated segmentation of the ocular surface structure is relatively unexplored and faces several challenges. Ocular surface structure boundaries are often inconspicuous and obscured by glare from reflections. In addition, the segmentation of different ocular structures always requires training of multiple individual models. Thus, developing a one-model-fits-all segmentation approach is desirable. In this paper, we introduce a randomness-restricted diffusion model for multiple ocular surface structure segmentation. First, a time-controlled fusion-attention module (TFM) is proposed to dynamically adjust the information flow within the diffusion model, based on the temporal relationships between the network's input and time. TFM enables the network to effectively utilize image features to constrain the randomness of the generation process. We further propose a low-frequency consistency filter and a new loss to alleviate model uncertainty and error accumulation caused by the multi-step denoising process. Extensive experiments have shown that our approach can segment seven different ocular surface structures. Our method performs better than both dedicated ocular surface segmentation methods and general medical image segmentation methods. We further validated the proposed method over two clinical datasets, and the results demonstrated that it is beneficial to clinical applications, such as the meibomian gland dysfunction grading and aqueous deficient dry eye diagnosis.

The existing and emerging demand for materials for life and health has contributed to the cultivation and development of respective markets. Nevertheless, the current generation of biomedical materials has yet to fully satisfy the clinical requirements of the market, which is still in its relative infancy. Research and development in this area must be prioritized in light of the pivotal role of new life and health materials in the biological field. Among many life and health materials, GQDs, an emerging nanomaterial, exhibit considerable promise in the biomedical field, primarily due to their exceptional properties. Furthermore, the direct preparation and functionalization of GQDs have facilitated the development of specific functional composites based on GQDs. The biological applications of GQDs are undergoing rapid growth, which makes it necessary to publish a review article presenting the latest advances in this field. This review provides an overview of the significant advances in synthesizing GQDs, the techniques employed for structural characterizations, and the properties that have been elucidated. Furthermore, it presents recent findings on applying GQDs in antimicrobial, anticancer, biosensing, drug delivery, and bioimaging applications. Finally, it explores the potential of GQDs in biomedicine and biotechnology, highlighting the current challenges that remain to be addressed., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Background: Sweet sorghum (Sorghum bicolor) displays an excellent potential to serve as a non-food bioenergy feedstock for bioethanol production in China due to its high potential yield on marginal lands. However, few studies have been conducted on the potential of sweet sorghum yield and appropriate industrial models in different marginal regions in China. This study explored the spatial distribution of potential sweet sorghum production using the Decision Support System for Agrotechnology Transfer (DSSAT) model and proposed three typical industrial models of sweet sorghum industry to calculate their economic and ecological benefits., Results: The results indicate that considering the factors of land use, annual precipitation, soil salinity, soil pH, and accumulated temperature, approximately 32.23 million ha of marginal land are suitable for sweet sorghum cultivation in China, and 130 million tonnes (t) of ethanol can be produced. Further, the development of the sweet sorghum industry under the three models can generate 1425.49 billion CNY potential, approximately accounting for 3.57% of industrial added value in China if measured against 2023 levels, and reduce CO 2 emissions by 4.68 million t., Conclusions: This study provides an innovative perspective for the multi-industry large-scale promotion of sweet sorghum in different marginal lands based on the high spatial resolution Geographic Information System (GIS) data by the DSSAT model with a Life Cycle Assessment (LCA) method, and this applies not only to China but also to the worldwide and other types of energy plants., (© 2024. The Author(s).)

Our study aimed to investigate the association between RFM and kidney stones, focusing specifically on the mediating role of high-density lipoprotein cholesterol (HDL-C). We performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2007 to 2018. Our analytical approach included multivariate logistic regression modeling, subgroup analysis, generalized additive modeling (GAM), smoothed curve fitting, and receiver operating characteristic (ROC) curve, as well as mediation analysis to assess the association between RFM and kidney stones. Finally, we categorized RFM into normal and elevated groups to conduct a sensitivity analysis. This study involved 29,712 participants, with a kidney stone prevalence of 9.88%. We discovered a positive association between RFM and kidney stones (OR = 1.41 per SD increment, 95% CI: 1.24, 1.60). Subgroup analysis revealed a consistent positive association across all subgroups, with a notably higher likelihood of developing kidney stones in young adulthood (P for interaction < 0.05). The smooth curve fitting shows that RFM is nonlinearly and positively correlated with the prevalence of kidney stones. Additionally, HDL-C was found to be negatively associated with kidney stones. Importantly, HDL-C demonstrated a significant mediating effect, with a mediation ratio of 13.52%. ROC analysis indicated that RFM (AUC = 0.616) provided better diagnostic accuracy than traditional measures such as BMI (AUC = 0.565) and WC (AUC = 0.599). Furthermore, the sensitivity analysis further supports the robustness of our findings. RFM is nonlinearly and positively correlated with the prevalence of kidney stones, with HDL cholesterol playing a significant mediating role in this relationship. However, further studies are needed to confirm these associations and explore potential mechanisms., (© 2024. The Author(s).)

Background: This study aims to explore the role of RIPK2 in lung cancer metastasis and its potential mechanisms., Methods: The expression levels of RIPK2 in lung cancer patients and cell lines were detected by immunohistochemistry, qRT-PCR, and Western blot. RIPK2 expression was knocked down using siRNA technology, and its effects on the proliferation, migration, and invasion capabilities of lung cancer cells were assessed through CCK-8, EdU, colony formation, and Transwell assays. Furthermore, by overexpressing RIPK2 and LAMP2, the regulatory effect of RIPK2 on the lysosomal pathway and its mechanism of action in lung cancer metastasis were investigated., Results: The results showed that the expression of RIPK2 was significantly increased in lung cancer patients and cell lines. Knockdown of RIPK2 significantly inhibited the migration, invasion, and proliferation capabilities of lung cancer cells, while overexpression of RIPK2 promoted these malignant behaviors. Further studies found that RIPK2 promoted lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. Additionally, overexpression of LAMP2 could reverse the promotive effects of RIPK2 overexpression on the malignant behaviors of lung cancer cells., Conclusion: This study reveals for the first time that RIPK2 promotes lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. In the future, targeted therapy against RIPK2 and LAMP2 may become an effective means to inhibit lung cancer metastasis., 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. Published by Elsevier Inc.)

This study aimed to investigate the effects of dietary fiber (DF) levels and copper concentrations on the production performance and cecal microbial diversity of finishing pigs. A 2 × 2 factorial experimental design was used, with different levels of dietary fiber (low [23% DF]: L and high [30% DF]: H) and copper concentrations (normal [25 mg/kg]: N and supplemented [45 mg/kg]: S) resulting in four diets (LN, LS, HN, and HS). Forty-eight hybrid barrows (Duroc × Landrace × Yorkshire), with an initial body weight of 76 kg ± 1.5 kg, were randomly assigned to four groups: LN, LS, HN, and HS, with 12 replicates per group and one pig per replicate. There was a 7-day adaptation period followed by a 56-day feeding trial, after which all pigs were slaughtered for sampling. Results indicated that in finishing pigs, the low dietary fiber group exhibited a higher final weight, a higher average daily gain, and a lower feed-to-gain ratio compared to the high fiber group ( p < 0.05). The LS group showed higher digestibility of dry matter, crude protein, crude fiber, ash, neutral detergent fiber, and DF than the HN and HS groups ( p < 0.05). Blood total protein levels were higher in the high fiber group, whereas blood Cu levels were higher in the supplemented copper group ( p < 0.05). High dietary fiber increased the activities of colonic carboxymethylcellulase and β-glucanase ( p < 0.05). Concentrations of acetic acid, propionic acid, and total volatile fatty acids were elevated in the high fiber group ( p < 0.05). Microbial α-diversity indices (observed species, Chao 1, and Shannon indices) increased with fiber but decreased with copper supplementation ( p < 0.05). The Firmicutes / Bacteroidetes ratio increased with fiber levels, with a higher relative abundance of Lactobacillus in the LS group. In conclusion, appropriate copper supplementation in diets can mitigate the negative effects of high fiber levels on finishing pig production performance by enhancing nutrient digestibility, fiber-degrading enzyme activity, regulating the microbial community, and its metabolic products.

Elucidating the detailed features of emerging SARS-CoV-2 strains both in vitro and in vivo is indispensable for the development of effective vaccines or drugs against viral infection. We thoroughly characterized the virological and pathogenic features of eight different pandemic SARS-CoV-2 strains, from the WT strain to current circulating sublineage EG.5.1, both in vitro and in vivo. Besides detailed virological features observed in Vero E6 cells, the Omicron variants, from BA.1 to EG.5.1, exhibited enhanced infectious effects to upper respiratory tract in K18 human angiotensin-converting enzyme (ACE2) (K18 hACE2) transgenic mice. Both XBB.1.9.1 and EG.5.1 presented stronger tropism to brain, which could be the main reason for the increased lethal effects on mice. In addition, the pathogenesis comparisons among all these viruses in C57BL/6JGpt mice indicated that Omicron variant BA.1 and two new sublineages XBB.1.9.1 and EG.5.1 possessed dual tropisms to both human and mice, which were further confirmed by subsequent bioinformatic analyses and actual affinity comparison between viral RBDs and mouse or human receptor ACE2. Furthermore, the immunocompromised BKS-db mice were found to be more susceptible to Omicron strains compared to C57BL/6JGpt mice, which revealed that viral infectivity was determined by both its affinity to the host receptor and host immunocompetence. Thus, this study not only contributes to a systematic understanding of the pathogenic features of SARS-CoV-2 in mice, but also provides new insights to combat potential future surges of new SARS-CoV-2 variants., (© 2024 Wiley Periodicals LLC.)

Purpose: Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival., Materials and Methods: InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia. Cases are patients who died of melanoma within 5 years from original diagnosis. Controls survived longer than 5 years without evidence of melanoma recurrence or relapse. Methylation classes, distinguished by consensus clustering of 850K methylation data, were evaluated for their clinicopathologic characteristics, 5-year survival status, and differentially methylated gene sets., Results: Among 422 InterMEL melanomas, consensus clustering revealed three primary melanoma methylation classes (MethylClasses): a CpG island methylator phenotype (CIMP) class, an intermediate methylation (IM) class, and a low methylation (LM) class. CIMP and IM were associated with higher AJCC stage (both P = .002), Breslow thickness (CIMP P = .002; IM P = .006), and mitotic index (both P < .001) compared with LM, while IM had higher N stage than CIMP ( P = .01) and LM ( P = .007). CIMP and IM had a 2-fold higher likelihood of 5-year death from melanoma than LM (CIMP odds ratio [OR], 2.16 [95% CI, 1.18 to 3.96]; IM OR, 2.00 [95% CI, 1.12 to 3.58]) in a multivariable model adjusted for age, sex, log Breslow thickness, ulceration, mitotic index, and N stage. Despite more extensive CpG island hypermethylation in CIMP, CIMP and IM shared similar patterns of differential methylation and gene set enrichment compared with LM., Conclusion: Melanoma MethylClasses may provide clinical value in predicting 5-year death from melanoma among patients with primary melanoma independent of other clinicopathologic factors.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD's complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (2, 6, and 8) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (12) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds 2, 6, and 8 (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)