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Acylaminoacyl-peptide hydrolase (APEH), a serine peptidase that belongs to the prolyl oligopeptidase (POP) family, catalyzes removal of N-terminal acetylated amino acid residues from peptides. As a key regulator of protein N-terminal acetylation, APEH was involved in many important physiological processes while its aberrant expression was correlated with progression of various diseases such as inflammation, diabetics, Alzheimer's disease (AD), and cancers. However, while emerging attention has been attracted in APEH-related disease diagnosis and drug discovery, the mechanisms behind APEH and related disease progression are still unclear; thus, further investigating the physiological role and function of APEH is of great importance. To date, enzyme-activated fluorescent probes targeting POPs have been extensively reported and adopted in relevant medical research and applications. Nevertheless, as an important member of the POP family, APEH was rarely referred in the field of bioimaging while the fluorescent probe for in vivo sensing of APEH activity has not been reported yet. Thus, acquiring an efficient APEH-targeted probe is in urgent need. Herein, an enzyme-activated fluorogenic probe for in vivo profiling of APEH was first discovered via a substrate mimic-based strategy. By combination of stimulated molecular docking-based preliminary screening and experiment-based secondary screening, the optimal probe (named as TMN-AcA ), which displayed high binding affinity, sensitivity, and specificity toward APEH, was screened out. Owing to the superior properties of TMN-AcA , endogenous APEH activity in various cell lines and transplanted tumor could be visualized while tissue distribution of APEH was revealed. Most importantly, APEH was first demonstrated to be a potential biomarker of multiple-organ injury via TMN-AcA -based bioimaging and immunohistochemistry (IHC) analysis while the newly developed probe could serve as a vital tool for APEH-related disease diagnosis and biological function study.

Ulinastatin is a protease-inhibiting drug with anti-inflammatory and other pharmacological properties. Little is known regarding its role following acute type A aortic dissection (ATAAD) surgery. We perform a randomized controlled trial to investigate the protective effect of ulinastatin against negative inflammatory response and organ dysfunction in ATAAD surgery (PANDA). The primary outcome of mean daily Sequential Organ Failure Assessment (SOFA) score from baseline to 7 days of surgery is 8.80 (SD, 4.11) in the ulinastatin group and 8.61 (SD, 4.47) in the control group (mean difference between groups was 0.04; 95% confidence interval [CI], -0.24 to 0.33; p = 0.765). Systemic inflammatory response syndrome (SIRS) within 7 days of surgery is lower in the ulinastatin group than in the control group (p < 0.001). Additional ulinastatin to standard treatment is likely to reduce SIRS rates instead of preventing organ dysfunction, highlighting the potential importance of the benefits of anti-inflammatory pharmacotherapeutics. The trial is registered on clinicaltrials.org (NCT04711889)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

As a well-established topic, single-atom catalyst has drawn growing interest for its high utilization of metal. However, researchers prefer to develop various active metals with single-atom form, the intrinsic roles of single-atom promoters are usually underrated, which are significant in boosting reaction activity. In this work, Ba single atoms were in situ prepared in the Co-Ba/Y 2 O 3 catalyst with crystallized BaCO 3 as the precursor under the ammonia decomposition reaction condition. The optimized Co-Ba/Y 2 O 3 catalyst achieves extremely high H 2 production rate of 138.3 mmolH 2  ⋅ g cat -1  ⋅ min -1 at very low temperature (500 °C, GHSV=840,000 mL ⋅ g -1  ⋅ h -1 ) and Co-Ba/Y 2 O 3 exhibits excellent durability during the 350 h test, which realizes the highest activity among all non-noble catalysts, and reaches or even exceeds numerous reported Ru-based catalysts. Both Y 2 O 3 and Co demonstrate positive interactions with Ba, which significantly facilitates the dispersion of Ba species at high temperatures (≥600 °C). Ba single atoms significantly enhance the charge density of Co and form additionally active Co-O-Ba-Y 2 O 3 interfacial sites, which alleviates hydrogen poisoning and decreases the reaction barrier of the N-H bond activation of *NH. The exploration of atomically dispersed promoters is groundbreaking in heterogeneous catalysis, which opens up a whole new domain of catalytic material., (© 2024 Wiley-VCH GmbH.)

Four previously undescribed cyclic peptides, reniochpeptins A-D (1-4), were isolated from the marine sponge Reniochalina sp. Their structures were elucidated through comprehensive spectroscopic analyses and a modified advanced Marfey's method. This method utilized ultra-high-performance liquid chromatography coupled with tandem multiple reaction monitoring mass spectrometry, employing a CORTECS T 3 column to achieve simultaneous separation of derivatized L -Leu, L -Ile, L -allo-Ile, D -Leu, D -Ile, and D -allo-Ile within 25 min in a single analytical run. Reniochpeptin A displayed moderate inhibitory activity against NCI-H460 cells, with an IC 50 value of 4.7 μM, by inducing cell cycle arrest at the G2/M phase and promoting apoptosis., 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. Published by Elsevier Ltd.)

Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice. Our results indicate that an increase in the abundance of Citrobacter rodentium leads to impaired intestinal barrier, elevated expression of inflammatory factors in blood and brain tissue, and promotes cognitive impairment in T2D mice. The specific pathway involves activation of farnesol X receptor (FXR) expression-mediated intestinal barrier dysfunction. The use of intestinal mucosal protectants and FXR inhibitors improved intestinal barrier function and brain cognitive function. Therefore, the research results provide a mechanistic link between the increased abundance of Citrobacter in the gut of T2D mice and brain cognitive function, and provide a reference for the occurrence of brain cognitive dysfunction in T2D., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Large-scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia-Shigella in patients with T2DM-related-ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe-/- T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability. Non-targeted metabolomic and proteomic analysis of mouse serum showed that T3SS caused abnormal glycerophospholipid metabolism in mice. Proteomics, RNA sequencing, and functional analyses showed that T3SS induced ferroptosis in intestinal epithelial cells, partly due to increased expression of ferritin heavy chains (FTH1). This findings first demonstrated that T3SS increases ferroptosis in intestinal epithelial cells, via disrupting the intestinal barrier and upregulation of phosphatidylcholine, thereby exacerbating T2DM-related ASCVD., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition. This shortage in aspartate, in turn, caused nucleotide deficiencies, leading to S phase cell cycle arrest, replication fork stalling, and enrichment of the p53 pathway, manifestations of replication stress. The addition of purine nucleobases adenine and guanine along with the pyrimidine nucleoside uridine restored replication fork progression and cell proliferation, whereas the supplementation of exogenous aspartate recovered the nucleotide pool, demonstrating a causal role of the aspartate shortage in OXPHOS inhibition-induced nucleotide deficiencies and consequently replication stress and reductions in proliferation. Moreover, we demonstrate that glutamic-oxaloacetic transaminase 1 (GOT1) is critical for maintaining the minimum aspartate pool when OXPHOS is inhibited, as knockdown of GOT1 further reduced aspartate levels and rendered CRC cells more sensitive to OXPHOS inhibition both in vitro and in vivo. These results propose GOT1 targeting as a potential avenue to sensitize cancer cells to OXPHOS inhibitors, thus lowering the necessary doses to efficiently inhibit cancer growth while alleviating their adverse effects., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Exploiting advanced solid particles is crucial to the construction of Pickering emulsions catalysis. Recently, metal-organic frameworks (MOFs) have been used as ideal emulsifiers stabilizing Pickering emulsions for interfacial catalysis. Although Pickering emulsions stabilized by core-shell MOFs have significant importance in practical studies, to date there have been very limited reports on this topic. Herein, ZIF-90@ZIF-67, a core-shell material with simultaneous acid-base bifunctionality, was synthesized by seeded epitaxial growth. It was firstly applied as an emulsifier in Pickering emulsions to catalyze the deacetalization-Knoevenagel tandem reaction, which exhibited excellent catalytic properties and achieved extremely high yields. Additionally, ZIF-90@ZIF-67 showed high stability and remained well repeatable after five cycles. This work provides a platform for the design of structurally and functionally diverse MOF-based Pickering emulsions interfacial catalysis., (© 2024 Wiley-VCH GmbH.)

Relativistic pseudopotentials (PPs) and basis sets are the workhorses for modeling heavy elements of lanthanides and actinides. The norm-conserving Goedecker-Teter-Hutter (GTH) PP is advantageous for modeling lanthanide and actinide compounds and condensed systems because of its transferability and accuracy. In this work, we develop a set of well-benchmarked GTH-type 5f-in-core PPs with scalar-relativistic effects together with associated Gaussian basis sets for the most commonly encountered trivalent and tetravalent actinides [An(III), An(IV); An = Pa-Lr]. The 5f-in-core GTH PPs are constructed by placing 5f-subconfiguration 5f n of An(III) and 5f n -1 of An(IV) ( n = 2-14) into the atomic core in the core-valence separation. The formalism of 5f-in-core GTH PPs circumvents the computational difficulty arising from the 5f open valence shell. The different performances of 5f-in-core GTH PPs for trivalent and tetravalent actinides are further analyzed from the chemical bonding features of actinides. We anticipate that the optimized 5f-in-core GTH PPs and Gaussian basis sets can be used to accelerate the costly first-principles modeling of structure-complicated actinide compounds and condensed-phase actinide systems.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. The present study aims to investigate the effects and mechanisms of cordycepin on MASLD. Male C57BL/6 mice were induced with a 90-day high-fat diet (HFD) and intraperitoneal administration with streptozotocin to establish MASLD murine model. Then they were randomly divided into the HFD and cordycepin groups (15, 30, 45 mg/kg). Cordycepin was orally given for 30 days. Serum total cholesterol (TC), triacylglyceride (TG), and aspartate aminotransferase (AST) levels were measured. L02 cells were induced by oleate acid (OA) or lipopolysaccharides (LPS), and treated with cordycepin or combined with inhibitors including chloroquine, 3-Methyladenine, and compound C. Atg7 and Parkin were knocked down in L02 cells using siRNA. Oil Red O and Nile Red staining for measuring lipid deposition. Mitochondria were visualized by transfection with mCherry-TOMM20-N10. Quantitative real-time PCR, Western blotting, and immunofluorescence staining were used to determine expressions of key molecules in inflammation, lipid metabolism, mitochondria homeostasis, and oxidative stress. Cordycepin significantly mitigated lipid deposition and ballooning in the livers of MASLD mice. Serum TC, TG, and AST levels were decreased by cordycepin. Cordycepin alleviated OA-induced lipid deposition and LPS-induced inflammation in L02 cells, attenuated oxidative stress, promoted autophagy, and maintained the autophagic flux by activating AMP-activated protein kinase (AMPK). Cordycepin reduced the accumulation of impaired mitochondria by enhancing Parkin-dependent mitophagy and promoting mitochondrial biogenesis. Cordycepin alleviates MASLD by restoring mitochondrial homeostasis and reducing oxidative stress via activating the Parkin-mediated mitophagy., 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 Inc. All rights reserved.)

Programming and synthesizing bifunctional materials for regulating the output of triboelectric nanogenerators (TENGs) and their photocatalytic efficiency is a promising strategy for energy harvesting to build self-powered systems. Herein, we tackle this challenge by introducing metal-organic frameworks (MOFs) as molecular catalysts and triboelectric layers for self-powered photocatalytic systems. A zeolite-like mixed-valence MOF ( Cu I Cu II -1 ) and a ladder-structured MOF ( Cu II -2 ) were obtained through structural transformation. Due to the excellent charge-trapping capability and surface potential of Cu I Cu II -1 , the outputs of Cu I Cu II -1-TENG (a short-circuit current ( I sc ) of 30.4 μA and an open-circuit voltage ( V oc ) of 524.1 V) were significantly superior to those of Cu II -2-TENG . The incorporation of Cu I Cu II -1 with ethylcellulose (EC) to form Cu I Cu II -1@EC composite films greatly improved the TENG outputs, and the 10% Cu I Cu II -1@EC-TENG offered the maximum I sc (57.2 μA) and V oc (986.8 V). Furthermore, multiple 10% Cu I Cu II -1@EC-TENG devices were integrated in parallel to assemble multiple TENG devices ( M-TENG ) to harvest biomechanical energy, which displayed significant potential to continuously power blue LEDs, generating blue-light irradiation to trigger the photocatalytic C(sp)-H/Si-H cross-coupling reactions of aromatic alkyne and trimethylsilane for alkynylsilane over the photocatalysts Cu I Cu II -1 and Cu II -2 . The results revealed that Cu I Cu II -1 achieved a cooperative effect on remarkable catalytic selectivity and activity. This work demonstrates that bifunctional MOFs can serve as friction electrode materials for the large-scale integration and assembly of MOF-based TENG, and photocatalysts for achieving self-powered photocatalytic systems.

Heavy metals （HMs） pollution in agricultural soil-rice systems has attracted worldwide attention as it directly threatens regional ecological security and human health. To understand the heavy metal pollution of agriculture soil and rice in the high geological background areas, a total of 200 paddy soil and rice samples were collected in southeast Chongqing. The concentrations of arsenic （As）, cadmium （Cd）, chromium （Cr）, copper （Cu）, mercury （Hg）, nickel （Ni）, lead （Pb）, and zinc （Zn） in paddy soil and rice were analyzed. The comprehensive impact index （IICQ） was used to evaluate the quality of heavy metals in soil-rice. The results showed that the mean concentrations of As, Cd, Cr, Hg, and Pb in soil were higher than their corresponding background values of Chongqing soil and the average values of Chinese surface soil, indicating the accumulation of HMs enrichment of these metals in the paddy soils. Compared with China's soil environmental quality standard of agricultural land （GB 15618-2018）, only 20.5% of rice samples containing Cd exceeded the national food safety standard （GB 2762-2022）, though the Cd and Hg sample contamination rates of the sampling sites were 82% and 22.5%, respectively. The evaluation results of heavy metal pollution, such as Cd in soil and crops, were quite different. With the increase in soil pH value, the average content of Cd in the soil gradually increased, but the average content of Cd in rice seeds decreased by 0.245 mg·kg -1 , and the excess rate of rice seeds decreased by 42.14%. The Cd content in rice seeds was significantly correlated with the Cd ion exchange state and water-soluble state in the soil. The higher the soil pH value, the lower the proportion of bioactive components in the soil, and the pH of the soil was the main factor affecting the safety of rice in the study area. The comprehensive quality evaluation results showed that moderate and severe pollution were the main pollution levels in the study area, but most of the rice seeds were in a clean state, a few were slightly polluted, and none showed mild or above pollution. The basic safety of rice was in the alkaline area with a pH&gt;7.5. In strongly acidic soil with pH&lt;5.5 and below, the excess rate of rice seeds could reach 45%. Moreover, it is recommended to apply quicklime or calcareous soil conditioner to improve soil acidification, reduce the activity of Cd bioactive components, and improve the safety of rice and other agricultural products.

H. longicornis is used as an experimental animal model for the study of three-host ticks due to its special life cycle and easy maintenance in the laboratory and in its reproduction. The life cycle of H. longicornis goes through a tightly regulated life cycle to adapt to the changing host and environment, and these stages of transition are also accompanied by proteome changes in the body. Here, we used the isobaric tags for a relative and absolute quantification (iTRAQ) technique to systematically describe and analyze the dynamic expression of the protein and the molecular basis of the proteome of H. longicornis in seven differential developmental stages (eggs, unfed larvae, engorged larvae, unfed nymphs, engorged nymphs unfed adults, and engorged adults). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differentially expressed proteins (DEPs) were used. In our study, A total of 2044 proteins were identified, and their expression profiles were classified at different developmental stages. In addition, it was found that tissue and organ development-related proteins and metabolism-related proteins were involved in different physiological processes throughout the life cycle through the GO and KEGG analysis of DEPs. More importantly, we found that the up-regulated proteins of engorged adult ticks were mainly related to yolk absorption, degradation, and ovarian development-related proteins. The abundance of the cuticle proteins in the unfed stages was significantly higher compared with those of the engorged ticks in the previous stages. We believe that our study has made a significant contribution to the research on H. longicornis , which is an important vector of SFTSV. In this study, we identified changes in the proteome throughout the H. longicornis development, and functional analysis highlighted the important roles of many key proteins in developmental events (ovarian development, the molting process, the development of midgut, the development and degeneration of salivary glands, etc.). The revelation of this data will provide a reference proteome for future research on tick functional proteins and candidate targets for elucidating H. longicornis development and developing new tick control strategies.

Nucleosides and polysaccharides are the main bioactive ingredients of Cordyceps genus. Nucleosides shows significant differences in different Cordyceps species. However, the differences of polysaccharides have not been decoded. Here, the structure characters of polysaccharides including molecular weight (Mw) distribution, compositional monosaccharides and glycosidic linkage types were compared in C. sinensis (CS), C. militaris (CM), silkworm-hosted C. militaris (SCM) and Cordyceps fermented products (CSF). Compositional monosaccharides including mannose, glucose and galactose, and 1,4-Glcp glycosidic linkage were found abundant in Cordyceps species. Chemometric analysis showed that Cordyceps exhibit significant differences in structural information especially glycosidic linkage types. Besides, polysaccharides in CS and CSF-4 had obviously strong capacity of stimulating phagocytic, NO production and cytokines secretion. Gray relational analysis and Pearson correlation analysis were performed to further investigate the relationship between key polysaccharide structure and immunomodulatory activities. The results indicated that polysaccharides with relatively large number of 1, 4-Glcp and Mw in range of 7.16 × 10 6  Da-7.99 × 10 7  Da and 1.43 × 10 4 D-6.94 × 10 5  Da probably contributed to its immunomodulatory activities. The chemical and biological evaluation of natural and various cultured cordyceps in this study is useful for understanding and regulating the quality of cultured Cordyceps., 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 B.V.)

The efficacy and safety of different Chinese patent medicines in the treatment of stable chronic obstructive pulmonary disease(COPD) were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for stable COPD were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to February 2024. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool. RevMan 5.4 and Stata 16.0 were used to establish the risk of bias diagram and perform the network Meta-analysis. A total of 113 RCTs were included, involving 8 265 patients and 14 Chinese patent medicines. The network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of improving the forced expiratory volume in 1 second to forced vital capacity(FEV1/FVC) ratio, the top three treatments were Jingshuibao Capsules + conventional western medicine, Yupingfeng San + conventional western medicine, and Sanzi Zhike Capsules + conventional western medicine.(2) In terms of improving the clinical efficacy, the top three treatments were Yifei Capsules + conventional western medicine, Yupingfeng Granules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3) In terms of improving the percentage of predicted FEV1(FEV1%pred), the top three treatments were Jingshuibao Capsules + conventional western medicine, Bufei Granules + conventional western medicine, and Bailing Capsules + conventional western medicine.(4) In terms of improving the distance in 6 min walking test(6MWT), the top three treatments were Jingshuibao Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Jianpi Yifei Oral Liquid + conventional western medicine.(5) In terms of reducing the COPD assessment test(CAT), the top three treatments were Bufei Granules + conventional western medicine, Yifei Capsules + conventional western medicine, and Yifei Huoxue Granules + conventional western medicine.(6) In terms of reducing the frequency of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) within 1 year, the top three treatments were Yupingfeng Capsules + conventional western medicine, Yupingfeng San + conventional western medicine, and Jianpi Yifei Oral Liquid + conventional western medicine.(7) In terms of safety, 28 RCTs have reported adverse reactions, mainly involving the digestive system, circulatory system, and nervous system. The results showed that Chinese patent medicines combined with conventional western medicine improved FEV1/FVC, FEV1%pred, clinical efficacy, and 6MWT, while reducing CAT and the frequency of AECOPD within 1 year. However, due to the limitations of the included studies and the lack of direct comparisons between different interventions, these results need further validation.

The ubiquitin-proteasome system influences cancer progression through multiple mechanisms. Due to the extensive proteasomal modifications observed in cancer tissues, ubiquitination is closely related to various biological functions with cancer. However, the roles of ubiquitin-related genes (UbRGs) in breast cancer (BC) have not been thoroughly investigated. In this study, we retrieved 763 reliable UbRGs and identified a potential prognostic signature for breast cancer patients. Additionally, we analyzed eight overall survival-associated UbRGs using univariate Cox proportional hazard regression in the Cancer Genome Atlas (TCGA) database. Subsequently, we used Lasso-Cox risk regression analysis to generate prognostic characteristics of UbRGs associated with overall survival (OS), validated in an external cohort (GSE158309). Next, we compared differences in tumor microenvironment and drug sensitivity between subgroups, describing the potential impact of UbRGs on the landscape of the tumor immune microenvironment and their predictive significance for therapeutic resistance to different strategies. Furthermore, a nomogram model containing eight genes, histology, subtype, T status, N status, and the American Joint Committee on Cancer (AJCC) stage was constructed. Finally, in vitro and in vivo experiments validated the effects of FBXL6 and PDZRN3 on breast cancer development. In conclusion, we demonstrate that ubiquitin-related genes are closely associated with breast cancer prognosis, immune environment, and drug sensitivity. Our results offer a new insight into breast cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein found in microglia within the brain, and its soluble form (sTREM2) has been shown to reduce amyloid deposition. Whether elevated TREM2-mediated microglial activity decreases the risk of Alzheimer's disease (AD) is unclear. The aim of this study was to assess whether high cerebrospinal fluid (CSF) levels of sTREM2 attenuate the risk of APOE ε4-associated amyloid pathology. We included 877 cognitively intact subjects from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, including APOE ε4 carriers (n = 136) and non-carriers (n = 741). The linear regression was used to examine the interaction effect between CSF sTREM2 levels and APOE ε4 status on CSF Aβ42 levels. Additionally, subgroup analyses stratified by sex and age were conducted. Our main finding was that higher concentrations of CSF sTREM2 attenuated the effect of APOE ε4 carriage (i.e., the sTREM2 × APOE ε4 interaction) on amyloid deposition (β = -2.701e-05, p = 0.023). Subgroup analyses showed that the effect of interaction was still significant only in male (p = 0.041) and mid-life (p = 0.013) subgroups. Our study suggested that in cognitively intact individuals, changes in sTREM2 levels are associated with biomarkers of AD, and higher concentrations of CSF sTREM2 attenuated the risk of APOE ε4-related amyloid pathology. The identified role of the sTREM2 × APOE ε4 interaction in amyloid pathology offers new insights into potential strategies for AD prevention in APOE ε4 carriers., (© 2024 International Society for Neurochemistry.)

Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8-16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 μM) and 16 (123.15 μM) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical 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 Ltd. All rights reserved.)

Iron overload-dependent ferroptosis is believed to contribute to the brain injury of ischemia/reperfusion (I/R), whereas toll-like receptor 4 (TLR4) can exert pro-ferroptosis effect via inhibiting the glutathione peroxidase 4 (GPX4) level, but the mechanisms behind these phenomenon are not fully elucidated. Tumor necrosis factor receptor correlated factor 3-interaction Jun amino-terminal kinase [JNK]-activating modulator (T3JAM) can activate specific molecule and its downstream signaling pathways, including TLR4. This study aims to explore whether targeting T3JAM can reduce I/R-induced ferroptosis in brain via downregulating TLR4. A Sprague Dawley (SD) rat model of cerebral I/R injury was established by 2 h-ischemia plus 24 h-reperfusion, which displayed brain injury (increases in neurological deficit score and infarct volume) and upregulation of T3JAM and TLR4, concomitant with the increased ferroptosis, reflected by increases in the levels of transferrin receptor protein 1 (TfR1), total iron, Fe 2+ and lipid peroxidation (LPO) while decreases in the levels of ferroportin (FPN) and GPX4. Consistently, similar results were achieved in the cultured HT22 cells subjected to 8h-oxygen-glucose deprivation plus 12 h-reoxygenation (OGD/R), and knockdown of T3JAM reversed these phenomena. Moreover, Telaprevir, an anti-hepatitis C virus (HCV) drug, could also provide beneficial effect on alleviating ischemic brain injury via inhibition of T3JAM. Based on these observations, we conclud that inhibition of T3JAM can reduce I/R-induced brain cell ferroptosis through downregulating TLR4 and that T3JAM could be a potential target for identifying novel or existing drugs (such as Telaprevir) to treat cerebral I/R injury., Competing Interests: Conflicts of interest The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuroinflammation mediated by microglia is widely recognized as a key pathophysiological mechanism in neurodegenerative diseases. Lappaconitine (LA) is a natural C 18 -diterpenoid alkaloid isolated from Aconitum sinomontanum Nakai, and previous study showed that LA and its derivatives inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. However, the anti-neuroinflammatory effects of LA and its derivatives on microglia are still not clear. Here, LA analogues were designed and synthesized, and the anti-neuroinflammatory activity of the synthesized compounds was screened using LPS-induced overexpression of NO in BV-2 microglia. The screening results showed that compound 10 displayed the highest ability to inhibit NO production (IC 50  = 9.98 ± 1.6 µM). Mechanistic investigations revealed that compound 10 attenuated LPS-activated neuroinflammation through suppression of TLR4/MyD88/NF-κB pathway in BV-2 microglia. Acute toxicity assays showed that compound 10 (LD 50  = 508.1 mg/kg) was safer relative to LA (LD 50  = 30.6 mg/kg). Collectively, our findings show that compound 10 could have potential as anti-neuroinflammatory agents., 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 Ltd.)

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia., Competing Interests: Declarations. Ethics Approval: All experimental procedures were conducted following the guidelines of the International Association for the Study of Pain and were approved by the Ethics Committee of the West China Hospital of Stomatology, Sichuan University (WCHSIRB-D-2022–479). Consent to Participate: Not applicable for this study. Consent to Publish: Not applicable for this study. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown., Results: This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2&#95;1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 - 14&#95;223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2 V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2 V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2's interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte., Conclusion: PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders., Competing Interests: Declarations. Ethics approval and consent to participate: The animal study protocol was approved by the Animal Care and Use Committee of Zhejiang University (ZJU20220464). Studies of human subjects were approved by the Ethics Committee of Sir Run Run Shaw Hospital (NO. 20220461). Informed consent was obtained from each participant as adhering to tenets of the Declarations of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare they have no conflict of interest., (© 2024. The Author(s).)

Objective: To verify the accuracy of collagen-specific SNP mutation loci of Kele pigs selected by whole genome resequencing, and to excavate collagen-related genes of Kele pigs, so as to lay a foundation for further molecular selection., Methods: Based on whole genome resequencing, candidate genes related to collagen trait of Kele pig were screened for gene annotation. Through KEGG and GO enrichment analysis of differential genes, we selected four genes that may affect collagen trait of collagen pig, namely COL9A1, COL6A5, COL4A3 and COL4A4. Then 14 specific SNP sites were randomly selected from the four genes for sanger sequencing verification, and finally RT-qPCR was used to verify the expression levels of related genes in different tissues of Kele pigs., Results: Our sequencing results revealed that 241.04 G of clean data, Q30 reached 93.96% and the average coverage depth was 9.04×. After data analysis, the SNP annotation of Kele pigs identified 4,570 high-impact mutation sites that could result in protein function loss, with SNPs primarily distributed in the intronic and exonic regions. There were 132,256 middle-impact mutation sites and 318,150 low-impact mutation sites that could potentially impact protein properties. Additionally, The INDEL annotation results revealed a total of 17,806 high-impact mutation sites that could potentially result in the loss of protein function. There were 4740 medium-impact mutation sites that have the potential to affect protein properties, as well as 19,298 low-impact mutation sites. Furthermore, there were 14,197,763 mutation sites of modification influence degree in the analysis. In addition, through real-time fluorescence quantitative PCR results, we found that the expression levels of collagen-related genes COL9A1 and COL6A5 in skin tissues were higher than those in other tissues, and the expression levels of COL4A4 and COL4A3 in kidney tissues were higher than those in other tissues. The SNP site verification results showed that the 14 SNP mutation sites randomly selected by us were the same as the SNP mutation sites screened by whole genome resequencing., Conclusion: A total of 307 genes related to collagen traits were excavated, including COL9A1, COL6A5, EP300, SOS2 and EPO, etc. It was found that COL9A1 and COL6A5 genes were significantly expressed in the skin tissue of Kele pigs, and COL4A4 and COL4A3 genes were significantly expressed in the kidney tissue of Kele pigs. The mutations of 14 randomly selected loci in the four related genes were consistent with the results of previous whole genome resequencing analysis, indicating that the specific SNP molecular marker information obtained by whole genome resequencing can be used as the basis for analyzing collagen traits of Kele pig. Our results are conducive to further research on collagen trait regulation of Kele pigs and development and utilization of Kele pigs in the future., Competing Interests: 作者已声明不存在利益竞争。, (Copyright: © 2024 Zhang 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.)

Background: With the increasing risk of nuclear exposure, more attention has been paid to the prevention and treatment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms., Methods: The content of serum amino acids was analyzed using metabolomic sequencing. The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet. Extracellular matrix (ECM) protein analysis was performed via proteomics analysis. Inflammatory factors were examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4 (S100A4) regulates macrophage polarization., Results: The survival time of irradiated mice was significantly associated with alterations in multiple amino acids, particularly methionine. A high methionine diet promoted irradiation tolerance, especially in the recovery of bone marrow hematopoiesis, yet with dose limitations. Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine. Mechanistically, high methionine levels maintained the abundance of ECM components, including collagens and glycoproteins, in the bone marrow post-irradiation, among which the level of S100A4 was significantly changed. S100A4 regulated macrophage polarization via the STAT3 pathway, inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells., Conclusions: We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Laboratory Animal Welfare and Ethics Committee of the Army Medical University (AMUWEC2020122, AMUWEC2020055, AMUWEC20211415, AMUWEC20224721). All experiments involving animals were performed following relevant policies. Consent for publication: No applicable. Competing interests: The authors declare that they have no competing financial interests., (© 2024. The Author(s).)

Background: Anxiety is a common psychological comorbidity in patients undergoing dialysis, yet its impact on treatment adherence and complication rates remains understudied. We designed a longitudinal observational study to investigate these relationships, based on the hypothesis that higher anxiety symptoms would be associated with increased complication rates and negatively associated with adherence to the dialysis regimen., Aim: To investigate the relationship between anxiety symptoms, dialysis adherence, and complication rates in patients undergoing dialysis over a 24-month period., Methods: This observational study analyzed data from 250 adult patients who underwent hemodialysis or peritoneal dialysis at three Affiliated Hospitals of Youjiang Medical University for Nationalities over a period of 24 months. Anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale-Anxiety subscale at baseline and every 6 months. Dialysis adherence was evaluated through attendance records, interdialytic weight gain, and patient-reported medication adherence. We recorded complications (infections, cardiovascular events, and hospitalizations) and used mixed-effects models and survival analyses to infer associations between anxiety symptoms, adherence measures, and complication rates., Results: Higher anxiety symptoms were significantly associated with poorer dialysis adherence, including increased missed sessions [incidence rate ratio = 1.32, 95% confidence interval (CI): 1.18-1.47, P < 0.001], greater interdialytic weight gain ( β = 0.24, 95%CI: 0.15-0.33, P < 0.001), and lower medication adherence (odds ratio = 0.85, 95%CI: 0.78-0.93, P < 0.001). Patients with clinically significant anxiety (Hospital Anxiety and Depression Scale-Anxiety subscale ≥ 8) had a higher risk of complications [hazard ratio (HR) = 1.68, 95%CI: 1.32-2.14, P < 0.001], particularly infections (HR = 1.89, 95%CI: 1.41-2.53, P < 0.001) and cardiovascular events (HR = 1.57, 95%CI: 1.18-2.09, P = 0.002). The relationship between anxiety and complications was partially mediated by adherence measures., Conclusion: Anxiety symptoms in patients undergoing dialysis are associated with poorer treatment adherence and increased complication rates. Regular screening and targeted interventions to address symptoms may improve adherence and clinical outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: As natural reservoirs of diverse pathogens, small mammals are considered a key interface for guarding public health due to their wide geographic distribution, high density and frequent interaction with humans., Methods: All formally recorded natural occurrences of small mammals (Order: Rodentia, Eulipotyphla, Lagomorpha, and Scandentia) and their associated microbial infections in China were searched in the English and Chinese literature spanning from 1950 to 2021 and geolocated. Machine learning models were applied to determine ecological drivers for the distributions of 45 major small mammal species and two common rodent-borne diseases (RBDs), and model-predicted potential risk locations were mapped., Findings: A total of 364 small mammal species collectively carrying 155 small mammal-associated microbes (SMAMs) combined with 215,791 human cases of eight RBDs were reported in 2484 counties in China. Murid rodents (Family: Muridae) including the brown rat ( Rattus norvegicus ), the house mouse ( Mus musculus ), and the striped field mouse ( Apodemus agrarius ) are the most widespread species, while Rattus norvegicus harbored the highest variety of SMAMs (75 species), followed by the tanezumi rat ( Rattus tanezumi ) (68 species). The top three SMAMs that infest the highest variety of small mammal species are Yersinia pestis (58 small mammal species), Bartonella grahamii (36 species), and Orientia tsutsugamushi (33 species). The 45 major species of small mammals were grouped into six ecological clusters based on their ecological niche, mainly driven by annual mean temperature, temperature seasonality, total precipitation, and elevation. Model-predicted presence areas for the 45 major small mammal species and two RBDs were 1-499% larger in geographic size than observed., Interpretation: The extensive intersection between small mammals and microbes with pathogenic potential in humans poses imminent threats to public health. Active field surveillance should be prioritized for potential high-risk areas identified in this study to prevent zoonotic transmission of SMAMs., Funding: National Key Research and Development Program of China; Natural Science Foundation of China; The U.S. Centers for Disease Control and Prevention., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)

Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder primarily linked with mutations in Exostosin-1 (EXT1) and Exostosin-2 (EXT2) genes. However, not all HME cases can be explained by these mutations, and its pathogenic mechanisms are not fully understood. Herein, utilizing whole-exome sequencing and genetic screening with a family trio design, we identify two novel rare mutations co-segregating with HME in a Chinese family, including a nonsense mutation (c.204G>A, p.Trp68*) in EXT1 and a missense mutation (c.893T>G, p.Phe298Cys) in FUT7. Functional assays reveal that the FUT7 mutation affects the cellular localization of FUT7 protein and regulates cell proliferation. Notably, the simultaneous loss of fut7 and ext1 in a zebrafish model results in severe chondrodysplasia, indicating a functional link between FUT7 and EXT1 in chondrocyte regulation. Additionally, we unveil that FUT7 p.Phe298Cys reduces EXT1 expression through IL6/STAT3/SLUG axis at the transcription level and through ubiquitination-related proteasomal degradation at the protein level. Together, our findings not only identify novel germline mutations in FUT7 and EXT1 genes, but also highlight the critical interaction between these genes, suggesting a potential 'second-hit' mechanism over EXT1 mutations in HME pathogenesis. This insight enhances our understanding of the mechanisms underlying HME and opens new avenues for potential therapeutic interventions., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods used in the present study were in accordance with the relevant guidelines and regulations. This study was approved by the Ethics Committee for Clinical Research and Animal Trials of the First Affiliated Hospital of Sun Yat-sen University (permit NO. [2020]363). Informed consent was obtained from all the participants. All work involving zebrafish was reviewed and approved by the Animal Research Advisory Committee of the South China University of Technology., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The long-term production and extensive use have resulted in the widespread presence of bisphenols (BPs) in the environment. In order to clarify the pollution characteristics and potential sources of BPs, the national scale surface soil samples were collected in China in 2019. The results demonstrated that 32 target BPs existed widely in soil with the highest concentration for bisphenol A (BPA), and at least 2 BPs were detected in each sample. The total concentration of Σ 32 BPs (from 0.387 to 713 ng/g) exhibited a stepwise decrease from southeastern coast to inland regions, and due to the presence of more pollution sources concentrations of Σ 32 BPs in urban areas were slightly higher than rural areas. The different industrial structures (such as plastics, epoxy resins, and thermal paper) may be the important factors for the different pollution levels between southeastern coast and other regions. In addition, the high organic matter content in soil and low temperature may be the reasons for high concentrations of Σ 32 BPs in Northeast China. The results of source identification using the Positive Matrix Factorization model indicated that BPs in soil were originated from three sources: old sources represented by BPA, relatively new sources characterized by bisphenol S, and sources from specific industries using bisphenol F. The estimated daily intake indicated that BPA exposure through soil accounted for only a small proportion of the total exposure compared to other exposure routes, and the risk by BPA in soil can be negligible to human health. In summary, the study provided basic pollution information of BPs in Chinese surface soil for future related studies., 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.)

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1β, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1β, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1β involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Treating methicillin-resistant Staphylococcus aureus (MRSA) infection remains one of the most difficult challenges in clinical practice, primarily due to the resistance of MRSA to multiple antibiotics. Therefore, there is an urgent need to develop novel antibiotics with high efficacy and low cross-resistance rates. In this study, a series of novel pleuromutilin derivatives with coumarin structures were synthesized and subsequently assessed for their biological activities. Most of these derivatives showed potent antimicrobial activity against drug-resistant Gram-positive bacterial strains. Compound 14b displayed particularly rapid bactericidal effects, slow resistance development, and low cytotoxicity. Moreover, it decreased bacterial loads in the lung, liver, kidney, spleen, and heart and exhibited better antibacterial efficacy (ED 50 = 11.16 mg/kg) than tiamulin (ED 50 = 28.93 mg/kg) in a mouse model of systemic MRSA infection. Both in vitro and in vivo analyses suggest that compound 14b is a promising agent for the treatment of MRSA infections.

Introduction: The Calligonum species is a typical shrub with assimilative branches (ABs) in arid regions in Central Asia. The nutrient distribution patterns at different reproductive stages are of great significance for further understanding the ecological adaptation and survival strategies of plants., Methods: In the present study, a common garden experiment was employed to avoid interference by environmental heterogeneity. Furthermore, the nitrogen (N), phosphorus (P), and potassium (K) allocation characteristics in the supporting organs (mature branches), photosynthetic organs (ABs), and reproductive organs (flowers and fruits) of Calligonum caput-medusae (CC), Calligonum arborescens (CA), Calligonum rubicundum (CR), and Calligonum klementzii (CK) during the flowering, unripe fruit, and ripe fruit phases were systematically analyzed., Results: Aboveground organs were the main factors affecting the variation of N, P, and K concentrations and their stoichiometric ratios, and the reproductive stages were secondary factors affecting N, P, and the P:K ratio and species were secondary factors affecting K and the N:P and N:K ratios. Meanwhile, significant interactions were found for all three of the aforementioned factors. The N and P concentrations in the ABs of the four species were highest during the flowering phase, while the N:P ratio was lowest, which then gradually decreased and increased, respectively, during plant growth. This result supported the growth rate hypothesis, i.e., that the growth rate is highest during the early growth stage. In the growth period, the N, P, and K concentrations in each organ of the four Calligonum species followed the power law, with the allocation rates of N and P being generally higher than K. There were differences among the species as the N-P scaling exponent in the ABs of CR was only 0.256; according to the scaling exponent law, this species was the least stressed and had the strongest environmental adaptability. Overall, the adaptability of the four species could be ranked as CR > CA > CC > CK. In conclusion, there were significant differences in nutrient traits among different aboveground organs, species, and reproductive stages., Discussion: The results of this study contribute to a deeper understanding of the nutrient allocation strategies of different Calligonum species and provide scientific evidence for the ex-situ conservation and fixation application of these species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang, Jin, Wang, Zhang and Wang.)

To determine the efficacy and adverse consequences between KangDuo and Da Vincii surgical robotic systems in facilitating radical prostatectomy. All the papers, that were included in the current analysis, were identified with PubMed, Embase, and the Cochrane Library through October 1, 2024. To make the comparison easier, only the English-language articles have been used for the analysis and only those focusing on comparing the use of the KangDuo and da Vinci robotic systems in radical prostatectomy were used. There are several avenues of bias when considering articles to include, when selecting the articles for this study to adopt the RCTs and cohort studies and excluding the others, the bias selection targeted was minimal. For the systematic review, 1 cohort study was found as well as 2 RCTs were found that involved 150 adult patients assigned to undergo urological surgery. Of those, 76 patients operated by the Kang Duo robotic system, and the remaining 74 patients operated by the Da Vinci system. In conclusion from this study, it was noted that though there was an increase in the operative time used in the KangDuo system, the estimated blood loss, number of days needed to stay in hospital, and the incidences of postoperative complications were comparable to the other system. Compared to the da Vinci robotic system, the KangDuo robotic system, while associated with longer operative times for radical prostatectomy, showed no significant difference in perioperative or short-term outcomes. In addition, the KangDuo system is more cost-effective and easier to implement in developing countries or other regions. However, further high-quality studies are needed to confirm these findings., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise gene targeting into the Rosa26 locus via embryonic stem (ES) cells under the control of the elongation factor 1α (EF1α) promoter. The Tert knock-in (TertKI) mice harboring the EF1α-Tert gene displayed elevated telomerase activity, elongated telomeres, and extended lifespan, with no spontaneous genotoxicity or carcinogenicity. The TertKI mice showed also enhanced wound healing, characterized by significantly increased expression of Fgf7, Vegf, and collagen. Additionally, TertKI mice exhibited robust resistance to the progression of colitis induced by dextran sodium sulfate (DSS), accompanied by reduced expression of disease-deteriorating genes. These findings foreshadow the potential of TertKI as an extraordinary rejuvenation force, promising not only longevity but also rejuvenation in skin and intestinal aging., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Chronic kidney disease (CKD) represents a significant global public health burden, affecting over 10% of the world's population. Its high morbidity, multifactorial complications, and substantial mortality impose significant burdens on healthcare systems and patients, necessitating considerable investment in healthcare resources. Renal fibrosis (RF) is a key pathological feature and driver of CKD progression. Extensive research indicates that autophagy participates in the complete pathogenesis of RF. Under physiological conditions, autophagy is essential for maintaining renal cellular homeostasis. However, under pathological conditions, perhaps aberrant and sustained activation of autophagy contributes to oxidative stress, apoptosis, inflammation, etc. Ultimately, they accelerate the development of RF. The role of autophagy in RF is currently controversial. This review investigates the molecular mechanisms by which intrinsic renal cell autophagy contributes to RF across diverse disease models, suggesting that autophagy and its associated regulatory pathways represent potential diagnostic and therapeutic targets for CKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhou, Huang, Liao, Chen and Ma.)

Objective: To understand the current knowledge, attitude, and practice (KAP) on influenza and influenza vaccine among pregnant women in Suzhou and to analyze its influencing factors to provide technical support data for public health strategies for promoting influenza vaccination in pregnant women. Methods: A questionnaire was designed, and a stratified sampling method was used to conduct a face-to-face survey among pregnant women at different stages of pregnancy who received antenatal examinations at different levels of medical institutions in Suzhou, Jiangsu Province, in 2023. KAP status and influencing factors were analyzed by χ ² test and logistic regression analysis. Results: A total of 2 195 valid questionnaires were collected in this survey. The M ( Q 1 , Q 3 ) of knowledge about influenza and influenza vaccine among pregnant women in Suzhou was 7.60 (5.23, 9.80) points, and the score range was 0.20-14.71 points, the passing rate was 34.12%, the awareness rate of influenza vaccine was 57.45%, and the vaccination rate of influenza vaccine was 1.91% within one year before the survey. The willingness to receive influenza vaccine during pregnancy was only 3.57%. Multivariate analysis of influenza and influenza vaccine-related knowledge scores showed that the passing rate was positively correlated with education level and gestational age. In contrast, family income was negatively correlated with living in rural areas, working as migrant workers, and having no medical insurance. Multivariate analysis of vaccination intention showed that decreased effectiveness of influenza vaccine and increased adverse reactions decreased vaccination intention during pregnancy. Conclusions: The pregnant women in Suzhou pay more attention to influenza, and vaccination rates and intentions are generally low. Pregnant women with early and second trimester of pregnancy, low education, living in rural areas, working as migrant workers, and not purchasing medical insurance are the key groups to popularize the knowledge about influenza and influenza vaccine.

Objective: To explore the clinical application pathway of the CT generative adversarial networks (CTGANs) algorithm in mandibular reconstruction surgery, aiming to provide a valuable reference for this procedure. Methods: A clinical exploratory study was conducted, 27 patients who visited the Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University between January 2022 and January 2024 and required mandibular reconstruction were selected. The cohort included 16 males and 11 females, with the age of (46.6±11.5) years; among them, 7 cases involved mandibular defects crossing the midline. The CTGANs generator produced 100 images, and the mean squared error (MSE) was calculated for differences between any two generated images. Preoperative cone-beam CT data from 5 patients were used to construct a labeled test database, divided into groups: normal maxilla, normal mandible, diseased mandible, and noise (each group containing 70 cross-sectional images). The CTGANs discriminator was used to evaluate the loss values for each group, and one-way ANOVA and intergroup comparisons were performed. Using the self-developed KuYe multioutcome-option-network generation system (KMG) software, the three-dimensional (3D) completion area of the mandible under cone-beam CT was defined for the 27 patients. The CTGANs algorithm was applied to obtain a reference model for the mandible. Virtual surgery was then performed, utilizing the fibular segment to reconstruct the mandible and design the surgical expectation model. The second-generation combined bone-cutting and prebent reconstruction plate positioning method was used to design and 3D print surgical guides, which were subsequently applied in mandibular reconstruction surgery for the 27 patients. Postoperative cone-beam CT was used to compare the morphology of the reconstructed mandible with the surgical expectation model and the mandibular reference model to assess the three-dimensional deviation. Results: The MSE for the CTGANs generator was 2 411.9±833.6 (95% CI : 2 388.7-2 435.1). No significant difference in loss values was found between the normal mandible and diseased mandible groups ( P >0.05), while both groups demonstrated significantly lower loss values than the maxilla and noise groups ( P <0.001). All 27 patients successfully obtained mandibular reference models and surgical expectation models. In total, 14 162 negative deviation points and 15 346 positive deviation points were observed when comparing the reconstructed mandible morphology with the surgical expectation model, with mean deviations of -1.32 mm (95% CI :-1.33- - 1.31 mm) and 1.90 mm (95% CI : 1.04-1.06 mm), respectively. Conclusions: The CTGANs algorithm is capable of generating diverse mandibular reference models that reflect the natural anatomical characteristics of the mandible and closely match individual patient morphology, thereby facilitating the design of surgical expectation models. This method shows promise for application in patients with mandibular defects crossing the midline.

Acute lung injury (ALI) is an inflammatory disorder accompanied by higher morbidity and mortality. The pathological mechanism of ALI has been reported to be associated with the release of inflammatory cytokines by macrophages. Sesquiterpene lactones (SLs) represent the principal anti-inflammatory components of many natural products. Tulipalin A is a natural small molecule and a conserved moiety in anti-inflammatory SLs. However, the anti-inflammatory potential of Tulipalin A has yet to be fully disclosed. The present study aims to investigate TulipalinA's anti-inflammatory activity and underlying mechanisms in vitro and in vivo. Tulipalin A suppressed inflammatory responses in lipopolysaccharide (LPS)-stimulated bone marrow-derived primary macrophages and ameliorated LPS-induced ALI in mice. Mechanistically, Tulipalin A directly targets the NF-κB p65 and disrupts its DNA binding activity, thereby impeding the activation of NF-κB. Inhibition of NF-κB attenuated M1 polarization of macrophages, consequently suppressing the production of pro-inflammatory mediators and ameliorating the onset and progression of ALI. These findings suggest Tulipalin A's potential to mitigate inflammatory disorders like ALI via targeting NF-κB p65 and disrupting its DNA binding activity., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pyroptosis has been found to contribute to myocardial ischemia/reperfusion (I/R) injury, but the exact mechanisms that initiate myocardial pyroptosis are not fully elucidated. Sonic hedgehog (SHH) signaling is activated in heart suffered I/R, and intervention of SHH signaling has been demonstrated to protect heart from I/R injury. Caspase recruitment domain-containing protein 10 (CARD10)-B cell lymphoma 10 (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex could transduce signals from the membrane and induce inflammatory pathways in non-hematopoietic cells, which could be a downstream effector of SHH signaling pathway. This study aims to explore the role of SHH signaling in I/R-induced myocardial pyroptosis and its relationship with the CBM complex. C57BL/6J mice were subjected to 45 min-ischemia followed by 24 h-reperfusion to establish a myocardial I/R model, and H9c2 cells underwent hypoxia/reoxygenation (H/R) to mimic myocardial I/R model in vitro. Firstly, SHH signaling was significantly activated in heart suffered I/R in an autocrine- or paracrine-dependent manner via its receptor PTCH1, and inhibition of SHH signaling decreased myocardial injury via reducing caspase-11-dependent pyroptosis, concomitant with attenuating CBM complex formation. Secondly, suppression of SHH signaling decreased protein kinase C α (PKCα) level, but inhibition of PKCα attenuated CBM complex formation without impacting the protein levels of SHH and PTCH1. Finally, disruption of the CBM complex prevented MALT1 from recruiting of TRAF6, which was believed to trigger the caspase-11-dependent pyroptosis. Based on these results, we conclude that inhibition of SHH signaling suppresses pyroptosis via attenuating PKCα-mediated CARD10-BCL10-MALT1 complex formation in mouse heart suffered I/R., 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.)

Objective: This study aimed to examine the levels of solute carrier family seven number 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the serum of patients with acute ischaemic stroke (AIS) and their relationship with disease severity., Methods: A total of 148 patients with AIS together with 148 healthy controls (HCs) were enrolled. The expression levels of SLC7A11 and GPX4 in serum were detected immediately as early as possible. Radiographic severity was detected by Alberta Stroke Program Early CT Score (ASPECTS). Disease severity was evaluated using modified Rankin Scale (mRS). High-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) expression levels were also measured. A correlation analysis was conducted to determine the relationship between the expression levels of SLC7A11 and GPX4 with the clinical severity of the disease and the levels of hs-CRP and MMP-9. Furthermore, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential of SLC7A11 and GPX4 as diagnostic markers., Results: Compared to the HC group, the serum expression levels of SLC7A11 and GPX4 were significantly lower in the AIS group. Serum SLC7A11 levels were positively associated with serum GPX4 levels. The AIS group included 50 patients with mild neurological impairment, 52 with moderate neurological impairment, and 46 with severe neurological impairment. AIS patients with mild neurological impairment had drastically higher serum SLC7A11 and GPX4 levels compared with those with moderate neurological impairment. AIS patients with moderate neurological impairment showed significantly higher serum SLC7A11 and GPX4 concentrations compared with those with severe neurological impairment. ROC curve analysis demonstrated that both serum SLC7A11 and GPX4 may both act as potential indicators for evaluating of AIS disease severity. In addition, both serum SLC7A11 and GPX4 levels were positively correlated with ASPECTS. Both serum SLC7A11 and GPX4 levels were negatively associated with hs-CRP as well as MMP-9 levels. Serum SLC7A11 and GPX4 levels were significantly increased following comprehensive therapy., Conclusions: Decreased SLC7A11 and GPX4 levels may reflect disease severity of AIS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This comprehensive study focused on evaluating and selecting seven distinct commercial membranes to develop BTESE/PA membranes. This method effectively facilitated the extraction of cynaroside from the complex composition of peony seed meal. We subsequently conducted a thorough investigation into its biological properties. These findings establish a robust foundation for future research and the development of related products. The peak concentration achieved by peony seed meal filtration (PSMF) was 234.84 ± 1.17 μg/mL. Among the commercial membranes evaluated, the PA membrane exhibited superior separation capabilities, leading to its selection for BTESE loading. Compared with BTESE treated with HCl and NH 3 , the HCl variant, once incorporated into the BTESE/PA membrane, enhanced cynaroside separation, achieving an impressive 90.23% recovery rate. A comprehensive investigation of the biological effects of cynaroside revealed its crucial antioxidant role, especially in SOD binding. Additionally, cynaroside has the potential to induce apoptosis in K562 cells through interactions with BCL-2 and CDK-2 enzymes. Pharmacophore screening revealed the affinity of cynaroside for the PDE5A, TNKS2, and DAPK1 proteins, suggesting that it has diverse potential applications., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

This study explores the main surface markers in the hemodialysis puncture catheterization pathway and the relative spatial position of venous vessels in the puncture results, providing data support for venous puncture. Seventy cadavers were studied; angles of vertical axis with superior vena cava, left and right brachiocephalic vein at the confluence and circumference of superior vena cava were the primary parameters. Bivariate correlation analysis was used to determine in relation to other body parameters, and a regression equation was also obtained. The angle of the vertical axis with the superior vena cava at the confluence was linearly correlated with the distances between the coracoid processes and the jugular notch to coracoid processes. The angle of the vertical axis with left brachiocephalic vein was linearly correlated with the thickness of thorax and the length from the upper pericardial margin to the confluence. The angle of the vertical axis with right brachiocephalic vein was correlated with clavicular midline length, acromial distance, intersection point of clavicle to clavicular midline, confluence to clavicular midline, superior edge of the blood vessels to superior edge of clavicle at the right intersection, and superior edge of pericardium to confluence. There is a linear relationship between the superior vena cava circumference and the distance from the superior vena cava to the aorta. A number of parameters influence angles of the vertical axis with superior vena cava, left and right brachiocephalic veins and the superior vena cava circumference which can provide guidance for intubation., Competing Interests: Declarations. Ethics approval and consent to participate: This study has been approved by the Ethics Committee of Zhengzhou University, and the informed consent of the next of kin of the research subject has been obtained, allowing the data in this paper to be used and published. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ligustilide, a phthalide compound extracted from Umbelliferae plants such as Angelica sinensis and Ligusticum chuanxiong, has been proven to possess various pharmacological activities, such as anti-inflammatory, anti-tumor, anti-atherosclerosis, anti-ischemic stroke injury, and anti-Alzheimer's disease properties. In recent years, it has shown great potential, particularly in the treatment of locomotor system diseases. Studies have shown that ligustilide has significant therapeutic effects on various locomotor system diseases, including osteoporosis, osteoarthritis, femoral head necrosis, osteosarcoma, and muscle aging and injury. Its mechanisms of action include enhancing the differentiation ability of osteoblasts(OBs), inhibiting the formation ability of osteoclasts(OCs), downregulating inflammatory factors, promoting the synthesis of extracellular matrix(ECM), improving local blood supply to the femoral head, balancing lipid metabolism, inhibiting the proliferation and migration of osteosarcoma cells, inducing cell cycle arrest, enhancing glucose utilization in skeletal muscle, and regulating autophagy and apoptosis. However, its clinical application is severely limited by drawbacks such as structural instability, poor water solubility, and low bioavailability. Currently, formulation techniques such as dripping pills, micropills, inclusion complexes, and liposomes are being used to improve its stability and water solubility, thereby enhancing its therapeutic efficacy. This article summarized the effects, mechanisms of action, and pharmacokinetics of ligustilide monomers and preparations in the treatment of locomotor system diseases in China and abroad in recent years, aiming to provide reference and guidance for further development and application of ligustilide in this field.

Background: Relapse was the major cause of treatment failure in patients with myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring. The most used first-line regimens for MRD are immunotherapies. However, for patients who were ineligible for or failed in first-line immunotherapies, options were limited., Methods: A total of 20 patients with myeloid malignancies with recurrent MRD after allo-HSCT were included in this study. The safety and efficacy of venetoclax-based regimens were analyzed., Results: There were 13 patients (65%) treated with venetoclax combined with hypomethylating agents concomitantly and seven patients (35%) treated with venetoclax monotherapy. After venetoclax-based regimens, MRD was eliminated in 11 patients (55%) with 6 subsequently developing recurrent MRD and 5 remaining in molecular remission. MRD declined in two patients (10%), and no responses in seven patients (35%). Among the two patients with declined MRD, one patient finally eliminated MRD after two cycles of the venetoclax-based regimen, and the other patient's MRD further declined after the second regimen. The objective response rate (ORR) was 65%. The median duration of response was 103 (12-313) days. The incidences of grades 3-4 neutropenia, anemia, and thrombocytopenia independently of pretreatment status were 30%, 20% and 20%, respectively., Conclusion: Venetoclax-based regimens are efficient and safe for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT.

Rationale and Objectives: Perineural invasion (PNI) is an important prognostic biomarker for prostate cancer (PCa). This study aimed to develop and validate a predictive model integrating biparametric MRI-based deep learning radiomics and clinical characteristics for the non-invasive prediction of PNI in patients with PCa., Materials and Methods: In this prospective study, 557 PCa patients who underwent preoperative MRI and radical prostatectomy were recruited and randomly divided into the training and the validation cohorts at a ratio of 7:3. Clinical model for predicting PNI was constructed by univariate and multivariate regression analyses on various clinical indicators, followed by logistic regression. Radiomics and deep learning methods were used to develop different MRI-based radiomics and deep learning models. Subsequently, the clinical, radiomics, and deep learning signatures were combined to develop the integrated deep learning-radiomics-clinical model (DLRC). The performance of the models was assessed by plotting the receiver operating characteristic (ROC) curves and precision-recall (PR) curves, as well as calculating the area under the ROC and PR curves (ROC-AUC and PR-AUC). The calibration curve and decision curve were used to evaluate the model's goodness of fit and clinical benefit., Results: The DLRC model demonstrated the highest performance in both the training and the validation cohorts, with ROC-AUCs of 0.914 and 0.848, respectively, and PR-AUCs of 0.948 and 0.926, respectively. The DLRC model showed good calibration and clinical benefit in both cohorts., Conclusion: The DLRC model, which integrated clinical, radiomics, and deep learning signatures, can serve as a robust tool for predicting PNI in patients with PCa, thus aiding in developing effective treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×10 10 viral particles) and B.1.1.529 variant (5×10 10 viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×10 10 viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

Background and Aim: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF., Methods: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction., Results: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM., Conclusion: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)