Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

The incidence of tumors among the elderly is notably high, presenting significant challenges in terms of harm, complexity, and treatment.The processes of diagnosis and treatment often lack a precise clinical foundation and robust experimental evidence, resulting in numerous difficulties and dilemmas.A collaborative approach that integrates traditional Chinese and Western medicine, leveraging the strengths of both, can substantially alleviate these challenges and ensure that elderly cancer patients can undergo systematic, comprehensive, and intensive cancer treatments.Traditional Chinese medicine can play a vital role throughout the entire continuum of diagnosis and treatment for elderly cancer patients, whether by leading, assisting, or complementing other treatment modalities.This article employs the concepts of ′righteousness′and ′evil′from traditional Chinese medicine, where ′righteousness′signifies the ′state of a person′and ′evil ′denotes the ′state of a tumor′.We systematically explore collaborative diagnosis and treatment strategies that integrate traditional Chinese and Western medicine for tumor management in the elderly, categorizing the approaches into four conditions: strong righteousness with strong evil, strong righteousness with weak evil, weak righteousness with strong evil, and weak righteousness with weak evil.In cases where both righteousness and evil are strong, the treatment strategy is primarily dominated by Western medicine, with support from traditional Chinese medicine.Conversely, when righteousness is strong and evil is weak, the strategy entails a combination of both Chinese and Western medicine.In situations characterized by weak righteousness and strong evil, the treatment approach is largely guided by traditional Chinese medicine, while also considering equal attention to both modalities.Finally, when both righteousness and evil are weak, the coordinated diagnosis and treatment strategy is primarily based on Chinese medicine, with Western medicine adapting to the circumstances and intervening appropriately throughout the process.By accurately assessing the concepts of ′righteousness′and ′evil′and implementing collaborative diagnostic and treatment strategies that integrate both traditional Chinese and Western medicine, we can significantly enhance the physical condition of elderly cancer patients.This comprehensive approach not only boosts immunity and improves organ function but also increases tolerance to tumor treatments, alleviates complications, reduces adverse reactions, and ensures that elderly cancer patients can undergo systemic cancer treatment to its fullest extent.Ultimately, this strategy aims to improve prognosis, enhance quality of life, and extend the effective survival period.

Objective To explore the levels of γ-aminobutyric acid complex(GABA+),glutamate and glutamine(Glx)in the bilateral hippocampal region of patients with temporal lobe epilepsy(TLE),and to analyze the potential clinical correlation.Methods The levels of GABA+and Glx in the hippocampal region of 23 TLE patients(TLE group)and 20 healthy volunteers(control group)were measured by quantitative Meshcher-Garwood point resolved spectroscopy(MEGA-PRESS)sequence.The differences of metabolite levels in bilateral hippocampal region were compared.At the same time,the differences of metabolites in hippocampal region between control group,TLE affected subgroup and TLE unaffected subgroup were compared.Spearman correlation coefficient was used to evaluate the correlation between hippocampal region metabolite levels and clinical.Results The levels of two metabolites in bilateral hipp-ocampal region of the control group were symmetrical distribution.The GABA+level in the affected hippocampal region of the TLE group was significantly lower than that in the bilateral hippocampal region of the control group,and the Glx level in the affected hip-pocampal region of the TLE group was not significantly different from that of the control group.The level of GABA+in the affected hippocampal region of the TLE group was significantly lower than that of the unaffected[(1.65±0.85)i.u.vs(1.86±0.58)i.u.;(1.68±0.67)i.u.vs(1.80±0.81)i.u.];The level of GABA+in the affected hippocampal region of the TLE subgroup with cogni-tive impairment(CI)was significantly lower than that of the TLE subgroup with normal cognition,and there was no significant difference in Glx content between the two subgroups(P>0.05).The level of GABA+in the TLE subgroup with CI was negatively correlated with the course of disease and attack frequency(r=-0.90,P<0.05;r=-0.91,P<0.05).Conclusion The change of GABA+level in hippocampal region is a marker of TLE occurrence and disease progression,and is closely related to CI.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective To analyze the transcriptome sequencing results of Nelson Bay virus(NBV)-infected murine RAW264.7 mac-rophages,and to screen for differentially expressed genes(DEGs)to provide a theoretical basis for exploring the mechanism of innate immune response in reovirus infection.Methods RAW264.7 cells were infected with the NBV-Miyazaki virus strain at a multiplicity of infection(MOI)of 30.We used transcriptome sequencing technologies,with q＜0.05 and|log2FC|≥ 1,for screening the DEGs in the infection and control groups.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for enrichment analysis of DEGs.Results A total of 442 genes were differentially expressed in the infection group,of which 381 genes were significantly upregulated and 61 genes were significantly downregulated.In the GO analysis,the enrichment of DEGs was primarily related to the innate immune response,defense response to viruses,cytokine production,and cell response to cytokine stimulation.In the KEGG analysis,the enrichment of DEGs were primarily related to the Toll-like receptor,retinoid acid inducible gene Ⅰ-like receptor,PI3K/Akt,and other signaling pathways.Conclusion RAW264.7 macrophages infected with the NBV-Miyazaki virus can activate pattern recognition receptors;promote the release of cytokines,chemokines,and other immune-related factors;and enhance antibody-dependent cell-mediated cytotoxicity to exert an immune effect.This study provides a theoretical basis for exploring the mechanisms of innate immu-nity during NBV-Miyazaki virus infection.

Objective To explore the levels of γ-aminobutyric acid complex(GABA+),glutamate and glutamine(Glx)in the bilateral hippocampal region of patients with temporal lobe epilepsy(TLE),and to analyze the potential clinical correlation.Methods The levels of GABA+and Glx in the hippocampal region of 23 TLE patients(TLE group)and 20 healthy volunteers(control group)were measured by quantitative Meshcher-Garwood point resolved spectroscopy(MEGA-PRESS)sequence.The differences of metabolite levels in bilateral hippocampal region were compared.At the same time,the differences of metabolites in hippocampal region between control group,TLE affected subgroup and TLE unaffected subgroup were compared.Spearman correlation coefficient was used to evaluate the correlation between hippocampal region metabolite levels and clinical.Results The levels of two metabolites in bilateral hipp-ocampal region of the control group were symmetrical distribution.The GABA+level in the affected hippocampal region of the TLE group was significantly lower than that in the bilateral hippocampal region of the control group,and the Glx level in the affected hip-pocampal region of the TLE group was not significantly different from that of the control group.The level of GABA+in the affected hippocampal region of the TLE group was significantly lower than that of the unaffected[(1.65±0.85)i.u.vs(1.86±0.58)i.u.;(1.68±0.67)i.u.vs(1.80±0.81)i.u.];The level of GABA+in the affected hippocampal region of the TLE subgroup with cogni-tive impairment(CI)was significantly lower than that of the TLE subgroup with normal cognition,and there was no significant difference in Glx content between the two subgroups(P>0.05).The level of GABA+in the TLE subgroup with CI was negatively correlated with the course of disease and attack frequency(r=-0.90,P<0.05;r=-0.91,P<0.05).Conclusion The change of GABA+level in hippocampal region is a marker of TLE occurrence and disease progression,and is closely related to CI.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.