Intestinal permeability plays a pivotal role in the gut-liver axis and has emerged as a critical target for the prevention and treatment of liver diseases. Based on recent studies in China and globally， this article reviews the definitions and interrelationship of intestinal barrier function and intestinal permeability， the methods for assessing intestinal permeability， and the mechanism of action and clinical significance of intestinal permeability in the development and progression of various liver diseases. Studies have shown that increased intestinal permeability is a significant hallmark and an important driving factor for multiple liver diseases， and this state leads to the translocation of bacteria and harmful substances， trigger a systemic inflammatory response， and thus exacerbates liver injury， fibrosis， and metabolic dysregulation. Therefore， it is closely associated with the development and progression of metabolic associated fatty liver disease， alcoholic liver disease， autoimmune liver diseases， and their end-stage events， including liver cirrhosis， liver failure， and hepatocellular carcinoma. Future research should focus on the standardization of assessment methods， the exploration of underlying mechanisms， and the clinical translation of these findings.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

Objective To assess the global and Chinese disease burden of early-onset lung cancer(di-agnosed in patients aged 15-49 years)and its major risk factors.Methods Based on the GLOBOCAN 2022 and Global Burden of Disease(GBD)2021 datasets,we evaluated the disease burden and associated risk fac-tors of early-onset lung cancer globally and in China,stratified by age,sex,geographic location,and human development index(HDI).Key indicators included age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and disability adjusted life years(DALYs)attributable to risk factors.Results In 2022,there were 137 705 new cases and 72 646 deaths from early-onset lung cancer globally,with ASIR and ASMR of 3.43 per 100 000 and 1.82 per 100 000 population,respectively.The disease burden was higher in males than in females(ASIR:3.72 per 100 000 vs.3.14 per 100 000;ASMR:2.31 per 100 000 vs.1.33 per 100 000).High-HDI regions exhibited the highest ASIR(5.51 per 100 000)and ASMR(2.57 per 100 000),with health inequality analysis revealing a concentration of disease burden in higher-HDI areas.China bore the heaviest burden,accounting for 48.69%of global new cases and 35.77%of deaths.China's ASIR(8.21 per 100 000)and ASMR(3.17 per 100 000)exceeded global averages,with incidence higher in fe-males(8.78 per 100 000 vs.7.67 per 100 000)but mortality higher in males(4.01 per 100 000 vs.2.29 per 100 000).Smoking and ambient particulate matter pollution were the leading risk factors globally(DALYs contribution:42.01%and15.62%)and in China(DALYs contribution:46.78%and 20.84%).Globally,household air pollution ranked third,whereas in China,secondhand smoke replaced it as the third leading risk factor,with household air pollution dropping to fifth.Risk factor profiles varied significantly across age groups,with modifiable risks contributing less to disease burden in the 15-24 age group.Conclusions The burden of early-onset lung cancer varies markedly by sex,region,and HDI,with China facing a disproportionately high burden.Policymakers should prioritize equitable resource allocation and targeted interventions,particularly in tobacco control and air pollution mitigation,to enhance cancer prevention and control efforts.

BACKGROUND:Whether coiled-coil-helix-coiled-coil-helix domain-containing 2(CHCHD2)can regulate the neuroprotective role of PINK1/Parkin-mediated mitochondrial autophagy in Parkinson's disease remains unknown.OBJECTIVE:To explore the role and mechanisms of CHCHD2 in the 6-hydroxydopamine-induced Parkinson's disease cell model in mediating the PINK1/Parkin signaling pathway and its involvement in mitochondrial autophagy.METHODS:Utilizing recombinant plasmid transfection technology to overexpress or knockdown CHCHD2,SH-SY5Y cells were constructed with a Parkinson's disease model using 6-hydroxydopamine,and divided into control group,model group,overexpression negative control+6-hydroxydopamine group,knockdown negative control+6-hydroxydopamine group,overexpression CHCHD2+6-hydroxydopamine group,and knockdown CHCHD2+6-hydroxydopamine group.Western blot assay and RT-qPCR were used to detect CHCHD2 expression.Western blot assay was utilized to detect the protein expression of LC3Ⅰ/Ⅱ,p62,MFN1,COXIV,DRP1,PINK1,Parkin,TIM23,Bax,Bcl-2,and cleaved-caspase 3.CCK-8 assay,JC-1,and reactive oxygen species assay kits were used to measure cell viability,mitochondrial membrane potential,and reactive oxygen levels.Monodansylcadaverine staining was used to observe cell autophagy.Transmission electron microscopy was used to observe autophagolysosomes.RESULTS AND CONCLUSION:(1)Compared with the control group,cell activity,mitochondrial membrane potential,and the protein expression levels of CHCHD2,PINK1,and Parkin were decreased,and the levels of reactive oxygen species,apoptosis,and LC3Ⅰ/Ⅱ and p62 proteins were increased(P＜0.05),and the presence of autophagic lysosomes was observed in the model group.(2)Compared with the model group,overexpression of CHCHD2 could reduce the level of cellular reactive oxygen species,increase the mitochondrial membrane potential,and the expression levels of PINK1,Parkin,and MFN1 proteins,and observed an increase in mitochondrial autolysosomes,and the knockdown of CHCHD2 had the opposite effect with the increase of COXIV,TIM23 and p-DRP1 protein expression(P＜0.05).(3)Compared with the model group,overexpression of CHCHD2 reduced apoptosis,up-regulated Bcl-2,and down-regulated the expression of Bax and cleaved-caspase3 proteins,while knockdown of CHCHD2 had the opposite effect(P＜0.05).(4)The results suggest that CHCHD2 can play a neuroprotective role by promoting PINK1/Parkin-mediated mitochondrial autophagy,improving mitochondrial function,and alleviating apoptosis in 6-hydroxydopamine-induced Parkinson's disease cell models.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.

Objective To assess the global and Chinese disease burden of early-onset lung cancer(di-agnosed in patients aged 15-49 years)and its major risk factors.Methods Based on the GLOBOCAN 2022 and Global Burden of Disease(GBD)2021 datasets,we evaluated the disease burden and associated risk fac-tors of early-onset lung cancer globally and in China,stratified by age,sex,geographic location,and human development index(HDI).Key indicators included age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and disability adjusted life years(DALYs)attributable to risk factors.Results In 2022,there were 137 705 new cases and 72 646 deaths from early-onset lung cancer globally,with ASIR and ASMR of 3.43 per 100 000 and 1.82 per 100 000 population,respectively.The disease burden was higher in males than in females(ASIR:3.72 per 100 000 vs.3.14 per 100 000;ASMR:2.31 per 100 000 vs.1.33 per 100 000).High-HDI regions exhibited the highest ASIR(5.51 per 100 000)and ASMR(2.57 per 100 000),with health inequality analysis revealing a concentration of disease burden in higher-HDI areas.China bore the heaviest burden,accounting for 48.69%of global new cases and 35.77%of deaths.China's ASIR(8.21 per 100 000)and ASMR(3.17 per 100 000)exceeded global averages,with incidence higher in fe-males(8.78 per 100 000 vs.7.67 per 100 000)but mortality higher in males(4.01 per 100 000 vs.2.29 per 100 000).Smoking and ambient particulate matter pollution were the leading risk factors globally(DALYs contribution:42.01%and15.62%)and in China(DALYs contribution:46.78%and 20.84%).Globally,household air pollution ranked third,whereas in China,secondhand smoke replaced it as the third leading risk factor,with household air pollution dropping to fifth.Risk factor profiles varied significantly across age groups,with modifiable risks contributing less to disease burden in the 15-24 age group.Conclusions The burden of early-onset lung cancer varies markedly by sex,region,and HDI,with China facing a disproportionately high burden.Policymakers should prioritize equitable resource allocation and targeted interventions,particularly in tobacco control and air pollution mitigation,to enhance cancer prevention and control efforts.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

BACKGROUND:Whether coiled-coil-helix-coiled-coil-helix domain-containing 2(CHCHD2)can regulate the neuroprotective role of PINK1/Parkin-mediated mitochondrial autophagy in Parkinson's disease remains unknown.OBJECTIVE:To explore the role and mechanisms of CHCHD2 in the 6-hydroxydopamine-induced Parkinson's disease cell model in mediating the PINK1/Parkin signaling pathway and its involvement in mitochondrial autophagy.METHODS:Utilizing recombinant plasmid transfection technology to overexpress or knockdown CHCHD2,SH-SY5Y cells were constructed with a Parkinson's disease model using 6-hydroxydopamine,and divided into control group,model group,overexpression negative control+6-hydroxydopamine group,knockdown negative control+6-hydroxydopamine group,overexpression CHCHD2+6-hydroxydopamine group,and knockdown CHCHD2+6-hydroxydopamine group.Western blot assay and RT-qPCR were used to detect CHCHD2 expression.Western blot assay was utilized to detect the protein expression of LC3Ⅰ/Ⅱ,p62,MFN1,COXIV,DRP1,PINK1,Parkin,TIM23,Bax,Bcl-2,and cleaved-caspase 3.CCK-8 assay,JC-1,and reactive oxygen species assay kits were used to measure cell viability,mitochondrial membrane potential,and reactive oxygen levels.Monodansylcadaverine staining was used to observe cell autophagy.Transmission electron microscopy was used to observe autophagolysosomes.RESULTS AND CONCLUSION:(1)Compared with the control group,cell activity,mitochondrial membrane potential,and the protein expression levels of CHCHD2,PINK1,and Parkin were decreased,and the levels of reactive oxygen species,apoptosis,and LC3Ⅰ/Ⅱ and p62 proteins were increased(P＜0.05),and the presence of autophagic lysosomes was observed in the model group.(2)Compared with the model group,overexpression of CHCHD2 could reduce the level of cellular reactive oxygen species,increase the mitochondrial membrane potential,and the expression levels of PINK1,Parkin,and MFN1 proteins,and observed an increase in mitochondrial autolysosomes,and the knockdown of CHCHD2 had the opposite effect with the increase of COXIV,TIM23 and p-DRP1 protein expression(P＜0.05).(3)Compared with the model group,overexpression of CHCHD2 reduced apoptosis,up-regulated Bcl-2,and down-regulated the expression of Bax and cleaved-caspase3 proteins,while knockdown of CHCHD2 had the opposite effect(P＜0.05).(4)The results suggest that CHCHD2 can play a neuroprotective role by promoting PINK1/Parkin-mediated mitochondrial autophagy,improving mitochondrial function,and alleviating apoptosis in 6-hydroxydopamine-induced Parkinson's disease cell models.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.