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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-rui Cao wei-Xiong Zheng Min-Jie Zhao Jun-hua Gong Cong Chen Zhong-Jun Wu rui Tao Department of Hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China Department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c Department of Hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2018-2037页

作者： Li Wang wei-hua Gong Department of Emergency The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Surgery The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell line

关键词： Ferroptosis Gastric cancer Helicobacter pylori infection Immune checkpoint protein Prognostic model Ferroptosis-related gene prognostic index

Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-hua Deng Shi-Hui Hao Jie-wei Chen Xiao-Dan Ma wei-Tao Zhuang Jing-hua Cao Yong-rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-wei Wang Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer development.Circular RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still lacking.Processing bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and RNA.Previous evidence suggests a connection between PBs dynamics and cancer progression.Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC.Herein,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient survival.Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells.Importantly,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the cytoplasm.Specifically,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins.The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC cells.Clinically,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival.Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

Different timing for abdominal paracentesis catheter placement and drainage in severe acute pancreatitis complicated by intraabdominal fluid accumulation

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 134-142页

作者： rui Chen hua-Qiang Chen rui-Die Li Hui-Min Lu Department of General Surgery Chengdu Sixth People’s HospitalChengdu 610058Sichuan ProvinceChina West China Center of Exellence for Pancreatitis Institute of Integrated Traditional Chinese and Western MedicineWest ChinaDivision of Pancreatic SurgeryDepartment of General SurgeryWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina HospitalSichuan University

BACKGROUND Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis(SAP).However,there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter place-ment and drainage.AIM To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumu-lation.METHODS Using a retrospective approach,184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement:group A(catheter placement within 2 d of symptom onset,n=89),group B(catheter placement between days 3 and 5 after symptom onset,n=55),and group C(catheter placement between days 6 and 7 after symptom onset,n=40).The differences in progression rate,mortality rate,and the number of cases with organ dysfunction were compared among the three groups.RESULTS The progression rate of group A was significantly lower than those in groups B and groups C(2.25%vs 21.82%and 32.50%,P0.05).At postoperative day 3,the levels of C-reactive protein(55.41±19.32 mg/L vs 82.25±20.41 mg/L and 88.65±19.14 mg/L,P<0.05),procalcitonin(1.36±0.51 ng/mL vs 3.20±0.97 ng/mL and 3.41±0.98 ng/mL,P<0.05),tumor necrosis factor-alpha(15.12±6.63 pg/L vs 22.26±9.96 pg/L and 23.39±9.12 pg/L,P<0.05),interleukin-6(332.14±90.16 ng/L vs 412.20±88.50 ng/L and 420.08±87.65ng/L,P<0.05),interleukin-8(415.54±68.43 ng/L vs 505.80±66.90 ng/L and 510.43±68.23ng/L,P<0.05)and serum amyloid A(270.06±78.49 mg/L vs 344.41±81.96 mg/L and 350.60±80.42 mg/L,P<0.05)were significantly lower in group A compared to those in groups B and group C.The length of hospital stay in group A was significantly lower than

关键词： Abdominal paracentesis catheter drainage Timing Severe acute pancreatitis Intra-abdominal fluid Application value

Identifying the best common factor model via exploratory eactor analysis

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Applied Mathematics(A Journal of Chinese Universities) 2024年第1期39卷 24-33页

作者： HE Bao-hua TANG rui TAGN Qi-yi School of Big Data Fuzhou University of International Studies and TradeFuzhou 350202China School of Mathematics Sun Yat-Sen UniversityGuangzhou 510275China Department of Computer Science University of BathUK Institute of Insect Science Zhejiang UniversityHangzhou 310058China.

Currently,there is no solid criterion for judging the quality of the estimators in factor analysis.This paper presents a new evaluation method for exploratory factor analysis that pinpoints an appropriate number of factors along with the best method for factor extraction.The proposed technique consists of two steps:testing the normality of the residuals from the fitted model via the Shapiro-Wilk test and using an empirical quantified index to judge the quality of the factor model.Examples are presented to demonstrate how the method is implemented and to verify its effectiveness.

关键词： factor analysis Shapiro-Wilk normality residuals

Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

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Zoological Research 2024年第2期45卷 242-252页

作者： Xiu-Sheng Chen rui Han Yan-Ting Liu wei huang Qi Wang Xin Xiong Ying Zhang Jian-Guo Zhao Shi-hua Li Xiao-Jiang Li wei-Li Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

关键词： PINK1 Parkin Mitochondria Phosphorylation Non-human primates Pigs

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Mechanism of local solidification time variations with melt rate during vacuum arc remelting process of 8Cr4Mo4V high-strength steel

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Journal of Iron and Steel Research(International) 2024年第2期31卷 377-388页

作者： Tao Pan Hong-chun Zhu Zhou-hua Jiang hua-bing Li rui Zhang Hao Feng School of Metallurgy Northeastern UniversityShenyang110819LiaoningChina State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang110819LiaoningChina

A 2D axisymmetric numerical model was established to investigate the variations of molten pool with different melt rates during the vacuum arc remelting of 8Cr4Mo4V high-strength steel,and the ingot growth was simulated by dynamic mesh techniques.The results show that as the ingot grows,the molten pool profile changes from shallow and flat to V-shaped,and both the molten pool depth and the mushy width increase.Meanwhile,the variation of both the molten pool shape and the mushy width melt rate is clarified by the thermal equilibrium analysis.As melt rate increases,both the molten pool depth and the mushy width increase.It is caused by the increment in sensible heat stored in the ingot due to the limitation of the cooling capacity of the mold.The nonlinear increment in sensible heat leads to a nonlinear increase in the mushy width.In addition,as melt rate increases,the local solidification time(LST)of ingot decreases obviously at first and then increases.When melt rate is controlled in a suitable range,LST is the lowest and the secondary dendrite arm spacing of the ingot is the smallest,which can effectively improve the compactness degree of 8Cr4Mo4V high-strength steel.

关键词： 8Cr4Mo4V high-strength steel Vacuum arc remelting process Melt rate Molten pool Local solidification time

MdbHLH162 connects the gibberellin and jasmonic acid signals to regulate anthocyanin biosynthesis in apple

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Journal of Integrative Plant Biology 2024年第2期66卷 265-284页

作者： Jian-Ping An rui-rui Xu Xiao-Na Wang Xiao-wei Zhang Chun-Xiang You Yuepeng Han Apple technology innovation center of Shandong Province College of Horticulture Science and EngineeringShandong Agricultural UniversityTai-An 271018China CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenHubei Hongshan LaboratoryThe Innovative Academy of Seed Design of Chinese Academy of SciencesWuhan 430074China College of Biology and Oceanography Weifang UniversityWeifang 261061China

Anthocyanins are secondary metabolites induced by environmental stimuli and developmental signals.The positive regulators of anthocyanin biosynthesis have been reported,whereas the anthocyanin repressors have been neglected.Although the signal transduction pathways of gibberellin(GA)and jasmonic acid(JA)and their regulation of anthocyanin biosynthesis have been investigated,the cross-talk between GA and JA and the antagonistic mechanism of regulating anthocyanin biosynthesis remain to be investigated.In this study,we identified the anthocyanin repressor MdbHLH162 in apple and revealed its molecular mechanism of regulating anthocyanin biosynthesis by integrating the GA and JA signals.MdbHLH162 exerted passive repression by interacting with MdbHLH3 and MdbHLH33,which are two recognized positive regulators of anthocyanin biosynthesis.MdbHLH162 negatively regulated anthocyanin biosynthesis by disrupting the formation of the anthocyanin-activated MdMYB1-MdbHLH3/33complexes and weakening transcriptional activation of the anthocyanin biosynthetic genes MdDFR and MdUF3GT by MdbHLH3 and MdbHLH33.The GA repressor MdRGL2a antagonized MdbHLH162-mediated inhibition of anthocyanins by sequestering MdbHLH162 from the MdbHLH162-MdbHLH3/33 complex.The JA repressors MdJAZ1 and MdJAZ2 interfered with the antagonistic regulation of MdbHLH162 by MdRGL2a by titrating the formation of the MdRGL2a-MdbHLH162 complex.Our findings reveal that MdbHLH162 integrates the GA and JA signals to negatively regulate anthocyanin biosynthesis.This study provides new information for discovering more anthocyanin biosynthesis repressors and explores the cross-talk between hormone signals.

关键词： anthocyanin biosynthesis bHLH transcription factor gibberellin jasmonic acid regulatory network transcriptional regulation

New role of platelets in schizophrenia:predicting drug response

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General Psychiatry 2024年第2期37卷 197-206页

作者： Yamin Zhang Yanghao Zheng Peiyan Ni Sugai Liang Xiaojing Li hua Yu wei wei Xueyu Qi Xueli Yu rui Xue Liansheng Zhao wei Deng Qiang Wang Wanjun Guo Tao Li Department of Neurobiology Zhejiang University School of Medicine Affiliated Mental Health Centre&Hangzhou Seventh People's HospitalHangzhouZhejiangChina Liangzhu Laboratory Zhejiang University MOE Frontier Science Center for Brain Science and Brain Machine IntegrationHangzhouZhejiangChina Mental Health Center and Psychiatric Laboratory West China Hospital of Sichuan UniversityChengduSichuanChina

Background Elevated platelet count(PLTc)is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis.However,the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups.Each group received one of seven antipsychotic treatments and was assessed at 2,4 and 6 weeks.Clinical symptoms were evaluated using the positive and negative syndrome scale(PANSS).Additionally,we measured blood cell counts and metabolic parameters,such as blood lipids.Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes,while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole(F=6.00,p=0.003),ziprasidone(F=7.10,p<0.001)and haloperidol(F=3.59,p=0.029).It exhibited a positive association with white blood cell count and metabolic indicators.Higher baseline PLTc was observed in non-responders,particularly in those defined by the PANSS-negative subscale.In the structural equation model,PLTc,white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores.Moreover,higher baseline PLTc was observed in individuals with less metabolic change,although this association was no longer significant after accounting for baseline metabolic values.Conclusions Platelet parameters,specifically PLTc,are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia.Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation.Given PLTc’s easy measur

关键词： schizophrenia assessed treatment