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SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

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World Journal of Gastroenterology 2024年第3期30卷 252-267页

作者： Qing Gu Huan Xia Yue-Qiong Song Jun Duan Yun Chen You Zhang He-Ping Chen Li Zhang Department of Elderly Digestive Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and TechnologyChengdu 610072Sichuan ProvinceChina Geriatrics Research Institute Sichuan Provincial People’s HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

关键词： Ulcerative colitis SLC6A1 NLRP3 Pyroptosis Inflammasome

Association analysis of genetic variants in critical patients with COVID-19 and validation in a Chinese population

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Virologica Sinica 2024年第2期39卷 347-350页

作者： Yi Yin Yi Zhang Lelin Sun Shuqiang Wang Yong Zeng Bo Gong Lulin Huang Yongquan He Zhenglin Yang Center for Natural Products Research Chengdu Institute of BiologyChinese Academy of SciencesChengdu610213China sichuan Provincial Key Laboratory for Human Disease Gene Study Center for Medical GeneticsDepartment of Laboratory MedicineSichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China Research Unit for Blindness Prevention of Chinese academy of Medical sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China University of Chinese academy of sciences Beijing100049China Infectious Disease Department Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China Department of Ophthalmology Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China

Dear Editor,Genome-wide association studies(GWASs)have reported a genetic association between certain populations and the severity of COVID-19.In severe patients,changes in the locus 3p21.31(including SLC6A20,LZTFL1,CCR9,FYCO1,CXCR6,and XCR1)are associated with COVID-19 hospitalization(Ellinghaus et al.,2020).Moreover,variations in 9p34.2 region(including genes related to the ABO blood grouping)can affect both susceptibility and severity of COVID-19;in particular,individuals with blood group A may have an increased risk of COVID-19 infection,while those with blood group O may have a protective effect(Ellinghaus et al.,2020;Shelton et al.,2021).

关键词： patients protective

Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

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Neural Regeneration Research 2024年第1期19卷 220-225页

作者： Yin Yang Zhaoxi Yang Maoxia Lv Ang Jia Junjun Li Baitao Liao Jing’an Chen Zhengzheng Wu Yi Shi Yang Xia Dezhong Yao Ke Chen Department of Ophthalmology Sichuan Provincial People’s HospitalMedical SchoolUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina The Clinical Hospital of Chengdu Brain science Institute MOE Key Lab for NeuroInformationSchool of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Research Unit of NeuroInformation Chinese Academy of Medical SciencesChengduSichuan ProvinceChina Institute of Basic Medical sciences Chinese academy of Medical sciences School of Basic Medicine Peking Union Medical CollegeBeijingChina Health Management Center Sichuan Provincial Key Laboratory for Human Disease Gene StudySichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Research Unit for Blindness Prevention of Chinese academy of Medical sciences(2019RU026) Sichuan Academy of Medical SciencesChengduSichuan ProvinceChina School of Electrical Engineering Zhengzhou UniversityZhengzhouHenan ProvinceChina

Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.

关键词： DBA/2J degeneration gamma band oscillations glaucoma primary visual cortex(V1) retina single-unit recording tuning curve

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

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Neural Regeneration Research 2024年第2期19卷 282-288页

作者： Zhuoyang Yu Yan Teng Jing Yang Lu Yang Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Laboratory of Aging Research School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

关键词： adult neurogenesis Alzheimer’s disease amyotrophic lateral sclerosis exosome Huntington’s disease neurodegenerative disease neurogenic niches Parkinson’s disease

Extensive prediction of drug response in mutation-subtype-specific LUAD with machine learning approach

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Oncology Research 2024年第2期32卷 409-419页

作者： KEGANG JIA YAWEI WANG QI CAO YOUYU WANG Department of Thoracic Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina School of Medicine University of Electronic Science and Technology of ChinaChengduChina Department of Assisted Reproductive Medicine Sichuan Provincial Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengduChina

Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide.Therapeutic failure in lung cancer(LUAD)is heavily influenced by drug resistance.This challenge stems from the diverse cell populations within the tumor,each having unique genetic,epigenetic,and phenotypic profiles.Such variations lead to varied therapeutic responses,thereby contributing to tumor relapse and disease progression.Methods:The Genomics of Drug Sensitivity in Cancer(GDSC)database was used in this investigation to obtain the mRNA expression dataset,genomic mutation profile,and drug sensitivity information of NSCLS.Machine Learning(ML)methods,including Random Forest(RF),Artificial Neurol Network(ANN),and Support Vector Machine(SVM),were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods.The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods,and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype.Finally,the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets.Results:Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs.Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response(area under the curve[AUC]0.875)using CIT,GAS2L3,STAG3L3,ATP2B4-mut,and IL15RA-mut as molecular features.Furthermore,the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance(AUC 0.780)in Gefitinib with CCL23-mut.Conclusion:This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.

关键词： Lung adenocarcinoma Drug resistance Machine learning Molecular features Personalized treatment

The biochemical behavior and mechanism of uranium(Ⅵ)bioreduction induced by natural Bacillus thuringiensis

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Journal of Environmental sciences 2024年第2期136卷 372-381页

作者： Shunzhang Chen Junyuan Gong Yanxia Cheng Yuqi Guo Feize Li Tu Lan Yuanyou Yang Jijun Yang Ning Liu Jiali Liao Key Laboratory of Radiation Physics and technology of the Ministry of Education Institute of Nuclear Science and TechnologySichuan UniversityChengdu 610064China

For a broader understanding of uranium migration affected by microorganisms in natural anaerobic environment,the bioreduction of uranium(Ⅵ)(U(Ⅵ))was revealed in Bacillus thuringiensis,a dominant bacterium strain with potential of uranium-tolerant isolated from uranium contaminated soil.The reduction behavior was systematically investigated by the quantitative analysis of U(Ⅳ)in bacteria,and mechanism was inferred from the pathway of electron transmission.Under anaerobic conditions,appropriate biomass and sodium lactate as electron donor,reduction behavior of U(Ⅵ)induced by B.thuringiensis was restricted by the activity of lactate dehydrogenase,which was directly affected by the initial pH,temperature and initial U(Ⅵ)concentration of bioreduction system.Bioreduction of U(Ⅵ)was driven by the generation of nicotinamide adenine dinucleotide(NADH)from enzymatic reaction of sodium lactate with various dehydrogenase.The transmission of the electrons from bacteria to U(Ⅵ)was mainly supported by the intracellular NADH dehydrogenase-ubiquinone system,this process could maintain the biological activity of cells.

关键词： Uranium Bacillus thuringiensis Bioreduction Electron transmission

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

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Neural Regeneration Research 2024年第12期19卷 2637-2648页

作者： Yi Guo Zhonghua Lin Zhen Fan Xin Tian Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina sichuan Provincial Center for Mental Health Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Geriatrics Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal discharges.Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice.An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic networks.In this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

关键词： electrophysiological techniques epilepsy functional brain network functional magnetic resonance imaging functional near-infrared spectroscopy machine leaning molecular imaging neuroimaging techniques structural brain network virtual epileptic models

Vanadium oxide nanospheres encapsulated in N-doped carbon nanofibers with morphology and defect dual-engineering toward advanced aqueous zinc-ion batteries

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Journal of Energy Chemistry 2024年第2期89卷 599-609,I0013页

作者： Yunfei Song Laiying Jing Rutian Wang Jiaxi Cui Mei Li Yunqiang Zhang School of Materials science and Engineering Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353ShandongChina Institute of Fundamental and Frontier sciences University of Electronic Science and Technology of ChinaChengdu 610054SichuanChina

Vanadium-based electrodes are regarded as attractive cathode materials in aqueous zinc ion batteries(ZIBs)caused by their high capacity and unique layered structure.However,it is extremely challenging to acquire high electrochemical performance owing to the limited electronic conductivity,sluggish ion kinetics,and severe volume expansion during the insertion/extraction process of Zn^(2+).Herein,a series of V_(2)O_(3)nanospheres embedded N-doped carbon nanofiber structures with various V_(2)O_(3)spherical morphologies(solid,core-shell,hollow)have been designed for the first time by an electrospinning technique followed thermal treatments.The N-doped carbon nanofibers not only improve the electrical conductivity and the structural stability,but also provides encapsulating shells to prevent the vanadium dissolution and aggregation of V_(2)O_(3)particles.Furthermore,the varied morphological structures of V_(2)O_(3)with abundant oxygen vacancies can alleviate the volume change and increase the Zn^(2+)pathway.Besides,the phase transition between V_(2)O_(3)and Zn_XV_(2)O_(5-m)·n H_(2)O in the cycling was also certified.As a result,the as-obtained composite delivers excellent long-term cycle stability and enhanced rate performance for coin cells,which is also confirmed through density functional theory(DFT)calculations.Even assembled into flexible ZIBs,the sample still exhibits superior electrochemical performance,which may afford new design concept for flexible cathode materials of ZIBs.

关键词： Aqueous zinc ion batteries Vanadium trioxide Oxygen vacancy Structure evolution Phase optimization

Dietary sodium acetate and sodium butyrate attenuate intestinal damage and improve lipid metabolism in juvenile largemouth bass(Micropterus salmoides) fed a high carbohydrate diet by reducing endoplasmic reticulum stress

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Animal Nutrition 2024年第1期16卷 443-456页

作者： Liulan Zhao Liangshun Cheng Yifang Hu Xiaohui Li Yihui Yang Jin Mu Lianfeng Shen Guojun Hu Kuo He Haoxiao Yan Qiao Liu Song Yang College of Animal science and technology Sichuan Agricultural University

High-carbohydrate(HC) diets decrease the intestinal levels of sodium acetate(SA) and sodium butyrate(SB) and impair the gut health of largemouth bass; however, SA and SB have been shown to enhance immunity and improve intestinal health in farmed animals. Thus, the present study was to investigate the effects of dietary SA and SB on HC diet-induced intestinal injury and the potential mechanisms in juvenile largemouth bass. The experiment set five isonitrogenous and isolipidic diets, including a lowcarbohydrate diet(9% starch)(LC), a high carbohydrate diet(18% starch)(HC), and the HC diet supplemented with 2 g/kg SA(HCSA), 2 g/kg SB(HCSB) or a combination of 1 g/kg SA and 1 g/kg SB(HCSASB).The feeding experiment was conducted for 8 weeks. A total of 525 juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were used. The results showed that dietary SA and SB improved the weight gain rate and specific growth rate (P<0.05) and ameliorated serum parameters(alkaline phosphatase, acid phosphatase, glutamate transaminase, and glutamic oxaloacetic transaminase)(P<0.05). And, importantly, dietary SA and SB repaired the intestinal barrier by increasing the expression levels of zonula occludens-1, occludin, and claudin-7(P<0.05), reduced HC-induced intestinal damage, and alleviated intestinal inflammation and cell apoptosis by attenuating HC-induced intestinal endoplasmic reticulum stress(P<0.05). Further results revealed that dietary SA and SB reduced HC-induced intestinal fat deposition by inhibiting adipogenesis and promoting lipolysis(P<0.05). In summary, this study demonstrated that dietary SA and SB attenuated HC-induced intestinal damage and reduced excessive intestinal fat deposition in largemouth bass.

关键词： Sodium acetate Sodium butyrate High carbohydrate diet Endoplasmic reticulum stress Intestine health Lipid metabolism