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Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation

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Chinese Medical Journal 2024年第1期137卷 120-122页

作者： Haohao Zhang Lijuan Sun Zhixin Zhao Yao Zhou Yuyao Liu Nannan Zhang Junya Yan Shibo wang Renlong Li Jing Zhang xueying wang Wenjiao Li Yan Pan Meixia wang Bing Luo Mengbin Li Zhihong Sun Yongxiang Zhao Yongzhan Nie State Key Laboratory of Targeting Oncology National Center for International Research of Bio-targeting TheranosticsGuangxi Key Laboratory of Bio-targeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Talent Highland of Bio-targeting TheranosticsGuangxi Medical UniversityNanningGuangxi 530021China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anShaanxi 710032China Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineNorthwest UniversityXi’anShaanxi 710000China Key Laboratory of Dairy Biotechnology and Engineering Ministry of EducationKey Laboratory of Dairy Products ProcessingMinistry of Agriculture and Rural AffairsInner Mongolia Key Laboratory of Dairy Biotechnology and EngineeringInner Mongolia Agricultural UniversityHohhotInner Mongolia 010018China

To the Editor:Probiotics are a promising treatment modality for functional constipation(FC);however,the factors affecting individual responses to probiotics remain unclear.Growing evidence has identified that there is a strong relationship among the gut microbiota and constipation and related gut-brain axis.[1]The gut microbiota may modulate the gut functions via gut metabolites or trigger the release of gut hormones,such as peptide YY,gastric inhibitory polypeptide,and 5-hydroxytryptamine.[2]In turn,gut hormones affect gut secretion,motility,and sensation through their receptors located on epithelial,enteric,and smooth muscle cells.[2]Based on these findings,exogenous probiotics have been used in patients with constipation;however,few have produced consistent results.[3]In this study,we investigated the efficacy and safety of several specific probiotics strains for constipation,and also examined the potential reasons for the individualized effects of probiotics,which may facilitate interventional decisionmaking for FC patients.

关键词： constipation patients sensation

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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Science China(Life Sciences) 2024年第5期67卷 1035-1050页

作者： Yaling wang Jingwen Chen xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo wang State Key Laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China Shanghai Key Laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced mosaicism.iSTOP enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for fertility.Here,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona pellucida.We further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO offspring.We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport.Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility

The OsBZR1-OsSPX1/2 module fine-tunes the growth-immunity trade-off in adaptation to phosphate availability in rice

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Molecular Plant 2024年第2期17卷 258-276页

作者： Yuqing He Yao Zhao Jitao Hu Lanlan wang Linying Li xueying Zhang Zhongjing Zhou Lili Chen Hua wangl Jiaoyu wang Gaojie Hong State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products Key Laboratory of Biotechnology in Plant Protection of MOA of China and Zhejiang ProvinceInstitute of Virology and BiotechnologyZhejiang Academy of Agricultural SciencesHangzhou 310021P.R.China Key Laboratory of Traceability for Agricultural Genetically Modified Organisms Ministry of Agriculture and Rural AffairsHangzhou 310021P.R.China College of Life Sciences Zhejiang Sci-Tech UniversityHangzhou 310018P.R.China State Key Laboratory for Managing Biotic and Chemical Threats to the Qualty and Safety of Agro-products Zhejang Academy of Agricultural SciencesHangzhou 310021P.R.China State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products Key Labory of Biotechnology in Plant Protection of MOA of China and Zhejiang ProvinceInstitute of Plant Protection and MicrobiologyZhejiang Academy of Agricultural SciencesHangzhou 310021P.R.China

The growth-promoting hormones brassinosteroids(BRs)and their key signaling component BZR1 play a vital role in balancing normal growth and defense reactions.Here,we discovered that BRs and OsBZR1 up-regulated sakuranetin accumulation and conferred basal defense against Magnaporthe oryzae infection under normal conditions.Resource shortages,including phosphate(Pi)deficiency,potentially disrupt this growth-defense balance.OsSPX1 and OsSPX2 have been reported to sense Pi concentration and interact with the Pi signal mediator OsPHR2,thus regulating Pi starvation responses.In this study,we discovered that OsSPX1/2 interacts with OsBZR1 in both Pi-sufficient and Pi-deficient conditions,inhibit-ing BR-responsive genes.When Pi is sufficient,OsSPX1/2 is captured by OsPHR2,enabling most of OsBzR1 to promote plant growth and maintain basal resistance.In response to Pi starvation,more OsSPX1/2 is released from OsPHR2 to inhibit OsBZR1 activity,resulting in slower growth.Collectively,our study reveals that the OsBZR1-SPX1/2 module balances the plant growth-immunity trade-off in responsetoPiavailability.He Y.,Zhao Y.,Hu J.,wang L.,Li L.,Zhang X.,Zhou Z.,Chen L.,wang H.,wang J.,and Hong G.(2024).The OsBZR1-OsSPX1/2 module fine-tunes the growth-immunity trade-off in adaptation to phosphate availability in esponse to Pi availability.

关键词： immunity maintain adaptation

Transcriptomic and machine learning analyses identify hub genes of metabolism and host immune response that are associated with the progression of breast capsular contracture

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Genes & Diseases 2024年第3期11卷 427-437页

作者： Yukun Mao xueying Hou Su Fu Jie Luan Breast Plastic and Reconstructive Surgery Center Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100144China

Capsular contracture is a prevalent and severe complication that affects the post-operative outcomes of patients who receive silicone breast implants.At present,prosthesis replacement is the major treatment for capsular contracture after both breast augmentation procedures and breast reconstruction following breast cancer surgery.However,the mecha-nism(s)underlying breast capsular contracture remains unclear.This study aimed to identify the biological features of breast capsular contracture and reveal the potential underlying mechanism using RNA sequencing.Sample tissues from 12 female patients(15 breast capsules)were divided into low capsular contracture(LCC)and high capsular contracture(HCC)groups based on the Baker grades.Subsequently,41 lipid metabolism-related genes were identified through enrichment analysis,and three of these genes were identified as candidate genes by SVM-RFE and LASSO algorithms.We then compared the proportions of the 22 types of im-mune cells between the LCC and HCC groups using a CIBERSORT analysis and explored the Cor-relation between the candidate hub features and immune cells.Notably,PRKAR2B was positively correlated with the differentially clustered immune cells,which were M1 macro-phages and follicular helper T cells(area under the ROC=0.786).In addition,the expression of PRKAR2B at the mRNA or protein level was lower in the HCC group than in the LCC group.Potential molecular mechanisms were identified based on the expression levels in the high and low PRKAR2B groups.Our findings indicate that PRKAR2B is a novel diagnostic biomarker for breast capsular contracture and might also influence the grade and progression of capsularcontracture.

关键词： Biomarker Breastcapsular contracture Immune infiltration Machinelearning algorithms PRKAR2B

Social-ecological perspective on the suicidal behaviour factors of early adolescents in China:a network analysis

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General Psychiatry 2024年第1期37卷 143-150页

作者： Yuan Li Peiying Li Mengyuan Yuan Yonghan Li xueying Zhang Juan Chen Gengfu wang Puyu Su Department of Maternal Child and Adolescent HealthSchool of Public HealthKey Laboratory of Population Health Across Life Cycle(Anhui Medical University)Ministry of Education of the People's Republic of ChinaAnhui Medical UniversityKey Laboratory of Population Health Across Life Cycle(Anhui Medical University)HefeiAnhuiChina Tianjin Anding Hospital Mental Health Center of Tianjin Medical UniversityTianjin Medical UniversityTianjinChina Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Afiliated Psychological Hospital of Anhui Medical University Anhui Mental Health CenterFourth People's Hospital of HefeiHefeiAnhuiChina

Background In early adolescence,youth are highly prone to suicidal behaviours.Identifying modifiable risk factors during this critical phase is a priority to inform effective suicide prevention strategies.Aims To explore the risk and protective factors of suicidal behaviours(ie,suicidal ideation,plans and attempts)in early adolescence in China using a social-ecological perspective.Methods Using data from the cross-sectional project‘Healthy and Risky Behaviours Among Middle School Students in Anhui Province,China',stratified random cluster sampling was used to select 5724 middle school students who had completed self-report questionnaires in November 2020.Network analysis was employed to examine the correlates of suicidal ideation,plans and attempts at four levels,namely individual(sex,academic performance,serious physical llness/disability,history of self-harm,depression,impulsivity,sleep problems,resilience),family(family economic status,relationship with mother,relationship with father,family violence,childhood abuse,parental mental illness),school(relationship with teachers,relationship with classmates,school-bullying victimisation and perpetration)and social(social support,satisfaction with society).Results In total,37.9%,19.0%and 5.5%of the students reported suicidal ideation,plans and attempts in the past 6 months,respectively.The estimated network revealed that suicidal ideation,plans and attempts were collectively associated with a history of self-harm,sleep problems,childhood abuse,school bullying and victimisation.Centrality analysis indicated that the most influential nodes in the network were history of self-harm and childhood abuse.Notably,the network also showed unique correlates of suicidal ideation(sex,weight=0.60;impulsivity,weight=0.24;family violence,weight=0.17;relationship with teachers,weight=-0.03;school-bullying perpetration,weight=0.22),suicidal plans(social support,weight=-0.15)and suicidal attempts(relationship with mother,weight=-0.10;parental mental llness,weight=0.61).Conclusions Thi

关键词： network analysis prevention

The RING zinc finger protein LbRZF1 promotes salt gland development and salt tolerance in Limonium bicolor

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Journal of Integrative Plant Biology 2024年第4期66卷 787-809页

作者： Zongran Yang Ziwei Zhang Ziqi Qiao xueying Guo Yixuan Wen Yingxue Zhou Chunliang Yao Hai Fan Baoshan wang Guoliang Han Shandong Provincial Key Laboratory of Plant Stress College of Life SciencesShandong Normal UniversityJi'nan 250014China National Center of Technology Innovation for Comprehensive Utilization of Saline-Alkali Land Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta of Shandong ProvinceDongying 257000China Dongying Institute Shandong Normal UniversityDongying 257000China

The recretohalophyte Limonium bicolor thrives in high-salinity environments because salt glands on the above-ground parts of the plant help to expel excess salt.Here,we characterize a nucleus-localized C3HC4(RING-HC)-type zinc finger protein of L.bicolor named RING ZINC FINGER PROTEIN 1(LbRZF1).LbRZF1 was expressed in salt glands and in response to NaCl treatment.LbRZF1 showed no E3 ubiquitin ligase activity.The phenotypes of overexpression and knockout lines for LbRZF1 indicated that LbRZF1 positively regulated salt gland development and salt tolerance in L.bicolor.lbrzf1 mutants had fewer salt glands and secreted less salt than did the wild-type,whereas LbRZF1-overexpressing lines had opposite phenotypes,in keeping with the overall salt tolerance of these plants.A yeast two-hybrid screen revealed that LbRZF1 interacted with LbCATALASE2(LbCAT2)and the transcription factor LbMYB113,leading to their stabilization.Silencing of LbCAT2 or LbMYB113 decreased salt gland density and salt tolerance.The heterologous expression of LbRZF1 in Arabidopsis thaliana conferred salt tolerance to this non-halophyte.We also identified the transcription factor LbMYB48 as an upstream regulator of LbRZF1 transcription.The study of LbRZF1 in the regulation network of salt gland development also provides a good foundation for transforming crops and improving their salt resistance.

关键词： LbRZF1 Limonium bicolor molecular mechanism salt gland development salt tolerance

Autophagy,ferroptosis,pyroptosis,and necroptosis in tumor immunotherapy

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2311-2336页

作者： Weitong Gao xueying wang Yang Zhou Xueqian wang Yan Yu Department of Medical Oncology Harbin Medical University Cancer HospitalHarbin 150081China Department of Otolaryngology Head and Neck Surgery Xiangya HospitalCentral South Universitychangsha 410008China Department of Head and Neck Surgery Harbin Medical University Cancer HospitalHarbin 150081China

In recent years,immunotherapy represented by immune checkpoint inhibitors(ICIs)has led to unprecedented breakthroughs in cancer treatment.However,the fact that many tumors respond poorly or even not to ICIs,partly caused by the absence of tumorinfiltrating lymphocytes(TILs),significantly limits the application of ICIs.Converting these immune“cold”tumors into“hot”tumors that may respond to ICIs is an unsolved question in cancer immunotherapy.Since it is a general characteristic of cancers to resist apoptosis,induction of non-apoptotic regulated cell death(RCD)is emerging as a new cancer treatment strategy.Recently,several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity.Specifically,autophagy,ferroptosis,pyroptosis,and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses.Thus,targeted therapies(inducers or inhibitors)against autophagy,ferroptosis,pyroptosis,and necroptosis in combination with immunotherapy may exert potent antitumor activity,even in tumors resistant to ICIs.This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD,including autophagy,ferroptosis,pyroptosis,and necroptosis,and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.

关键词： immunotherapy immunity breakthrough

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang xueying An wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling wang xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo wang Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential.However,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited.Here,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are infertile.The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes.We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm.Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in sperm.We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility.Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling