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Functional characterization of Bmcap in uric acid metabolism in the silkworm

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Insect Science 2024年第1期31卷 147-156页

作者： Linmeng Tang Dehong Yang Zhiwei Liu Yaohui Wang Xu Yang Yujia Liu Dongbin Chen Zheng Tang Yongping Huang Key Laboratory of Insect Developmental and Evolutionary Biology Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghaiChina CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijingChina Central Research Institute Shanghai Pharmaceuticals Holding Co.Ltd.ShanghaiChina Departments of Neonatology International Peace Maternity and Child Health Hospital of China Welfare InstitutionSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

After a millennium of domestication,numerous silkworm mutants have emerged that exhibit transparent epidermis,which is caused by abnormally low levels of uric acid.We identified the Bombyx mori gene Bmcap(BMSK0003832)as the homolog of cappuccino,a subunit of the biogenesis of lysosome-related organelles complex-1(BLOC-1)that has been extensively characterized in human,mouse,and insect species,by analyzing the amino acid sequences of putative purine metabolism genes.Using the clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9 system,we disrupted Bmcap,resulting in decreased uric acid levels in the silkworm epidermis and a translucent skin phenotype.In the Bmcap mutant,the purine metabolism,nitrogen metabolism,pyrimidine metabolism,and membrane system were altered compared to the wild type.Biogenesis of lysosome-related organelle complex genes play a role in the pigmentation and biogenesis of lysosome-related organelles(LROs)in platelets,melanocytes,and megakaryocytes.LROs exhibit unique morphologies and functions in various tissues and cells.Investigation of the Bmcap mutant will enhance our understanding of the uric acid metabolic pathway in silkworms,and this mutant offers a valuable silkworm model for LRO studies.

关键词： BLOC-1 subunit Bombyx mori cappuccino translucent mutation uric acid

Advanced nano drug delivery systems for neuroprotection against ischemic stroke

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Chinese Chemical Letters 2024年第2期35卷 151-162页

作者： Chenchen Xie Jun Liao Ning Zhang Yuhan Sun Yi Li Liyan Xiong Yingnan Zhang Xiaoyan Liu Wei Su Heming Chen Ping Zeng Xiaoqing Zhang Ying Lu Tingfang Wang Chuan Zhang Shanghai Engineering Research Center of Organ Repair School of MedicineShanghai UniversityShanghai 200444China Department of Pharmaceutical Science School of PharmacyNaval Medical UniversityShanghai 200433China Department of pharmacy the International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China School of Pharmacy Shanghai Jiao Tong UniversityShanghai 200040China

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

关键词： Target Blood-brain barrier Ischemic stroke Nano drug delivery Neuroprotection

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive Medicine and Offspring health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of maternity and child health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Untargeted metabolomic profiling， nutritional composition and enzyme changes on Bigeye tuna(Thunnus obesus) during cold storage by HPLC-MS coupled with logistic regression

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Food Science and Human Wellness 2024年

作者： Xin-Yun Wang Zi-Xuan Zhao Jun Yan Jing Xie Shanghai Engineering Research Center of Aquatic Product Processing & Preservation Shanghai Ocean University the international peace maternity and child health hospital School of Medicine Shanghai Jiao Tong University National Experimental Teaching Demonstration Center for Food Science and Engineering Shanghai Ocean University College of Food Science & Technology Shanghai Ocean University

Bigeye tuna is a protein-rich fish that is susceptible to spoilage during cold storage， however， there is limited information on untargeted metabolomic profiling of bigeye tuna concerning spoilage-associated enzymes and metabolites. This study aimed to investigate how cold storage affects enzyme activities， nutrient composition， tissue microstructures and spoilage metabolites of bigeye tuna. The activities of cathepsin B， H， L increased， while Na+/K+-ATPase and Mg2＋-ATPase decreased， α-glucosidase （AG） and β-1，4-N-acetylglucosaminidase （NAG）， lipase and lipoxygenase first increased and then decreased during cold storage， suggesting that proteins undergo degradation and ATP metabolism occurs at a faster rate during cold storage. Nutrient composition （moisture， protein， and lipid content）， free amino acids， total amino acids decreased， suggesting that the nutritional value of bigeye tuna was reduced. Besides， a logistic regression equation has been established as a food analysis tool and assess the dynamics and correlation of the enzyme of bigeye tuna during cold storage. Based on untargeted metabolomic profiling analysis， a total of 484 metabolites were identified as significantly differential metabolites in the bigeye tuna contained several spoilage metabolites involved in lipid metabolism （1-Acyl-sn-glycero-3phosphocholine， Glycerophosphocholine， Choline phosphate）， amino acid metabolism (L-Histidine， 5-Deoxy-5'-（methylthio）adenosine， 5-Methylthioadenosine)， carbohydrate metabolism （D-Gluconicacid， beta-D-Fructose 1，6-bisphosphate， D-Glyceraldehyde 3-phosphate）. The results of tissue microstructures of tuna showed a looser network and visible deterioration of tissue fiber during cold storage. Therefore， metabolomic analysis and tissue microstructures provide insight into the spoilage mechanism investigations on bigeye tuna during cold storage.

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Nomogram to predict severe retinopathy of prematurity in Southeast China

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international Journal of Ophthalmology(English edition) 2024年第2期17卷 282-288页

作者： Dan Liu Xing-Yong Li Hong-Wu He Ka-Lu Jin Ling-Xia Zhang Yang Zhou Zhi-Min Zhu Chen-Chen Jiang Hai-Jian Wu Sui-Lian Zheng Department of Ophthalmology the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Eye hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Taizhou Optometry hospital Taizhou 318001Zhejiang ProvinceChina Department of Ophthalmology Jiaxing Maternity and Child Health Care HospitalJiaxing 314009Zhejiang ProvinceChina Department of Ophthalmology Taizhou Women and Children’s Hospital of Wenzhou Medical UniversityTaizhou 318001Zhejiang ProvinceChina Clinical Medical Research Center the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Department of Ophthalmology Taizhou Municipal HospitalTaizhou 318099Zhejiang ProvinceChina

AIM:To define the predictive factors of severe retinopathy of prematurity(ROP)and develop a nomogram for predicting severe ROP in southeast China.METHODS:Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated hospital and Yuying children’s hospital of Wenzhou Medical University and hospitalized in Taizhou Women and children’s hospital were included.Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively.Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction,which was compared with WINROP model and Digirop-Birth model.RESULTS:Infants from the Second Affiliated hospital and Yuying children’s hospital of Wenzhou Medical University(n=478)were randomly allocated into training(n=402)and internal validation group(n=76).Infants from Taizhou Women and children’s hospital were set as external validation group(n=76).Severe ROP were found in 52 of 402 infants,12 of 76 infants,and 7 of 76 infants in training group,internal validation group,and external validation group,respectively.Birth weight[odds ratio(OR),0.997;95%confidence interval(CI),0.996-0.999;P<0.001],multiple births(OR,1.885;95%CI,1.013-3.506;P=0.045),and non-invasive ventilation(OR,0.288;95%CI,0.146-0.570;P<0.001)were identified as predictive factors for the prediction of severe ROP,by univariate analysis and multivariate analysis.For predicting severe ROP based on the internal validation group,the areas under receiver operating characteristic curve(AUC)was 78.1(95%CI,64.2-92.0)for the nomogram,32.9(95%CI,15.3-50.5)for WINROP model,70.2(95%CI,55.8-84.6)for Digirop-Birth model.In external validation group,AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model(80.2 versus 51.1 and 63.4).The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model.The calibration curves demonstrated a good consistency between the actual seve

关键词： retinopathy of prematurity nomogram predictive factor birth weight multiple births non-invasive ventilation

Bifidobacterium longum subsp. infantis CCFM1269 promotes intestinal barrier and release of IFN-β through TLR4-TRIF dependent way in growing mice

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Food Science and Human Wellness 2024年

作者： Mengfan Ding Bo Yang Bowen Li Haiqin Chen Renqiang Yu R.Paul Ross Catherine Stanton Shilong Jiang Jianxin Zhao Wei Chen State Key Laboratory of Food Science and Resources Jiangnan University Teagasc Food Research Centre Nutrition and Metabolism Research Division Innovation Center Heilongjiang Feihe Dairy Co. Ltd. Department of Neonatology Wuxi maternity and child health Care hospital Affiliated Women's hospital of Jiangnan University National Engineering Research Center for Functional Food Jiangnan University School of Food Science and Technology Jiangnan University PKUHSC-China Feihe Joint Research Institute of Nutrition and healthy Lifespan Development international Joint Research Center for Probiotics & Gut health Jiangnan University APC Microbiome Ireland University College Cork

Bifidobacterium longum subsp. infantis is a commensal bacterium that predominates in the infant gut， playing a critical role in both preventing foreign infections and facilitating immune development. This study aimed to explore the effects of B. longum subsp. infantis supplementation on interferon-beta (IFN-β) secretion and intestinal barrier improvement in growing mice. Female and male mice were orally administered either saline or B. longum subsp. infantis CCFM1269 or I5TI (1 × 109CFU/mice per day， n = 8) from 1-week-age until 3-， 4-， and 5-week-age. RNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2’-5’ oligoadenylate synthetase (OAS). Additionally， CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLR4-TRIF-dependent signaling pathway. However， this effect was not observed in 4- and 5-week-old mice. Furthermore， both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-， 4-， and 5-week-old mice. In summary， the results of this study suggested that B. longum subsp. infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.

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ROS-responsive thioether-containing hyperbranchede polymer micelles for light-triggered drug releas

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SmartMat 2022年第3期3卷 522-531页

作者： Guanchun Wang Ping Huang Lei Wang Xinliang Chen Yongfeng Zhou Wei Huang Deyue Yan School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghaiChina the international peace maternity and child health hospital School of MedicineShanghai Jiao Tong UniversityShanghaiChina

As a kind of promising drug carriers,smart polymers have attracted much attention due to the effective and controlled drug release in target cells.Herein,a reactive oxygen species(ROS)-responsive thioether-containing amphiphilic hyperbranched polymer prepared from MTPA and TMPTGE(HBPMT)is synthesized from 3-(methylthio)propylamine(MTPA)and trimethylolpropane triglycidyl ether(TMPTGE)by the amine-epoxy click reaction via A2+B3 onepot approach.Benefiting from its inherent amphiphilic nature,HBPMT can selfassemble into stable micelles in water.Triggered by H_(2)O_(2),these micelles can be dissociated rapidly because hydrophobic thioether segments in their cores are oxidized into hydrophilic sulfoxide or sulfone groups.Additionally,the ROS produced by photosensitizer under light irradiation can also play the same role of H_(2)O_(2).Such HBPMT micelles can be utilized to encapsulate anticancer drug paclitaxel(PTX)and photosensitizer chlorin e6(Ce6)simultaneously for drug delivery and control release.The methyl thiazolyl tetrazolium assay toward MCF-7 tumor cells(a human breast adenocarcinoma cell line)indicates that these micelles encapsulated with PTX and Ce6 exhibit a significant combinational efficacy of cell proliferation inhibition,which means the promising potential for synergistic chemo-photodynamic cancer therapy.Such a novel nanocarrier based on amphiphilic to hydrophilic transition would provide a candidate for controlled drug release and cancer combination therapy.

关键词： drug delivery hyperbranched polymer photosensitizer ROS-responsiveness triggered drug release

Clinical characteristics of perineal endometriosis:A case series

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World Journal of Clinical Cases 2021年第5期9卷 1037-1047页

作者： Yan Liang Duo Zhang Ling Jiang Yuan Liu Jian Zhang Department of Obstetrics and Gynecology International Peace Maternity and Child Health HospitalShanghai 200030China Department of Radiology International Peace Maternity and Child Health HospitalShanghai 200030China Department of Pathology International Peace Maternity and Child Health HospitalShanghai 200030China

BACKGROUND The prevalence of perineal endometriosis(PEM)is low among women with endometriosis(EM)treated by surgery.It manifests as hard or cystic nodules with pain in the perineal wounds and surrounding areas.Implantation theory is regarded as the main pathogenesis of PEM.There are few clinical studies on the incidence and clinical characteristics of PEM.This study aims to summarize the clinical data of 14 PEM cases and analyze the factors that may be related to the incubation period and pain.AIM To analyze the medical history,clinical manifestations,diagnosis,treatment and treatment effect of PEM.METHODS The present study is a case series.We collected the clinical data and follow-up data of 14 patients with PEM who visited The international peace Maternal and child health hospital Affiliated to Shanghai Jiaotong University from January 2009 to December 2019.Paired t test and Pearson correlation analysis were used for statistical analysis.P<0.05 was considered statistically significant.RESULTS The 14 patients included had a history of vaginal delivery.All patients underwent PEM lesion resection.Three patients were treated by levator ani muscle repair at the same time and 1 patient underwent extensive PEM lesion resection and anal sphincter repair.Body mass index(BMI)at delivery and BMI within 1 mo after delivery were negatively correlated with the latent period,respectively(R2=0.53/0.86,P<0.05).The average visual analog scale score in lesions at the third month after surgery was 0.57±1.28 for all patients,which was significantly lower than that prior to surgery(P<0.05).One patient relapsed during the sixth month after surgery,and to date,no recurrence occurred after the second surgery.CONCLUSION The higher the BMI during delivery and within 1 mo after delivery,the shorter the incubation period of PEM.It is very important to evaluate the location of lesions before surgery.Surgical resection of the lesion is the best treatment for PEM and results in significant alleviation of symptoms.Therefore,following the diagn

关键词： Perineal endometriosis Incubation period Pain in the perineum Surgery Body mass index Clinical characteristics

H_(2)O_(2)-responsive polymer prodrug nanoparticles with glutathione scavenger for enhanced chemo-photodynamic synergistic cancer therapy

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Bioactive Materials 2023年第7期25卷 189-200页

作者： Guanchun Wang Yue Su Xinliang Chen Yongfeng Zhou Ping Huang Wei Huang Deyue Yan School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai200240China the international peace maternity and child health hospital School of MedicineShanghai Jiao Tong UniversityShanghaiChina

The combination of chemotherapy and photodynamic therapy(PDT)based on nanoparticles(NPs)has been extensively developed to improve the therapeutic effect and decrease the systemic toxicity of current treatments.However,overexpressed glutathione(GSH)in tumor cells efficiently scavenges singlet oxygens(^(1)O_(2))generated from photosensitizers and results in the unsatisfactory efficacy of PDT.To address this obstacle,here we design H_(2)O_(2)-responsive polymer prodrug NPs with GSH-scavenger(Ce6@P(EG-a-CPBE)NPs)for chemo-photodynamic synergistic cancer therapy.They are constructed by the co-self-assembly of photosensitizer chlorin e6(Ce6)and amphiphilic polymer prodrug P(EG-a-CPBE),which is synthesized from a hydrophilic alternating copolymer P(EG-a-PD)by conjugating hydrophobic anticancer drug chlorambucil(CB)via an H_(2)O_(2)-cleavable linker 4-(hydroxymethyl)phenylboronic acid(PBA).Ce6@P(EG-a-CPBE)NPs can efficiently prevent premature drug leakage in blood circulation because of the high stability of the PBA linker under the physiological environment and facilitate the delivery of Ce6 and CB to the tumor site after intravenous injection.Upon internalization of Ce6@P(EG-a-CPBE)NPs by tumor cells,PBA is cleaved rapidly triggered by endogenous H_(2)O_(2)to release CB and Ce6.Ce6 can effectively generate abundant^(1)O_(2)under 660 nm light irradiation to synergistically kill cancer cells with CB.Concurrently,PBA can be transformed into a GSH-scavenger(quinine methide,QM)under intracellular H_(2)O_(2)and prevent the depletion of^(1)O_(2),which induces the cooperatively strong oxidative stress and enhanced cancer cell apoptosis.Collectively,such H_(2)O_(2)-responsive polymer prodrug NPs loaded with photosensitizer provide a feasible approach to enhance chemo-photodynamic synergistic cancer treatment.

关键词： H_(2)O_(2)-responsiveness Alternating copolymer prodrug GSH-scavenger Photosensitizer Chemo-photodynamic synergistic cancer therapy