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Multi-endpoint assays reveal more severe toxicity induced by chloraminated effluent organic matter than chloraminated natural organic matter

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Journal of Environmental Sciences 2024年第1期135卷 310-317页

作者： hai-yan wang De-Xiu Wu Ye Du Xiao-Tong Lv Qian-Yuan Wu State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Environmental Protection Key Laboratory of Microorganism Application and Risk Control Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental SafetyTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China College of Architecture and Environment Sichuan UniversityChengdu 610000China

Disinfection by chloramination produces toxic byproducts and the difference in toxicity of reclaimed and drinking water treated by chloramination remains unclear.This study investigated cytotoxic effects at the same concentrations of dissolved organic matter and showed that chloraminated effluent organic matter(EfOM)induced 1.7 times higher cytotoxicity than chloraminated natural organic matter(NOM)applied to simulate drinking water.Chloraminated EfOM induced more reactive nitrogen species than chloraminated NOM,and chloraminated EfOM and NOM induced similar and higher levels of reactive oxygen species than the negative control,respectively.Consequently,intracellular macromolecule damage indicated by DNA/RNA damage marker 8–hydroxy-(deoxy)guanosine and the intracellular protein carbonyl concentration induced by chloraminated EfOM was higher and slightly more than that induced by chloraminated NOM,respectively.These data were consistent with the effects on cell physiological processes.Cell cycle arrest mainly occurred in G2 phase by chloraminated EfOM and NOM.Early apoptotic cells,which could return to normal,increased upon exposure to high concentrations of chloraminated EfOM and NOM.Moreover,necrotic cells were significantly increased from 0.5%to 2.5%when the concentration increased from 20-to 60-fold chloraminated EfOM,but were not obviously changed by chloraminated NOM.These results indicated that the comprehensive intracellular changes induced by toxic substances in chloraminated EfOM were more irreversible and induced more cell death than chloraminated NOM.

关键词： Cytotoxicity Intracellular active nitrogen/oxygen Intracellular oxidative damage Cell necrosis Reclaimed water

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Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo hai-yan wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas therapy.In this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine scaffold.Under the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation energy.We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target mitochondria.Under an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging.Collectively,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

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Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

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World Journal of Gastroenterology 2024年第10期30卷 1431-1449页

作者： Zheng-yang Li Yu-Qing Mao Qian Hua Yong-Hong Sun hai-yan wang Xuan-Guang Ye Jing-Xian Hu Ya-Jie wang Miao Jiang Department of Gastroenterology Jinshan Hospital of Fudan UniversityShanghai 201508China Department of Gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Gastroenterology Dalian Friendship HospitalDalian 116001Liaoning ProvinceChina Department of Pathology Jinshan Hospital of Fudan UniversityShanghai 201508China

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracell

关键词： Diarrhea-predominant irritable bowel syndrome Serotonin receptor 2B Transient receptor potential vanilloid type-1 Visceral hypersensitivity Abdominal pain

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Nanocrystalline WSe_(2)excels at high-performance anode for Na storage via a facile one-pot hydrothermal method

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Tungsten 2024年第1期6卷 248-258页

作者： hai-yan Zou Lei Fang Gang Yu Dong wang State Key Laboratory of Chem/Bio-Sensing and Chemometrics Provincial Hunan Key Laboratory for Graphene Materials and DevicesCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China Changxing County Quality and Technology Supervision and Testing Center Huzhou 313100China

For the next large-scale energy storage systems,sodium-ion batteries(SIBs)with excellent electrochemical performance are promising.However,the exploration of anode materials with high specific capacity,fascinating cycling stability and rate capability is still restricted.Among transition metal dichalcogenides(TMDs),tungsten diselenide(WSe_(2))has been regarded as an effective anode material for SIBs and has been extensively studied,due to high theoretical capacity and unique twodimensional layered structure.Herein,nanocrystalline WSe_(2)is prepared by a facile one-pot hydrothermal method.Compared with the micro-scale WSe_(2),benefiting from the high specific surface area of highly ordered nano-flake structures and short ion/electron transport paths,nanocrystalline WSe_(2)shows excellent electrochemical performance in Na storage.After 1000 cycles at a current density of 2 A·g^(-1),a high specific capacity of 264.4 mA·h·g^(-1)is still maintained.The full cell matched with the Na_(3)V_(2)(PO_(4))_(3) cathode can deliver an excellent reversible specific capacity of 196.5 mA·h·g^(-1)after 100 cycles at 0.5 A·g^(-1).

关键词： Tungsten diselenide Transition metal dichalcogenides Hydrothermal Sodium-ion batteries Layered structure

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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-yan Shi Yarong wang Ying Shi Ruofei Tian Xiaohong Chen hai Zhang Ke wang Zhinan Chen Ruo Chen National Translational Science Center for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

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Current and Potential Roles of Ferroptosis in Bladder Cancer

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Current Medical Science 2024年第1期44卷 51-63页

作者： Wen-xin AN Radheshyam Gupta Kun Zhai Ya-ru wang Wan-hai XU yan CUI Department of Urology Harbin Medical University Cancer HospitalHarbin 150081China Department of Internal Medical Oncology Harbin Medical University Cancer HospitalHarbin 150081China

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

关键词： ferroptosis bladder cancer ferroptosis-associated tumor signaling pathway ferroptosis inducer

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Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease

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World Journal of Diabetes 2024年第1期15卷 92-104页

作者： Lu-Lu Han Sheng-hai wang Ming-yan Yao Hong Zhou Department of Endocrinology The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Department of Endocrinology Baoding No.1 Central HospitalBaoding 071000Hebei ProvinceChina Department of Critical Care Medicine The Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina

BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)hain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with

关键词： Urinary exosome MicroRNA-145-5p MicroRNA-27a-3p Diabetic kidney disease Diagnostic biomarkers

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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

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Cancer Biology & Medicine 2024年第1期21卷 83-103页

作者： Yumei wang haiyan wang Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong wang School of Basic Medical Sciences State Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu University of Traditional Chinese MedicineChengdu 611137China Department of Pathology School of MedicineQinghai UniversityXining 810001China Omics Biosciences Inc Beijing 100871China Laboratory of Integrative Medicine Clinical Research Center for BreastState Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China State Key Laboratory of Southwestern Chinese Medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity ResearchMedical Center for Comprehensive Weight ControlThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

关键词： Epigenetic regulators breast cancer regulatory network HTS^(2)

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Bionic Hand Motion Control Method Based on Imitation of Human Hand Movements and Reinforcement Learning

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Journal of Bionic Engineering 2024年第2期21卷 764-777页

作者： Jibo Bai Baojiang Li Xichao wang haiyan wang Yuting Guo The School of Electrical Engineering Shanghai DianJi UniversityShanghai201306China

Bionic hands are promising devices for assisting individuals with hand disabilities in rehabilitation robotics.Controlled primarily by bioelectrical signals such as myoelectricity and EEG,these hands can compensate for lost hand functions.However,developing model-based controllers for bionic hands is challenging and time-consuming due to varying control parameters and unknown application environments.To address these challenges,we propose a model-free approach using reinforcement learning(RL)for designing bionic hand controllers.Our method involves mimicking real human hand motion with the bionic hand and employing a human hand motion decomposition technique to learn complex motions from simpler ones.This approach significantly reduces the training time required.By utilizing real human hand motion data,we design a multidimensional sampling proximal policy optimization(PPO)algorithm that enables efficient motion control of the bionic hand.To validate the effectiveness of our approach,we compare it against advanced baseline methods.The results demonstrate the quick learning capabilities and high control success rate of our method.

关键词： Bionic hand Reinforcement learning Motion decomposition Multidimensional sampling PPO algorithm

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Associations between Geriatric Nutrition Risk Index,bone mineral density and body composition in type 2 diabetes patients

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World Journal of Diabetes 2024年第3期15卷 403-417页

作者： Xiao-Xiao Zhu Kai-Feng Yao hai-yan Huang Li-Hua wang Department of Pediatrics The Second Affiliated Hospital of Nantong UniversityFirst People’s Hospital of Nantong CityNantong 226001Jiangsu ProvinceChina Department of Nursing The Second Affiliated Hospital of Nantong UniversityFirst People’s Hospital of Nantong CityNantong 226001Jiangsu ProvinceChina Department of Endocrinology The Second Affiliated Hospital of Nantong UniversityFirst People’s Hospital of Nantong CityNantong 226001Jiangsu ProvinceChina

BACKGROUND Type 2 diabetes mellitus(T2DM),a fast-growing issue in public health,is one of the most common chronic metabolic disorders in older individuals.Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities.In people with T2DM,the association between nutrition,sarcopenia,and osteoporosis has rarely been explored.AIM To evaluate the connections among nutrition,bone mineral density(BMD)and body composition in patients with T2DM.METHODS We enrolled 689 patients with T2DM for this cross-sectional study.All patients underwent dual energy X-ray absorptiometry(DXA)examination and were categorized according to baseline Geriatric Nutritional Risk Index(GNRI)values calculated from serum albumin levels and body weight.The GNRI was used to evaluate nutritional status,and DXA was used to investigate BMD and body composition.Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index.RESULTS Of the total patients,394 were men and 295 were women.Compared with patients in tertile 1,those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c,higher BMD at all bone sites,and higher appendicular skeletal muscle index(ASMI).These important trends persisted even when the patients were divided into younger and older subgroups.The GNRI was positively related to ASMI(men:r=0.644,P<0.001;women:r=0.649,P<0.001),total body fat(men:r=0.453,P<0.001;women:r=0.557,P<0.001),BMD at all bone sites,lumbar spine(L1-L4)BMD(men:r=0.110,P=0.029;women:r=0.256,P<0.001),FN-BMD(men:r=0.293,P<0.001;women:r=0.273,P<0.001),and hip BMD(men:r=0.358,P<0.001;women:r=0.377,P<0.001).After adjustment for other clinical parameters,the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck.Additionally,a low lean mass index and higherβ-collagen special sequence were associated with low BMD at all bone sites.Age was negatively correlated with ASMI,whereas weight was positively correlated w

关键词： Geriatric Nutrition Risk Index Bone mineral density Skeletal muscle mass Type 2 diabetes

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