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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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Numerical manifold method for thermo-mechanical coupling simulation of fractured rock mass

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 1977-1992页

作者： Jiawei Liang defu tong Fei Tan Xiongwei Yi Junpeng Zou Jiahe lv Faculty of Engineering China University of GeosciencesWuhan430074China department of Civil Engineering Monash UniversityClaytonVIC3800Australia Badong National Observation and Research Station of Geohazards China University of GeoscienceWuhan430074China

As a calculation method based on the Galerkin variation,the numerical manifold method(NMM)adopts a double covering system,which can easily deal with discontinuous deformation problems and has a high calculation accuracy.Aiming at the thermo-mechanical(TM)coupling problem of fractured rock masses,this study uses the NMM to simulate the processes of crack initiation and propagation in a rock mass under the influence of temperature field,deduces related system equations,and proposes a penalty function method to deal with boundary conditions.Numerical examples are employed to confirm the effectiveness and high accuracy of this method.By the thermal stress analysis of a thick-walled cylinder(TWC),the simulation of cracking in the TWC under heating and cooling conditions,and the simulation of thermal cracking of the SwedishÄspöPillar Stability Experiment(APSE)rock column,the thermal stress,and TM coupling are obtained.The numerical simulation results are in good agreement with the test data and other numerical results,thus verifying the effectiveness of the NMM in dealing with thermal stress and crack propagation problems of fractured rock masses.

关键词： Heat conduction Fractured rock mass Crack propagation Galerkin variation Numerical manifold method(NMM)

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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-tong Zhou Dan lv Jing-tong Zhai Hai-Li Qian Fei Ma department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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Random change point model with an application to the China Household Finance Survey

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Science China Mathematics 2024年

作者： Meng Li Lingxi Gao Guangming lv Xingwei tong School of Statistics Beijing Normal University

We consider a linear model with a change point according to the unknown random threshold of a covariate. We give the expectation-maximization(EM) estimation of the regression and change point parameters. The existence of the random change point is detected by the supremum(SUP) test of score statistics. Theoretically, we establish the convergence and asymptotic distribution of the estimation and show that the EM estimates converge in distribution to a normal distribution. In addition, the numerical performance of the proposed approach is demonstrated through simulation studies. Finally, applying our methodology to household financial decisions, we see that the average debt tolerance of Chinese households is estimated to be 1.1364 times the sum of total household income and financial assets. The effect of assets and income on consumption shows a rapid decline if the household exceeds the average debt tolerance.

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Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella(MMAF)and ICSI outcomes

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Asian Journal of Andrology 2024年第1期26卷 91-98页

作者： Zhong-Mei Shao Yu-tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong Tang Yu-Ping Xu Ming-Rong lv Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China department of Obstetrics and Gynecology Fuyang Hospital of Anhui Medical UniversityFuyang 236112China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) Hefei 230032China Key Laboratory of Population Health Across Life Cycle(Anhui Medical University) Ministry of Education of the People'sRepublicof ChinaHefei 230032China

Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.

关键词： asthenoteratospermia DNAH6 intracytoplasmic sperm injection male infertility

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The Earth Summit Mission-2022:Successful ozone soundings contribute to source identification in the north Mt.Qomolangma region

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Journal of Environmental Sciences 2024年第2期136卷 412-421页

作者： Jinqiang Zhang Chunxiang Ye Yuejian Xuan Zhixuan Bai Weili Lin Dan Li Lingkun Ran Baofeng Jiao YaomingMa Weiqiang Ma Nan Yao Yunshu Zeng Daren lv tong Zhu Key Laboratory of Middle Atmosphere and Global Environment Observation Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China College of Environmental Sciences and Engineering Center for Environment and HealthPeking UniversityBeijing 100871China Key Laboratory of Ecology and Environment in Minority Areas(Minzu University of China) National Ethnic Affairs CommissionBeijing 100081China Key Laboratory of Cloud-Precipitation Physics and Severe Storms Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Land-Atmosphere Interaction and Its Climatic Effects Group State Key Laboratory of Tibetan Plateau Earth SystemResources and Environment(TPESRE)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China College of Earth and Planetary Sciences University of Chinese Academy of SciencesBeijing 100049China College of Atmospheric Science Lanzhou UniversityLanzhou 730000China National Observation and Research Station for Qomolongma Special Atmospheric Processes and Environmental Changes Dingri 858200China Kathmandu Center of Research and Education Chinese Academy of SciencesBeijing 100101China China-Pakistan Joint Research Center on Earth Sciences Chinese Academy of SciencesIslamabad 45320Pakistan Electronic Engineering College Chengdu University of Information TechnologyChengdu 610225China

As part of“The Earth Summit Mission-2022”during the second Tibetan Plateau Scientific Expedition and Research(STEP)in April and May 2022,we conducted the ozone sounding experiment(an ozonesonde mated to a radiosonde)at Mt.Qomolangma Base Camp(MQBC;86.85°E,28.14°N;5200 m),a location at an extremely high altitude.A total of ten sounding profiles were obtained between April 30 and May 06,2022,of which seven profiles were above35 km in altitude,with a maximum detection altitude up to 39.0 km.This study presents the temporal variation and vertical distributions of atmospheric temperature,humidity,and ozone during the MQBC campaign.The averaged ozone concentration was high(68.3 ppbv)at the surface and then increased smoothly until peaking(~110 ppbv)in the middle troposphere(approximately 10 km),and afterward,the ozone concentration increased rapidly from the upper troposphere to a maximum of~10 ppmv at~30 km.The enhanced ozone concentration in the middle troposphere was associated with the blocking high pressure,and transport from the southern flank of the Himalayas occurred during the campaign period.The average total ozone column was 291.9±21.4 DU for the seven profiles exceeding 35km in altitude.The ozonesonde measurements were also compared with the vertical ozone profiles retrieved from the space-borne ozone products from the Microwave Limb Sounder(MLS)onboard the Aura satellite and the Atmospheric Infrared Sounder(AIRS)onboard the Aqua satellite.

关键词： Ozone soundings Mt.Qomolangma Vertical ozone structure Ozone source Satellite data

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High critical current density in Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12) electrolyte via interfacial engineering with complex hydride

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Rare Metals 2024年第2期43卷 692-701页

作者： Ying-tong lv Teng-Fei Zhang Zhao-tong Hu Guang-Lin Xia Ze-Ya Huang Zhen-Hua Liu Li-Hua Que Cai-Ting Yuan Fang-Qin Guo Takayuki Ichikawa Xue-Bin Yu College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing210016China Centre for Hydrogenergy College of Materials Science and TechnologyNanjing University of Aeronautics and AstronauticsNanjing210016China department of Materials Science Fudan UniversityShanghai200433China Graduate School of Advanced Science and Engineering Hiroshima University1-4-1 KagamiyamaHigashi-Hiroshima739-8527Japan

Garnet-type solid-state batteries(SSBs)are considered to be one of the most promising candidates to realize next-generation lithium metal batteries with high energy density and safety.However,the dendrite-induced short-circuit and the poor interfacial contact impeded the practical application.Herein,interface engineering to achieve low interfacial resistance without high temperature calcination was developed,which Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZTO)was simply coated with complex hydride(Li_(4)(BH_(4))_(3)I(3L1L))in various mass ratios n(Li_(4)(BH_(4))_(3)I)-(100−n)LLZTO(10≤n≤40).The interfacial conductivity increases by more than three orders of magnitude from 8.29×10^(−6)S·cm^(−1)to 1.10×10^(−2)S·cm^(−1).Symmetric Li cells exhibit a high critical current density(CCD)of 4.0 mA·cm^(−2) and an excellent cycling stability for 200 h at 4.0 mA·cm^(−2).SSBs with polymeric sulfur-polyacrylonitrile(SPAN)cathode achieve a high discharge capacity of 1149 mAh·g^(−1) with a capacity retention of 91%after 100 cycles(0.2 C).This attempt guides a simple yet efficient strategy for obtaining a stable Li/LLZTO interface,which would promote the development of solid-state batteries.

关键词： Hydrides Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZTO) Critical current density Solid-state electrolytes(SSEs) Lithium-sulfur batteries

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Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis:A systematic review and meta-analysis

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Cancer Innovation 2024年第3期3卷 22-32页

作者： Wenhua Song Nan Zhang tonglian lv Yang Zhao Guangping Li Gary Tse tong Liu Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina department of Radiology Second Hospital of Tianjin Medical UniversityTianjinChina School of Nursing and Health Studies Hong Kong Metropolitan UniversityHong KongChina Cardiac Electrophysiology Unit Cardiovascular Analytics GroupPowerHealth LimitedHong KongChina

Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

关键词： breast surgery causal inference deep learning metastatic breast cancer

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HIV encephalopathy is contributed by macrophages and microglia

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Science China(Life Sciences) 2024年第4期67卷 836-838页

作者： Si-Meng Liu Man Li Chunhui Ma Chunying Liu An lv Qing Li Yamei Niu Peng Wang Bo Huang Wei-Min tong department of Pathology China Medical UniversityShenyang 110122China department of Pathology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeNeuroscience CenterChinese Academy of Medical SciencesBeijing 100005China department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Molecular Pathology Research Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Center For Experimental Animal Research Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China department of Immunology and National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100010China department of Biochemistry and Molecular Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。

关键词： encephalopathy immunodeficiency

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Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 118-132页

作者： Shi-Lin lv Pei Guo Jun-Rong Zou Ren-Sheng Chen Ling-Yu Luo de-Qiang Huang Hospital of Gastroenterology Institute of Digestive DiseasesThe First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina department of Pathology Shenzhen Hospital of Southern Medical UniversityShenzhen 518000Guangdong ProvinceChina Institute of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina department of Pathology The First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of

关键词： Gastric cancer pSMAD3L(S204) pSMAD3C(S423/425) Survival Transforming growth factor-β1 VEGFR-1

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