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Creep rupture life predictions for Ni-based single crystal superalloys with automated machine learning

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Rare Metals 2024年第6期43卷 2884-2890页

作者： Chang-lu Zhou Rui-Hao Yuan Wei-Jie Liao Ting-Huan Yuan Jiang-Kun Fan Bin Tang ping-Xiang Zhang Jin-Shan Li Turab Lookman State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi'an 710072China Chongqing Innovation Center Northwestern Polytechnical UniversityChongqing 401120China AiMaterials Research LLC Santa FeNM 87501USA

The state of the art for data-driven creep rupture life predictions incorporates microstructural and deformation characteristics into machine ***,the microstructures and deformation mechanisms for unknown alloys are inaccessible and uncertain before experiments are carried out,and therefore prevents extrapolations of the learned models.

关键词： deformation life creep

Analysis of status and influencing factors of mental health in patients with systemic lupus erythematosus

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World Journal of Psychiatry 2024年第6期14卷 829-837页

作者： Xuan Zhang Zhe wang Gui-Ling Lin Fang-Zhi Wei Yan-ping Zhuang Wen-lu Xu Qi Zhang Hui-Tao Wu Zi-Man He Xi-Yu Yin Ying Liu Long Mi Ai-Min Gong School of Traditional Chinese Medicine Hainan Medical UniversityHaikou 571101Hainan ProvinceChina Department of Rheumatology and Immunology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311Hainan ProvinceChina Department of Radiology The First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityHaikou 570100Hainan ProvinceChina

BACKGROUND Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disorder with varied clinical courses and prognoses,not only did the patients suffer from physical impairment,but also various physical and psychiatric *** evidence have suggested that mental disorders in SLE patients,can lead to various adverse *** To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social *** results would provide a basis for psychological intervention in patients with *** The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were *** assessment and correlation analysis were conducted using the Symptom Checklist-90(SCL-90)and Perceived Social Support Scale,and the collected data were compared with the national norms in *** relevant factors influencing mental health were identified by statistical analysis.A general information questionnaire,the Revised Life Orientation Test,and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life(QoL),*** Patients with SLE obtained higher scores for the somatization,depression,anxiety,and phobic anxiety subscales than national norms(Pluenced by hormone dosage and ***’menta

关键词： Systemic lupus erythematosus Mental health Quality of life Influencing factors

Intraperitoneal injection but not oral administration of ellagic acid: A novel immunomodulator via targeting casein kinase 2 signaling pathway

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Food Science and Human Wellness 2024年

作者： Wen-Hui Qi Bing Han Ting-Ting Cui Pei-Xin Shen Zhuo-Hua Zhao Ya-ping Yan Li-Bin wang Xin-Yu lu Yuan Zhang Xing Li Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University) The Ministry of Education College of Life Sciences Shaanxi Normal University Department of Pharmacology School of Pharmacy Fourth Military Medical University The Nervous System Disease Diagnosis and Treatment Engineering Technology Research Center of Ningxia School of Medical Technology Xi'an Medical University

Immunosuppressants currently approved for the treatment of autoimmune diseases and organ transplant rejection present diverse adverse effects that impair the life quality of patients. Therefore， the development of novel immunomodulators with high efficiency and low toxicity is essential. Ellagic acid (EA)， a natural polyphenol compound widely distributed in berries， is metabolically transformed by gut microbiome to exert systemic health benefits. Here， we identified that intraperitoneal administration of EA with no cytotoxicity， beyond its well-known oral metabolic fate， effectively decreased clinical severity and CNS inflammation/demyelination in experimental autoimmune encephalomyelitis (EAE)， a mouse model of an autoimmune disease multiple sclerosis (MS). Interestingly， intraperitoneal EA administration at incredibly low doses (0.1 mg/kg/d) is dose-sparing with fingolimod (FTY720)， the first FDA-approved oral drug for MS. In addition， intraperitoneal EA also ameliorated the brain damage in a neuromyelitis optica (NMO) model， and significantly prevented the immune rejection of allograft skin graft. Evidence from pharmacological studies combined with RNA-seq indicate that prototype EA functions by a mechanism that involves direct inhibition of casein kinase II (CKII) to suppress the expression of IL-17 and promote the expression of Cpt1a to regulate Th17 differentiation. In conclusion， our study demonstrates that the prototype EA entering the blood circulation acts as a novel therapeutic immunomodulator for the treatment of autoimmune diseases and transplant rejection through the CKⅡ-mediated JAK/STAT/Cpt1a signaling pathway.

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Reshaping the active pocket of an aldo-keto reductase to enhance its detoxification activity towards 3-keto-deoxynivalenol

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Food Science and Human Wellness 2024年

作者： Jiafeng Niu Bin Ma Hao Zhu Huawei Liu Haizhen Zhao Xiaomei Bie Fengxia lu ping Zhu College of Food Science and Technology Nanjing Agricultural University State Key Laboratory of Desert and Oasis Ecology Xinjiang Institute of Ecology and Geography Chinese Academy of Sciences

Deoxynivalenol （DON）， the most common mycotoxin in the world， poses serious health hazards to both humans and animals and causes significant economic losses to the food and feed industry. An intriguing method for DON detoxification involves enzymatic cascade catalysis by dehydrogenase （DADH） and aldo-keto reductase （AKR13B3）. However， the poor catalytic activity of AKR13B3 has limited its usefulness. Here， structure-guided steric hindrance engineering， computer-assisted protein engineering， and combinatorial mutagenesis were carried out to increase the catalytic efficiency of AKR13B3. The best mutant in this project was M28S/S65V， which outperformed wild-type AKR13B3 in terms of catalytic efficiency (kcat/Km) and specific activity by factors of 45.08 and 43.11， respectively. Kinetic parameter determination revealed that the enhanced catalytic efficiency of M28S/S65V toward 3-keto-DON was attributed to the decreased Kmand increased kcatvalues. Moreover， the engineered enzyme was applied to degrade DON in contaminated corn steep liquor， for a 90.62% removal rate. Structure-based computational analysis provided insights into the enhanced catalytic efficiency of M28S/S65V， which was attributed to the enlarged substrate-binding pocket and reshaped pocket with a favorable hydrophilic attack distance. The results provide a reference for improving the catalytic activity of an enzyme toward non-native bulky substrates and pave the way for the development of enzymes as detoxification agents to mitigate DON in the food and feed industry.

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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重组人凝血因子Ⅶ的临床试验分析

中国新药杂志 2024年第13期33卷 1321-1328页

作者：王延琳于爱平鲁爽国家药品监督管理局药品审评中心北京100163

目前,多家医药企业利用基因重组技术研发重组人凝血因子Ⅶ,其中NovoSeven和Sevenfact已获批上市,我国有多个研发中的重组凝血因子Ⅶ处于临床试验阶段。本文简要介绍NovoSeven和Sevenfact的临床试验内容,重点分析其针对血友病A/B的临床... 详细信息

目前,多家医药企业利用基因重组技术研发重组人凝血因子Ⅶ,其中NovoSeven和Sevenfact已获批上市,我国有多个研发中的重组凝血因子Ⅶ处于临床试验阶段。本文简要介绍NovoSeven和Sevenfact的临床试验内容,重点分析其针对血友病A/B的临床试验设计关键要素,包括临床试验开展顺序、药动学和药效学研究、给药方案探索、有效性评价指标、安全性评价关注问题等。希望国内医药企业借鉴已上市产品研发经验,结合自身特点和临床实际情况,完成合理的临床试验方案设计并获得足够的临床试验数据,进而充分说明在研产品的临床有效性和安全性特征,最终实现国产重组人凝血因子Ⅶ的成功研制。

关键词：重组凝血因子Ⅶ 临床试验有效性评价安全性评价

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第7期30卷 579-587页

作者： ZHANG Shao-yan QIU Lei ZHANG Shun-xian XIAO He-ping CHU Nai-hui ZHANG Xia ZHANG Hui-qiang ZHENG Pei-yong ZHANG Hui-yong lu Zhen-hui Institute of Respiratory Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai200032China Clinical Research Center Shanghai University of Traditional Chinese MedicineShanghai200032China Department of Tuberculosis Shanghai Pulmonary HospitalTongji UniversityShanghai200433China Department of Tuberculosis Beijing Chest HospitalCapital Medical UniversityBeijing101100China Department of Tuberculosis the Second Hospital of NanjingNanjing210003China Department of Tuberculosis the First Hospital Affiliated to Xinxiang Medical CollegeXinxiangHenan Province453100China

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all Plusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of pati

关键词： alternative medicine Chinese herbal formula Bufei Jiedu Granules multidrug-resistant tuberculosis long-course chemotherapy regimen randomized controlled trial

Salinity fronts shape spatial patterns in zooplankton distribution in Hangzhou Bay

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Acta Oceanologica Sinica 2024年第6期43卷 96-106页

作者： Yepeng Xu Yiqi wang Lin Zhan Yijun Ou Kangning Jia Ming Mao Xuyu Zhu Zhibing Jiang Yuanli Zhu Wei Huang ping Du Jiangning Zeng lu Shou Feng Zhou Key Laboratory of Marine Ecosystem Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China Key Laboratory of Nearshore Engineering Environment and Ecological Security of Zhejiang Province Hangzhou 310012China State Key Laboratory of Satellite Ocean Environment Dynamics Ministry of Natural ResourcesHangzhou 310012China Nantong Marine Environmental Monitoring Center Ministry of Natural ResourcesNantong 226002China Key Laboratory of Ocean Space Resource Management Technology Ministry of Natural ResourcesHangzhou 310012China Observation and Research Station of Marine Ecosystem in the Yangtze River Delta Ministry of Natural ResourcesZhoushan 316021China

Ocean fronts play important roles in nutrient transport and in the shaping ecological *** zones in small bays are typically small in scale,have a complex structure,and they are spatially and temporally variable,but there are limited data on how biological communities respond to this *** Bay,a mediumsized estuary in China,is an ideal place in which to study the response of plankton to small-scale ocean fronts,because three water masses(Qiantang River Diluted Water,Changjiang River Diluted Water,and the East China Sea current) converge here and form dynamic salinity fronts throughout the *** investigate zooplankton communities,and temperature,salinity and chlorophyll a(Chl a) in Hangzhou Bay in June(wet perio d) and December(dry period) of 2022 and examine the dominant environmental factors that affect zooplankton community spatial *** then match the spatial distributions of zooplankton communities with those of salinity fronts.S alinity is the most important explanatory variable to affect zooplankton community spatial variability during both wet and dry periods,in that it contributes>60% of the variability in community ***,the spatial distributions of zooplankton match well with salinity *** December,with weaker Qiantang River Diluted Water and a stronger secondary Changjiang River Plume,zooplankton communities occur in moderate salinity(MS,salinity range 15.6±2.2) and high salinity(HS,22.4±1.7) regions,and their ecological boundaries closely match the Qiantang River Diluted Water *** June,different zooplankton communities occur in low salinity(LS,3.9±1.0),MS(11.7±3.6) and HS(21.3±1.9) *** the LS region occurs abnormally in the central bay rather than its apex because of the anomalous influence of rising and falling tides during the sampling perio d,the ecological boundaries still match salinity ***-salinity or brackish-water zooplankter taxa are relatively more abunda

关键词： zooplankton spatial distribution salinity fronts Hangzhou Bay

Microstructured fluorescence in liquid crystals with femtosecond laser excitation

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Chinese Optics Letters 2024年第3期22卷 154-158页

作者：孟霞金萍葛士军刘娇李炳祥王磊陆延青 College of Electronic and Optical Engineering&College of Flexible Electronics(Future Technology) Nanjing University of Posts and TelecommunicationsNanjing 210023China National Laboratory of Solid State Microstructures College of Engineering and Applied SciencesNanjing UniversityNanjing 210093China State Key Laboratory of Millimeter Waves Southeast UniversityNanjing 210096China

This study investigated direct fluorescence generation from a nematic liquid crystal(NLC)NJU-LDn-4 under femtosecond laser *** absorption,transmittance,excitation,and emission spectra of the NLC were *** relationship between the femtosecond pump power and fluorescence intensity was analyzed,revealing a quadratic increase and indicating that two-photon absorption(2PA)is the primary fluorescence *** LC microstructure was designed using photoalignment technology,allowing the generated fluorescence to reflect the corresponding *** research can establish a foundation for tunable LC microstructured fluorescence,with potential applications in fluorescence microscopy and optoelectronics.

关键词： liquid crystal femtosecond laser fluorescence microstructure