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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

International Journal of Extreme Manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath Mitra Sushant Ciliveri Jose D Avila William Dernell Stuart B Goodman Susmita Bose W.M.Keck Biomedical Materials Research laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America veterinary clinical Sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America Department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. Mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3D printing antibacterial performance

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clinical applications of metagenomics next-generation sequencing in infectious diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 471-484页

作者： Ying LIU Yongjun MA Department of clinical laboratory Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000China

Infectious diseases are a great threat to human *** and accurate detection of pathogens is important in the diagnosis and treatment of infectious *** next-generation sequencing(mNGS)is an unbiased and comprehensive approach for detecting all RNA and DNA in a *** the development of sequencing and bioinformatics technologies,mNGS is moving from research to clinical application,which opens a new avenue for pathogen *** studies have revealed good potential for the clinical application of mNGS in infectious diseases,especially in difficult-to-detect,rare,and novel ***,there are several hurdles in the clinical application of mNGS,such as:(1)lack of universal workflow validation and quality assurance;(2)insensitivity to high-host background and low-biomass samples;and(3)lack of standardized instructions for mass data analysis and report ***,a complete understanding of this new technology will help promote the clinical application of mNGS to infectious *** review briefly introduces the history of next-generation sequencing,mainstream sequencing platforms,and mNGS workflow,and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

关键词： Metagenomics next-generation sequencing(mNGS) Infectious disease Cerebrospinal fluid(CSF) Oxford Nanopore Technologies(ONT) Microbiome

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Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2024年第20期30卷 2633-2637页

作者： Wafaa Mohamed Ezzat Department of Internal Medicine Medical Research and Clinical Studies InstituteNational Research CenterGiza 12311Egypt

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et *** carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of *** discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance ***,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and *** insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

关键词： Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Diet Physical activity Life style

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First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang Chan Zhu Dongsheng Chen Baorui Liu Juan Du The comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

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Quantitative estimation of global mean precipitation throughout the Phanerozoic era

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Science China Earth Sciences 2024年第5期67卷 1616-1624页

作者： Xiujuan BAO Yongyun HU laboratory for Climate and Ocean-Atmospheric studies Department of Atmospheric and Oceanic SciencesSchool of PhysicsPeking UniversityBeijing 100871China

Quantitatively estimating the global mean precipitation(GMP)throughout Earth's history is crucial for enhancing our understanding of long-term climate evolution and the hydrological ***,currently there is no established methodology for estimating global mean ***,we present the first study that estimates GMP in the Phanerozoic *** relationship between GMP and global mean surface temperature(GMST)is investigated by analyzing data from 23 models in the Coupled Model Intercomparison Project phase 6(CMIP6).The result reveals consistent and significant impact of temperature on precipitation,with a sensitivity range of 2–3%K^(-1).Additionally,we propose a method for accessing latitudinal variations in precipitation caused by land area distributions and paleo-Koppen climatic *** climatic belts are determined based on geological indicators such as coals,evaporites,and glacial *** GMP is thus quantitatively estimated by combining variations in GMST,land area distributions,and paleo-koppen climatic belts,spanning from 540 Ma to the present *** quantitative GMP curve demonstrates fluctuations in GMP about 500 mm yr^(-1),with values ranging from 948 to1442 mm yr-1over the Phanerozoic *** curve aligns closely with findings derived from numerical *** presented paleoprecipitation variations facilitate a more comprehensive understanding of the interconnected geological and paleoclimatic developments.

关键词： Paleoprecipitation Paleoclimate K?ppen climatic belts Global mean precipitation Hydrological cycle

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang Department of laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical Medicine Shandong UniversityJinanChina Core Unit of National clinical Research Center for laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of clinical laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of clinical laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Comparative analysis of two digestive tract reconstruction methods in total laparoscopic radical total gastrectomy

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1109-1120页

作者： Tian-Xiang Dong Dong Wang Qun Zhao Zhi-Dong Zhang Xue-Feng Zhao Bi-Bo Tan Yu Liu Qing-Wei Liu Pei-Gang Yang Ping-An Ding Tao Zheng Yong Li Zi-Jing Liu Third Department of Surgery of the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric CancerShijiazhuang 050011Hebei ProvinceChina

BACKGROUND The incidence of gastric cancer has significantly increased in recent *** resection is the main treatment,but the method of digestive tract reconstruction after gastric cancer surgery remains *** the current study,we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after *** this end,we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction(DTR)and esophageal jejunum Roux-en-Y reconstruction(RY).AIM To explore the application effect of DTR in total laparoscopic radical total gastrectomy(TLTG)and evaluate its safety and *** We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January *** them,35 cases were treated with DTR,and the remaining 42 cases were treated with traditional *** 1:1 propensity score matching,the cases were grouped into 31 cases per group,with evenly distributed *** clinical characteristics and short-and long-term clinical outcomes of the two groups were statistically *** The two groups showed no significant differences in basic data,intraoperative blood loss,number of lymph node dissections,first defecation time after operation,postoperative hospital stay,postoperative complications,and laboratory examination results on the 1st,3rd,and 5th days after *** operation time of the DTR group was longer than that of the RY group[(307.58±65.14)min vs(272.45±62.09)min,P=0.016],but the first intake of liquid food in the DTR group was shorter than that in the RY group[(4.45±1.18)d vs(6.0±5.18)d,P=0.028].The incidence of reflux heartburn(Visick grade)and postoperative gallbladder disease in the DTR group was lower than that in the RY group(P=0.033 and P=0.038).Although there was no significant difference in bod

关键词： Gastric cancer Jejunal interposition double-tract reconstruction Roux-en-Y reconstruction Laparoscope

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Transition-Metal-Free Allylic Defluorination Cross-Electrophile Coupling Employing Rongalite

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Chinese Journal of Chemistry 2024年第12期42卷 1360-1366页

作者： Xiang-Long Chen Chun-Yan Wu Dong-Sheng Yang Bo-Cheng Tang Huai-Yu Wang Zhi-Cheng Yu Anling Li Yan-Dong Wu An-Xin Wu National Key laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhanHubei 430079China state Key laboratory of Chemical Biology and Drug Discovery Department of Applied Biology and Chemical Technology The HongKong Polytechnic UniversityKowloonHong Kong SARChina Department of clinical laboratory Center for Gene Diagnosisand Program of Clinical Laboratory MedicineZhongnan Hospital of Wuhan UniversityWuhanHubei 430062China

comprehensive Summary The conversion of CF3-alkenes to gem-difluoroalkenes using reductive cross-coupling strategy has received much attention in recent years,however,the use of green and readily available reducing salt to mediate these reactions remains to be *** this work,a concise construction of gem-difluoroalkenes,which requires neither a catalyst nor a metal reducing agent,was ***,a safe and inexpensive industrial product,was employed as both a radical initiator and *** procedure was compatible with both linear and cyclic diaryliodonium salts,enabling a wide variety of substrates(>70 examples).The utility of this approach was demonstrated through gram-scale synthesis and efficient late-stage functionalizations of anti-inflammatory drugs.

关键词： Defluoroarylation Transition metal free gem-Difluoroalkenes Rongalite Single electron transfer C-C coupling Redox reactions Cross-coupling

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Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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World Journal of Stem Cells 2024年第2期16卷 70-88页

作者： Min Meng Wei-Wei Zhang Shuang-Feng Chen Da-Rui Wang Chang-Hui Zhou Department of Central laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of clinical laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues *** diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung *** umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage ***,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung *** searched the Public clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary *** this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical ***,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in *** brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

关键词： Pulmonary diseases Mesenchymal stem cells Human umbilical cord Cell therapy clinical trials

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