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Actin(g) toward a revised understanding of the role of cytoskeletal dynamics in neuronal bioenergetics

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Neural Regeneration Research 2024年第10期19卷 2109-2110页

作者： Sabrina M.Holland Gianluca Gallo Department of Neural Sciences Shriners Pediatric Research CenterLewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

Neurons are energy-demanding *** in energy metabolism can quickly interrupt neuronal function,leading to cell death and *** instance,ischemia rapidly depletes adenosine triphosphate(ATP)thereby disrupting energy-dependent cellular processes crucial for homeostasis,and axon degeneration is preceded by a collapse of axonal ATP levels.

关键词： metabolism homeostasis degeneration

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational Biology St.Jude Children's Research HospitalMemphisTN 38105USA Center for Proteomics and Metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural Biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

Enhancing single-cell encapsulation in droplet microfluidics with fine-tunable on-chip sample enrichment

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Microsystems & Nanoengineering 2024年第1期10卷 149-160页

作者： Tao Tang Hao Zhao Shaofei Shen Like Yang Chwee Teck Lim Department of Biomedical Engineering National University of Singapore117583 SingaporeSingapore Integrative Sciences and Engineering Programme NUS Graduate SchoolNational University of Singapore119077 SingaporeSingapore Shanxi Key Lab for Modernization of TCVM College of Life ScienceShanxi Agricultural UniversityTaiguShanxi 030801China institute for health Innovation&Technology National University of Singapore117599 SingaporeSingapore Mechanobiology institute National University of Singapore117411 SingaporeSingapore institute for Digital Molecular Analytics and Science Nanyang Technological University636921 SingaporeSingapore

Single-cell encapsulation in droplet microfluidics is commonly hindered by the tradeoff between cell suspension density and on-chip focusing *** this study,we introduce a novel droplet microfluidic chip to overcome this *** chip comprises a double spiral focusing unit,a flow resistance-based sample enrichment module with fine-tunable outlets,and a crossflow droplet generation *** a low-density cell/bead suspension(2×10^(6) objects/mL),cells/beads are focused into a near-equidistant linear arrangement within the double spiral *** excess water phase is diverted while cells/beads remain focused and sequentially encapsulated in individual *** performance was assessed through numerical simulations and experiments at three flow rates(40,60,80μL/min),demonstrating successful focusing at 40 and 80μL/min for beads and cells,*** addition,both simulation and experimental results revealed that the flow resistance at the sample enrichment module is adjustable by punching different outlets,allowing over 50%of the aqueous phase to be ***8n-based droplet detection algorithms realized the counting of cells/beads in droplets,statistically demonstrating single-cell and bead encapsulation rates of 72.2%and 79.2%,*** the results indicate that this on-chip sample enrichment approach can be further developed and employed as a critical component in single-cell encapsulation in water-in-oil droplets.

关键词： beads outlet sample

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.Nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

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

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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

Systematic pan-cancer analysis reveals OGT and OGA as potential biomarkers for tumor microenvironment and therapeutic responses

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Genes & Diseases 2024年第4期11卷 1-4页

作者： Chunyan Hou Ci Wu Wenge Zhu Huadong Pei Junfeng Ma Department of Oncology Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDC 20007USA Department of Biochemistry and Molecular Medicine School of Medicine and Health ScienceGeorge Washington UniversityWashingtonDC20052USA

Protein O-linkedβ-N-acetylglucosamine(O-GlcNAc)modification(O-GlcNAcylation)is a unique monosaccharide modification of essential importance in physiology and pathology.1,2 As a highly dynamic process,O-GlcNAcylation is mediated by two paired enzymes:O-GlcNAc transferase(OGT)and O-GlcNAcase(OGA),which add or remove the modification from proteins,*** evidence demonstrates that the aberrant O-GlcNAcylation underlies the initiation,progression,and metastasis of cancer.

关键词： metastasis pathology therapeutic

Prevalence of retinal pathologies in people over 60 years:the Tehran Geriatrics Eye Study

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 721-728页

作者： Abolghasem Mortazavi Alireza Hashemi Alirerza Jamali Hassan Hashemi Mohammadreza Aghamirsalim Mehdi Khabazkhoob Department of Neurosurgery Sina HospitalTehran University of Medical SciencesTehran ***Iran Noor Ophthalmology Research Center Noor Eye HospitalTehran ***Iran Rehabilitation Research Center Department of OptometrySchool of Rehabilitation SciencesIran University of Medical SciencesTehran ***Iran Noor Research Center for Ophthalmic Epidemiology Noor Eye HospitalTehran ***Iran Translational Ophthalmology Research Center Tehran University of Medical SciencesTehran ***Iran Department of Basic Sciences School of Nursing and MidwiferyShahid Beheshti University of Medical SciencesTehran ***Iran

AIM:To determine the prevalence of some retinal pathologies in people over 60y and their association with demographic and ocular ***:A cross-sectional study was conducted in Tehran using multistage cluster *** selecting subjects aged 60 and over,optometric,and ophthalmic examinations were *** retinal examination,a 90 D lens was used and indirect ophthalmoscopy was performed after instilling tropicamide *** was done using the IOL Master for all ***:Of 3791 people that were invited through cluster sampling,3310 participated in the study(response rate=82%).The prevalence of retinal pigmented epithelium(RPE)change,drusen,geographic atrophy(GA),hypertensive retinopathy(HTR),nonproliferative diabetic retinopathy(NPDR),proliferative diabetic retinopathy(PDR),choroidal neovascularization(CNV),central retinal artery occlusion(CRAO),myopic retinopathy(MR),branch retinal vein occlusion(BRVO),and central retinal vein occlusion(CRVO)was 27.42%,11.08%,4.52%,3.03%,4.05%,0.54%,0.82%,0.39%,0.20%,0.49%,and 0.19%,*** removing the effect of age,the odds of NPDR were 1.68 times higher in women compared to men(P=0.014).After removing the effect of sex,the odds of drusen,RPE change,GA,CNV,BRVO,and CRVO increased with ***:There is a higher prevalence of RPE change,drusen,GA,CNV and a lower prevalence of MR and CRAO in the elderly population of Tehran aged over 60y compared to global average *** the correlation of most of the diseases with age and their effects on vision,attention should be paid to these diseases and the related screening programs to prevent vision impairment.

关键词： retinal pathologies cross-sectional study vision impairment

Bioinspired nanomaterials for the treatment of bacterial infections

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Nano Research 2024年第2期17卷 691-714页

作者： Xiaojing Ma Wenjing Tang Rong Yang Robert F.Smith School of Chemical&Biomolecular Engineering Cornell UniversityIthacaNY 14853USA

Infectious diseases pose a serious threat to global *** immunizations can control most viral infections,bacterial infections,particularly those caused by drug-resistant strains,continue to cause high rates of illness and ***,the creation of new antibiotics has come to a grinding halt in the last ten *** response to this crisis,nanotechnology has emerged as a hopeful solution to tackle drug resistance and enhance treatment results.A large variety of biomimetic nanomaterials,termed nanozymes,have demonstrated strong antimicrobial *** the inherent toxicity of nanomaterials is a concern,recent studies have harnessed the stimuli-responsiveness of nanomaterials to enable local and/or targeted delivery to reduce the treatment side ***,the physicochemical versatility of nanomaterials affords many degrees of freedom that enable rational design of smart or autonomous therapeutics,which cannot be achieved using conventional *** design straddles the fields of catalysis,nanoscience,microbiology,and translational *** provide an overview of this interdisciplinary landscape,this review is organized based on composition into lipid,metal,metal oxide,and non-metallic *** as a delivery vehicle enhance bioavailability and reduce ***-and metal oxide-based nanomaterials inhibit bacterial growth by mimicking natural enzymatic activities such as peroxidase(POD)and ***,carbon-,polymer-,and cell membrane-based nanomaterials are combined into a discussion on non-metallic *** the end of this review,potentially fruitful directions for future bioinspired nanomaterials in infectious disease treatment are included.

关键词： bioinspired nanomaterial bacteria infectious disease antimicrobial liposome nanozyme

Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for Tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： Tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design