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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA division of Cellular&Molecular research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Genome-Wide Analysis for Yield-Related Agronomic and Biochemical Traits of Chinese and Bangladeshi Grass Pea Genotypes Using SSR Markers

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Phyton-International Journal of Experimental Botany 2024年第8期93卷 1781-1804页

作者： Md.Mosiur Rahman Md.Ruhul Quddus Quanle Xu Muhammad Malek Hossain Rong Liu Mengwei Li Xin Yan Guan Li Yishan Ji Chenyu Wang Ashutosh Sarker Tao Yang Xuxiao Zong Md.Monoar Hossain Saleh Alfarraj Mohammad Javed Ansari Sagar Maitra Akbar Hossain Institute of Crop Sciences Chinese Academy of Agricultural Sciences(CAAS)Beijing100081China Pulses research Center Bangladesh Agricultural Research Institute(BARI)Gazipur1701Bangladesh Hybrid Rice division Bangladesh Rice Research Institute(BRRI)Gazipur1701Bangladesh Northwest Agriculture&Forestry University Yangling712199China International Center for Agricultural research in the Dry Areas(ICARDA) New Delhi110012India Wheat Breeding division Bangladesh Wheat and Maize Research InstituteDinajpur5200Bangladesh Zoology Department College of ScienceKing Saud UniversityRiyadh11451Saudi Arabia Department of Botany Hindu College Moradabad(Mahatma Jyotiba Phule Rohilkhand UniversityBareilly)Moradabad244001India Department of Agronomy and Agroforestry Centurion University of Technology and ManagementOdisha761211India Soil Science division Bangladesh Wheat and Maize Research InstituteDinajpur5200Bangladesh

Grass pea(Lathyrus sativus L.)is an imperative food crop cultured in dryland agricultural *** is a vital source of dietary protein to millions of populaces living in low-income countries in South-East Asia and *** study highlights the improvement of genomic properties and their application in marker-trait relationships for 17 yield-related characters in 400 grass pea genotypes from China and *** characters were assessed via 56 polymorphic markers using general linear model(GLM)(P+G+Q)and mixed linear model(MLM)(P+G+Q+K)in the tassel software based on the linkage disequilibrium and population structure *** structure analysis showed two major groups and one admixed group in the *** significant loci pairs of linkage disequilibrium(LD)mean value(D′)was 0.479.A total of 99 and 61 marker-trait associations in GLM and MLM models allied to the 17 traits were accepted at a 5%level of *** these markers,21 markers were associated with more than one trait;12 marker-trait associations passed the Bonferroni correction *** models found six markers C41936,C39067,C34100,C47146,C47638,and C43047 significantly associated with days to maturity,flower color,plant height,and seed per pod were detected in the Hebei and Liaoyang location(p≤0.01),and the interpretation rate(R^(2)value)11.2%to 43.6%.Conferring to the consequences,the association analysis methodology may operative system for quantitative,qualitative,and biochemical traits related to gene position mapping and support breeders in improving novel approaches for advancing the grass pea quality.

关键词： Grass pea dryland agriculture genome-wide association yield contributing traits SSR markers

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Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure

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World Journal of Gastroenterology 2024年第34期30卷 3850-3855页

作者： Swati Katoch Vikram Patial division of Dietetics and Nutrition Technology Institute of Himalayan Bioresource TechnologyPalampur 176061Himachal PradeshIndia Academy of Scientific and Innovative research Ghaziabad 201002Uttar PradeshIndia

In this editorial,we comment on the article by Zhou et *** study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1(SIRT1)activation in acute liver failure(ALF).ALF is characterized by a sudden and severe liver injury resulting in significant hepatocyte damage,often posing a high risk of *** predominant form of hepatic cell death in ALF involves apoptosis,ferroptosis,autophagy,pyroptosis,and *** peroxidase 4(GPX4)inhibition sensitizes the cell to ferroptosis and triggers cell death,while Gasdermin D(GSDMD)is a mediator of *** study showed that ferroptosis and pyroptosis in ALF are regulated by blocking the p53/GPX4/GSDMD pathway,bridging the gap between the two *** inhibition of p53 elevates the levels of GPX4,reducing the levels of inflammatory and liver injury markers,ferroptotic events,and GSDMDN protein *** p53 expression and increased GPX4 on deletion of GSDMD indicated ferroptosis and pyroptosis ***1 is a NAD-dependent deacetylase,and its activation attenuates liver injury and inflammation,accompanied by reduced ferroptosis and pyroptosis-related proteins in ***1 activation also inhibits the p53/GPX4/GSDMD axis by inducing p53 acetylation,attenuating LPS/D-GalN-induced ALF.

关键词： Acute liver failure Ferroptosis Gasdermin D Pyroptosis p53 Silent information regulator sirtuin 1

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Metabolomics for the diagnosis of bladder cancer: A systematic review

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Asian Journal of Urology 2024年第2期11卷 221-241页

作者： Herney Andrés García-Perdomo Angélica María Dávila-Raigoza Fernando Korkes division of Urology/Urooncology Department of SurgerySchool of MedicineUniversidad del ValleCaliColombia UROGIV research Group School of MedicineUniversidad del ValleCaliColombia Urologic Oncology Division of UrologyABC Medical SchoolSao PauloBrazil

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa ***: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic ***: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes ***: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, rib

关键词： Metabolite Metabolomics Bladder cancer Metabolomicsprofile

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Cholangiocarcinoma combined with biliary obstruction:an exosomal circRNA signature for diagnosis and early recurrence monitoring

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2642-2654页

作者： Ningyuan Wen Dingzhong Peng Xianze Xiong Geng Liu Guilin Nie Yaoqun Wang Jianrong Xu Shaofeng Wang Sishu Yang Yuan Tian Bei Li Jiong Lu Nansheng Cheng division of Biliary Surgery Department of General SurgeryWest China HospitalSichuan UniversityChengduSichuanChina research Center for Biliary Diseases West China HospitalSichuan UniversityChengduSichuanChina

Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic *** present a novel system to monitor CCA using exosomal circular RNA(circRNA)via serum and biliary liquid biopsies.A pilot cohort consisting of patients with CCA-induced biliary obstruction(CCA-BO,n=5)and benign biliary obstruction(BBO,n=5)was used to identify CCA-derived exosomal circRNAs through microarray *** was followed by a discovery cohort(n=20)to further reveal a CCA-specific circRNA complex(hsa-circ-0000367,hsa-circ-0021647,and hsa-circ-0000288)in both bile and serum *** vitro and in vivo studies revealed the three circRNAs as promoters of CCA *** and prognostic models were established and verified by two independent cohorts(training cohort,n=184;validation cohort,n=105).An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature(Bile-DS,AUROC=0.947,RR=6.05)and serum exosomal circRNA signature(Serum-DS,AUROC=0.861,RR=4.04)compared with conventional CA19-9(AUROC=0.759,RR=2.08).A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score,verified with bile samples(Bile-ERS,C-index=0.783)and serum samples(Serum-ERS,C-index=0.782).These models,combined with other prognostic factors revealed by COX-PH model,enabled the establishment of nomograms for recurrence monitoring of *** study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

关键词： biliary diagnosis Serum

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Experimental and computational optimization of Prussian blue analogues as high-performance cathodes for sodium-ion batteries:A review

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Journal of Energy Chemistry 2024年第6期93卷 627-662,I0015页

作者： Gwangeon Oh Junghoon Kim Shivam Kansara Hyokyeong Kang Hun-Gi Jung Yang-Kook Sun Jang-Yeon Hwang Department of Energy Engineering Hanyang UniversitySeoul 04763Republic of Korea Energy Storage research Center Clean Energy Research DivisionKorea Institute of Science and TechnologySeoul 02792Republic of Korea Department of Energy Science Sungkyunkwan UniversitySuwon 16419Republic of Korea KIST-SKKU Carbon-Neutral research Center Sungkyunkwan UniversitySuwon 16419Republic of Korea Department of Battery Engineering Hanyang UniversitySeoul 04763Republic of Korea

In this review,we discuss the electrochemical properties of Prussian blue(PB)for Na^(+)storage by combining structural engineering and electrolyte *** integrated experimental data and density functional theory(DFT)in sodium-ion battery(SIB)research to refine the atomic arrangements and crystal lattices and introduce substitutions and *** changes affect the lattice stability,intercalation,electronic and ionic conductivities,and electrochemical *** unraveled the intricate structure-electrochemical behavior relationship by combining experimental data with computational models,including first-principles *** holistic approach identified techniques for optimizing PB and Prussian blue analog(PBA)structu ral properties for *** also discuss the tuning of electrolytes by systematically adjusting their composition,concentration,and additives using a combination of molecular dynamics(MD)simulations and DFT *** review offers a comprehensive assessment of strategies for enhancing the electrochemical properties of PB and PBAs through structural engineering and electrolyte modifications,combining experimental insights with advanced computational simulations,and paving the way for next-generation energy storage systems.

关键词： Prussian blue analogs(PBAs) Sodium ion batteries(SIBs) Structural engineering Electrolyte modifications Experiments Density functional theory(DFT)

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New pharmacological tools:the use of diterpenes to promote adult hippocampal neurogenesis

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Neural Regeneration research 2024年第8期19卷 1629-1630页

作者： Ricardo Gomez-Oliva Pedro Nunez-Abades Carmen Castro Department of Biomedicine Biotechnology and Public HealthDivision of PhysiologyUniversity of CadizCadizSpain Biomedical research and Innovation Institute of Cadiz(INiBICA) CadizSpain Department of Physiology University of SevilleSevilleSpain

Tissue regeneration maintains homeostasis and preserves the functional features of each ***,not all tissues show a strong repairing *** is the case of the central nervous *** is now well established that the generation of new functional neurons from stem cells in the adult brain occurs in specific regions of the brain of different species such as rodents,birds,primates,and humans(Eriksson et al.,1998).

关键词： capacity maintain preserve

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Prevention of ventilator-associated pneumonia with inhaled antibiotics

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World Journal of Emergency Medicine 2024年第3期15卷 165-168页

作者： Stephan Ehrmann Jie Li Intensive Care Medicine INSERM CIC 1415CRICS-TriggerSep FCRIN research networkUniversity Hospital Center in ToursTours 37044France Respiratory Pathology research Center National Institute of Health and Medical ResearchTours 37000France Department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicago 60612USA

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable *** interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated *** high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

关键词： pneumonia ventilator respiratory

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Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni division of Brain Science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral ***,there are few effective clinical treatments for neonatal hypoxic-ischemic brain ***,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain *** this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours *** results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental *** mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury *** reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin *** analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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Wharton’s jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury

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World Journal of Stem Cells 2024年第7期16卷 742-759页

作者： Prashasti Sharma Dharmendra Kumar Maurya Life Sciences Homi Bhabha National InstituteMumbai 400094MaharashtraIndia Radiation Biology&Health Sciences division Bhabha Atomic Research CentreMumbai 400085MaharashtraIndia

Wharton’s jelly mesenchymal stem cells(WJ-MSCs)are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation ***-MSCs are more naïve and have a better safety profile,making them suitable for both autologous and allogeneic *** review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation *** this review,we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and ***,the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.

关键词： Stem cells Wharton’s jelly mesenchymal stem cells Radiotherapy Xerostomia Lung fibrosis

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