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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

gram-negative bacterial diversity and evidence of international clones of multidrug-resistant strains in zoo animals

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Integrative Zoology 2024年第3期19卷 417-423页

作者： João Pedro Rueda FURLAN Micaela Santana RAMoS Fábio Parra SELLERA Irys Hany Lima goNZALEZ Patrícia Locosque RAMoS Eliana guedes STEHLINg Department of clinical Analyses Toxicology and Food ScienceSchool of Pharmaceutical Sciences of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil Department of Internal Medicine School of Veterinary Medicine and Animal ScienceUniversity of São PauloSão PauloBrazil School of Veterinary Medicine Metropolitan University of SantosSantosBrazil Coordination of Wild Fauna Secretary of EnvironmentInfrastructure and LogisticsSão PauloBrazil

Antimicrobial resistance(AMR)is a growing phenomenon that poses a major public health challenge worldwide(Dhingra et al.2020;Antimicrobial Resistance Collaborators 2022).The selective pressure exerted in clinical settings has contributed to the longlasting successful dissemination of multidrug-resistant(MDR)gram-negative bacteria in these environments(Chia et al.2020).

关键词： multidrug clinical

Diagnostic and prognostic performances of gALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

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World Journal of gastroenterology 2024年第17期30卷 2343-2353页

作者： oraphan Jitpraphawan Witchakorn Ruamtawee Mala Treewatchareekorn Supatsri Sethasine division of gastroenterology and Hepatology Department of MedicineNavamindradhiraj UniversityDusit 10300BangkokThailand clinical Research Center Research Facilitation DivisionNavamindradhiraj UniversityDusit 10300BangkokThailand division of clinical Chemistry and Immunology Navamindradhiraj UniversityDusit 10300BangkokThailand

BACKgRoUND The gALAD score has improved early hepatocellular carcinoma(HCC)detection *** role of the gALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular *** To determine the diagnostic/prognostic performances of the gALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the gALAD score with those of other serum *** This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira *** patients had HCC staging allocation using the Barcelona Clinic Liver Cancer(BCLC)***,HCC etiology,and HCC features were *** and the gALAD score were obtained at *** performance of the gALAD score and biomarkers were prospectively *** Exactly 115 individuals were diagnosed with *** gALAD score increased with disease *** BCLC-0/A and BCLC-B/C/D,the gALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of gALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the gALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of gALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of gALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year *** The gALAD model can diagnose HCC at the curative stage,includin

关键词： Alpha-fetoprotein Barcelona clinic liver cancer gALAD score Hepatocellular carcinoma Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence-II

A giant scrotal pendulous fibroma mimicking a supernumerary testis

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Asian Journal of Andrology 2024年第2期26卷 227-228页

作者： Luigi Quaresima Rocco Francesco Delle Fave giordano Polisini Daniela Fasanella Willy giannubilo Urology division Civitanova Marche HospitalCivitanova Marche 62012Italy Department of clinical and Specialist sciences Division of UrologyPolytechnic University of the Marche Region Medical SchoolAncona 60126Italy Department of Life Health and Environmental SciencesUniversity of L'AquilaL'Aquila 67100Italy

DearEditor,Pendulous fibroma,also called acrochordon,is a benign skin neoplasm,originating from the ***,small in size,it can arise from any point of the dermis(frequently from the axillary area,inguinal region,eyelid,or neck),and in some cases,it can be *** fibromas are more frequent in obese subjects,and most of the time,they are sporadic,although sometimes,they can be observed in Birt-Hogg-Dube *** some rare cases,they can reach considerable ***,they are associated with diabetes mellitus,obesity,and intestinal ***,the pedicle undergoes torsion,causing pain and ischemic necrosis of the fibroma,which requires rapid removal of the *** present a case of giant pendulous fibroma of the *** patient has given his consent to the publication of his clinical information and photographic images in an anonymous form.

关键词： frequent obesity clinical

High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione(C3),as a novel EgFR—HER2 dual inhibitor in gastric tumors

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oncology Research 2024年第2期32卷 251-259页

作者： MESFER AL SHAHRANI REEM gAHTANI MoHAMMAD ABoHASSAN MoHAMMAD ALSHAHRANI YASSER ALRAEY AYED DERA MoHAMMAD RAJEH ASIRI PRASANNA RAJAgoPALAN Department of clinical Laboratory sciences College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia

gastric cancers are caused primarily due to the activation and amplification of the EgFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and *** therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic ***,dual inhibition strategies are recommended to increase potency and reduce *** this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EgFR/HER2 kinase ***-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EgFR and *** atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand ***/HER2 kinase enzymes,KAToIII,and Snu-5 cells were used for in vitro *** atomistic Molecular Dynamics simulations followed by solvent-based gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EgFR and *** predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EgFR and HER2 residues.C3 inhibited EgFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,*** gI50 values of C3 to inhibit KAToIII and Snu-5 cells were 84.76 and 48.26 nM,*** on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EgFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.

关键词： Dual inhibitor Drug discovery EgFR/HER2 kinase gastric cancer High-throughput screening

glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

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Neural Regeneration Research 2024年第8期19卷 1637-1638页

作者： Pete A.Williams Robert J.Casson Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden ophthalmic Research Laboratories Discipline of Ophthalmology and Visual SciencesUniversity of AdelaideAdelaideAustralia

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic *** refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

关键词： metabolism glaucoma globally

Endotoxin-induced alterations of adipose tissue function:a pathway to bovine metabolic stress

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1391-1407页

作者： Miguel Chirivi g.Andres Contreras Department of Large Animal clinical sciences Michigan State UniversityEast LansingMIUSA

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues(AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.

关键词： Adipose tissue dysfunction Endotoxin Inflammation Insulin resistance

Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates

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Asian Journal of Urology 2024年第1期11卷 48-54页

作者： Michele Marchioni giulia Primiceri Alessandro Veccia Marta Di Nicola Umberto Carbonara Fabio Crocerossa Ugo Falagario Ambra Rizzoli Riccardo Autorino Luigi Schips Laboratory of Biostatistics Department of MedicalOral and Biotechnological Sciences“G.d'Annunzio”University of ChietiChietiItaly Urology Unit Department of MedicalOral and Biotechnological Sciences“G.d'Annunzio”University of ChietiChietiItaly division of Urology VCU HealthRichmondVAUSA

objective:Prostate cancer(PCa)patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia(BPH).Some of them might be treated for their lower urinary tract symptoms instead of *** aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery,namely complication and mortality ***:Within the American College of Surgeons National Surgical Quality Improvement Program database(2011-2016),we identified patients who underwent transurethral resection of the prostate,photoselective vaporization,or laser *** were stratified according to postoperative diagnosis(PCa ***).Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality.A formal test of interaction between diagnosis and surgical technique used was ***:overall,34542 patients were *** all,2008(5.8%)had a diagnosis of *** multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients(odds ratio:0.9,95%confidence interval:0.7-1.1;p=0.252).Moreover,similar rates of perioperative mortality(p=0.255),major acute cardiovascular events(p=0.581),transfusions(p=0.933),and length of stay of more than or equal to 30 days(p=0.174)were ***,all tests failed to show an interaction between post-operative diagnosis and surgical technique ***:Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH ***,the diagnosis seems to not influence surgical technique outcomes.

关键词： Prostatecancer Transurethral surgery of the prostate Prostate surgery Population-based analysis Benign prostatic hyperplasia Lasersurgery

Molecular insights of exercise therapy in disease prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2564-2597页

作者： David Walzik Tiffany Y.Wences Chirino Philipp Zimmer Niklas Joisten division of Performance and Health(Sports Medicine) Institute for Sport and Sport ScienceTU Dortmund University44227 DortmundNorth Rhine-WestphaliaGermany division of Exercise and Movement Science Institute for Sport ScienceUniversity of Göttingen37075 GöttingenLower SaxonyGermany

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases,the underlying biological mechanisms have not been fully *** exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle,cardiac muscle,adipose,and liver *** signaling molecules,which are collectively termed exerkines,form a heterogenous group of bioactive substances,mediating inter-organ crosstalk as well as structural and functional tissue *** scientific endeavors have focused on identifying and characterizing new biological mediators with such ***,some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes.A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and ***,we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various *** emphasizing different aspects of exerkine research,we provide a comprehensive overview of(i)the molecular underpinnings of exerkine secretion,(ii)the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption,and(iii)the clinical implications of these mechanisms in disease prevention and treatment.

关键词： prevention treatment collective