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Homeostatic regulation of NAD(H)and NADP(H)in cells

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Genes & Diseases 2024年第5期11卷 285-299页

作者： Luojun Chen Xiaoke Xing Pingfeng Zhang Lulu Chen Huadong Pei Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430062China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA

Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and cellular ***^(+)and NADH redox couple plays a vital role in catabolic redox reactions,while NADPH is crucial for cellular anabolism and antioxidant *** NAD(H)and NADP(H)homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms,such as biosynthesis,consumption,recycling,and conversion between NAD(H)and NADP(H).The conversions between NAD(H)and NADP(H)are controlled by NAD kinases(NADKs)and NADP(H)phosphatases[specifically,metazoan SpoT homolog-1(MESH1)and nocturnin(NOCT)].NADKs facilitate the synthesis of NADP^(+)from NAD^(+),while MESH1 and NOCT convert NADP(H)into NAD(H).In this review,we summarize the physiological roles of NAD(H)and NADP(H)and discuss the regulatory mechanisms governing NAD(H)and NADP(H)homeostasis in three key aspects:the transcriptional and posttranslational regulation of NADKs,the role of MESH1 and NOCT in maintaining NAD(H)and NADP(H)homeostasis,and the influence of the circadian clock on NAD(H)and NADP(H)*** conclusion,NADKs,MESH1,and NOCT are integral to various cellular processes,regulating NAD(H)and NADP(H)*** of these enzymes results in various human diseases,such as cancers and metabolic ***,strategies aiming to restore NAD(H)and NADP(H)homeostasis hold promise as novel therapeutic approaches for these diseases.

关键词： MESH1 NAD(H) NADK NADP(H) Nocturnin

Fantastic voyage: The journey of NLRP3 inflammasome activation

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Genes & Diseases 2024年第2期11卷 819-829页

作者： Xiangyong Que Sihao Zheng Qibin Song Huadong Pei Pingfeng Zhang Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA

NLRP3 inflammasome,an intracellular multiprotein complex,can be activated by a range of pathogenic microbes or endogenous hazardous *** activation results in the release of cytokines such as IL-1β and IL-18,as well as Gasdermin D which eventually causes *** activation of NLRP3 inflammasome is under strict control and regulation by numerous pathways and *** excessive activation can lead to a persistent inflammatory response,which is linked to the onset and progression of severe *** studies have revealed that the subcellular localization of NLRP3 changes significantly during the activation *** this review,we review the current understanding of the molecular mechanism of NLRP3 inflammasome activation,focusing on the subcellular localization of NLRP3 and the associated regulatory *** aim to provide a comprehensive understanding of the dynamic transportation,activation,and degradation processes of NLRP3.

关键词： Inflammasome activation Innate immunity NLRP3 NLRP3 inflammasome Subcellular localization

Mechanism of PARP inhibitor resistance and potential overcoming strategies

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Genes & Diseases 2024年第1期11卷 306-320页

作者： Xiaoyu Fu Ping Li Qi Zhou Ruyuan He Guannan Wang Shiya Zhu Amir Bagheri Gary Kupfer Huadong Pei Juanjuan Li Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Thoracic Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China

PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)*** is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair *** the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the *** this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.

关键词： Drug resistance Homologous recombination PARP PARP inhibitor Poly(ADP-ribose)polymerase

State,Communal,and Individual Identities in Iran

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International Relations and Diplomacy 2024年第1期12卷 1-17页

作者： Mehran Kamrava georgetown university in Qatar DohaQatar

Cultural identity in Iran is comprised of four primary elements,each of which have proven to be highly resonant in the country political *** vexing issue of modernity,and where individuals and collectivities are placed in relation to it,has been one of the most prominent of these elements of Iranian identity.A second constitutive factor has been the role of the state as a deliberate crafter of cultural,in turn directly influencing the salience,interpretation,extent,and direction of modernity,or its antithesis,in *** defining has been the role and significance of religion,which has emerged as a marker of individual and collective,as well as political,***,and its compelling impulse across Iranian society especially from the early 1900s and continuing until today,has also emerged as an integral and inseparable feature of Iranian ***,these four elements―modernity,a culturally intrusive state,religion and religiosity,and nationalism―constitute fluid yet constant,sometimes complementary and sometimes competing,dimensions of Iranian identity.

关键词： Iranian identity nationalism religiosity modernity social change

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

Three cases of uncommon medication-associated osteonecrosis of temporal bone

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第3期10卷 237-240页

作者： Hunter VanDolah Jason R.Crossley H.Jeffrey Kim georgetown university School of Medicine Washington DCUSA Department of Otolaryngology–Head and Neck Surgery MedStar Georgetown University HospitalWashington DCUSA

Introduction:Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic ***,we present the first case of tyrosine-kinase inhibitor-related external auditory canal(EAC)osteonecrosis as well as two cases related to anti-resorptive ***:A retrospective case ***:Case one:an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs *** had a history of osteoporosis treated with denosumab and risedronic *** successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed *** two:a 69-year-old male presented with osteonecrosis of the right *** had a history of osteoporosis treated with alendronic acid and zoledronic *** osteonecrosis is conservatively managed with local debridement and antibiotic *** three:a 60-year-old male presented with osteonecrosis of the right inferior *** had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor,*** failing conservative therapy,he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his ***:Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone *** a local debridement and antibiotic therapy fail,definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

关键词： bisphosphonates denosumab external auditory canal imatinib medication-related osteonecrosis osteonecrosis temporal bone tyrosine-kinase Inhibitors

Emerging mechanisms of ferroptosis and its implications in lung cancer

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Chinese Medical Journal 2024年第7期137卷 818-829页

作者： Qian Li Qibin Song Huadong Pei Yali Chen Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashington D.C.20057USA State Key Laboratory of Medical Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Lung cancer is one of the most common malignancies and has the highest number of deaths among all *** continuous advances in medical strategies,the overall survival of lung cancer patients is still low,probably due to disease progression or drug *** is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides,and its dysregulation is implicated in cancer *** evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment *** this review,we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.

关键词： Lung cancer Ferroptosis Ferroptosis regulators Ferroptosis inducers Cancer treatment

The role of selective serotonin reuptake inhibitors and tricyclic antidepressants in addressing reduction of Meniere's disease burden:A scoping review

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第3期10卷 206-212页

作者： Alexander A.Missner Mana Sheykhsoltan Amir Hakimi Michael Hoa georgetown university School of Medicine WashingtonDistrict of ColumbiaUSA Department of Otolaryngology-Head and Neck Surgery Georgetown University Medical CenterWashingtonDistrict of ColumbiaUSA Auditory Development and Restoration Program National Institute on Deafness and Other Communication DisordersNational Institutes of HealthBethesdaMarylandUSA

Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and ***:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional ***:The literature search yielded 23 results,which were screened by three independent *** studies and three duplicates were *** examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately *** studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment *** studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or *** study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment ***:Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome *** remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common MD symptoms.

关键词： aural fullness clinical trials Meniere's disease scoping review sensorineural hearing loss serotonin specific reuptake inhibitors tricyclic antidepressants vertigo

Multiplicity dependence of the freezeout parameters in high energy hadron-hadron collisions

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Chinese Physics C 2024年第5期48卷 124-133页

作者： Muhammad Ajaz Majid Shehzad Muhammad Waqas Haifa I.Alrebdi Mohammad Ayaz Ahmad Antalov Jagnandan Shawn Jagnandan Murad Badshah Jalal Hasan Baker Abdul Mosawir Quraishi Department of Physics Abdul Wali Khan University MardanMardan 23200Pakistan School of Mathematics Physics and Optoelectronic EngineeringHubei University of Automotive TechnologyShiyan 442002China Department of Physics College of SciencePrincess Nourah bint Abdulrahman UniversityP.O.Box 84428Riyadh 11671Saudi Arabia Department of Mathematics Physics and StatisticsFaculty of Natural SciencesUniversity of Guyana101110 GeorgetownGuyananSouth America Department of Physics Faculty of ScienceUniversity of TabukTabukKingdom of Saudi Arabia Department of Electrical Engineering College of EngineeringQassim UniversityUnaizahSaudi Arabia

We examined the transverse momentum(pT)spectra of various identified particles,encompassing both light-flavored and strange hadrons(π++π−,K++K−,p+p¯,ϕ,K0s,Λ+Λ¯,Ξ−+Ξ¯+,andΩ−+Ω¯+),across different multiplicity classes in proton-proton collisions(p-p)at a center-of-mass energy of s√=7 *** the Tsallis and Hagedorn models,parameters relevant to the bulk properties of nuclear matter were *** models exhibit good agreement with experimental *** our analyses,we observed a consistent decrease in the effective temperature(T)for the Tsallis model and the kinetic or thermal freeze-out temperature(T0)for the Hagedorn model,as we transitioned from higher multiplicity(class-I)to lower multiplicity(class-X).This trend is attributed to the diminished energy transfer in higher multiplicity ***,we observed that the transverse flow velocity(βT)experiences a decline from class-I to *** normalization constant,which represents the multiplicity of produced particles,was observed to decrease as we moved toward higher multiplicity *** the effective and kinetic freeze-out temperatures,as well as the transverse flow velocity,show a mild dependency on multiplicity for lighter particles,this dependency becomes more pronounced for heavier *** multiplicity parameter for heavier particles was observed to be smaller than that of lighter particles,indicating a greater abundance of lighter hadrons compared to heavier *** particle species were observed to undergo decoupling from the fireball at distinct temperatures:lighter particles exhibit lower temperatures,while heavier ones show higher temperatures,thereby supporting the concept of multiple freeze-out ***,we identified a positive correlation between the kinetic freeze-out temperature and transverse flow velocity,a scenario where particles experience stronger collective motion at a higher freeze-out *** reason for this positive correlation is th

关键词： multiplicity dependence collective properties thermal energy