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Circadian disturbance induces erectile dysfunction by impairing endothelial function

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Asian Journal of Andrology 2024年第2期26卷 205-211页

作者： Tao Li Yi-Ting Jiang Xin-Zhu Qi Peng Chen Jun-Hao Zhang Fu Luo Jun Qiao Jiang Gu Guang-Shi Du Qiang Wang department of Urology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China department of Urology Guizhou Provincial People's HospitalGuiyang 550002China department of Otorhinolaryngology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Guizhou Institute for Food and Drug Control Guiyang 550004China department of Reproductive Center Guizhou Provincial People's HospitalGuiyang 550002China translational Medicine research Center of Guizhou Medical University Guiyang 550025China

In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 *** off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 *** on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for *** maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control *** LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein *** production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying *** disturbance impaired endothelial function and contributed to erectile *** the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly ***,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 *** significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly ***,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein *** altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial ***,the core circadian elements were detected in the corpora cavernosa,but these were ***,which circadian element regulates erectile function and how it works need further analysis.

关键词： circadian disturbance endothelial function erectile function light/dark cycle NO/cGMP

Structural changes in the obese brain

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Neural Regeneration research 2024年第12期19卷 2561-2562页

作者： Anna R.R.Da Conceicao Marcelo N.N.Vieira Fernanda G.De Felice D’Or Institute for research and Education Rio de JaneiroBrazil Institute of Medical Biochemistry Leopoldo De Meis Federal University of Rio de JaneiroRio de JaneiroBrazil Centre for Neuroscience Studies Department of Biomedical and Molecular Sciences&Department of PsychiatryQueen’s UniversityKingstonONCanada

Obesity represents a major global health concern,with widespread growing prevalence and severe consequences for the quality of life and life expectancy of affected individuals and for the economic burden of healthcare systems(Prospective Studies Collaboration,2009).Obesity is a well-established risk factor for a variety of conditions including metabolic,vascula r,and heart diseases,and seve ral types of cancer(Prospective Studies Collaboration,2009).

关键词： diseases consequences prevalence

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Infectious Disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical Key Laboratory of Emergency and Trauma research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1187-1203页

作者： Yongyun Li Tianyu Zhu Jie Yang Qianqian Zhang Shiqiong Xu Shengfang Ge Renbing Jia Jianming Zhang Xianqun Fan department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology Shanghai 200001China National research Center for translational Medicine(Shanghai) State Key Laboratory of Medical GenomicsShanghai Institute of HematologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of translational Medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular *** search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer ***,elevated expression of EHMT2 had been validated in UM ***,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T *** immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of *** transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA *** constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic *** blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key *** summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

关键词： Uveal melanoma EHMT2 RhoA pathway ARHGAP29 G protein GNAQ GNA11

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren Tan Mary C.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh Tuck Wah Soong Jason K.W.Lee Ivan C.C.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human Potential translational research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Centre for translational Magnetic Resonance research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance Centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore Campus for research Excellence and Technological Enterprise(CREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity Cognition Heat stress Hyperthermia Motor function

Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine translational research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2024年第4期13卷 2289-2309页

作者： Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu Kamil Kuca Tushuai Li Wenda Wu School of Biology and Food Engineering Changshu Institute of TechnologySuzhou 215500China Center for Clinical Mass Spectrometry School of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China MOE Joint International research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic College of Life Science Yangtze UniversityJingzhou 434025China Wuxi Medical College Jiangnan UniversityWuxi 214122China Wuxi translational Medicine research Center and Jiangsu translational Medicine research Institute Wuxi Branch Wuxi 214013China

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to *** podocytes are terminally differentiated epithelial ***_(1)induces podocyte inflammation,proteinuria and renal *** the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse *** of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte *** also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway *** of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney *** findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte *** study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关键词： Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation

Clinical effects of nonconvulsive electrotherapy combined with mindfulness-based stress reduction and changes of serum inflammatory factors in depression

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World Journal of psychiatry 2024年第5期14卷 653-660页

作者： Zhi-Wen Gu Chun-Ping Zhang Li-Ping Chen Xiong Huang department of psychiatry Guangzhou First People's HospitalSouth China University of TechnologyGuangzhou 510180Guangdong ProvinceChina department of psychiatry The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou HuiAi Hospital)Guangzhou 510370Guangdong ProvinceChina

BACKGROUND Depression is a common and serious psychological condition,which seriously affects individual well-being and functional *** treatment methods include drug therapy and psychological counseling;however,these methods have different degrees of side effects and *** recent years,nonconvulsive electrotherapy(NET)has attracted increasing attention as a noninvasive treatment ***,the clinical efficacy and potential mechanism of NET on depression are still *** hypothesized that NET has a positive clinical effect in the treatment of depression,and may have a regulatory effect on serum inflammatory factors during *** To assess the effects of NET on depression and analyze changes in serum inflammatory *** This retrospective study enrolled 140 patients undergoing treatment for depression between May 2017 and June 2022,the observation group that received a combination of mindfulness-based stress reduction(MBSR)and NET treatment(n=70)and the control group that only received MBSR therapy(n=70).The clinical effectiveness of the treatment was evaluated by assessing various factors,including the Hamilton Depression Scale(HAMD)-17,self-rating idea of suicide scale(SSIOS),Pittsburgh Sleep Quality Index(PSQI),and levels of serum inflammatory factors before and after 8 wk of *** quality of life scores between the two groups were *** were made using t and χ^(2) *** After 8 wk of treatment,the observation group exhibited a 91.43%overall effectiveness rate which was higher than that of the control group which was 74.29%(64 vs 52,χ^(2)=7.241;P<0.05).The HAMD,SSIOS,and PSQI scores showed a significant decrease in both ***,the observation group had lower scores than the control group(10.37±2.04 vs 14.02±2.16,t=10.280;1.67±0.28 vs 0.87±0.12,t=21.970;5.29±1.33 vs 7.94±1.35,t=11.700;P both<0.001).Additionally,there was a notable decrease in the IL-2,IL-1β,and IL-6 in both gr

关键词： Depression Nonconvulsive electrotherapy Mindfulness-based stress reduction Serum inflammatory factors Clinical effect Hamilton Depression Scale

Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy