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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural Regeneration research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of Dayton Premedical Program University of Dayton center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton The Integrative Science and Engineering center University of Dayton center for genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research center of Digital Healthcare for Neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

Aspirin interruption before neurosurgical interventions:A controversial problem

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World Journal of Cardiology 2024年第4期16卷 191-198页

作者： Alexander Kulikov Anton Konovalov Pier Paolo Pugnaloni Federico Bilotta Department of Anesthesiology Burdenko National Medical Research Center of NeurosurgeryMoscow 125047Russia Department of vascular Neurosurgery Burdenko National Medical Research Center of NeurosurgeryMoscow 125047Russia Department of Anesthesiology Critical Care and Pain MedicineUniversity of Rome“Sapienza”Rome 00161Italy

Aspirin is widely used for primary or secondary prevention of ischemic *** the same time,chronic aspirin consumption can affect blood clot formation during surgical intervention and increase intraoperative blood *** is especially important for high-risk surgery,including *** European Society of Cardiology guidelines recommend aspirin interruption for at least 7 d before neurosurgical intervention,but this suggestion is not supported by clinical *** narrative review presents evidence that challenges the necessity for aspirin interruption in neurosurgical patients,describes options for aspirin effect monitoring and the clinical implication of these methods,and summarizes current clinical data on bleeding risk associated with chronic aspirin therapy in neurosurgical patients,including brain tumor surgery,cerebrovascular procedures,and spinal surgery.

关键词： Aspirin Neurosurgery Postoperative complications Bleeding risk Brain tumor surgery Cerebrovascular surgery Spinal surgery

Gut microbial-host-isozymes are new targets for diseases

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Science China(Life Sciences) 2024年第7期67卷 1525-1527页

作者： Zhiwei Zhang Kai Wang Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Female Fertility PromotionCenter for Reproductive MedicinePeking UniversityBeijing 100191China center for Obesity and Metabolic Disease research School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019;Fan and Pedersen,2021;Krautkramer et al.,2021).Recently,a new interaction pattern was identified,i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes.

关键词： diseases pattern

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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

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Science China(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou Division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of vascular Diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(Sun Yat-sen University) Guangzhou 510080China Guangdong Provincial Engineering and Technology center for Diagnosis and Treatment of vascular Diseases Guangzhou 510080China Division of vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Division of Hypertension and vascular Diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

Empowerment in chronic wound care——exploring the scope for patient contribution

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Frontiers of Nursing 2024年第1期11卷 1-16页

作者： Benedikt Hackert Ewa Klara Stürmer Ulrich Weger Department of Psychology and Psychotherapy University of Witten/HerdeckeAlfred-Herrhausen-Straße 5058448 WittenGermany Department for vascular Medicine University Heart and Vascular Center HamburgUniversity Medical Center Hamburg-EppendorfMartinistreet 5220246 HamburgGermany

Objective:In this study,we investigated the concept of empowerment in chronic wound care and propose to facilitate patient control by making use of degrees of freedom(DOF):that is,shaping of everyday wound care tasks initiated by patients and based on their wishes,mostly in terms of patients executing treatment steps,requesting or directing health care professionals to under take changes,or modifications of internal ***:As a first step,we conducted a systematic literature search,followed by an inductive form of qualitative content analysis,which resulted in the identification of 5 dimensions as main elements of empowerment:education and shared decision making,adherence to self-care behaviors,responsibility and control,general call for empowerment,and ***,the latter are noticeably absent in the *** investigate patients'freedom in shaping the wound care process,we conducted a second literature ***:A number of possibilities for patients to influence the wound care process could be identified,but experimental or clinical evidence about their effects is missing,their variety is limited,and they are only inadequately ***:However,DOF should be an indispensable aspect of genuine empowerment,since they allow patients to occupy the role of the agent in the treatment process and give rise to the subjective experience of feeling ***,in the third part,we develop a research proposal on how to investigate and include DOF in the clinical practice of wound ***,limitations about implementations are discussed(e.g.,patients being reluctant to overcome their passive role,resulting in frustration for health care professionals).

关键词： adherence chronic wounds control degrees of freedom empowerment shared decision making

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi Guo Ya-Jie Guo Bing-Qian Guo Yu-Fang Lv Hong-Hong Wang Juan-Juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo center for genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in ***,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and *** compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and *** showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and *** analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal ***,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association ***,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal *** comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

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Science China(Life Sciences) 2024年第5期67卷 854-864页

作者： Bo Chen Guangyi Zeng Lulu Sun Changtao Jiang center of Basic Medical research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China center for Obesity and Metabolic Disease research School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Women’s Reproductive Health and Fertility Promotion Peking UniversityBeijing 100191China Department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and *** previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these *** tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and *** review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and *** also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host ***,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

关键词： tobacco smoking gut microbiota dysbiosis nicotine smoking cessation

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Chromosome-level genome assembly of the Asian citrus psyllid,Diaphorina citri

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Insect Science 2024年第1期31卷 13-27页

作者： Shuang Lei Shi-Jiang Yu Qi Pan Li-Li Ding Si-Chen Li Lu-Yan Cheng Shu-Qi Wang Bing-Hai Lou Jun He Cui-Yun Lei Lin Cong Hao-Qiang Liu Xue-Feng Wang Chun Ran Citrus research Institute Southwest University/Chinese Academy of Agricultural SciencesNational Engineering Research Center for CitrusChongqingChina

Diaphorina citri is a global citrus *** a vector insect,it can transmit the causative agents of citrus huanglongbing,causing irreversible losses to the citrus *** acquisition of genomic information can provide a molecular genetic basis for effective control of ***,the DNBSEQ™,Oxford Nanopore Technologies,and Hi-C technologies are applied to generate a high-quality chromosome-level genome of *** genome size of *** was 523.78 Mb with a scaffold N50 of 47.05 Mb distributed on 13 chromosomes.A total of 250.64 Mb(47.85%)repeat sequences and 24048 protein-coding genes were *** resequencing of female and male individuals indicated that the sex chromosome system of *** is *** analysis demonstrated that *** and Pachypsylla venusta,which separated from their most recent common ancestor about 336.62 million years ago,were the most closely ***,we identified genes potentially involved in detoxification metabolism,pathogen transmission,and honeydew secretion for further *** high-quality genome provides an important reference for developing effective management strategies of ***.

关键词： Asian citrus psyllid chromosome-level genome comparative genomics cytochrome P450 detoxification Huanglongbing