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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou national Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong provincial Key Laboratory of pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(pDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or pDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Intertwined depressive and cognitive trajectories and the risk of dementia and death in older adults:a competing risk analysis

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General psychiatry 2024年第2期37卷 207-215页

作者： Ziyang Ren Lirong Nie Yushan Du Jufen Liu institute of Reproductive and Child health/national health Commission Key Laboratory of Reproductive health Peking UniversityBeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina

Background Depressive symptoms and cognitive impairment often interact,rendering their associations *** date,their joint trajectories and associations with dementia and death remain *** To explore the interactions between depressive symptoms and cognitive function,their developmental trajectories and the associations with all-cause dementia,Alzheimer’s disease(AD)and all-cause death in older *** Data were from the health and Retirement *** symptoms and cognitive function were measured using the 8-item Centre for Epidemiologic Studies Depression Scale and the Telephone Interview of Cognitive Status,***-cause dementia and AD were defined by self-reported or proxy-reported physician ***-cause death was determined by *** restricted cubic spline,group-based trajectory modelling and subdistribution hazard regression were *** Significant interactions between depressive symptoms and cognitive function in 2010 in their association with new-onset all-cause dementia and AD from 2010 to 2020 were found,especially in women(p for interactionpendent trajectory analysis showed that emerging or high(vs no)depressive trajectories and poor or rapidly decreased cognitive trajectories(vs very good)from 1996 to 2010 were at significantly higher risk of subsequent all-cause dementia,AD and all-cause death.15 joint trajectories of depressive symptoms and cognitive function from 1996 to 2010 were determined,where rapidly decreased cognitive function was more common in those with no depressive *** with older adults with the trajectory of no depressive symptoms and very good cognitive function,those with the trajectory of no depressive symptoms but rapidly decreased cognitive function were much more likely to develop new-onset all-cause dementia and death,with subdistribution hazard ratios(95%confidence intervals)of 4.47(2.99 to 6.67)and 1.84(1.43 to 2.36),especially in wome

关键词： death analysis rendering

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Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model

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Research 2024年第3期2023卷 217-231页

作者： Renje Wu Bangyan Zhou Wei Wang Feng Liu national Laboratory of Solid State Microstructures Department of Physicsand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093P.R.China institute for Brain Sciences Nanjing UniversityNanjing 210093P.R.China.

Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each comprising a series of state transitions;transcriptional bursting is characterized as a sequence of 4 events, capable of being organized in various configurations, in addition to the beginning and ending events. By associating transcriptional kinetics with mean durations and recurrence probabilities of the events, we unravel how transcriptional bursting is modulated by various regulators including transcription factors. Through analytical derivation and numerical simulation, this study reveals key state transitions contributing to transcriptional sensitivity and specificity, typical characteristics of burst profiles, global constraints on intrinsic transcriptional noise, major regulatory modes in individual genes and across the genome, and requirements for fast gene induction upon stimulation. It is illustrated how biochemical reactions on different time scales are modulated to separately shape the durations and ordering of the events. Our results suggest that transcriptional patterns are essentially controlled by a shared set of transcriptional events occurring under specific promoter architectures and regulatory modes, the number of which is actually limited.

关键词： kinetics essentially constraints

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Standardized Volume power Density Boost in Frequency-Up Converted Contact-Separation Mode Triboelectric Nanogenerators

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Research 2024年第2期2023卷 691-702页

作者： Zhongjie Li Chao Yang Qin Zhang Geng Chen Jingyuan Xu Yan peng Hengyu Guo School of Mechatronic Engineering and Automation Shanghai UniversityShanghai 200444P.R.China institute of Artificial Intelligence Shanghai UniversityShanghai 200444P.R.China national Engineering Research Center of Turbo-Generator Vibration School of Energy and EnvironmentSoutheast UniversityNanjing 210096P.R.China institute of Microstructure Technology Karlsruhe Institute of TechnologyKarlsruhe 76344Germany Shanghai Artificial Intelligence Laboratory Shanghai 200444P.R.China Department of Applied physics Chongqing UniversityChongqing 400044P.R.China

The influence of a mechanical structure's volume increment on the volume power density (VpD) of triboelectric nanogenerators (TENGs) is often neglected when considering surface charge density and surface power density. This paper aims to address this gap by introducing a standardized VpD metric for a more comprehensive evaluation of TENG performance. The study specifically focuses on 2 frequency-up mechanisms, namely, the integration of planetary gears (pG-TENG) and the implementation of a double-cantilever structure (DC-TENG), to investigate their impact on VpD. The study reveals that the pG-TENG achieves the highest volume average power density, measuring at 0.92 W/m^(3). This value surpasses the DC-TENG by 1.26 times and the counterpart TENG by a magnitude of 69.9 times. Additionally, the pG-TENG demonstrates superior average power output. These findings introduce a new approach for enhancing TENGs by incorporating frequency-up mechanisms, and highlight the importance of VpD as a key performance metric for evaluating TENGs.

关键词： increment neglected considering

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Discovery of partial Differential Equations from Highly Noisy and Sparse Data with physics-Informed Information Criterion

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Research 2024年第1期2023卷 247-259页

作者： Hao Xu Junsheng Zeng Dongxiao Zhang BIC-ESAT EREand SKLTCSCollege of EngineeringPeking UniversityBeijing 100871P.R.China institute of Applied physics and Computational Mathematics Beijing 100088P.R.China Eastern institute for Advanced Study Eastern Institute of TechnologyNingbo 315200ZhejiangP.R.China national Center for Applied Mathematics Shenzhen(NCAMS) Southern University of Science and TechnologyShenzhen 518055GuangdongP.R.China Department of Mathematics and Theories Peng Cheng LaboratoryShenzhen 518000GuangdongP.R.China

Data-driven discovery of partial differential equations(pDEs)has recently made tremendous progress,and many canonical pDEs have been discovered successfully for proof of ***,determining the most proper pDE without prior references remains challenging in terms of practical *** this work,a physics-informed information criterion(pIC)is proposed to measure the parsimony and precision of the discovered pDE *** proposed pIC achieves satisfactory robustness to highly noisy and sparse data on 7 canonical pDEs from different physical scenes,which confirms its ability to handle difficult *** pIC is also employed to discover unrevealed macroscale governing equations from microscopic simulation data in an actual physical *** results show that the discovered macroscale pDE is precise and parsimonious and satisfies underlying symmetries,which facilitates understanding and simulation of the physical *** proposition of the pIC enables practical applications of pDE discovery in discovering unrevealed governing equations in broader physical scenes.

关键词： process canonical proof

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In vivofluorescenceflow cytometry reveals that the nanoparticle tumor vaccine OVA@HA-pEI effectively clears circulating tumor cells

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Journal of Innovative Optical health Sciences 2024年第6期17卷 107-123页

作者： Wei Jin Yuting Fu Sisi Ge Han Sun Kai pang Xunbin Wei The Department of Biomedical Engineering institute of Advanced Clinical Medicine Peking University Beijing 100191P.R.China institute of Medical Technology peking University health Science Center Beijing 100191 P.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital&InstituteBeijing 100142P.R.China School of Instrument Science and Opto-Electronics Engineering Beijing Information Science&Technology University Beijing 100192 P.R.China

Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side ***,it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery *** vaccines often fail to elicit a su±ciently robust immune response against progressive tumors,thereby limiting their clinical e±*** this study,we developed a nanoparticle-based tumor vaccine,OVA@HA-pEI,utilizing ovalbumin(OVA)as the presenting antigen and hyaluronic acid(HA)and polyethyleneimine(pEI)as adjuvants and *** formulation significantly enhanced the proliferation of immune cells and cytokines,such as CD3,CD8,interferon-,and tumor necrosis factor-,in vivo,effectively activating an immune response against B16–F10 *** vivofluorescenceflow cytometry(IVFC)has already become an effective method for monitoring circulating tumor cells(CTCs)due to its direct,noninvasive,and long-term detection *** study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-pEI tumor vaccine and an anti-programmed death-1(pD-1)*** results demonstrated that the combined treatment of OVA@HA-pEI and anti-pD-1 antibody significantly improved the survival time of mice compared to anti-pD-1 antibody treatment ***,this combination therapy substantially reduced the number of CTCs in vivo,increased the clearance rate of CTCs by the immune system,and slowed tumor *** greatly enhance the clinical application prospects of IVFC and tumor vaccines.

关键词： Tumor vaccines circulating tumor cells in vivofluorescenceflow cytometry.

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Stakeholders' satisfaction assessment in heritage conservation: Case study of a project performance model for Thiruvananthapuram Fort Area, Kerala, India

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Frontiers of Architectural Research 2024年第2期13卷 285-304页

作者： Sunena Abdul Huq Bimal puthuvayi Department of Architecture and planning National Institute of Technology Calicut NIT Campus P.O.Kozhikode 673601India

Stakeholder satisfaction is an important factor in determining the success of urban heritage conservation *** research attempts to propose a model for assessing stakeholder satisfaction and project significant factors that need to be considered when determining the performance of a conservation project,taking the Thiruvananthapuram Fort Area,India as a case *** study employed a mixed-method approach of using expert consultations,physical surveys,and statistical analysis in the development of the *** influencing the outcome of an urban heritage conservation project were listed from the literature and further refined through expert discussions to be utilized for the stakeholder survey.A questionnaire survey is administered within a heritage-sensitive urban area to identify the present state of heritage buildings and the living conditions of the stakeholders pertaining to the six aspects that determine the outcome of an urban heritage conservation *** overall satisfaction of the stakeholder group was modelled using ordinal logistic regression against the various factors to arrive at factors that positively and negatively influenced *** model assessed that the satisfaction of the stakeholders who were a part of the historic site was highly influenced by their economic needs and the project's economic sustainability over other factors in the *** economy consolidation,a known mechanism of improving an area's economic sustainability negatively affected the stakeholders'*** results indicate that the factors under the social aspect were not significant determinants for the stakeholders of this urban heritage conservation *** methodology developed in this study can aid researchers and planners in identifying factors determining the outcome of an urban heritage conservation project while planning for development within a heritage-sensitive urban area.

关键词： Heritage conservation Thiruvananthapuram Fort Area Kerala India Assessment Stakeholder satisfaction Model

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Suicide risk in juvenile open angle glaucoma patients

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1880-1886页

作者： Hye-Jeong Seong Sukyoung Jung Sooyeon Choe Department of Ophthalmology Chungnam National University HospitalDaejeon 35015Republic of Korea Department of Ophthalmology Chungnam National University College of MedicineDaejeon 35015Republic of Korea Department of health Care policy Research Korea Institute for Health and Social AffairsSejong 30147Republic of Korea

AIM:To investigate the association between juvenile open angle glaucoma(JOAG)and mental health among ***:This study used nationally representative data from the 8th Korea national health and Nutrition Examination Survey(KNHANES)*** diagnosis followed the International Society of Geographical and Epidemiological Ophthalmology criteria based on glaucomatous structural defects,visual field defects,corrected vision,and intraocular *** outcomes,suicidal behaviors,psychiatric counseling,and depression were evaluated through mental health *** ratios(ORs)with 95%confidence intervals(CIs)were estimated using logistic regression models,adjusting for ***:Among 7090 participants,3446 met the inclusion criteria for analysis,and 88(2.6%)were diagnosed with open angle glaucoma(OAG).After adjusting for age,sex,and best-corrected visual acuity(VA),participants with OAG were revealed to have significantly higher odds of suicidal behaviors(i.e.,ideation,planning,or attempts)compared with those without OAG(OR:2.70;95%CI:1.12-6.54;p=0.028).This association remained significant after further adjustments for socioeconomic status,lifestyle factors,and presence of chronic conditions(p=0.031 and 0.035,respectively).However,there was no significant difference for the other two outcomes,psychiatric counseling and *** age-stratified analysis revealed a stronger association between OAG and suicidal behaviors in younger JOAG participants(participants(≥40y;OR:3.80 vs 2.22;95%CI:0.79-18.22 vs 0.56-8.80,respectively).CONCLUSION:OAG patients show a higher risk of suicidal behaviors than those without glaucoma particularly in JOAG patients.

关键词： glaucoma juvenile open angle glaucoma suicide suicidal behavior

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Assessing the performance of urban heritage conservation projects-influencing factors,aspects and priority weights

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Built Heritage 2024年第1期8卷 46-66页

作者： Sunena Abdul Huq Bimal puthuvayi Department of Architecture&planning National Institute of Technology CalicutNIT CampusP.O.673601KozhikodeKeralaIndia

Heritage conservation in urban areas involves complex systems often faced with the dilemmas of maintaining the built form's historical character,improving infrastructure,and managing development through stakeholder *** present,the performance of any conservation project is solely vested in conserving the built *** tools for urban heritage conservation projects do not have provisions for measuring the subjective value of stakeholders who are part of the heritage *** study tries to identify and prioritise the factors that need to be considered when developing a conservation project performance assessment model for an urban heritage conservation project from the perspective of experts that can be further evaluated from the perspective of *** these complex systems can be better viewed in the context of developing countries,the case of India is *** a literature review,factors that contribute to the outcome of an urban heritage conservation project were identified and categorised into six aspects:the physical,social,economic,cultural,political,and continuity *** an expert survey,the factors that constituted each aspect were filtered using the feature selection method of correlation to avoid factors that may seem *** factors under each aspect were ranked using a weighted average ranking method to identify the most prioritised factors determining the outcome of an urban heritage conservation *** priority weights of the aspects were calculated using Saaty's analytic hierarchy *** results show that the cultural aspect was the most important aspect,followed by the continuity *** social and physical aspects were prioritised similarly,followed by the economic and political *** study is distinctive because it identifies the influential factors that can help develop a conservation project performance assessment model for an urban heritage conservation project.

关键词： heritage conservation urban conservation performance influential factors AHp filter-based feature selection

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Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes

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World Journal of Hepatology 2024年第1期16卷 54-64页

作者： Sabhita Shabir Shaikh Fakhar Ali Qazi-Arisar Saba Nafay Sidra Zaheer Hafeezullah Shaikh Zahid Azam national institute of Liver and GI Diseases Dow University of Health SciencesSindhKarachi 75330Pakistan School of public health Dow University of Health SciencesSindhKarachi 75330Pakistan

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is a liver condition marked by excessive fat buildup in the absence of heavy alcohol *** is primarily linked with metabolic issues like insulin resistance,obesity,and abnormal lipid levels,and is often observed with other conditions such as type 2 diabetes and cardiovascular ***,whether the subtypes of MAFLD based on the metabolic disorder differentially impact liver fibrosis is not well explicated,especially in the Asian *** To compare the severity of liver fibrosis among different MAFLD *** A total of 322 adult patients of either gender with fatty liver on ultrasound were enrolled between January to December *** was defined as per the Asian pacific Association for the Study of the Liver ***-4 index(Fib-4)and nonalcoholic fatty liver disease fibrosis score(NFS)were employed to evaluate liver *** The mean age was 44.84±11 ***-two percent of the patients were *** hundred and seventy-three patients were classified as having MAFLD,of which 110(40.3%)carried a single,129(47.3%)had two,and 34(12.5%)had all three metabolic *** cumulative number of metabolic conditions was related to elevated body mass index,triglyceride(TG)levels,and glycated hemoglobin,lower high-density lipoprotein(HDL)levels,higher liver inflammation(by aspartate aminotransferase andγ-glutamyl transferase),and higher likelihood of fibrosis(by NFS and Fib-4 scores)(pproportion of advanced fibrosis also increased with an increase in the number of metabolic conditions(4.1%,25.5%,35.6%,and 44.1%by NFS and 6.1%,10.9%,17%,and 26.5%by Fib-4 for no MAFLD and MAFLD with 1,2,and 3 conditions,respectively).Among MAFLD patients,those with diabetes alone were the eldest and had the highest mean value of NFS score and Fib-4 score(ppatients diagnosed with lean metabolic dysfunction exhibited the highest levels of TG and a

关键词： Metabolic syndrome Diabetes Fatty liver disease Dyslipidemia Obesity

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