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Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements

Journal of Genetics and Genomics 2018年第6期45卷 299-313页

作者： Hongmei Ke Zhi Feng Min Liu Tianhui Sun Jianli Dai Mengqi Ma Lu-Ping Liu Jian-Quan Ni jos carlos pastor-Pareja School of Life Sciences Tsinghua University School of Medicine Tsinghua University

Collagens are large secreted trimeric proteins making up most of the animal extracellular *** of collagen has been a focus of interest for cell biologists in recent years because collagen trimers are too large and rigid to fit into the COPII vesicles mediating transport from the endoplasmic reticulum（ER） to the Golgi. Collagen-specific mechanisms to create enlarged ER-to-Golgi transport carriers have been postulated, including cargo loading by conserved ER exit site（ERES） protein ***, we report an RNAi screening for genes involved in collagen secretion in Drosophila. In this screening, we examined distribution of GFP-tagged Collagen IV in live animals and found 88 gene hits for which the knockdown produced intracellular accumulation of Collagen IV in the fat body, the main source of matrix proteins in the larva. Among these hits, only two affected collagen secretion specifically：PH4 a EFB and Plod, encoding enzymes known to mediate posttranslational modification of collagen in the ER. Every other intracellular accumulation hit affected general secretion, consistent with the notion that secretion of collagen does not use a specific mode of vesicular transport, but the general secretory pathway. Included in our hits are many known players in the eukaryotic secretory machinery, like COPII and COPI components, SNAREs and Rab-GTPase regulators. Our further analysis of the involvement of Rab-GTPases in secretion shows that Rab1, Rab2 and Rab X3, are all required at ERES, each of them differentially affecting ERES morphology. Abolishing activity of all three by Rep knockdown, in contrast,led to uncoupling of ERES and Golgi. We additionally present a characterization of a screening hit we named trabuco（tbc）, encoding an ERES-localized TBC domain-containing Rab-GAP. Finally, we discuss the success of our screening in identifying secretory pathway genes in comparison to two previous secretion screenings in Drosophila S2 cells.

关键词： Collagen Ⅳ COPⅡ vesicles RNAi screening Secretory pathway Rab-GTPases ER exit site

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Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

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World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia Labrador-Velandia María Luz Alonso-Alonso Sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio josé carlos pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： Mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

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Nickel-based cerium zirconate inorganic complex structures for CO_(2)valorisation via dry reforming of methane

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Journal of Environmental Sciences 2024年第6期140卷 12-23页

作者： Juan Luis Martín-Espejo Loukia-Pantzechroula Merkouri Jesús Gándara-Loe josé Antonio Odriozola Tomas Ramirez Reina Laura pastor-Pérez Department of Inorganic Chemistry and Material Sciences Institute of Seville University of Seville-CSICSeville 41092Spain Department of Chemical and Process Engineering University of SurreyGuildford GU27XHUnited Kingdom

The increasing anthropogenic emissions of greenhouse gases(GHG)is encouraging extensive research in CO_(2)*** reforming of methane(DRM)depicts a viable strategy to convert both CO_(2)and CH4into syngas,a worthwhile chemical *** the different active phases for DRM,the use of nickel as catalyst is economically favourable,but typically deactivates due to sintering and carbon *** stabilisation of Ni at different loadings in cerium zirconate inorganic complex structures is investigated in this work as strategy to develop robust Ni-based DRM *** and TPR-H2analyses confirmed the existence of different phases according to the Ni loading in these ***,superficial Ni is observed as well as the existence of a CeNiO_(3)perovskite *** catalytic activity was tested,proving that 10 wt.%Ni loading is the optimum which maximises *** catalyst was also tested in long-term stability experiments at 600and 800℃in order to study the potential deactivation issues at two different *** 600℃,carbon formation is the main cause of catalytic deactivation,whereas a robust stability is shown at 800℃,observing no sintering of the active phase evidencing the success of this strategy rendering a new family of economically appealing CO_(2)and biogas mixtures upgrading catalysts.

关键词： CO_(2)conversion Dry reforming of methane Nickel catalysts Pyrochlore Cerium zirconate

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Inflammatory markers,oxidative stress,and mitochondrial dynamics:Repercussions on coronary artery disease in diabetes

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World Journal of Diabetes 2024年第9期15卷 1853-1857页

作者： josécarlos Tatmatsu-Rocha Luan Santos Mendes-Costa College of Medicine Postgraduate Program in Physiotherapy and FunctionalityFederal University of Ceará-UFCFortaleza 60430-450CearáBrazil Physical Therapy Federal University of CearáFortaleza 60000-000CearáBrazil

Inflammatory markers and mediators that affect the development of cardiovascular diseases have been the focus of recent scientific ***,the purpose of this editorial is to promote a critical debate about the article titled“Nε-carboxymethyl-lysine and inflammatory cytokines,markers,and mediators of coronary artery disease progression in diabetes”,published in the World Journal of Diabetes in *** work directs us to reflect on the role of advanced glycation end products,which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyllysine(NML).Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease(CAD),especially tumor necrosis factor alpha,interleukins,and C-reactive *** inflammatory agents increase the production of reactive oxygen species(ROS),of which people with diabetes are known to have an increased *** increase in ROS promotes lipid peroxidation,which causes damage to myocytes,promoting myocardial ***,oxidative stress induces the binding of NML to its receptor RAGE,which in turn activates the nuclear factor-kB,and consequently,inflammatory *** inflammatory cytokines induce endothelial dysfunction,with increased expression of adhesion molecules,changes in endothelial permeability and changes in the expression of nitric *** this sense,the therapeutic use of monoclonal antibodies(inflammatory reducers such as statins and sodium-glucose transport inhibitors)has demonstrated positive results in the regression of atherogenic plaques and consequently *** the other hand,many studies have demonstrated a relationship between mitochondrial dynamics,diabetes,and cardiovascular *** link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix,and this imbalance can have its origin in inadequate diet as well as

关键词： Mitochondrial dynamics Diabetes Oxidative stress Coronary artery disease Nε-carboxymethyl-lysine

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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration Research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor carlos Spuch josé Antonio Lamas Lucas C.González-Matías Federico Mallo Biomedical Research Centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience Research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical Research Centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control *** glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry *** review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkins

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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Diabetes mellitus and comorbidities in elderly people from the Lugu community:A critical-reflective analysis

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World Journal of Diabetes 2024年第11期15卷 2162-2166页

作者： josécarlos Tatmatsu-Rocha josécarlos Gomes-Pinto College of Medicine Postgraduate Program in Physiotherapy and FunctionalityFederal University of Ceará-UFCFortaleza 60810-786Brazil College of Medicine Postgraduate Program in Physiotherapy and FunctionalityFederal University of CearáFortaleza 60000-000Brazil

Ageing has a close relationship with chronic non-communicable diseases,such as diabetes mellitus and high blood *** pathologies are often associated with changes in eating habits and promote crucial physiological changes which act silently in the long term in the elderly *** to the speed of urban development and technological advances,there has been an increase in the population's life ***,it is essential to know the socio-demographic profile and prevalent comorbidities of the elderly population,which can provide a reliable and broad database to enable the outline of strategies and the promotion of efficient health *** this sense,the purpose of this editorial is to contribute to the debate surrounding the article that analysed epidemiological data from the Lugu *** mellitus,hypertension and cardiovascular pathologies and their comorbidities were the most prevalent conditions in this *** data could contribute to develop public policies constructively and assertively,allowing investments in the prevention and treatment of these pathologies.

关键词： Diabetes mellitus Quality indicators Health care Hypertension Comorbidity Exercise

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Health Vigilance and Risk Factors for Cervical Cancer: A Study in the State of Maranhão, Brazil

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Open Journal of Epidemiology 2024年第1期14卷 75-89页

作者： josé Márcio Soares Leite carlos Tomaz School of Medicine CEUMA University S&#227o Luís Brazil Master’s Program in Environment CEUMA University S&#227o Luís Brazil

The purpose of this cross-sectional study was to investigate the importance of health vigilance in the prevention of cervical cancer. The sample consisted of 536 women. To identify which risk factors were associated with cervical cancer or with an increase in the mortality rate of this kind of cancer, a logistic regression model was used. The Odds Ratios (OR) and their respective 95% confidence intervals were also calculated. Most of them were at the age of highest incidence of cervical cancer (21 - 59 years old), had an unstable conjugal situation, minimal educational level (78.7%), low income (58.3%), consumed alcoholic beverages (56.4%), had a history of smoking (57.0%) and possessed limited knowledge about the prevention. These results are discussed in terms of a predictive model for cervical cancer that considers the importance of public health vigilance in the screening and precocious diagnosis.

关键词： Cancer Cervix Uteri Public Health Surveillance Epidemiology

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Biomass gasification,catalytic technologies and energy integration for production of circular methanol:New horizons for industry decarbonisation

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Journal of Environmental Sciences 2024年第6期140卷 306-318页

作者： Luis F.Bobadilla Lola Azancot Miriam González-Castañ Estela Ruíz-López Laura pastor-Pérez Francisco J.Durán-Olivencia Runping Ye Katie Chong Paula HBlanco-Sánchez Zenthao Wu Tomás R.Reina joséA.Odriozola Departamento de Química Inorgánica e Instituto de Ciencia de Materiales de Sevilla Centro Mixto CSIC-Universidad de SevillaAvda.Américo Vespucio 49Sevilla 41092Spain Departamento de Ingeniería Universidad Loyola AndalucíaAvda.de Las Universidades s/nSevilla 41704Spain Key Laboratory of Jiangxi Province for Environment and Energy Catalysis School of Chemistry and Chemical EngineeringNanchang UniversityNanchang330031China Energy and Bioproducts Research Institute(EBRI) Aston UniversityBirminghamB47ETUnited Kingdom Department of Chemical and Process Engineering University of SurreyGuildfordGU27XHUnited Kingdom

The Intergovernmental Panel on Climate Change(IPCC)recognises the pivotal role of renewable energies in the future energy system and the achievement of the zero-emission *** implementation of renewables should provide major opportunities and enable a more secure and decentralised energy supply *** fuels provide long-term solutions for the transport sector,particularly for applications where fuels with high energy density are *** addition,it helps reducing the carbon footprint of these sectors in the *** on biomass characteristics feedstock is essential for scaling-up gasification from the laboratory to *** review deals with the transformation biogenic residues into a valuable bioenergy carrier like biomethanol as the liquid sunshine based on the combination of modified mature technologies such as gasification with other innovative solutions such as membranes and microchannel *** abatement is a critical process in product gas upgrading since tars compromise downstream processes and equipment,for this,membrane technology for upgrading syngas quality is discussed in this *** reactor technology with the design of state-of-the-art multifunctional catalysts provides a path to develop decentralised biomethanol synthesis from biogenic ***,the development of a process chain for the production of(i)methanol as an intermediate energy carrier,(ii)electricity and(iii)heat for decentralised applications based on biomass feedstock flexible gasification,gas upgrading and methanol synthesis is analysed.

关键词： Biogenic residues Gasification Biomethanol Circular Economy Microreactors

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Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study

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Journal of Geriatric Cardiology 2024年第7期21卷 723-732页

作者： Francisco Marín Manuel Anguita Sánchez Iñaki Lekuona Marcelo Sanmartín Fernán-dez Vivencio Barrios carlos Perez Muñoz Juan Cosín-Sales Alejandro IPérez Cabeza Vanesa Roldán Schilling Carles Rafols Priu Esteban Orenes-Piñero María Asunción Es-teve-pastor Department of Cardiology Hospital Clínico Universitario Virgen de la ArrixacaIMIB-ArrixacaUniversity of MurciaCIBERCVMurciaSpain Department of Cardiology Hospital Reina Sofía CórdobaIMIBICUniversity of CordobaCIBERCVCórdobaSpain Hospital Galdakao-Usansolo BizkaiaSpain Department of Cardiology Hospital Uni-versitario Ramony CajalCIBERCVMadridSpain Department of Cardiology University Hospital Ramóny CajalAl-caláUniversityMadridSpain Medical Center La Capillita Sanlúcar de Barrameda.Private cardiology clinicJerez de la FronteraSpain Department of Cardiology Hospital Arnau de VilanovaValenciaSpain Department of Car-diology Virgen de la Victoria University HospitalCIBERCV.MalagaSpain Department of Haematology Hospital Clínico Universitario Virgen de la ArrixacaUniversity of MurciaMurciaSpain Department of Medical Affairs Bayer HispaniaBarcelonaSpain Department of Biochemistry and Molecular Biology-A University of MurciaMurciaSpain

Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation(AF),taking rivaroxaban in clinical *** Observational and non-interventional study that included AF adults recruited from 79 Spanish centers,anticoagulated with rivaroxaban ≥ 6 months before being *** were analyzed according to age(≥ 80 vs.< 80 years) at *** Out of 1433 patients,453(31.6%) were octogenarians at *** to younger patients,octogenarians had more comorbidities,higher CHA2DS2-VASc(4.5 ± 1.3 vs.3.0 ± 1.4;P < 0.001) and HAS-BLED scores(2.0 ± 1.0 vs.1.4 ± 1.0;P < 0.001).Overall,the dose of rivaroxaban was adequately prescribed in 83.4% of patients,but more frequently in the younger population(71.1% vs.89.1%;P = 0.039).After a mean follow-up of 2.2 ± 0.6 years,annual rates of stroke + systemic embolism + transient ischemic attack,MACE,cardiovascular death and major bleeding were 1.03%,1.24%,1.03% and 1.75%,respectively,in octogenarian *** for progressive heart failure death and major bleeding,rates of outcomes in octogenarians were similar compared to younger *** octogenarians,the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke,whereas previous coronary revascularization and heart failure with MACE,and higher HAS-BLED score with major *** In clinical practice,around one third of patients taking rivaroxaban are *** patients have many comorbidities and a high thromboembolic *** that,rates of adverse events remain *** is adequately prescribed in the majority of octogenarians.

关键词： patients atrial bleeding

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Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： Laura García-Mendívil María Pérez-Zabalza Antoni Oliver-Gelabert joséMaría Vallejo-Gil Javier Fañanás-Mastral Manuel Vázquez-Sancho Javier AndréBellido-Morales Alexánder Sebastián Vaca-Núñez carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental Medicine and Biology of Cuyo(IMBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

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