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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen h.M.Prehn hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

The analysis of composite laminated beams using a 2D interpolating meshless technique

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Acta Mechanica Sinica 2018年第1期34卷 99-116页

作者： S.h.M.Sadek J.Belinha M.P.L.Parente R.M.Natal Jorge J.M.A.César de Sá A.J.M.Ferreira Department of Mechanical Engineering Faculty of EngineeringUniversity of Porto Institute of Mechanical Engineering and Industrial Management University of Porto

Laminated composite materials are widely implemented in several engineering constructions. For its relative light weight, these materials are suitable for aerospace, military, marine, and automotive structural applications. To obtain safe and economical structures, the modelling analysis accuracy is highly relevant. Since meshless methods in the recent years achieved a remarkable progress in computational mechanics, the present work uses one of the most flexible and stable interpolation meshless technique available in the literature—the Radial Point Interpolation Method(RPIM).here, a 2 D approach is considered to numerically analyse composite laminated beams. Both the meshless formulation and the equilibrium equations ruling the studied physical phenomenon are presented with detail. Several benchmark beam examples are studied and the results are compared with exact solutions available in the literature and the results obtained from a commercial finite element software. The results show the efficiency and accuracy of the proposed numeric technique.

关键词： Radial point interpolators RPIM Laminated beam Meshless method

Towards next generation Internet of Energy system: Framework and trends

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Energy and AI 2023年第4期14卷 660-681页

作者： Muqit Farhan Tanzim N.Reza Faisal R.Badal md.R.Islam S M Muyeen Z.Tasneem md.Mehedi hasan md.F.Ali md.h.Ahamed S.h.Abhi md.Manirul Islam Subrata K.sarker Sajal K.Das Prangon Das Department of Mechatronics Engineering Rajshahi University of Engineering TechnologyRajshahi 6204Bangladesh Department of Electrical Engineering Qatar UniversityDohaQatar

The quickening propensity of growth within the areas of information and communications technology and en-ergy networks has triggered the emergence of a central idea termed as Internet of Energy(IoE).Such a concept relates the internet of things,which is the term used in describing the usage of sophisticated digital control devices with the capability of transmitting data via IT *** concept of an interconnected energy network is being formed in the upcoming days through upgrades in the field of intelligent energy systems to control real-time energy optimization and *** energy industry has had a sustained expansion,reaching the IoE milestone and continuing to this cutting-edge power system,which is the next generation of IoE.A directional pathway from the traditional power system to the IoE has been conducted in this research work by addressing the importance of integrating the smart transmission and communication infrastructure,smart metering,pricing and energy management scheme.A detailed investigation of the IoE with respect to technical angles,such as communication architecture,IoE on the supply&demand side,and IoE protocol based on fundamental elements and essential technologies has been carried out to indicate the blueprint and jurisdiction *** inte-gration,security and energy management challenges may deviate the performance of the IoE technology that has been focused with proper control issues and ***,a directional framework to establish the next-generation IoE system has been constructed with future scopes to insure higher resiliency,cyber-security and stability.

关键词： Internet of Energy IoT Microgrid Smart grid Virtual power plant Next generation power system

Effects of Root Growth of Deep and Shallow Rooting Rice Cultivars in Compacted Paddy Soils on Subsequent Rice Growth

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Rice science 2023年第5期30卷 459-472,I0022-I0024页

作者： md.Dhin ISLAM Adam h.PRICE Paul D.hALLETT School of Biological Sciences University of AberdeenSt Machar DrAberdeen AB243UUthe United Kingdom Faculty of Agriculture Bangabandhu Sheikh Mujibur Rahman Agricultural UniversityGazipur-1706Bangladesh

Rice is often grown as multiple seasons in one year,alternating between flooded and upland systems.A major constraint,introduced from the flooded system,is a plough pan that may decrease rooting depth and productivity of follow-on upland *** penetrating the plough pan under flooded rice system can leave a legacy of weaker root growth *** rooting rice cultivars could have a bigger impact,but no direct evidence is *** explore whether a deep rather than a shallow rooting rice cultivar grown in a flooded cropping cycle benefited deeper root growth of follow-on rice in an upland,reduced tillage cropping cycle,a simulated flooded paddy in greenhouse was planted with deep(Black Gora) and shallow(IR64) rooting cultivars and a plant-free *** plough pans were made in between the topsoil and subsoil to form different treatments with no plough pan(0.35 MPa),soft plough pan(1.03 MPa) and hard plough pan(1.70 MPa).After harvest of this ‘first season’ rice,the soil was drained and undisturbed to simulate zero-tillage upland and planted rice cultivar BRRI Dhan *** overall root length density(RLD),root surface area,the numbers of root tips and branching of BRRI Dhan 28 did not vary between plough pan and no plough pan *** with the shallow rooting rice genotype,the deep rooting rice genotype as ‘first season’ crop produced 19% greater RLD,34% greater surface area and 29% more branching of BRRI Dhan 28 in the *** the topsoil,however,BRRI Dhan 28 had 28% greater RLD,35% greater surface area and 43% more branching for the shallow rather than deep rooting genotype planted in the ‘first season’.The results suggested that rice cultivar selection for a paddy cycle affects root growth of a follow-on rice crop grown under no-till,with benefits to subsoil access from deep rooting cultivars and topsoil proliferation for shallow rooting cultivars.

关键词： plough pan root growth biopores crop rotation Oryza sativa preceding crop zero-tillage

Understanding bark thickness variations for Araucaria angustifolia in southern Brazil

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Journal of Forestry Research 2021年第3期32卷 1077-1087页

作者： Emanuel Arnoni Costa Veraldo Liesenberg César Augusto Guimaraes Finger AndréFelipe hess Cristine Tagliapietra Schons Graduate Program in Forest Engineering Santa Catarina State University(UDESC)LagesSC 88520-000Brazil Department of Forest Engineering Federal University of Uberlandia(UFU)Monte CarmeloMG 38500-000Brazil Graduate Program in Forest Engineering Federal University of Santa Maria(UFSM)Santa MariaRS 97105-900Brazil Graduate Program in Agroecosystems Federal Technological University of Parana(UFTPR)Dois VizinhosPR 85660-000Brazil

This study aimed to understand bark thickness variations of Araucaria angustifolia(Bertol.)Kuntze trees growing in natural forest remnants in southern Brazil,and their relationship with quantitative and qualitative *** thickness must be accurately estimated in order to determine timber volume *** is an important variable for the sustainable management and conservation of araucaria *** spite of its importance and visibility,bark thickness variations have not been evaluated for this key species in southern Brazil.A total of 104 trees were selected,and their qualitative and quantitative attributes such as diameter at breast height(D_(Bh)),height(h),crown base height(C_(Bh)),crown length(C_(L)),social position(S_(P)),stoniness(S_(T)),position on the relief(P_(R)),vitality(V_T)and branch arrangement(B_(A))were *** trees were categorized into two groups:red bark or gray *** analysis and artificial neural networks(ANN)were used for modelling bark *** results indicate that:(1)bark thickness showed good correlation to D_(Bh),with 0.76 as coefficient of determination(RS_P),0.540 as Mean Absolute Error(M_(AE))and 22.4 root-meansquare error in percentage(R_(MSE%));(2)the trend changed according to bark colour,with significant differences for the intersection(_0–Pr>F:p=0.0124)and slope(β_(1)–Pr>F:p=0.0126)of bark thickness curves between groups;(3)the highest correlation of bark thickness was found with:D_(Bh)(ρ=0.88),h(ρ=0.58),C_(Bh)(ρ=0.46),S_(P)(ρ=-0.52),and B_(A)(ρ=-0.32);(4)modelling with ANN confirmed high adjustment(R^(2)=0.99)and accuracy(R_(MSE%)=3.0)of the *** is an efficient and robust technique for the modelling of various qualitative and quantitative attributes commonly used in forest *** effective use of ANN to estimate araucaria bark in natural forests reinforces its potential,besides the possibility of application for other forest species.

关键词： Dendrometry attributes Crown characteristics Prediction models Bark factor Parana-pine

Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

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World Journal of Gastroenterology 2024年第28期30卷 3418-3427页

作者： Anja h W M Lemlijn-Slenter Karolina AP Wijnands Gijs van der hamsvoort Luuk P van Iperen Nico Wolter Angelique E de Rijk Ad AM Masclee Department of Social Medicine Faculty of HealthMedicine and Life sciencesCare and Public Health Research Institute Maastricht UniversityMaastricht 6200 MDLimburgNetherlands Division of Gastroenterology and hepatology Department of Internal MedicineSchool of Nutrition and Translational Research in MetabolismMaastricht 6200 MDLimburgNetherlands Social Medical Affairs Employee Insurance Agency(UWV)Heerlen 6400 ACLimburgNetherlands Department of Research Academic Knowledge Center Work and Health South-East Netherlands(AKAG-ZON)Heerlen 6400 ACLimburgNetherlands

BACKGROUND The concept of positive health(Ph)supports an integrated approach for patients by taking into account six dimensions of *** approach is especially relevant for patients with chronic *** gastrointestinal and hepatopancreatico-biliary(GI-hPB)disorders are among the top-6 of the most prevalent chronically affected organ *** impact of chronic GI-hPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIhPB disorders are often younger than persons with chronic diseases in other organ *** To describe and quantify the dimensions of Ph in patients with chronic GI-hPB *** Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIhPB disorder attending the Outpatient Department of the Maastricht University Medical *** questionnaires and data from patient files were used to quantify the six dimensions of *** consistency was tested with McDonald’s ***-order Pearson correlations and t-tests were used to assess associations and differences.A P valuehe GI-hPB patients scored significantly worse in all dimensions of Ph compared to control data or norm scores from the general *** quality of life,participation and daily functioning,GI-hPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-hPB *** scores between the six dimensions were only very weak to weak,forcing us to quantify each domain *** All six dimensions of Ph are impaired in the GI-hPB *** and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

关键词： Positive health Chronic gut disorders Gastrointestinal disorders hepato-pancreatico-biliary disorders Integrated care

The Practice of Physical Medicine and Rehabilitation in subSaharan Africa and Antarctica：A White Paper or a Black Mark？

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中国康复医学杂志 2009年第5期24卷 385-389页

作者： Andrew J. haig md Jonathan Im Ayodeji Adewole, md Virgina S. Nelson, md, M.P.h Brian Krabak, md, M.B.A. Department of Physical Medicine and Rehabilitation University of Michigan Ann Arbor Michigan USA. College of Liberal Arts and Sciences Wayne State University Detroit Michigan USA. SOS International Accra Ghana. Department of Physical Medicine and Rehabilitation University of Michigan Ann Arbor Michigan USA. Department of Rehabilitation Medicine University of WashingtonSeattle Washington USA.

Objective:To explore the practice of PM&R in subSaharan Africa and ***:Medline searches,membership data searches,fax survey of medical schools,Internet searches,and interviews with ***:The continents are dissimilar in terms of climate and *** both Antarctica and subSaharan Africa have no PM&R training programs,no professional organizations,no specialty board requirements,and no practicing physicians in the *** there is no known disabled child on Antarctica and adults are airlifted to world-class health care,the consequences of this deficit are minimal *** the 788,000,000 permanent residents of subSaharan Africa including approximately 78 million persons with disability are left ***:Antarctica is doing *** is in a *** medical schools,hospitals doctors,and persons with disability;along with foreign volunteers,aid groups,and policymakers can impact the *** government-specifically national ministries of health-is ultimately responsible for the health and wellbeing of citizens.

关键词：体格检查医学文献资料因特网

Ecology and local knowledge of the Baird’s tapir (Tapirella bairdii) in the Sierra Madre de Oaxaca, Mexico

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Integrative Zoology 2016年第5期11卷 361-374页

作者： Mario César LAVARIEGA NOLASCO Miguel BRIONES-SALAS Amado MAZAS-TEODOCIO Elvira DURÁN-MEDINA Interdisciplinary Research Center for Integral Development Oaxaca UnitNational Polytechnic InstituteOaxacaMexico

As well as being of global cultural importance(from local tribal folklore to being an iconic species for conservation),the tapir plays an important role in its ecosystem as a herbivore and seed ***,the ecology and ethnozoology of the endangered Baird’s tapir in the north of Oaxaca,Mexico is poorly *** used camera traps to estimate its relative abundance and density and to describe the activity patterns of the northernmost population of Baird’s tapir in the Sierra Madre de *** knowledge concerning the tapir was also documented,along with the conservation strategies undertaken by the 2 indigenous communities that own the land where the study site is *** adult tapirs were photographed,and these were active 14 h per day,but were mainly nocturnal and *** estimated relative abundance(12.99±2.24 events/1000 camera days)and density values(0.07-0.24 individuals/km2)were both similar to those found in another site in Mexico located within a protected ***-structured interviews revealed that people have a basic understanding of the eating habits,activity and main predators of the *** were reports of hunting,although not among those respondents who regularly consume bush ***,the relative abundance and density estimates of tapir at the study site could be related to the favorable condition of the forest and the absence of hunting and consumption of tapir ***,the local people are conducting initiatives promoting the conservation of this ungulate and its habitat that combine to constitute a regional trend of habitat and wildlife protection.

关键词： camera-trapping density estimation random encounter model tapir conservation

Improvement in renal functions with transcatheter aortic valve implantation

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Journal of Geriatric Cardiology 2013年第4期10卷 317-322页

作者： Telat Keleş huseyin Ayhan Durmaz sarı Aslan AN Erdoğan KE Kasapkara Bilen Bayram Akçay Bozkurt Department of Cardiology Yıldırım Beyazıt University Bilkent 06800 Ankara Turkey Department of Cardiology Ankara Ataturk Education and Research Hospital Bilkent 06800 Ankara Turkey Department of Cardiovascular Surgery Ankara Ataturk Education and Research Hospital Bilkent 06800 Ankara Turkey.

BACKGROUND & OBJECTIVES:In recent years, emerging transcatheter aortic valve implantation (TAVI) has become an alternative for surgery。 however, with advanced age, several co-morbid factors together with contrast agent usage can cause deterioration in renal function and increase in the risk of acute kidney injury (AKI) with poor prognosis in patients with AKI。 Therefore, many patients cannot benefit from this treatment。 In this study, we aim to examine the effects of TAVI on renal functions。 METhODS AND RESULTS: Seventy patients, mean age of 77.6 years, underwent TAVI between July 2011 and December 2012。 Estimated glomerular filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula。 Patients were monitored for 48 h for urine output。 Stage 1 AKI, according to the VARC-2 AKIN system, developed in only five (7.1%) of the patients after the procedure。 There was a statistically significant increase between the mean 1(st) month eGFRs before (68。2 vs。 61.0, P he TAVI in the cohort。 After TAVI (48。5 mL/min, P he 1(st) month (52.1 mL/min, P he eGFR of the 36 (51.4%) patients diagnosed with chronic kidney disease before the procedure showed a statistically significant increase in renal functions。 The hospital mortality rate was higher in the group which developed AKI (P h eGFR showed a more statistically significant increase than pre-TAVI eGFR (62.8 and 69.8, P his difference - though statistically not significant - continued into the sixth month。 CONCLUSIONS: In this study, we showed that the treatment of aortic stenosis through TAVI allows improvement of renal functions, and that AKI rates will be lower with careful patient selection, proper pre-procedural hydration, and careful use of contrast agent。

关键词： Improvement Kidney injury Transcatheter aortic valve implantation