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Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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chronic Diseases and Translational Medicine 2024年第2期10卷 102-117页

作者： Nicholas r.Powell Tyler Shugg Jacob Leighty Matthew Martin rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd c.Skaar Division of clinical Pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA Department of cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger rNA(mrNA)is endogenously bound by mir-122-5p and rs699 A>G decreases reporter mrNA in the microrNA functional-assay *** AGT promoter variant rs5051 c>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 c>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase mir-122-5p binding affinity by 3%.Mir-ecLIP results show rs699 is 40–45 nucleotides from the strongest microrNA-binding site in the AGT ***,rs699 A>G increases AGT mrNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 c>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mrNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 c>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 c>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

Basis for the diversity and extent in loss of digestible nutrients created by dietary phytin: Emphasis on fowl and swine

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动物营养学报 2024年第1期16卷 422-428页

作者： Edwin T. Moran Michael r. Bedford Poultry Science Department Auburn University AL 36830-5416 USA AB Vista Woodstock Court Blenheim Road Marlborough Wiltshire SN8 4AN UK

Phytin is the ca 2+ -Mg 2+ -K + salt of phytic acid that is created and deposited in the aleurone layer and/or germ of grains and legumes. Its high presence in feedstuffs for fowl and swine diets results in it being a universal and significant impediment to optimum performance. Phytin impairs gastrointestinal recovery of a wide array of nutrients, the effect varying with the nutrient concerned. On exposure to low pH during gastric digestion, phytin dissociates into phytic acid and solubilized ca 2+ . Even at low gastric pH, phytic acid is negatively charged which forms the basis of its anti-nutritive behavior. Pepsinogen has extensive basic amino acids on its activation peptide that are presented as cations at low pH which are targeted by pepsin for activation. Partially crystalized ca 2+ near the enzyme's active site further stabilizes its newly formed structure. Thus, phytic acid appears to interfere with gastric digestion by several mechanisms; interfering with pepsinogen activation by binding to the polypeptide's basic amino acids; coordinating free ca 2+ , destabilizing pepsin; binding some dietary proteins directly, further compromising gastric proteolysis. Upon digesta attaining neutrality in the duodenum, ca 2+ and other cations re-bind with accessible anions, phytic acid being a significant contender. Phytate not only binds free cations but can also strip them from enzymes (e.g. ca 2+ , Zn 2+ ) which reduces their structural resistance to autolysis and ability as co-factors (e.g. Zn 2+ ) to increase enzyme activity. Goblet cells initially employ ca 2+ as an electronic shield between mucin layers enabling granule formation and cell storage. After mucin granule release, ca 2+ is progressively displaced by Na + to free the viscous mucins enabling its translocation. Mucin entangles with the glycocalyx of adjacent enterocytes thereby constructing the unstirred water layer (USWL). Excessive removal of ca 2+ from mucin by phytic acid increases its fluidity facilit

关键词： Digestive enzyme calcium Endogenous protein Mucin Phytin

Synthesis of coral-like structures of Pr-Yb co-doped YIG: Structural,optical, magnetic and antimicrobial properties

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Journal of rare Earths 2024年第3期42卷 543-554,I0004页

作者： A.Fernandez Francisca P.Araujo Y.Guerra S.castro-Lopes J.Matilla-Arias Idglan S.de Lima Edson c.Silva-Filho Josy A.Osajima F.Guerrero r.Pena-Garcia Federal University of Piau Graduate Program in Materials Science and EngineeringTeresinaPIBrazil Federal rural University of Pernambuco Academic Unit of Cabo de Santo AgostinhoCabo de Santo AgostinhoPEBrazil Federal University of Piaui Department of PhysicTeresinaPBrazil Federal University of Pernambuco Graduate Program in Materials ScienceRecifePEBrazil University of Granma Departmentof Basic Sciences and Applied InformaticsFaculty of Technical SciencesBayamoCuba Federal University of Amazonas Department of PhysicManausAMBrazil Federal University of Pernambuco Department of PhysicRecifePEBrazil

coral-like structures of the Y_(3-x)Pr_(x)Fe_(5-y)Yb_(y)O_(12),(0.00 ≤ x ≤ 0.04, 0.00 ≤ y ≤ 0.02) compound were synthesized using the sol-gel method. Structural investigation certified the YIG cubic crystal structure formation, without any secondary phase. It is shown that, the relatively large ionic radius of the dopant cations results in an expansion of the lattice parameter, variations in the Iona-O-Iondangle, Iona-O,Iond-O and Ionc-O bond distances and decrease in the average crystallite size. Fourier transform infrared(FTIr) and raman measurements are essential to testify the single-phase formation of YIG crystal structure and are observed changes in the stretching and vibrational modes, respectively. The morphological study, energy dispersive spectroscopy(EDS) spectra and textural properties show corallike structures, peaks associated with Pr^(3+) and Yb^(3+) atoms and the effect of dopants on surface area,diameter, and pore volume, respectively. The optical analysis from diffuse reflectance spectra witnessed an increase in the optical gap band, a decrease in Urbach energy and blue shift in the charge transfer,correlated with the expansion of the unit cell due to the dopant's insertion in the YIG structure. A typical ferrimagnetic behavior is exhibited by the Y_(3-x)Pr_(x)Fe_(5-y)Yb_(y)O_(12)compound. The saturation magnetization(M_(s)), cubic anisotropy constant(K_(1)) and coercive field(H_(c)) increase with the Pr^(3+)cations content, as consequence of their magnetic nature and distribution around of Fe^(3+)ions due to the coexistence with the Yb^(3+). Finally, for the first time, antibacterial tests by mean of the direct contact method were performed for YIG co-doped with Pr^(3+)and Yb^(3+)and it is shown that, relatively high dosages of Pr^(3+) cations favored the activity against S. aureus, therefore, a new biological property for YIG doped with rare earths is presented.

关键词： Yttrium iron garnet(YIG) coral-like structures rare earths Band gap energy Magnetic properties Antimicrobial properties

A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng rex c.Haydon Hue H.Luu russell r.reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

GrP7 phase separation as an interpreter of temperature cues

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Molecular Plant 2024年第6期17卷 842-844页

作者： Sunita Pathak Lucia c.Strader Department of Biology Duke UniversityDurhamNCUSA

Plants are exposed to a range of daily and seasonal temperatures and thus are required to regulate their cellular processes under fluctuating temperature *** various temperature-responsive genes,GLYcINE-rIcH rNA BINDING PrOTEIN7(GrP7)encodes a glycine-rich rNA-binding protein that provides freezing tolerance to plants(carpenter et al.,1994;Kim et al.,2008)by acting as an rNA chaperone(Kwak et al.,2011).

关键词： conditions. separation

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

Automated Machine Learning Algorithm Using recurrent Neural Network to Perform Long-Term Time Series Forecasting

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computers, Materials & continua 2024年第3期78卷 3529-3549页

作者： Ying Su Morgan c.Wang Shuai Liu Department of Statistics and Data Science University of Central FloridaOrlandoFL32816-2370USA School of Mathematics and Statistics Beijing Technology and Business UniversityBeijing100048China

Long-term time series forecasting stands as a crucial research domain within the realm of automated machine learning(AutoML).At present,forecasting,whether rooted in machine learning or statistical learning,typically relies on expert input and necessitates substantial manual *** manual effort spans model development,feature engineering,hyper-parameter tuning,and the intricate construction of time series *** complexity of these tasks renders complete automation unfeasible,as they inherently demand human intervention at multiple *** surmount these challenges,this article proposes leveraging Long Short-Term Memory,which is the variant of recurrent Neural Networks,harnessing memory cells and gating mechanisms to facilitate long-term time series ***,forecasting accuracy by particular neural network and traditional models can degrade significantly,when addressing long-term time-series ***,our research demonstrates that this innovative approach outperforms the traditional Autoregressive Integrated Moving Average(ArIMA)method in forecasting long-term univariate time *** is a high-quality and competitive model in time series prediction,and yet it requires significant preprocessing *** multiple accuracy metrics,we have evaluated both ArIMA and proposed method on the simulated time-series data and real data in both short and long ***,our findings indicate its superiority over alternative network architectures,including Fully connected Neural Networks,convolutional Neural Networks,and Nonpooling convolutional Neural *** AutoML approach enables non-professional to attain highly accurate and effective time series forecasting,and can be widely applied to various domains,particularly in business and finance.

关键词： Automated machine learning autoregressive integrated moving average neural networks time series analysis

community-based knowledge towards rangeland condition, climate change, and adaptation strategies: the case of Afar pastoralists

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Ecological Processes 2017年第1期6卷 310-322页

作者： Minyahel Tilahun Ayana Angassa aster Abebe college of Agriculture and Natural resources Wolkite UniversityGubreiEthiopia Botswana University of Agriculture and Natural resources GaboroneBotswana School of Animal and range Sciences Hawassa UniversityHawassaEthiopia

Introduction:Pastoral communities have a comprehensive knowledge of their *** knowledge was acquired through extensive observation of the local environment and continuous herding ***’wisdom about their local environment and adaptation strategies to climate change is essential for sustainable ***,appreciation of pastoralists’knowledge about their environment is also important for the integration of indigenous knowledge with the proper application of scientific approach to fit with the prevailing ecological potential of pastoral ***:Data were collected using focus group discussions,key informant interviews,and in-depth *** in-depth interviews were conducted using a semi-structured questionnaire that was administered to 100 household heads with the age of above 50 years *** were randomly drawn from selected Pastoralists Associations(PAs)of two study *** were analyzed using descriptive statistics as well as the logit *** logit model was used to analyze the different coping strategies of pastoralists to overcome the failure of rain during different *** was done by complementing pastoralists’indigenous knowledge of time-series-based analysis across four seasons(Kerma,Gillal,Hagay,and Sugum)*** existing meteorological *** years(from 1971 to 2011)of existing metrological data were used to compare the empirical evidence with pastoralists’***:respondents mentioned that livestock number was the best indicator for evaluating rangeland condition in Afar *** existing empirical evidence based on metrological data did not show any significant decline in precipitation for the last four decades between 1971 and 2011 as opposed to the perception of pastoralists where 80%of them reported a decline in precipitation.A one unit increase in labor force suggested about 16.1%decrease in the choice of livestock selling as coping strategy in Afar pastoral

关键词： climate change Adaptation Perception Precipitation Temperature Afar rangelands

Hierarchical control Strategy for Load regulation Based on Stackelberg Game Theory considering randomness

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cSEE Journal of Power and Energy Systems 2024年第3期10卷 929-941页

作者： Tingyu Jiang Ping Ju c.Y.chung Yuzhong Gong college of Energy and Electrical Engineering Hohai UniversityNanjing 211100China Department of Electrical Engineering City University of Hong KongHong Kong CF624China Department of Electrical and computer Engineering University of SaskatchewanSaskatoonSK S7N 5A9Canada cSEE IEEE

Demand response has been recognized as a valuable functionality of power systems for mitigating power *** paper proposes a hierarchical control strategy among the distribution system operator(DSO),load aggregators(LAs),and thermostatically controlled loads(TcLs);the strategy includes a scheduling layer and an executive layer to provide load *** the scheduling layer,the DSO(leader)offers compensation price(cP)strategies,and the LAs(followers)respond to cP strategies with available regulation power(ArP)*** of the DSO and LAs are modeled according to their behaviors during the load regulation *** game is adopted to capture interactions among the players and leader and to obtain the optimal strategy for each participant to achieve ***,considering inevitable random factors in practice,e.g.,renewable generation and behavior of users,two different stochastic models based on sample average approximation(SAA)and parameter modification are formulated with improved scheduling *** the executive layer,distributed TcLs are triggered based on strategies determined in the scheduling layer.A self-triggering method that does not violate user privacy is presented,where TcLs receive external signals from the LA and independently determine whether to alter their operation *** simulations are performed on the modified IEEE-24 bus system to verify effectiveness of the proposed strategy.

关键词： Demand response hierarchical control load regulation self-triggering method Stackelberg game