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Therapeutic advances in neural regeneration for Huntington’s disease

Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini Michele d’Angelo department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, num

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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Tracking the change in Spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： Paula Fernández González María José Presno Manuel Landajo department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this century.In this paper we pursue two objectives.First,we analyze the evolution of GHG emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining factors.Second,we propose several actions specifically oriented to more tightly controlling the level of emissions.Our results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita effect.We detected somewhat different patterns among the various sectors analyzed.While the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of industry.The carbonization effect was revealed as crucial in the commerce sector.The above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in emissions.Additional efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition Spain GHG emissions

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Hydrochar and synthetic natural gas co-production for a full circular economy implementation via hydrothermal carbonization and methanation:An economic approach

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Journal of Environmental Sciences 2024年第6期140卷 69-78页

作者： Judith González-Arias Guillermo Torres-Sempere Miriam González-Castaño Francisco MBaena-Moreno Tomás RReina Inorganic Chemistry department and Materials Sciences Institute University of Seville-CSICSevilleSpain Materials Sciences Institute(ICMSE) CSIC-University of SevilleSevilleSpain department of Chemistry and Chemical Engineering Chalmers University of TechnologyGothenburgSE 41296Sweden

Herein we study the economic performance of hydrochar and synthetic natural gas coproduction from olive tree pruning.The process entails a combination of hydrothermal carbonization and methanation.In a previous work,we evidenced that standalone hydrochar production via HTC results unprofitable.Hence,we propose a step forward on the process design by implementing a methanation,adding value to the gas effluent in an attempt to boost the overall process techno-economic aspects.Three different plant capacities were analyzed(312.5,625 and 1250 kg/hr).The baseline scenarios showed that,under the current circumstances,our circular economy strategy in unprofitable.An analysis of the revenues shows that hydrochar selling price have a high impact on NPV and subsidies for renewable coal production could help to boost the profitability of the process.On the contrary,the analysis for natural gas prices reveals that prices 8 times higher than the current ones in Spain must be achieved to reach profitability.This seems unlikely even under the presence of a strong subsidy scheme.The costs analysis suggests that a remarkable electricity cost reduction or electricity consumption of the HTC stage could be a potential strategy to reach profitability scenarios.Furthermore,significant reduction of green hydrogen production costs is deemed instrumental to improve the economic performance of the process.These results show the formidable techno-economic challenge that our society faces in the path towards circular economy societies.

关键词： Hydrothermal carbonization CO_(2)waste valorization Methanation Profitability analysis

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Long-term monitoring of cycles in Clethrionomys rutilus in the Yukon boreal forest

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Integrative Zoology 2024年第1期19卷 27-36页

作者： Charles J.KREBS Alice J.KENNEY B.Scott GILBERT Rudy BOONSTRA department of Zoology University of British ColumbiaVancouverBritish ColumbiaCanada Renewable Resources Management Program Yukon UniversityWhitehorseYukonCanada department of Biological Sciences University of Toronto ScarboroughTorontoOntarioCanada

Baseline studies of small rodent populations in undisturbed ecosystems are rare.We report here 50 years of mon-itoring and experimentation in Yukon of a dominant rodent species in the North American boreal forest,the red-backed vole Clethrionomys rutilus.These voles breed in summer,weigh 20–25 g,and reach a maximum density of 20 to 25 per ha.Their populations have shown consistent 3–4-year cycles for the last 50 years with the only change being that peak densities averaged 8/ha until 2000 and 18/ha since that year.During the last 25 years,we have measured food resources,predator numbers,and winter weather,and for 1-year social interactions,to estimate their contribution to changes in the rate of summer increase and the rate of overwinter decline.All these potential limiting factors could contribute to changes in density,and we measured their relative contributions statistically with multiple regressions.The rate of winter decline in density was related to both food supply and winter severity.The rate of summer increase was related to summer berry crops and white spruce cone production.No measure of predator numbers was related to winter or summer changes in vole abundance.There was a large signal of climate change effects in these populations.There is no density dependence in summer population growth and only a weak one in winter population declines.None of our results provide a clear understanding of what generates 3–4-year cycles in these voles,and the major missing piece may be an understanding of social interactions at high density.

关键词： boreal forest climate change density dependence population cycles predation winter severity

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Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression

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Current Medical Science 2024年第1期44卷 144-155页

作者： Lin WANG Qing-guang CHEN Hao LU department of Endocrinology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China department of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China

Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated

关键词： Jianpi Qinghua formula diabetic cardiomyopathy AP-1 transcription factor apoptosis inflammation

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Targeted NGS analysis reveals a complex genetic background of idiopathic erythrocytosis in a large Venetian family

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Genes & Diseases 2024年第2期11卷 561-563页

作者： Bertozzi Irene Benetti Andrea Regazzo Daniela Polese Francesca Biagetti Giacomo Ceolotto Giulio Randi Maria Luigia First Medical Clinic University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy Transfusion Medicine department Ospedale dell'Angelo - Venezia MestreVia Paccagnella 1Venice 30174Italy Emergency Medicine University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy

Absolute erythrocytosis,due to an increased production of red blood cells,becomes manifest with hemoglobin(Hb)levels above 165 or 160 g/L or with a hematocrit(HCT)above 51%and 48%in males and females,respectively.1 A minority of patients have polycythemia vera(PV);acquired secondary erythrocytosis frequently occurs due to appropriate or inappropriate erythropoietin(EPO)excess,while congenital secondary erythrocytosis may derive from genetic defects causing tissue hypoxia.Hereditary erythrocytosis occurs in patients with genetic mutations of the oxygen-sensing pathway(VHL,PHD2,_HIF-1-alpha)or the erythropoietin receptor(EPOR)genes.2 Recently,HFE gene variants have been described in sporadic erythrocytoses.3 In a high proportion(about 70%)of patients with erythrocytosis,a specific etiology remains elusive despite extensive testing,and the diagnosis of idiopathic erythrocytosis(IE)is ruled out.

关键词： diagnosis patients congenital

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Solar Radiation Estimation Based on a New Combined Approach of Artificial Neural Networks (ANN) and Genetic Algorithms (GA) in South Algeria

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Computers, Materials & Continua 2024年第6期79卷 4725-4740页

作者： Djeldjli Halima Benatiallah Djelloul Ghasri Mehdi Tanougast Camel Benatiallah Ali Benabdelkrim Bouchra Material Sciences department Faculty of Material SciencesMathematics and Computer ScienceLaboratory of Sustainable Development and Computer Science(LSDCS)University of AdrarAdrar01000Algeria department of Civil Engineering University of Sistan and BaluchestanZahedan98167-45845Iran Laboratory of Computer Production and Maintenance Engineering(LGIPM)University of LorraineChieulles57070France Laboratory of Energy Environment and Information System(LEEIS) University of AdrarAdrar01000Algeria

When designing solar systems and assessing the effectiveness of their many uses,estimating sun irradiance is a crucial first step.This study examined three approaches(ANN,GA-ANN,and ANFIS)for estimating daily global solar radiation(GSR)in the south of Algeria:Adrar,Ouargla,and Bechar.The proposed hybrid GA-ANN model,based on genetic algorithm-based optimization,was developed to improve the ANN model.The GA-ANN and ANFIS models performed better than the standalone ANN-based model,with GA-ANN being better suited for forecasting in all sites,and it performed the best with the best values in the testing phase of Coefficient of Determination(R=0.9005),Mean Absolute Percentage Error(MAPE=8.40%),and Relative Root Mean Square Error(rRMSE=12.56%).Nevertheless,the ANFIS model outperformed the GA-ANN model in forecasting daily GSR,with the best values of indicators when testing the model being R=0.9374,MAPE=7.78%,and rRMSE=10.54%.Generally,we may conclude that the initial ANN stand-alone model performance when forecasting solar radiation has been improved,and the results obtained after injecting the genetic algorithm into the ANN to optimize its weights were satisfactory.The model can be used to forecast daily GSR in dry climates and other climates and may also be helpful in selecting solar energy system installations and sizes.

关键词： Solar energy systems genetic algorithm neural networks hybrid adaptive neuro fuzzy inference system solar radiation

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The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

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Oncology Research 2024年第6期32卷 1037-1045页

作者： MAHER KURDI ALAA ALKHOTANI ABDULRAHMAN SABBAGH EYAD FAIZO AHMED I.LARY AHMED K.BAMAGA MAJID ALMANSOURI BADR HAFIZ THAMER ALSHARIF SALEH BAEESA department of Pathology Faculty of MedicineKing Abdulaziz UniversityRabighSaudi Arabia department of Pathology College of MedicineUmm Al-Qura UniversityMakkahSaudi Arabia department of Surgery Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Surgery Faculty of MedicineUniversity of TabukTabukSaudi Arabia Section of Neurosurgery Department of SurgeryKing Abdulaziz Medical CityJeddahSaudi Arabia department of Pediatrics Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Clinical Biochemistry Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Neurosciences King Faisal Specialist Hospital and Research CenterJeddahSaudi Arabia department of Surgery King Abdulaziz Specialist HospitalTaifSaudi Arabia

Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

关键词： Grade 4 astrocytoma Glioblastoma Isocitrate dehydrogenase(IDH) O-6-methylguanine-DNA methyltransferase(MGMT) Protein methyltransferase proteins-5(PRMT5) Progression-free survival(PFS)

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Importance of dietary supplementation of soluble and insoluble fibers to sows subjected to high ambient temperatures during late gestation and effects on lactation performance

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Animal Nutrition 2024年第1期16卷 73-83页

作者： Seung Min Oh Abdolreza Hosseindoust Sang Hun Ha Jun Young Mun Joseph Moturi Habeeb Tajudeen Yo Han Choi Su Hyup Lee Jin Soo Kim Gyeongbuk Livestock Research Institute department of Animal Industry Convergence Kangwon National University Swine Division National Institute of Animal Science Rural Development Administration department of Swine Science Korea National University of Agriculture and Fisheries

Heat stress adversely affects sows' performance, which can be improved by applying proper nutritional strategies. This study was conducted to investigate the interactive effects of dietary fiber levels and sources on sows' reproductive performance, metabolic response during gestation, and the carry-over influence on litter performance in the lactation period during heat stress(average room temperature of 27.1°C). Fifty-four multiparous sows(Landrace × Yorkshire; initial body weight of 236.3 ± 16 kg; 2, 3and 4 parities) at d 90 of gestation were assigned to a 2 × 3 factorial arrangement(9 sows/treatment),involving 2 dietary fiber levels(4.5% and 6% crude fiber) and 3 dietary fiber sources(wheat bran [WB],palm kernel meal [PK], and beet pulp [BP]). Sows fed the BP diet had highest(P production was increased in the WB and BP treatments compared with the PK. Sows in the BP treatment showed the lowest(P = 0.036) hair cortisol. The blood insulin concentration of sows was higher(P = 0.026) in the high fiber(6%) treatment compared with the low fiber(4.5%) treatment at 90 min and120 min after the meal. The concentration of phthalic acid, succinic acid, phenylethylamine, hydrocinnamic acid, iron, linoleic acid, glycerol, ketone, and formamide were increased(P < 0.05) in the BP treatment compared with the WB. The BP treatment with high soluble fiber content improved the constipation index, farrowing duration, and litter performance, while high insoluble fibers increased sows comfort and reduced stress factors including respiratory rate and rectal temperature. Therefore,both soluble and insolub

关键词： Soluble fiber Insoluble fiber Beet pulp Wheat bran Palm kernel Metabolites

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The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

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Food Science and Human Wellness 2024年第2期13卷 748-764页

作者： Ruonan Yan Chi-Tang Ho Yanan Liu Shengnan Zhan Zufang Wu Xin Zhang department of Food Science and Engineering Ningbo UniversityNingbo 315211China department of Food Science Rutgers UniversityNew BrunswickNew Jersey 08901USA

The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health.Our present research showed that oolong tea polyphenols(OTP)improved the structural disorder of the intestinal flora caused by continuous darkness,thereby modulating the production of metabolites related to pyruvate metabolism,glycolysis/gluconeogenesis,and tryptophan metabolism to alleviate the steady-state imbalance.After fecal microbiota transplantation from the OTP group,the single-cell transcriptomic analysis revealed that OTP significantly increased the number of hypothalamus cell clusters,up-regulated the number of astrocytes and fibroblasts,and enhanced the expression of circadian rhythm genes Cry2,Per3,Bhlhe41,Nr1d1,Nr1d2,Dbp and Rorb in hypothalamic cells.Our results confirmed that OTP can actively improve the intestinal environmental state as well as internal/peripheral circadian rhythm disorders and cognitive impairment,with potential prebiotic functional characteristics to notably contribute to host health.

关键词： Gut microbiota Circadian rhythm Oolong tea polyphenols Single-cell sequencing Metabolism

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