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Empagliflozin reduces brain pathology in Alzheimer's disease and type 2 diabetes

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Neural Regeneration Research 2024年第6期19卷 1189-1190页

作者： Carmen Hierro-Bujalance Monica Garcia-Alloza Division of Physiology School of MedicineUniversidad de Cadiz Instituto de Investigacion e Innovacion en Ciencias Biomedicas de la Provincia de Cadiz (INIBICA) Salus Infirmorum-Universidad de Cadiz

Alzheimer’s disease(AD) and type 2 diabetes(T2D): More than 55 million people suffer from dementia, and it is expected that over 150 million people will suffer from this disease by 2050. AD is the most common type of dementia and while aging remains the main risk factor to suffer it, previous studies have also shown that metabolic disorders, and T2D specifically, are also major contributors(Wang et al., 2012).

关键词： INHIBITORS

Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli Kazim A.Sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba departamento de Química Biológica-Centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCK Y-27632

From partial to complete:Wing-and tail-feather moult sequence and intensity depend on species,life-cycle stage,and moult completeness in passerines

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Avian Research 2024年第1期15卷 98-107页

作者： Santi Guallar departament de Vertebrats Museu de Ciencies Naturals de BarcelonaBarcelona08003Spain

Passerines moult during various life-cycle stages.Some of these moults involve the retention of a variable quantity of wing and tail feathers.This prompts the question whether these partial moults are just arrested complete moults or follow different processes.To address it,I investigated whether three relevant features remain constant across partial and complete moults:1) moult sequence(order of activation) within feather tracts(e.g.,consecutive outward moult of primaries) and among tracts(e.g.,starting with marginal coverts,followed by greater coverts second,tertials,etc.);2) dynamics of moult intensity(amount of feathers growing along the moult progress);and 3) protection of wing quills by overlapping fully grown feathers.To study the effect of moult completeness on these three features,I classified moults of 435 individuals from 61 species in 3 groups:i) complete and partial,ii) without and iii) with retention of feathers within tracts.To study the effect of life-cycle stage,I used postbreeding,postjuvenile,and prebreeding moults.I calculated phylogenetically corrected means to establish feather-moult sequence within tracts.I applied linear regression to analyse moult sequence among tracts,and polynomial regression to study the dynamics of moult intensity as moult progresses.Sequence and intensity dynamics of partial moults tended resemble those of the complete moult as moult completeness increased.Sequence within and among feather tracts tended to shift as moult intensity within tracts and number of tracts increased.Activation of primaries advanced in relation to the other feather tracts as number of moulted primaries increased.Tertial quills were protected by the innermost greater covert regardless of moult completeness.These findings suggest that moult is a self-organised process that adjusts to the degree of completeness of plumage renewal.However,protection of quills and differences among species and between postjuvenile-and prebreeding-moult sequences also suggest an active control linked to feather fun

关键词： Mass-gap index Moult extent Moult regulation Polynomial regression

A neural branch-and-price for truck scheduling in cross-docks

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Science China Mathematics 2024年第6期67卷 1341-1358页

作者： Rahimeh Neamatian Monemi Shahin Gelareh Nelson Maculan Wei-Kun Chen Sharkey Predictim Globe Villeneuve d’Ascq59650France Département R&T IUT de BéthuneUniversitéd’ArtoisBéthuneF-62000France Federal university of Rio de Janeiro COPPE-PESCRio de JaneiroRJ 21941-972Brazil School of Mathematics and Statistics Beijing Institute of TechnologyBeijing100081China

In this paper,we address the complex problem of dock-door assignment and truck scheduling within cross-docking operations.This is a problem that requires frequent resolution throughout the operational day,as disruptions often invalidate the optimal plan.Given the problem's highly combinatorial nature,finding an optimal solution demands significant computational time and resources.However,the distribution of data across problem instances over a lengthy planning horizon remains consistently stable,with minimal concern regarding distribution shift.These factors collectively establish the problem as an ideal candidate for a learn-to-optimize solution strategy.We propose a Dantzig-Wolfe reformulation,solving it via both a conventional branch-and-price approach and a neural branch-and-price approach,the latter of which employs imitation learning.Additionally,we introduce some classes of valid inequalities to enhance and refine the pricing problem through a branch-and-cut scheme.Our computational experiments demonstrate that this methodology is not only feasible but also presents a viable alternative to the traditional branch-and-price algorithms typically utilized for such challenges.

关键词： cross-docking MILP modeling Dantzig-Wolfe decomposition graph convolutional network

Scanning transmission electron microscopy and atom probe tomography analysis of non-stoichiometry long-period-stacking-ordered structures in Mg-Ni-Y/Sm alloys

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Journal of Magnesium and Alloys 2024年第3期12卷 954-965页

作者： Yimeng Chen Manuel Legrée Jean-Louis Bobet Alexander Kvit CAMECA Instruments Inc MadisonWI 53711USA ICMCB Universitéde BordeauxPessacCEDEX 33608France NIAC&Materials Science department University of WisconsinMadisonWI 53706USA

The long-period-stacking-ordered(LPSO)structure affects the mechanical,corrosion and hydrolysis properties of Mg alloys.The current work employs high angle annular dark field-scanning transmission electron microscopy(HAADF-STEM)and atom probe tomography(APT)to investigate the structural and local chemical information of LPSO phases formed in Mg-Ni-Y/Sm ternary alloys after extended isothermal annealing.depending on the alloying elements and their concentrations,Mg-Ni-Y/Sm develops a two-phase LPSO+α-Mg structure in which the LPSO phase contains defects,hybrid LPSO structure,and Mg insertions.HAADF-STEM and APT indicate non-stoichiometric LPSO with incomplete Ni_(6)(Y/Sm)_(8) clusters.In addition,the APT quantitatively determines the local composition of LPSO and confirms the presence of Ni within the Mg bonding layers.These results provide insight into a better understanding of the structure and hydrolysis properties of LPSO-Mg alloys.

关键词： Magnesium alloys Long-range ordering Atom probe tomography(APT) STEM HAADF Hydrolysis properties.

Women Breast Cancer: Knowledge, Attitudes, Practices and Factors Associated with Early Screening in the Municipality of Abomey-Calavi in Benin in 2018

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Open Journal of Epidemiology 2024年第1期14卷 131-156页

作者： Stéphane Arold Bidossessi Senahoun Nicolas Hamondji Amegan Mahougnon Hugues Serge Dohou Hermann Comlanvi Agbedjinou Lucresse Corine Fassinou Tècle Edwige Korogone Armand Ibikounle Dieudonné Fambo Joël Gamêlé Mikponhoué Christiane Tshabu Aguemon Ecole Doctorale des Sciences de la Santé Université d’Abomey-Calavi Cotonou Bénin Ecole de Santé Publique de l’université de Montréal Québec Canada Unité de Formation et de Recherche en Médecine Cardiovasculaire Faculté de Médecine de l’Université de Parakou Parakou Bénin Ecole de Santé Publique Université Libre de Bruxelles Bruxelles Belgique Ecole Nationale des Techniciens Supérieurs en Santé Publique et en Surveillance Epidémiologique Université de Parakou Parakou Bénin Faculté des Sciences de la Santé Université d’Abomey-Calavi Cotonou Bénin

Background: Breast cancer is the dominant cancer in women in both developed and developing countries. The objective of this study was to assess the knowledge, attitudes, practices and factors associated with early breast cancer screening among women in the Municipality of Abomey-Calavi in Benin. Methods: This was a cross-sectional, descriptive, analytical study with prospective data collection from October 1 to 8, 2018, involving 1740 women in the Municipality of Abomey-Calavi, aged 18 years or older and selected by WHO four-stage random cluster sampling. Consenting women who were mentally competent, 18 years of age or older at the time of the survey, and residing continuously in the Municipality of Abomey-Calavi for the last six months prior to the survey were included. On the other hand, women who belonged to a breast cancer prevention service, women in whom secondary screening was noted, or non-consenting women were not included. The initial minimum size was estimated by the Schwartz formula with a cluster effect of k = 2. Information was collected by questionnaire survey, entered with Epidata 3.1. Fr and analyzed with R Studio 3.5.1. software. Results: The mean age of the women surveyed was 32.0 ± 11.5 years with a range of 18 and 71 years. Regarding knowledge, the clinical manifestation known by the majority of women was the presence of a nodule (68.50%). In the series, 1308 (75.17%) declared having heard about breast cancer once before, either on the radio, television or from friends and 726 (55.50%) had heard about breast cancer screening. Five hundred and twelve (70.52%) of the 726 who had heard of breast cancer said they knew that breast cancer could be screened earlier. Breast self-examination was the most cited screening method (67.58%). The disease is of natural origin according to 37.84% of them. Regarding attitudes and practices, the prevalence of early breast cancer screening was 12.93%, of which 11.67% declared that they had checked themselves to know whether they were carriers of the disease or n

关键词： Breast Cancer Early Screening Knowledge Practices Attitudes Associated Factors

Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site

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Journal of Environmental Sciences 2024年第9期143卷 60-70页

作者： Hao Li Jun Yao Jianli Liu Ning Min Geoffrey Sunahara Dongyang Men Robert Duran School of Water Resources and Environment Research Center of Environmental Science and EngineeringChina University of Geosciences(Beijing)Beijing 100083China department of Natural Resource Sciences McGill University21111Lakeshore DriveSte-Anne-de-BellevueQuebecH9X 3V9Canada Equipe Environnement et Microbiologie MELODY groupUniversitéde Pau et des Pays de l’AdourE2S-UPPAIPREM UMR CNRS 5254BP 115564013 Pau CedexFrance

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological environment.Soil samples were collected from different depths(0 to 13 m)and analyzed for metal(loid)s content and fractionation,as well as microbial activities.The potential ecological risk indices for the different soil depths(ordered from high to low)were:1 m(D-1)>surface(S-0)>5 m(D-5)>13 m(D-13)>9 m(D-9),ranging between 1840.65-13,089.62,and representing extremely high environmental risks,of which Cd(and probably not arsenic)contributed to the highest environmental risk.A modified combined pollution risk index(MCR)combining total content and mobile proportion of metal(loid)s,and relative toxicities,was used to evaluate the degree of contamination and potential environmental risks.For the near-surface samples(S-0 and D-1 layers),the MCR considered that As,Cd,Pb,Sb,and Zn achieved high and alarming degrees of contamination,whereas Fe,Mn,and Ti were negligible or low to moderate pollution degrees.Combined microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity characteristics.Correlation analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics(pdered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

关键词： Abandoned chemical smelting sites Microbial activities Modified combined pollution risk Microcalorimetry Enzymatic activities

Numerical Modeling of Mass Transfer in the Interaction between River Biofilm and a Turbulent Boundary Layer

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Open Journal of Fluid Dynamics 2024年第1期14卷 1-23页

作者： Falilou Coundoul Evrad M. D. Ngom Frédéric Y. Moulin Institut Polytechnique de Saint-Louis Université Gaston Berger Saint-Louis Senegal Institut de Mécanique des Fluides de Toulouse UMR 5502-Université de Toulouse Occitanie France

In this article dedicated to the modeling of vertical mass transfers between the biofilm and the bulk flow, we have, in the first instance, presented the methodology used, followed by the presentation of various results obtained through analyses conducted on velocity fields, different fluxes, and overall transfer coefficients. Due to numerical constraints (resolution of relevant spatial scales), we have restricted the analysis to low Schmidt numbers (Sc=0.1, Sc=1, and Sc=10) and a single roughness Reynolds number (Re*=150). The analysis of instantaneous concentration fields from various simulations revealed logarithmic concentration profiles above the canopy. In this zone, the concentration is relatively homogeneous for longer times. The analysis of results also showed that the contribution of molecular diffusion to the total flux depends on the Schmidt number. This contribution is negligible for Schmidt numbers Sc≥0.1, but nearly balances the turbulent flux for Sc=0.1. In the canopy, the local Sherwood number, given by the ratio of the total flux (within or above the canopy) to the molecular diffusion flux at the wall, also depends on the Schmidt number and varies significantly between the canopy and the region above. The exchange velocity, a purely hydrodynamic parameter, is independent of the Schmidt number and is on the order of 10% of in the present case. This study also reveals that nutrient absorption by organisms near the wall depends on the Schmidt number. Such absorption is facilitated by lower Schmidt numbers.

关键词： Epilithic Biofilm Passive Scalar Transport Direct Numerical Simulation Navier-Stokes

Small molecules to target tau amyloid aggregation

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Neural Regeneration Research 2024年第3期19卷 509-511页

作者： Zoe Manglano-Artuñedo Samuel Peña-Díaz Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain

Protein aggregation has been linked with many neurodegenerative diseases,such as Alzheimer’s disease(AD)or Parkinson’s disease.AD belongs to a group of heterogeneous and incurable neurodegenerative disorders collectively known as tauopathies.They comprise frontotemporal dementia,Pick’s disease,or corticobasal degeneration,among others.The symptomatology varies with the specific tau protein variant involved and the affected brain region or cell type.However,they share a common neuropathological hallmark-the formation of proteinaceous deposits named neurofibrillary tangles.Neurofibrillary tangles,primarily composed of aggregated tau(Zhang et al.,2022),disrupt normal neuronal functions,leading to cell death and cognitive decline.

关键词： tau degeneration aggregation