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Hypothalamic circuits and aging:keeping the circadian clock updated

Neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa Vázquez-Lizarraga Lucia Mendoza-Viveros Carolina Cid-Castro Sareni ruiz-Montoya Erick Carreño-Vázquez ricardo Orozco-Solis Instituto Nacional de Medicina Genómica(INMEGEN) México CityMéxico Centro de Investigacíon sobre el Envejecimiento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalamus intranasal drug administration metabolic control nutrient sensor SIRT1 sleep homeostasis

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Influence of biomass burning on ozone levels in the Megalopolis of Central Mexico during the COVID-19 lockdown

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Journal of Environmental Sciences 2024年第9期143卷 99-115页

作者： Victor Almanza Luis Gerardo ruiz-Suárez ricardo Torres-Jardón Agustín García-Reynoso Iván Y.Hernández-Paniagua Institute for Atmospheric Sciences and Climate Change National Autonomous University of MexicoCoyoacan 04510Mexico CityMexico

The massive reductions in anthropogenic emissions resulting from the COVID-19 lockdown provided a unique opportunity to evaluate the effect of mitigation measures aiming to abate air pollution.In Mexico,the total lockdown period took place during the dry-hot season when biomass burning activity is enhanced.Here,we investigate the role of biomass burning emissions on regional ozone levels in the Megalopolis of Central Mexico.The studied period covers the lockdown phases 2 and 3,and the first month of the New Normal.We applied a factor separation technique and process analysis to estimate the pure and synergistic contributions of emission reductions under lockdown and that from biomass burning to daily ozone maximum concentrations in 7 metropolitan areas of different states in the Megalopolis.The results revealed that biomass burning plumes likely masked the effect of massive reductions from mobile emissions,impacted the PBL development during phase 3 and favored transition and mixed NO_(x)-limited and VOC-limited regional regimes.This contributed to increased ozone production in the middle to lower PBL by changing the regional background levels which potentially could bias high ozone production efficiency estimations.Given the Megalopolis contribution to economic and societal development at national scale,our study suggests that ozone mitigation measures during the dry-hot season targeting mainly mobile emissions will likely be offset by biomass burning plumes.A regional and synergic policy aiming to control biomass burning would help to reduce the occurrence of high ozone levels in Central Mexico with the co-benefit of tackling short-lived climate pollutants.

关键词： COVID-19 Mexico Megalopolis Ozone Factor Separation Process Analysis

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Stand-level biomass models for predicting C stock for the main Spanish pine species

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Forest Ecosystems 2021年第2期8卷 387-402页

作者： Ana Aguirre Miren del Río ricardo ruiz-peinado Sonia Condés Department of Natural Systems and Resources School of Forest Engineering and Natural ResourcesUniversidad Politécnica de MadridMadridSpain INIA Forest Research CenterDepartment of Forest Dynamics and ManagementMadridSpain iuFOR Sustainable Forest Management Research InstituteUniversity of Valladolid and INIAValladolidSpain

Background:National and international institutions periodically demand information on forest indicators that are used for global reporting.Among other aspects,the carbon accumulated in the biomass of forest species must be reported.For this purpose,one of the main sources of data is the National Forest Inventory(NFI),which together with statistical empirical approaches and updating procedures can even allow annual estimates of the requested indicators.Methods:Stand level biomass models,relating the dry weight of the biomass with the stand volume were developed for the five main pine species in the Iberian Peninsula(Pinus sylvestris,Pinus pinea,Pinus halepensis,Pinus nigra and Pinus pinaster).The dependence of the model on aridity and/or mean tree size was explored,as well as the importance of including the stand form factor to correct model bias.Furthermore,the capability of the models to estimate forest carbon stocks,updated for a given year,was also analysed.Results:The strong relationship between stand dry weight biomass and stand volume was modulated by the mean tree size,although the effect varied among the five pine species.Site humidity,measured using the Martonne aridity index,increased the biomass for a given volume in the cases of Pinus sylvestris,Pinus halepensis and Pinus nigra.Models that consider both mean tree size and stand form factor were more accurate and less biased than those that do not.The models developed allow carbon stocks in the main Iberian Peninsula pine forests to be estimated at stand level with biases of less than 0.2 Mg·ha^(-1).Conclusions:The results of this study reveal the importance of considering variables related with environmental conditions and stand structure when developing stand dry weight biomass models.The described methodology together with the models developed provide a precise tool that can be used for quantifying biomass and carbon stored in the Spanish pine forests in specific years when no field data are available.

关键词： Martonne aridity index Dry weight biomass Carbon stock National Forest Inventory Peninsular pine forest Biomass expansion factor

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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

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Scotogenic dark symmetry as a residual subgroup of Standard Model symmetries

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Chinese Physics C 2020年第8期44卷 108-114页

作者： Salvador Centelles Chuliá ricardo Cepedello Eduardo peinado Rahul Srivastava AHEP Group Institut de Física Corpuscular-CSIC-Universitat de ValènciaParc Científic de Paterna.C/Catedrático JoséBeltrán2 E-46980 Paterna(Valencia)-SPAIN Instituto de Física Universidad Nacional Autónoma de MéxicoA.P.20-364Ciudad de México 01000México Department of Physics Indian Institute of Science Education and Research-BhopalBhopal Bypass RoadBhauriBhopalIndia

We demonstrate that a scotogenic dark symmetry can be obtained as a residual subgroup of the global U(1)B−L symmetry already present in the Standard Model.In addition,we propose a general framework in which the U(1)B−L symmetry is spontaneously broken into an even Z2n subgroup,setting the general conditions for neutrinos to be Majorana and for dark matter stability to exist in terms of the residual Z2n.As an example,under this general framework,we build a class of simple models where,in a scotogenic manner,the dark matter candidate is the lightest particle running inside the mass loop of a neutrino.The global U(1)B−L symmetry in our framework,being anomaly free,can also be gauged in a straightforward manner leading to a richer phenomenology.

关键词： neutrino masses dark matter symmetries scotogenic

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Secondary sclerosing cholangitis after critical COVID-19:Three case reports

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World Journal of Hepatology 2022年第8期14卷 1678-1686页

作者： Juan M Mayorquín-Aguilar Aldo Lara-Reyes Luis Alberto Revuelta-Rodríguez Nayelli C Flores-García Astrid ruiz-Margáin Marco Antonio Jiménez-Ferreira ricardo Ulises Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Department of Pathology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

BACKGROUND The global coronavirus disease 2019(COVID-19)pandemic has caused more than 5 million deaths.Multiorganic involvement is well described,including liver disease.In patients with critical COVID-19,a new entity called"post-COVID-19 cholangiopathy"has been described.CASE SUMMARY Here,we present three patients with severe COVID-19 that subsequently developed persistent cholestasis and chronic liver disease.All three patients required intensive care unit admission,mechanical ventilation,vasopressor support,and broad spectrum antibiotics due to secondary infections.Liver transplant protocol was started for two of the three patients.CONCLUSION Severe COVID-19 infection should be considered a potential risk factor for chronic liver disease and liver transplantation.

关键词： SARS-CoV-2 Persistent cholestasis Liver chemistry Hypoxic cholangiopathy Case report

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Systematic exploration of signal-based indicators for failure diagnosis in the context of cyber-physical systems

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Frontiers of Information Technology & Electronic Engineering 2019年第2期20卷 152-175页

作者： Santiago ruiz-ARENAS Zoltán RUSáK Imre HORVáTH ricardo MEJí-GUTIERREZ Faculty of Industrial Design Engineering Delft University of Technology Grupo de Investigación en Ingeniería de Diseno Universidad EAFIT

Malfunction or breakdown of certain mission critical systems(MCSs) may cause losses of life, damage the environments, and/or lead to high costs. Therefore, recognition of emerging failures and preventive maintenance are essential for reliable operation of MCSs. There is a practical approach for identifying and forecasting failures based on the indicators obtained from real life processes. We aim to develop means for performing active failure diagnosis and forecasting based on monitoring statistical changes of generic signal features in the specific operation modes of the system. In this paper, we present a new approach for identifying emerging failures based on their manifestations in system signals. Our approach benefits from the dynamic management of the system operation modes and from simultaneous processing and characterization of multiple heterogeneous signal sources. It improves the reliability of failure diagnosis and forecasting by investigating system performance in various operation modes, includes reasoning about failures and forming of failures using a failure indicator matrix which is composed of statistical deviation of signal characteristics between normal and failed operations, and implements a failure indicator concept that can be used as a plug and play failure diagnosis and failure forecasting feature of cyber-physical systems. We demonstrate that our method can automate failure diagnosis in the MCSs and lend the MCSs to the development of decision support systems for preventive maintenance.

关键词： Failure indicators Failure classification Failure detection and diagnosis Complex systems

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Clinical assessment and management of liver fibrosis in nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2020年第39期26卷 5919-5943页

作者： Alejandro Campos-Murguía Astrid ruiz-Margáin JoséA González-Regueiro ricardo U Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression of liver fibrosis.This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD,analyzing the currently available literature.In the assessment of NAFLD patients,it is important to identify clinical,genetic,and environmental determinants of fibrosis development and its progression.To properly detect fibrosis,it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores,followed by a complementary imaging study(transient elastography,magnetic resonance elastography or acoustic radiation force impulse)and finally a liver biopsy,when needed.To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review,describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis.Finally,treatment should always include diet and exercise,as well as controlling the components of the metabolic syndrome,+/-vitamin E,considering the presence of sleep apnea,and when available,allocate those patients with advanced fibrosis or high risk of progression into clinical trials.The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD,aiming to decrease/stop its progression and improve their prognosis.

关键词： Non-alcoholic fatty liver disease Liver fibrosis Clinical assessment Diagnosis Treatment Test accuracy

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Modelling Thermo-Electro-Mechanical Effects in Orthotropic Cardiac Tissue

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Communications in Computational Physics 2020年第1期27卷 87-115页

作者： ricardo ruiz-Baier Alessio Gizzi Alessandro Loppini Christian Cherubini Simonetta Filippi Mathematical Institute University of OxfordWoodstock RoadOxford OX26GGUnited Kingdom Laboratory of Mathematical Modelling Institute of Personalised MedicineSechenov UniversityMoscowRussian Federation Nonlinear Physics and Mathematical Modeling Department of EngineeringUniversity Campus Bio-Medico of RomeVia A.del Portillo 2100128RomeItaly International Center for Relativistic Astrophysics(ICRA) and ICRANetPiazza delle Repubblica 10I-65122 PescaraItaly

In this paper we introduce a new mathematical model for the active contraction of cardiac muscle,featuring different thermo-electric and nonlinear conductivity properties.The passive hyperelastic response of the tissue is described by an orthotropic exponential model,whereas the ionic activity dictates active contraction in-corporated through the concept of orthotropic active strain.We use a fully incompressible formulation,and the generated strain modifies directly the conductivity mechanisms in the medium through the pull-back transformation.We also investigate the influence of thermo-electric effects in the onset of multiphysics emergent spatiotem-poral dynamics,using nonlinear diffusion.It turns out that these ingredients have a key role in reproducing pathological chaotic dynamics such as ventricular fibrillation during inflammatory events,for instance.The specific structure of the governing equations suggests to cast the problem in mixed-primal form and we write it in terms of Kirchhoff stress,displacements,solid pressure,dimensionless electric potential,activation generation,and ionic variables.We also advance a new mixed-primal finite element method for its numerical approximation,and we use it to explore the properties of the model and to assess the importance of coupling terms,by means of a few computational experiments in 3D.

关键词： Cardiac electromechanics orthotropic active strain thermo-electric coupling scroll wave propagation numerical simulations

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Pharmacological strategies in extracorporeal membrane oxygenation weaning failure: a call to action

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Emergency and Critical Care Medicine 2023年第2期3卷 43-45页

作者： Francisco J.González-ruiz Francisco M.Baranda-Tovar Luis A.Baeza-Herrera JoséD.Utrilla-Álvarez ricardo E.Quirázco-Cordova Gustavo Rojas-Velasco Department of Cardiovascular Critical Care National Institute of Cardiology“Dr.Ignacio Chávez”Mexico CityMexico National Institute of Cardiology.Juan Badiano 1 Belisario Dominguez Secc 16Tlalpan14080Mexico CityMexico

Extracorporeal membrane oxygenation has emerged as a viable alternative for stabilizing and improving critically ill patients in acute cardiovascular diseases.However,the weaning stage has been associated with a high morbidity and mortality rate.This makes searching for strategies that reduce failure in this final process necessary.Implementing a new approach must be tried and included in our protocols,seeking the patient’s well-being at all times.In this article,the authors discuss their point of view regarding potential pharmacological alternatives and the mechanism of action involved,which could decrease the mortality associated with this therapeutic.

关键词： β-Blockers Extracorporeal membrane oxygenation Inodilators Mechanical circulatory support Pharmacological strategies

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