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Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

Journal of Clinical and Translational Hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad regina.oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari Division of Pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary Center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics

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Photosynthetic response to a winter heatwave in leading and trailing edge populations of the intertidal red alga Corallina offi-cinalis(Rhodophyta)

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Acta Oceanologica Sinica 2024年第7期43卷 70-77页

作者： regina Kolzenburg Federica Ragazzola Laura Tamburello Katy R.Nicastro Christopher D.McQuaid Gerardo I.Zardi UmeåMarine Sciences Centre UmeåUniversity90571 NorrbynSweden University of Portsmouth Institute of Marine SciencePortsmouth PO49LYUK Stazione Zoologica Anton Dohrn Genova Marine CenterGenova 16126Italy Stazione Zoologica Anton Dohrn Sicily Marine CenterPalermo 90149Italy Department of Zoology and Entomology Rhodes UniversityMakhanda(Grahamstown)6139South Africa Centre of Marine Sciences University of AlgarveFaro 8005-139Portugal Laboratoire d’Océanologie et de Géosciences Universitéde LilleLille 59000France Universitéde Caen Normandie Laboratoire de Biologie des Organismes et des Ecosystèmes AquatiquesCaen 14032France

Marine heatwaves(MHWs)caused by anthropogenic climate change are becoming a key driver of change at the ecosystem *** conditions experienced by marine organisms across their distribution,particularly towards the equator,are likely to approach their physiological limits,resulting in extensive mortality and subsequent changes at the population *** at the margins of their species’distribution are thought to be more sensitive to climate-induced environmental pressures than central populations,but our understanding of variability in fitness-related physiological traits in trailing versus leading-edge populations is *** a laboratory simulation study,we tested whether two leading(Iceland)and two trailing(Spain)peripheral populations of the intertidal macroalga Corallina officinalis display different levels of maximum potential quantum efficiency(Fv/Fm)resilience to current and future winter MHWs *** study revealed that ongoing and future local winter MHWs will not negatively affect leading-edge populations of ***,which exhibited stable photosynthetic efficiency throughout the *** edge populations showed a positive though non-significant trend in photosynthetic efficiency throughout winter MHWs *** and equatorward populations did not produce significantly different results,with winter MHWs having no negative affect on Fv/Fm of either ***,we found no long-term regional or population-level influence of a winter MHWs on this species’photosynthetic ***,we found no statistically significant difference in thermal stress responses between leading and trailing ***,*** showed a trend towards higher stress responses in southern than northern *** responses rest on a variety of local population traits,they are difficult to predict based solely on thermal pressures.

关键词： marginal population coralline algae climate change ecophysiology photophysiology macroalgae Fv/Fm

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Hydrogen Storage Performance During Underground Hydrogen Storage in Depleted Gas Reservoirs:A Review

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Engineering 2024年第9期40卷 211-225页

作者： Lingping Zeng regina Sander Yongqiang Chen Quan Xie CSIRO Energy MelbourneVIC 3168Australia Hydrogen Industry Mission CSIROMelbourneVIC 3168Australia CSIRO Energy KensingtonWA 6151Australia Permanent Carbon Locking Future Science Platform CSIRO EnergyKensingtonWA 6151Australia WA School of Mines:Minerals Energy and Chemical EngineeringCurtin UniversityKensingtonWA 6151Australia

Hydrogen has emerged as a promising alternative to meet the growing demand for sustainable and renewable energy *** hydrogen storage(UHS)in depleted gas reservoirs holds significant potential for large-scale energy storage and the seamless integration of intermittent renewable energy sources,due to its capacity to address challenges associated with the intermittent nature of renewable energy sources,ensuring a steady and reliable energy *** the existing infrastructure and well-characterized geological formations,depleted gas reservoirs offer an attractive option for large-scale hydrogen storage ***,significant knowledge gaps regarding storage performance hinder the commercialization of UHS *** deliverability,hydrogen trapping,and the equation of state are key areas with limited *** literature review critically analyzes and synthesizes existing research on hydrogen storage performance during underground storage in depleted gas reservoirs;it then provides a high-level risk assessment and an overview of the techno-economics of *** significance of this review lies in its consolidation of current knowledge,highlighting unresolved issues and proposing areas for future *** these gaps will advance hydrogen-based energy systems and support the transition to a sustainable energy *** efficient and safe deployment of UHS in depleted gas reservoirs will assist in unlocking hydrogen’s full potential as a clean and renewable energy *** addition,this review aids policymakers and the scientific community in making informed decisions regarding hydrogen storage technologies.

关键词： Underground hydrogen storage Storage performance Hydrogen deliverability Hydrogen trapping Risk assessment Techno-economic analysis

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Anticancer therapeutic strategies for targeting mutant p53-Y220C

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Journal of Biomedical Research 2024年第3期38卷 222-232页

作者： Vitaly Chasov Damir Davletshin Elvina Gilyazova regina Mirgayazova Anna Kudriaeva Raniya Khadiullina Youyong Yuan Emil Bulatov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazan 420008Russia Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesMoscow 117997Russia Institute of Life Sciences School of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China

The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback *** the same time,TP53 is the most frequently mutated gene in human *** p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic *** oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and *** cavity accommodates stabilizing small molecules that have therapeutic *** development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant *** this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.

关键词： p53 Y220C mutation small molecule DNA-binding domain immunotherapy T cell receptor mimic antibody

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Using TiO2-Biocharcoal and TiO2-Diatomite for Photodisinfection in Washing Machine Wastewater

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Journal of Geoscience and Environment Protection 2024年第8期12卷 62-79页

作者： Daphne Montesuma Ferro Paloma Otsuka Kotani regina Affonso Nilce Ortiz Chemistry and Environment Center Nuclear and Energy Research Institute IPEN So Paulo Brazil Biotechnology Center Nuclear and Energy Research Institute IPEN So Paulo Brazil

The photodisinfection process using biomolded semiconductor photocatalysts can inactivate bacteria in wastewater washing machine samples. The comparative study evaluated the photocatalyst material titanium dioxide (TiO2) synthesized with diatomite and biocharcoal biotemplate (TiO2-Biocharcoal and TiO2-Diatomite) in photodisinfection processes using domestic washing machine wastewater samples, the results of bacterial inactivation were above 96%. The efficiency of the photodisinfection process was evaluated by counting the number of colonies of the bacteria. Experiments under LED solar lamps presented similar bacterial inactivation, and a correlation with kinetic models. The kinetic study demonstrated a curved regression, indicating a better fit with the Hom model. A tail at the end of the modeling curve indicates the presence of a high concentration of inactive bacteria in the medium, while a shoulder at the beginning of the curve suggests a heterogeneous sample with a high concentration of gram-positive bacteria. The toxicity tests performed with wastewater samples without light exposure indicated low toxicity for both materials. The study presented promising disinfection results for an accessible and efficient photo-sterilization process of water contaminated with bacteria using abundant solar and renewable energy throughout the national territory. .

关键词： Photodisinfection Diatomite Biocharcoal Wastewater Titanium Dioxide

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Motivational and Methodological Factors Involved in the Helping Behavior Test in Laboratory Rodents

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Journal of Behavioral and Brain Science 2024年第8期14卷 240-254页

作者： Gabriela F. Marinho Jaqueline M. Wuo João Paulo Kurita Alvaro C. Lima regina H. Silva Pharmacology Department Federal University of So Paulo So Paulo Brazil

Empathy allows humans and other animals to share the emotional state of another, adopting that individual’s perspective on a given situation. This ability is fundamental for species living in groups. Helping behavior in laboratory animals has been used to study empathy. In this test, subjects are exposed to a conspecific that is trapped and learn to open the cage to release the other animal. However, the interpretation of helping behavior as an emphatically motivated action is still controversial. Here we review the studies that use the helping behavioral test proposed by Ben-Ami Bartal and colleagues in 2011 to better understand motivational factors for this behavior. In addition, we compare methodological aspects of these studies. In conclusion, helping behavior can be driven by empathy, but other factors such as the desire for social contact and learning components cannot be ruled out as motivators. In addition, studies focused on evaluating neurobiological mechanisms underlying helping behavior in laboratory rodents can help elucidate the factors involved in releasing the trapped co-specific.

关键词： Animal Models Empathy Prosocial Behavior Rats

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Computer simulation of the coagulation of suspended solids——The applicability of the Müller–Smoluchowski theory

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Journal of Environmental Sciences 2016年第6期28卷 197-203页

作者： regina Wardzynska Beata Zaleska-Chróst Department of Chemistry University of Warmia and Mazury in Olsztyn

The results of studies carried out using a computer programme simulating the coagulation of suspensions containing spherical sol particles and spherical coagulant particles are *** influence of the degree of dispersion of the system on the coagulation reaction kinetics was investigated. The obtained results of kinetic studies were tested in the light of classical Müller–Smoluchowski equations. The influence of the physical properties of the coagulant,such as size, density and mass, on the coagulation rate was tested. It was found that within the range described in this paper, the rate of the simulated coagulation process fulfils both the kinetic equation of a first-order reaction, and the kinetic equation of a second-order *** the tested range, a significant influence of the mass and size of the coagulant on the coagulation rate was ascertained. The kinetic Müller–Smoluchowski dependence is fulfilled in a broader range of the degree of dispersion, when the coagulant particle mass and the sol particle mass are equal. When the particle mass increases with an increase in the particle radius, the coagulation rate increases faster that it would result from the Müller＇s dependence.

关键词： Aggregation Computer simulation Coagulation rate Sol

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Combined Oxidative Phosphorylation Deficiency-20-Exome as a Diagnostic Implement

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Journal of Biosciences and Medicines 2024年第6期12卷 7-12页

作者： Paulo Roberto Matos-Neto Lucas Antonissen Lima Verde Airton Ferreira da Ponte-Filho Luís Eduardo Oliveira Matos Amandha Espavier Trés Paulo Roberto Lacerda Leal Gerardo Cristino-Filho regina Coeli de Carvalho Porto Carneiro Faculty of Medicine Federal University of Cear Sobral Cear Brazil Department of Neurosurgery Federal University of Cear Sobral Cear Brazil Department of Neuropediatrics Federal University of Cear Sobral Cear Brazil

Mitochondrial disorders are phenotypically varied, with serious clinical repercussions. Among them, there is the deficiency of combined oxidative phosphorylation of type 20, which occurs due to a defect in the VARS2 gene. This article presents a case of a 2-year-old female with progressive myoclonic epilepsy and psychomotor regression, with refractoriness to multiple anticonvulsants. The diagnosis was only made after the examination was carried out. Therefore, this article highlights the aspects of this rare disease and the importance of the exome for the diagnosis of rare conditions.

关键词： Oxidative Phosphorylation Epilepsy Exome Mitochondrial Defect VARS2

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Nielsen coincidence theory on infra-solvmanifolds of Sol

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Science China Mathematics 2021年第8期64卷 1861-1884页

作者： Jong Bum Lee Karen regina Panzarin Department of Mathematics Sogang UniversitySeoul 121-742Korea Departamento de Matematica Universidade Federal de Sao CarlosSao CarlosSP 13565-905Brazil

We derive averaging formulas for the Lefschetz coincidence numbers,the Nielsen coincidence numbers and the Reidemeister coincidence numbers of maps on infra-solvmanifolds modeled on a connected and simply connected solvable Lie group of type(R).As an application,we compare our formula for the Nielsen coincidence numbers with a result of Jezierski(1992)for pairs of maps on some infra-solvmanifolds of *** all the pairs of self-maps of a nonorientable infra-solvmanifold of Sol,we determine the sets of all the possible values of the Nielsen coincidence numbers and the Reidemeister coincidence numbers.

关键词： averaging formula infra-solvmanifold Lefschetz coincidence number Nielsen coincidence number Reidemeister coincidence number Sol-geometry

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