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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

The Knowledge of Antibiotics in Veternary Students and Repercution in Human Health

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Health 2020年第12期12卷 1632-1639页

作者： Silvia D. peña betancourt Silvia Denise Posadas peña Lyda Y. Parra-Forero Departamento de Producción Agrícola y Animal Laboratorio de Toxicología Universidad Autonoma Metropolitana Ciudad de México Mexico Instituto de Estudios Superiores de Monterrey Ciudad de México México Departamento de Producción Agrícola y Animal Ciudad de México Mexico

The concept of single health is currently undoubtedly one of the most relevant in pandemic times, where humans and animals are together in the same world. penicillin was discovered in the last century by Alexander Fleming, used against infectious agents mainly of bacterial types, such as Staphylococcus aureus, Corynebacterium, Streptococcus, Brucella and Mycobacterium are examples of cattle pathogens. The bacteria have developed defense mechanisms allowing them to survive in the host cell (mutation) even in the presence of antimicrobials (bacterial selection). The aim of the study was to examine the degree of knowledge of antibiotics through a structured survey of ten questions, addressed to eighty-six students from the Bachelor of Veterinary Medicine and Zootechnics in 2019. Based on the information collected and after analyzing their answers, 63.14% of the students work in Clinics and Universities, 89.47% recognize the need for a quantified prescription, 47.36% mentioned that the Veterinary Medicine can prescribe antimicrobials, 52.63% support the use of antimicrobials for all microorganisms including viruses, 52.63% use the labeling to consult the withdrawal time and 100% identify that it is the withdrawal time and the practices that lead to the development of antimicrobial resistance. It is concluded that most of the students identify malpractice as the trigger for bacterial resistance, however their knowledge is not adequate to avoid antibiotic resistance to humans. It is recommended to reinforce the courses of microbiology, pharmacology and virology in the Veterinary Medicine and Zootechnics degree, as well as to be updated on alternatives such as the use of phytobiotics.

关键词： Antibiotics Resistance Bacteria Veterinary Students

Output feedback adaptive super twisting sliding mode control for quadrotor UAVs

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Control Theory and Technology 2024年第1期22卷 92-105页

作者： Oscar Salas-peña Jesus DeLeón-Morales Susana V.Gutiérrez-Martínez École Centrale de Nantes-LS2N UMR 6004 CNRS44300NantesFrance Facultad de Ingeniería Mecánica y Eléctrica Universidad Autónoma de Nuevo León66451San Nicolás de Los GarzaMexico

In this paper, a sliding mode control with adaptive gain combined with a high-order sliding mode observer to solve the tracking problem for a quadrotor UAV is addressed, in presence of bounded external disturbances and parametric uncertainties. The high order sliding mode observer is designed for estimating the linear and angular speed in order to implement the proposed scheme. Furthermore, a Lyapunov function is introduced to design the controller with the adaptation law, whereas an analysis of finite time convergence towards to zero is provided, where sufficient conditions are obtained. Regarding previous works from literature, one important advantage of proposed strategy is that the gains of control are parameterized in terms of only one adaptive parameter, which reduces the control effort by avoiding gain overestimation. Numerical simulations for tracking control of the quadrotor are given to show the performance of proposed adaptive control–observer scheme.

关键词： Adaptive super twisting controller High-order sliding modes observer UAV

Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

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Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human cancers.Among various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of cases.Despite intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 func-tion.In this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in vivo.Methods:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system.Moreover,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal instabil-ity.Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way analysis.In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models.Results:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based methods.The introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell proliferation.Transcriptome analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA damage.Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double-strand breaks arising fro

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

Porphyrins,phthalocyanines,and related covalent-organic frameworks in the photochemical and electrochemical water splitting:A review

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Particuology 2024年第7期90卷 236-265页

作者： Oxana V.Kharissova Yolanda peña Méndez Boris I.Kharisov Aleksandr LNikolaev Edith Luévano-Hipólito Lucy T.González Universidad Autónoma de Nuevo León Ave.Universidad s/nSan Nicolás de los GarzaNuevo León66455Mexico Department of Chemistry Moscow State UniversityVorobievy HillsMoscowRussia CONACYT-Universidad Autónoma de Nuevo León Facultad de Ingeniería Civil-Departamento de Ecomateriales y EnergíaCd.UniversitariaC.P.66455San Nicolás de los GarzaNLMexico Tecnologico de Monterrey Escuela de IngenieríaCienciasMonterreyNuevo León 64890Mexico Tecnologico de Monterrey Centro del AguaMonterreyNuevo León 64890Mexico

In this review,the possibilities of photochemical and electrochemical water splitting(WS)using porphyrins,phthalocyanines,related macrocycles,and their metal complexes are discussed.Significant efforts are being carried out in order to develop novel and cheap methods for water decomposition to generate inexhaustible greener energy sources(molecular hydrogen)instead of oil and gas.The processes of WS in heterogeneous and homogeneous media require novel photo-and electrocatalysts,in particular those on macrocycle basis.A high WS efficiency has been observed for porphyrins and phthalocyanines,showing their suitability both for HER and OER processes are available using these relative compounds for WS purposes.Porphyrins can be used in photocatalytic and electrocatalytic WS processes both in their free forms or as metal porphyrins/porphyrinates,mainly loaded on various inorganic materials,such as Au NPs,C_(3)N_(4),GaP,KTaO_(3),GaP,and so on,as part of porphyrin-containing polymers or on electrode surface as modifying coatings,being sometimes better than commercial catalysts,such as Pt/C.Photocatalytic H2 evolution can be considerably depended on the shape of porphyrin particles;in particular,porphyrin nanowires can yield up to 20 times more H2 than its powder.In certain cases,both HER and OER can be driven in the same electrolyte using metal porphyrins.The capacity of metal porphyrins to generate ROS(in particular,singlet oxygen 1O_(2))under ultrasonic treatment is known and can be successfully used for H_(2)O_(2) and O_(2) generation.Phthalocyanines can be used in similar processes in free form or as composites with inorganic or organic counterparts,being immobilized on nanocarbons,metal oxides and salts,or simply dissolved in water acting in a homogeneous medium.An additional use of ultrasound can lead to better results due to the synergistic effect of the sonochemical treatment and light.Covalent-organic frameworks are also applied for WS purposes and are mainly based on a variety of N-containing ligands,such as tr

关键词： Porphyrins Phthalocyanines COFs Water splitting Photocatalysis Electrocatalysis

An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads:Experimental studies and molecular dynamics analysis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2669-2684页

作者： Jamie Anne Lugtu-pe Xuning Zhang Sako Mirzaie Hao Han R.Chang Nour AL-Mousawi Kuan Chen Yongqiang Li Anil Kane Daniel Bar-Shalom Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoToronto M5S 3M2Canada Candoo Pharmatech Company Inc. Mississauga L5N 5M1Canada Department of Pharmacy University of CopenhagenCopenhagen DK-2100Denmark Patheon by Thermo Fisher Scientific Toronto Region Operations(TRO)Mississauga L5N 3X4Canada

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

关键词： Controlled release amorphous solid dispersion Poorly soluble drug Internal recrystallization Membrane-reservoir coated beads Molecular dynamics simulation Effect of pore formers Terpolymer nanogel Drug-polymer interactions

Hydroxyapatite composites with carbon allotropes:Preparation,properties,and applications

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Particuology 2024年第5期88卷 239-265页

作者： Boris I.Kharisov Oxana V.Kharissova Lucy T.González Yolanda peña Méndez Igor E.Uflyand Idalia Gómez de la Fuente Universidad Autónoma de Nuevo León Ave.UniversidadCiudad UniversitariaSan Nicolás de los GarzaNuevo León 66455Mexico Tecnologico de Monterrey Escuela de Ingeniería y CienciasMonterreyNuevo Leon 64890Mexico Department of Chemistry Southern Federal UniversityRostov-on-DonRussia

Hydroxyapatite(HA)and its composites with inorganic additives,dopants,and polymers is a rapidly developing branch in the materials chemistry.In particular,carbon allotropes are widely used in these composites being widely applied for medical purposes.Observing a gap of insufficient generalization of recent achievements in the field of the HA/Carbon composites,in this review we present the state of the art of the field of HA composites and hybrids with classic carbon allotropes and nanocarbons.These composites are known for carbon nanotubes,nanofibers,graphene and its oxidized forms,as well as,in a lesser grade,for graphite,fullerenes,nanodiamonds,carbon nanofoams,etc.These composites can be fabricated by a variety of classic and less-common methods,such as co-precipitation(with or without ultrasonic treatment),CVD,hot isostatic pressing,hydrothermal,spark plasma sintering,biomimetic mineralization,thermal and plasma spray,electrochemical and electrophoretic deposition,self-assembling,3D printing,electrospinning,and lyophilisation,among others.Combination of various synthesis techniques can be also carried out for composite preparation.Natural or synthetic HA can be used as it is for further interaction with carbon allotropes or it can be first prepared and then reacted with carbon counterpart;similarly,carbon allotropes can be introduced into the interaction with HA directly or they can be first synthesized,in particular from biomass.Resulting biocompatible composites can be produced in the form of coatings,powders,and scaffolds and can additionally contain quantitative amounts of third phases,frequently natural or synthetic polymers.In these composites,especially with O-containing functionalizing groups,HA disadvantages could be considerably decreased with simultaneous enhancement of mechanical properties,becoming similar to human bone,chemical stability and biocompatibility,as well as possessing antibacterial effect.GO→G reduction and higher HA decoration were observed in several experiments.The morphology of p

关键词： Hydroxyapatite Carbon nanotubes Graphene Quantum dots Fullerenes Nanodiamonds

Linking leaf elemental traits to biomass across forest biomes in the Himalayas

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Science China Earth Sciences 2024年第5期67卷 1518-1528页

作者： Nita DYOLA Eryuan LIANG Josep peÑUELAS J.Julio CAMARERO Shalik Ram SIGDEL Sugam ARYAL Wentao LIN Xiang LIU Yongwen LIU Xingliang XU Sergio ROSSI State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Laboratoire sur lesécosystèmes terrestres boréaux Département des Sciences FondamentalesUniversitédu QuébecàChicoutimi555Boulevard de l′UniversitéChicoutimi(QC)G7H2B1Canada CSIC Global Ecology Unit CREAF-CSIC-UABBellaterraE-08193 CataloniaSpain CREAF Cerdanyola del VallèsE-08193 CataloniaSpain Instituto Pirenaico de Ecología(Ipe-CSIC) Avenida Montañana 1005Zaragoza 50059Spain Friedrich-Alexander-Universität Erlangen-Nürnberg Institut für GeographieErlangen 91058Germany State Key Laboratory of Grassland Agro-Ecosystems College of EcologyLanzhou UniversityLanzhou 730000China Key Laboratory of Ecosystem Network Observation and Modeling Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China

Plants require a number of essential elements in different proportions for ensuring their growth and development.The elemental concentrations in leaves reflect the functions and adaptations of plants under specific environmental conditions.However,less is known about how the spectrum of leaf elements associated with resource acquisition,photosynthesis and growth regulates forest biomass along broad elevational gradients.We examined the influence of leaf element distribution and diversity on forest biomass by analyzing ten elements(C,N,P,K,Ca,Mg,Zn,Fe,Cu,and Mn)in tree communities situated every 100 meters along an extensive elevation gradient,ranging from the tropical forest(80 meters above sea level)to the alpine treeline(4200 meters above sea level)in the Kangchenjunga Landscape in eastern Nepal Himalayas.We calculated communityweighted averages(reflecting dominant traits governing biomass,i.e.,mass-ratio effect)and functional divergence(reflecting increased trait variety,i.e.,complementarity effect)for leaf elements in a total of 1,859 trees representing 116 species.An increasing mass-ratio effect and decreasing complementarity in leaf elements enhance forest biomass accumulation.A combination of elements together with elevation explains biomass(52.2%of the variance)better than individual elemental trait diversity(0.05%to 21%of the variance).Elevation modulates trait diversity among plant species in biomass accumulation.Complementarity promotes biomass at lower elevations,but reduces biomass at higher elevations,demonstrating an interaction between elevation and complementarity.The interaction between elevation and mass-ratio effect produces heterogeneous effects on biomass along the elevation gradient.Our research indicates that biomass accumulation can be disproportionately affected by elevation due to interactions among trait diversities across vegetation zones.While higher trait variation enhances the adaptation of species to environmental changes,it reduces biomass accumulation,especially at higher elevat

关键词： Ecosystem function Elevational gradient Functional diversity Functional traits Leaf elements Niche complementarity

permafrost carbon cycle and its dynamics on the Tibetan Plateau

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Science China Life Sciences 2024年

作者： Leiyi Chen Guibiao Yang Yuxuan Bai Jinfeng Chang Shuqi Qin Futing Liu Mei He Yutong Song Fan Zhang Josep pe?uelas Biao Zhu Guoying Zhou Yuanhe Yang Key Laboratory of Tibetan Medicine Research Chinese Academy of Sciences State Key Laboratory of Vegetation and Environmental Change Institute of Botany Chinese Academy of Sciences China National Botanical Garden College of Environmental and Resource Sciences Zhejiang University Key Laboratory of Forest Ecology and Environment of National Forestry and Grassland Administration Ecology and Nature Conservation Institute Chinese Academy of Forestry University of Chinese Academy of Sciences Consejo Superior de Investigaciones Científicas (CSIC) Global Ecology Unit CREAF-CSIC-UAB (Universitat Autònoma de Barcelona) Centre for Ecological Research and Forestry (CREAF) Barcelona Institute of Ecology College of Urban and Environmental Sciences and Key Laboratory for Earth Surface Processes of the Ministry of Education Peking University Northwest Institute of Plateau Biology Chinese Academy of Sciences

Our knowledge on permafrost carbon（C） cycle is crucial for understanding its feedback to climate warming and developing nature-based solutions for mitigating climate change. To understand the characteristics of permafrost C cycle on the Tibetan Plateau, the largest alpine permafrost region around the world, we summarized recent advances including the stocks and fluxes of permafrost C and their responses to thawing, and depicted permafrost C dynamics within this century. We find that this alpine permafrost region stores approximately 14.1 Pg(1 Pg=1015g) of soil organic C（SOC） in the top 3 m. Both substantial gaseous emissions and lateral C transport occur across this permafrost region. Moreover, the mobilization of frozen C is expedited by permafrost thaw, especially by the formation of thermokarst landscapes,which could release significant amounts of C into the atmosphere and surrounding water bodies. This alpine permafrost region nevertheless remains an important C sink, and its capacity to sequester C will continue to increase by 2100. For future perspectives, we would suggest developing long-term in situ observation networks of C stocks and fluxes with improved temporal and spatial coverage, and exploring the mechanisms underlying the response of ecosystem C cycle to permafrost thaw. In addition, it is essential to improve the projection of permafrost C dynamics through in-depth model-data fusion on the Tibetan Plateau.

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