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Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 529-535页

作者： Sandro Huenchuguala juan Segura-Aguilar Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos CarrerasOsornoChile Molecular&Clinical Pharmacology Instituto de Ciencias Biomedicas(ICBM)Faculty of medicineUniversity of ChileIndependenciaSantiagoChile

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriata

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6-hydroxydopamine aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase M2-2

Quality assessment of the Topo-Iberia CGPS stations and data quality's effects on postfit ionosphere-free phase residuals

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Geodesy and Geodynamics 2024年第2期15卷 189-199页

作者： juan A.García-Armenteros Center for Advanced Studies in Earth Sciences Energy and Environment(CEACTEMA)University of Jaén23071 JaenSpain

This paper analyzed GPS data from the Topo-Iberia network spanning almost 12 years(2008-2020).The data quality information for all 26 Topo-Iberia stations is provided for the first time,complementing the Spanish Geological Survey’s storage work.Data analyses based on quality indicators obtained using TEQC have been carried out.The guidelines and data quality information from the IGS stations have been considered as the quality references,with the stations ALJI,EPCU,and TIOU standing out as the worst stations,while on the contrary,FUEN,PALM,PILA,and TRIA meet the quality requirements to become an IGS station.The relationship between the GPS data quality and their GAMIT-and Gipsy X-derived postfit ionosphere-free phase residuals has also been investigated,and the results reveal an inversely proportional relationship.It has been found that the stations showing an increase in elevation of the horizon line,also show an increase in cycle slips and multipath,are among the poorest quality stations,and among those with the highest postfit RMS of phase residuals.Moreover,the evolution of the vegetation around the antenna should be considered as it could cause a progressive loss of quality,which is not complying with the IGS standards.The quality assessment shows that the Topo-Iberia stations are appropriate for geodetic purposes,but permanent monitoring would be necessary to avoid the least possible loss of data and quality.In addition,a method to characterize the GNSS data quality is proposed.

关键词： GPS dataquality's effects IGS quality standard Postfit LC phase residual Qualityassessment Topo-Iberia CGPS network

Temporal stability and directional change in a color cline of a marine snail from NW Spain

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Current Zoology 2024年第2期70卷 163-173页

作者： juan Gefaell Ramon Vigo A.Honorato Gonzalez-Vazquez juan Galindo Emilio Rolan-Alvarez Centro de Investigacion Marina Universidade de VigoDepartamento de BioquimicaGenetica e Inmunologia36310 VigoSpain

The evolution and maintenance of color clines is a classic topic of research in evolutionary ecology.However,studies analyzing the temporal dynamics of such clines are much less frequent,due to the difficulty of obtaining reliable data about past color distributions along environmen-tal gradients.In this article,we describe a case of decades-long temporal stability and directional change in a color cline of the marine snail Littorina saxatilis along the coastal inlet of the Ria de Vigo(NW Spain).L.saxatilis from this area shows a clear color cline with 3 distinct areas from the innermost to the more wave-exposed localities of the Ria:the inner,protected localities show an abundance of fawn-like individuals;the intermediate localities show a high diversity of colors;and the outer,wave-exposed localities show populations with a high frequency of a black and lineated morph.We compare data from the 1970s and 2022 in the same localities,showing that the cline has kept relatively stable for at least over half a century,except for some directional change and local variability in the frequency of certain morphs.Multiple regression analyses and biodiversity measures are presented to provide clues into the selective pressures that might be involved in the maintenance of this color cline.Future research avenues to properly test the explanatory power of these selective agents as well as the possible origins of the cline are discussed.

关键词： clinal variation color polymorphism ecological gradient Littorina saxatilis natural selection wave exposure.

Intensive care unit-acquired weakness: Recent insights

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Journal of Intensive Medicine 2024年第1期4卷 73-80页

作者： juan Chen Man Huang Department of General Intensive Care Unit The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009ZhejiangChina

Intensive care unit-acquired weakness(ICU-AW)is a common complication in critically ill patients and is associated with a variety of adverse outcomes.These include the need for prolonged mechanical ventilation and ICU stay;higher ICU,in-hospital,and 1-year mortality;and increased in-hospital costs.ICU-AW is associated with multiple risk factors including age,underlying disease,severity of illness,organ failure,sepsis,immobilization,receipt of mechanical ventilation,and other factors related to critical care.The pathological mechanism of ICUAW remains unclear and may be considerably varied.This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors,pathophysiology,diagnosis,and treatment strategies;this provides new perspectives for future research.

关键词： Intensive care unit-acquired weakness Muscle weakness Muscle atrophy Risk factor Mechanism Treatment

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

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World Journal of Clinical Cases 2024年第4期12卷 814-819页

作者： Fen-juan Zhang Wen-juan Fang Cang-Jian Zhang Department of Hematology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

关键词： Monomorphic epithelial intestinal T-cell lymphoma Autologous stem cell transplantation Chemotherapeutics Case report

Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

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World Journal of Clinical Cases 2024年第5期12卷 966-972页

作者： Chong-Min Huang juan-juan Li Wei-Ke Wei Department of Intensive Medicine The Second People's Hospital of Haining CityHaining 314419Zhejiang ProvinceChina Department of Integrated Traditional Chinese and Western Medicine Qingyang HospitalHangzhou 310023Zhejiang ProvinceChina

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value

关键词： Sepsis Acute respiratory distress syndrome Platelet leukocyte aggregates Platelet mononuclear cell aggregates,Biomarker

Thermodynamic property of sandwich cylindrical shell structure with metallic wire mesh:Numerical modeling and experimental analysis

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Chinese Journal of Aeronautics 2024年第1期37卷 138-152页

作者： Xin XUE Guojian SHEN juan LIAO Institute of Metal Rubber&Vibration Noise School of Mechanical Engineering and AutomationFuzhou UniversityFuzhou 350116China Fujian Shuikou Power Generation Group Co. LTDFuzhou 350000China

As a new addition to lightweight composite structures,the sandwich cylindrical shell with a metallic wire mesh core has emerged as a promising solution for thermodynamic performance analysis at elevated temperatures.The intricate interwoven cellular formations within the metallic wire mesh pose difficulties for thermo-mechanical modeling and property evaluation.First,the constitutive models employed to characterize hysteresis phenomena were presented,comprising isotropic elasticity,Bergstrom-Boyce model,Ogden hyper-elasticity,and parameter identification through mechanical examinations at varying temperatures.Second,the finite element modeling of cylindrical shell structures was determined for modal and steady-state dynamic analyses.Third,the experimental procedures were carried out,including the preparation of the sandwich cylindrical shell and the dynamic testing platform.The first-order natural frequency of the cylindrical shell structure is close to the resonance frequency of the dynamic test results,with a maximum error of 6.5%,demonstrating the accuracy of the simulation model.When compared to the solid-core cylindrical shell,the average insertion loss of the sandwich cylindrical shell structure within the frequency range of 10–1000 Hz at room temperature is up to 11.09 dB.Furthermore,at elevated temperatures,the average insertion loss of the sandwich cylindrical shell decreases but fluctuates as the temperature changes.

关键词： Energy dissipation Metallic matrix composites Numerical analysis Sandwich structure Thermodynamic properties

Interface property of dissimilar Ti-6Al-4V/AA1050 composite laminate made by non-equal channel lateral co-extrusion and heat treatment

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Defence Technology（防务技术） 2024年第3期33卷 197-208页

作者： juan Liao Mengmeng Tian Xin Xue School of Mechanical Engineering and Automation Fuzhou UniversityFuzhou 350116China

The purpose of this paper is to examine the effect of processing parameters and subsequent heat treatments on the microstructures and bonding strengths of Ti-6Al-4V/AA1050 laminations formed via a non-equal channel lateral co-extrusion process.The microstructural evolution and growth mechanism in the diffusion layer were discussed further to optimize the bonding quality by appropriately adjusting process parameters.Scanning electron microscopes(SEM),energy dispersive spectrometer(EDS),and X-ray diffraction(XRD)were used to characterize interfacial diffusion layers.The shear test was used to determine the mechanical properties of the interfacial diffusion layer.The experimental results indicate that it is possible to co-extrusion Ti-6Al-4V/AA1050 compound profiles using non-equal channel lateral co-extrusion.Different heat treatment processes affect the thickness of the diffusion layer.When the temperature and time of heat treatment increase,the thickness of the reaction layers increases dramatically.Additionally,the shear strength of the Ti-6Al-4V/AA1050 composite interface is proportional to the diffusion layer thickness.It is observed that a medium interface thickness results in superior mechanical performance when compared to neither a greater nor a lesser interface thickness.Microstructural characterization of all heat treatments reveals that the only intermetallic compound observed in the diffusion layers is TiAl_(3).Due to the inter-diffusion of Ti and Al atoms,the TiAl_(3) layer grows primarily at AA1050/TiAl_(3) interfaces.

关键词： Shear strength Co-extrusion Heat treatment Microstructure Intermetallic compounds

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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Chinese Journal of Integrative Medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG Xia LIU Xia ZHAO juan Medical Examination Center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental Center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis