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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： aditi singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit singh Department of Biology University of Dayton Premedical Program University of Dayton Center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton The Integrative Science and Engineering Center University of Dayton Center for Genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Hippo signaling:bridging the gap between cancer and neurodegenerative disorders

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Neural Regeneration Research 2021年第4期16卷 643-652页

作者： Neha Gogia Anuradha Venkatakrishnan Chimata Prajakta Deshpande aditi singh Amit singh Department of Biology University of DaytonDaytonOHUSA Medical Candidate University of Toledo College of Medicine and Life SciencesToledoOHUSA Premedical Program University of DaytonDaytonOHUSA Center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

During development,regulation of organ size requires a balance between cell proliferation,growth and cell *** of these fundamental processes can cause a variety of *** cell proliferation results in cancer whereas excessive cell death results in neurodegenerative *** signaling pathways known-to-date have a role in growth *** them,evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and ***,a complex process of progressive death of neuronal population,results in fatal disorders with no available cure to *** normal development,cell death is required for sculpting of an ***,aberrant cell death in neuronal cell population can result in neurodegenerative *** pathway has gathered major attention for its role in growth regulation and cancer,however,other functions like its role in neurodegeneration are also emerging *** review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo *** Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.

关键词： animal models cell death mechanisms cell-signaling chemical inhibitors Drosophila eye Hippo pathway neurodegeneration neurological diseases therapeutic targets

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Alzheimer's disease: the silver tsunami of the 21^(st) century

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Neural Regeneration Research 2016年第5期11卷 693-697页

作者： Ankita Sarkar Madison Irwin aditi singh Matthew Riccetti Amit singh Department of Biology University of Dayton Department of Biological Science University of Pittsburgh Premedical Program University of Dayton Center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton

Alzheimer＇s disease（AD）, a fatal progressive neurodegenerative disorder, has no cure to date. One of the causes of AD is the accumulation of amyloid-beta 42（Aβ42） plaques, which result in the onset of neurodegeneration. It is not known how these plaques trigger the onset of neurodegeneration. There are several animal models developed to（i） study etiology of disease,（ii） look for genetic modifiers, and（iii） identify chemical inhibitors that can block neurodegeneration and help to find cure for this disease. An insect model of Drosophila melanogaster has also provided new insights into the disease. Here we will discuss the utility of the Drosophila eye model to study Alzheimer＇s disease.

关键词： Alzheimer's disease neurodegeneration amyloid plaques amyloid hypothesis animal models drosophila melanogaster drosophila eye

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Strategies for translating proteomics discoveries into drug discovery for dementia

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Neural Regeneration Research 2024年第1期19卷 132-139页

作者： aditi Halder Eleanor Drummond School of Medical Sciences and Brain&Mind Center University of SydneyNSWSydneyAustralia Department of Aged Care Prince of Wales HospitalSydneyNSWAustralia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia *** there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing *** such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug *** this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired *** highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this *** propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

关键词： Alzheimer's disease biomarkers drug development drug discovery druggability frontotemporal dementia interactome proteomics tau tauopathies therapeutics

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Insights into the interface of NiCo_(2)O_(4) spinel/LaCoO_(3) perovskite nano-composite for CO and soot oxidation

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Journal of Environmental Sciences 2024年第4期138卷 339-349页

作者： Neha Harshita singh Satya Vir singh Department of Chemical Engineering Indian Institute of Technology(BHU)Varanasi221005India Department of Botany Institute of ScienceBanaras Hindu UniversityVaranasi221005India

In the quest for the development of thermally stable,highly active and low-cost catalysts for use in catalyzed diesel particulate filter,nano-composites are new areas of ***,we reported the easy synthesis of spinel NiCo_(2)O_(4)/perovskite LaCoO_(3) nano-composite,and its individual oxides NiCo_(2)O_(4)and LaCoO_(3) for *** detailed insights into the physio-chemical characteristics of formed NiCo_(2)O_(4)/LaCoO_(3) nano-composite were done based on various characterization analysis such as X-ray diffraction(XRD),Fourier transform infrared(FT-IR),N_(2) physiosorption,scanning electron microscopy-energy dispersive spectroscopy(SEM-EDX),transmission electron microscopy(TEM),and X-ray photoelectron spectroscopy(XPS).The characterization analysis of NiCo_(2)O_(4)/LaCoO_(3) revealed the successful formation of a chemical interface possessing strong interfacial interaction,resulting in desirable physicochemical characteristics such as small crystallite size,abundant mesoporosity,high specific surface area and activation of surface lattice *** to the desirable characteristics,the activity results over NiCo_(2)O_(4)/LaCoO_(3) nano-composite showed the excellent CO oxidation performance and high soot oxidation activity,recyclability and thermal *** work mainly attempts to emphasize the effectiveness of the facile,inexpensive and conventionally used precipitation method for the successful formation of highly efficient nano-composites.

关键词： LaCoO_(3) NiCo_(2)O_(4) Spinel/perovskite CO oxidation Soot oxidation Chemical interface

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Snow and regolith albedo variations using CRISM data at McMurdo crater,Mars

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Earth and Planetary Physics 2024年第2期8卷 338-355页

作者： Sehajpal singh Deepak singh Centre of Studies in Resources Engineering Indian Institute of Technology BombayMumbaiIndia

The cryosphere component provides the most reliable and insightful indications of any planet’s climate *** data from the Compact Reconnaissance Imaging Spectrometer for Mars(CRISM),we develop a novel approach to determining the broadband Visible and Near Infrared(VNIR)albedo of the Martian *** study focuses on albedo changes in the McMurdo crater,part of Mars’s south polar layer *** compare seasonal and interannual variations of the McMurdo surface albedo before,during,and after the Global Dust Storm(GDS)of Martian Year(MY)*** the seasons progressed from spring to summer,the mean albedo in MY 32 and 34 plunged by over 40%,by about 35%in MY 33,and by slightly more than 30%in MY *** interannually,however,mean albedo values within both seasons(spring and summer)exhibited no significant differences in those same ***,interannual albedo difference maps reveal albedo variation of more than±0.3 in certain regions of the *** only snow-covered pixels,interannual albedo differences suggest that Mars dust had a pervasive impact on Mars’s *** in maximum and minimum albedo values as high as 0.5 were observed,depending upon differences in the dust levels in Martian snow/*** maximum and the minimum snow albedo values were lowest in MY 34,indicating the effect of the intense dust storm event that *** average snow albedo decreased from 0.45 in MY 32 to 0.40 in MY 33 and to 0.33 in MY 34,and then rose back to 0.40 in MY *** trajectory suggests a temporary deposition of dust,partially reversed after the GDS by self-cleaning mechanisms(local aeolian process and CO_(2)sublimation/deposition cycle).

关键词： Mars Martian ice albedo dust storm Mars surface Martian climate

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Transfer Learning-Based Class Imbalance-Aware Shoulder Implant Classification from X-Ray Images

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Journal of Bionic Engineering 2024年第2期21卷 892-912页

作者： Marut Jindal Birmohan singh Department of Computer Science and Engineering Sant Longowal Institute of Engineering and TechnologySangrur148106PunjabIndia

Total shoulder arthroplasty is a standard restorative procedure practiced by orthopedists to diagnose shoulder arthritis in which a prosthesis replaces the whole joint or a part of the *** is often challenging for doctors to identify the exact model and manufacturer of the prosthesis when it is *** paper proposes a transfer learning-based class imbalance-aware prosthesis detection method to detect the implant’s manufacturer automatically from shoulder X-ray *** framework of the method proposes a novel training approach and a new set of batch-normalization,dropout,and fully convolutional layers in the head *** employs cyclical learning rates and weighting-based loss calculation *** modifications aid in faster convergence,avoid local-minima stagnation,and remove the training bias caused by imbalanced *** proposed method is evaluated using seven well-known pre-trained models of VGGNet,ResNet,and DenseNet *** is performed on a shoulder implant benchmark dataset consisting of 597 shoulder X-ray *** proposed method improves the classification performance of all pre-trained models by 10–12%.The DenseNet-201-based variant has achieved the highest classification accuracy of 89.5%,which is 10%higher than existing ***,to validate and generalize the proposed method,the existing baseline dataset is supplemented to six classes,including samples of two more implant *** results have shown average accuracy of 86.7%for the extended dataset and show the preeminence of the proposed method.

关键词： Biomedical engineering Artificial intelligence Total shoulder arthroplasty Prosthesis identification Biomedical image classification

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Long-term fertilizer nitrogen management—Soil health conundrum

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Pedosphere 2024年第1期34卷 23-25页

作者： BIJAY-singh Department of Soil Science Punjab Agricultural UniversityLudhiana 141004India

The mental model that fertilizer nitrogen (N) acts as a replacement for N mineralized from soil organic matter (SOM) needs to be revisited. Soil organic matter, the storehouse of N in soil, is one of the most important indicators of soil health. It supplies more N to crop plants than the current-year fertilizer N even when applied at high rates. Limited research shows that the application of fertilizer N above the optimum levels on a long-term basis deteriorates soil health by mineralizing SOM and depleting the soil N pool. Because soil N includes portions of fertilizer N applied in several previous years, year after year application of fertilizer N below the optimum levels will also lead to a gradual decline in soil N pool or soil health. To sustain high crop yield levels, fertilizer N needs to be applied on a long-term basis neither above nor below the optimum levels to ensure that soil health in terms of sustaining supply of soil N is maintained, if not enhanced.

关键词： soil Soil optimum

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Application of Response Surface Methodology for Analysing and Optimizing the Finned Solar Air Heater

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Journal of Thermal Science 2024年第3期33卷 985-1009页

作者： Vineet singh Vinod singh YADAV Vaibhav TRIVEDI Manoj KUMAR Niraj KUMAR Department of Mechanical Engineering School of Engineering&TechnologyIFTM UniversityMoradabadUttar PradeshIndia Department of Mechanical Engineering NITUttarakhandPauriUttarakhandIndia Department of Electronics and Communication Engineering Jaypee Institute of Information TechnologyNoidaUttar Pradesh201309India

In this research paper,a solar air heater with triangular fins has been experimentally analysed and ***,an experimental set-up of a solar air heater having triangular fins has been developed at the location of 28.10°N,78.23°*** heat transfer rate through fins and fins efficiency has been determined by the Finite Difference Method model *** experimental data and modeled data of response parameters have been optimized in MINITAB-17 software by the Response Surface Methodology *** creating the response surface design,three input parameters have been selected namely solar intensity,Reynolds number,and fin base-to-height *** range of solar intensity,Reynolds number,and fin base-to-height ratio is 600 to 1000W/m^(2),4000 to 6000,and 0.4 to 0.8 *** response surface design has been analyzed by calculating the outlet temperature,friction factor,Nusselt number,fin efficiency,thermal performance factor,and exergy *** optimum settings of input parameters:solar intensity is 1000 W/m^(2);Reynolds number is 4969.7,and the fin base to height ratio is 0.6060,on which these response:namely outlet temperature of 92.531℃,friction factor of 0.2350,Nusselt number of 127.761,thermal efficiency of 50.836%,thermal performance factor of 1.4947,and exergy efficiency of 8.762%.

关键词： solar air heater optimization fins exergy response surface methodology air

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Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals

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Chinese Journal of Integrative Medicine 2024年第1期30卷 75-84页

作者： Anchal Trivedi Adria Hasan Rumana Ahmad Sahabjada Siddiqui aditi Srivastava Aparna Misra Snober S.Mir Department of Biochemistry Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India Molecular Cell Biology Laboratory Integral Information and Research Centre-4(IIRC-4)Department of BioengineeringFaculty of EngineeringIntegral UniversityLucknow(226026)India Department of Biotechnology Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India Department of Biosciences Faculty of ScienceIntegral UniversityLucknow(226026)India

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial(antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

关键词： myricetin flavonoids anticancer nutraceuticals Chinese medicine Ayurveda complementary and alternative medicine

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