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Liquiritigenin promotes osteogenic differentiation and prevents bone loss via inducing auto-lysosomal degradation and inhibiting apoptosis

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Genes & Diseases 2023年第1期10卷 284-300页

作者： Yu Qiu Yueyang Zhao Zhimin Long Aijia Song Peng Huang Kejian Wang Ling Xu david paul molloy Guiqiong He College of Stomatology Chongqing Medical UniversityChongqing Key Laboratory of Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqing400016China Chongqing Key Laboratory of Neurobiology Chongqing Medical UniversityChongqing 400016China Department of Anatomy Chongqing Medical UniversityChongqing 400016China Laboratory of Medical Experiment Technology Institute of Life ScienceChongqing Medical UniversityChongqing 400016China Department of Biochemistry and Molecular Biology Chongqing Medical UniversityChongqing 400016China

Osteoporosis(OP)is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk.A novel therapeutic intervention for OP by manipulating cellular autophagy-apoptosis processes to promote skeletal homeostasis is presented.Protective effects of the naturally occurring plant extract Liquiritigenin(LG)were demonstrated in an ovariectomy(OvX)-OP mouse model and preosteoblast MC3T3-E1 cells.Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy(TEM).The effects of LG on chloroquine(CQ)-and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red,Alizarin red S and alkaline phosphatase(ALP)staining and Western blot assays.Treatment with LG prevented bone loss,increased osteogenic differentiation in vivo and in vitro,and inhibited osteoclast formation to some extent.TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells.The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation.Overall,LG stimulates bone growth in Oovx mice through increased osteogenic differentiation and regulation of autophagyapoptosis mechanisms,presenting an auspicious natural therapy for Op.

关键词： Apoptosis Auto-lysosomal degradation Liquiritigenin Osteogenic differentiation Osteoporosis

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The great catastrophe: causes of the Permo-Triassic marine mass extinction

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National Science Review 2024年第1期11卷 37-50页

作者： paul B.Wignall david P.G.Bond School of Earth & Environment University of Leeds School of Environmental Sciences University of Hull

The marine losses during the Permo-Triassic mass extinction were the worst ever experienced. All groups were badly affected, especially amongst the benthos(e.g. brachiopods, corals, bryozoans, foraminifers,ostracods). Planktonic populations underwent a fundamental change with eukaryotic algae being replaced by nitrogen-fixing bacteria, green-sulphur bacteria, sulphate-reducing bacteria and prasinophytes. Detailed studies of boundary sections, especially those in South China, have resolved the crisis to a ～55 kyr interval straddling the Permo-Triassic boundary. Many of the losses occur at the beginning and end of this interval painting a picture of a two-phase extinction. Improved knowledge of the extinction has been supported by numerous geochemical studies that allow diverse proposed extinction mechanisms to be studied. A transition from oxygenated to anoxic-euxinic conditions is seen in most sections globally, although the intensity and timing shows regional variability. Decreased ocean ventilation coincides with rapidly rising temperatures and many extinction scenarios attribute the losses to both anoxia and high temperatures.Other kill mechanisms include ocean acidification for which there is conflicting support from geochemical proxies and, even less likely, siltation(burial under a massive influx of terrigenous sediment) which lacks substantive sedimentological evidence. The ultimate driver of the catastrophic changes at the end of the Permian was likely Siberian Trap eruptions and their associated carbon dioxide emissions with consequences such as warming, ocean stagnation and acidification. Volcanic winter episodes stemming from Siberian volcanism have also been linked to the crisis, but the short-term nature of these episodes(

关键词： ocean anoxia ocean acidification siltation productivity collapse volcanic winter

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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang david P.molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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A Study on the Challenges of Human-Centric Cyber-Security and the Guarantee of Information Quality

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Journal of Information Security 2024年第2期15卷 218-231页

作者： Mohammed Hussein Kurdi Mohsen Denden david paul Department of Cyber-Security National Events Center Riyadh Saudi Arabia Department of Computer and Information Technologies Technical College of Telecommunication and Information Riyadh TCTI Technical and Vocational Training Corporation TVTC Riyadh Saudi Arabia Department of Computer Science Higher Institute of Applied Sciences of Sousse University of Sousse Sousse Tunisia School of Science & Technology University of New England Armidale Australia

Information security and quality management are often considered two different fields. However, organizations must be mindful of how software security may affect quality control. This paper examines and promotes methods through which secure software development processes can be integrated into the Systems Software Development Life-cycle (SDLC) to improve system quality. Cyber-security and quality assurance are both involved in reducing risk. Software security teams work to reduce security risks, whereas quality assurance teams work to decrease risks to quality. There is a need for clear standards, frameworks, processes, and procedures to be followed by organizations to ensure high-level quality while reducing security risks. This research uses a survey of industry professionals to help identify best practices for developing software with fewer defects from the early stages of the SDLC to improve both the quality and security of software. Results show that there is a need for better security awareness among all members of software development teams.

关键词： Cyber Security Development Methodology Information Quality Human-Centric SDLC Quality Assurance

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Amyloid-beta and tau protein beyond Alzheimer's disease

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Neural Regeneration Research 2024年第6期19卷 1262-1276页

作者： Morteza Abyadeh Vivek Gupta Joao A.paulo Arezoo Gohari Mahmoudabad Sina Shadfar Shahab Mirshahvaladi Veer Gupta Christine T.O.Nguyen david I.Finkelstein Yuyi You paul A.Haynes Ghasem H.Salekdeh Stuart L.Graham Mehdi Mirzaei ProGene Technologies Pty Ltd. 2. Department of Clinical Medicine Faculty of Medicine Health and Human Sciences Macquarie Medical School Macquarie University Department of Cell Biology Harvard Medical School School of Medicine Deakin University Department of Optometry and Vision Sciences School of Health Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne The Florey Institute of Neuroscience and Mental Health The University of Melbourne School of Natural Sciences Macquarie University

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer’s disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, posttranslational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

关键词： amyloid-beta cancer cardiovascular diseases diabetes neurodegeneration Tau traumatic brain injury

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Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li david Shu Cheong Hui paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)expression.This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of pneumonia.Remarkably,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G.The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient.Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

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AI for science: Predicting infectious diseases

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Journal of Safety Science and Resilience 2024年第2期5卷 130-146页

作者： Alexis Pengfei Zhao Shuangqi Li Zhidong Cao paul Jen-Hwa Hu Jiaojiao Wang Yue Xiang Da Xie Xi Lu Institute of Automation Chinese Academy of SciencesUniversity of Chinese Academy of SciencesBejing 100090China Systems Engineering Cornll UniversityIthacaNY 14853USA david Eccles School of Business the University of UtahUtahUSA Collge of Electrical Engineering Sichuan UniversityChina Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Electrical Engineering Southeast UniversityNanjing 210096China

The global health landscape has been persistently challenged by the emergence and re-emergence of infectious diseases.Traditional epidemiological models,rooted in the early 2oth century,have provided foundational in-sights into disease dynamics.However,the intricate web of modern global interactions and the exponential growth of available data demand more advanced predictive tools.This is where AI for Science(AI4S)comes into play,offering a transformative approach by integrating artificial intelligence(Al)into infectious disease pre-diction.This paper elucidates the pivotal role of AI4s in enhancing and,in some instances,superseding tradi-tional epidemiological methodologies.By harnessing AI's capabilities,AI4S facilitates real-time monitoring,sophisticated data integration,and predictive modeling with enhanced precision.The comparative analysis highlights the stark contrast between conventional models and the innovative strategies enabled by AI4S.In essence,Al4S represents a paradigm shift in infectious disease research.It addresses the limitations of traditional models and paves the way for a more proactive and informed response to future outbreaks.As we navigate the complexities of global health challenges,Al4S stands as a beacon,signifying the next phase of evolution in disease prediction,characterized by increased accuracy,adaptability,and efficiency.

关键词： AI for science(AI4S) Data integration Global healthchallenges Infectious disease prediction Predictive modeling Real-timemonitoring

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Cosmetic or Dietary Vegetable Oils Sampled in the Cameroonian Market May Not Expose Consumers to Lipid Oxidation Products Generating Oxidative Stress and Inflammation

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American Journal of Plant Sciences 2024年第3期15卷 193-202页

作者： Ferdinand Kouoh Elombo Erika Van Damme Clara Delepine david Depraetere Ludovic Chaveriat paul Lunga Keilah Nico Fréderic Njayou Patrick Martin Laboratory of Toxicology and Pharmacology Department of Biochemistry Faculty of Sciences University of Yaound&#233 I Yaound&#233 Cameroon Dé partement de Chimie IUT B&#233thune Universit&#233 d&#8217Artois B&#233thune France Unité Transformations & Agroressources (ULR7519) Universit&#232 d&#8217Artois-UniLaSalle Bethune France

Vegetable oils are a source of energy, essential fatty acids, antioxidants and fat-soluble vitamins useful for human health care and development. These oils also contribute to organoleptic quality of their products’ derivatives. However, their chemical and physical properties can be modified by the mode of their extraction, storage and distribution. These modifications might negatively affect the nutritional quality of the oils. The goals of this study were to: sample different vegetable oils for cosmetic or dietary use marketed in Cameroon, and verify purity and oxidation states of each kind of oil through determination of its acidity, iodine, peroxide, saponification, refractive indexes and the conformity of the labeling. The carotene content, the level of polar components and specific absorbance were also determined. As the result, six oils namely palm, palm kernel, coconut, black cumin, peanut and shea butter were collected. Apart from labeling, chemicals and physicals parameters analyzed were generally in accordance with the Cameroonian and Codex Alimentarius standard. This study suggests that vegetable oils sampled in the Cameroonian market may not expose consumers to lipid oxidation products generating pathological oxidative stress and inflammation. However, efforts in application of existing standard need to be done as far as labeling are concerned.

关键词： Vegetable Oils Quality Control Labeling Compliance Lipid Oxidation Oxidative Pathology

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A social computing method for energy safety

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Journal of Safety Science and Resilience 2024年第1期5卷 64-82页

作者： Pengfei Zhao Shuangqi Li Zhidong Cao paul Jen-Hwa Hu Daniel Dajun Zeng Da Xie Yichen Shen Jiangfeng Li Tianyi Luo Institute of Automation Chinese Academy of SciencesUniversity of Chinese Academy of SciencesBeijing 100090China Systems Engineering Cornell UniversityIthacaNY 14853USA david Eccles School of Business the University of UtahUtahUSA Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China China University of Mining and Technology China

Information and communication technologies enable the transformation of traditional energy systems into cyber-physical energy systems(CPESs),but such systems have also become popular targets of cyberattacks.Currently,available methods for evaluating the impacts of cyberattacks suffer from limited resilience,efficacy,and practical value.To mitigate their potentially disastrous consequences,this study suggests a two-stage,discrepancy-based optimization approach that considers both preparatory actions and response measures,integrating concepts from social computing.The proposed Kullback-Leibler divergence-based,distributionally robust optimization(KDR)method has a hierarchical,two-stage objective function that incorporates the operating costs of both system infrastructures(e.g.,energy resources,reserve capacity)and real-time response measures(e.g.,load shedding,demand-side management,electric vehicle charging station management).By incorporating social computing principles,the optimization framework can also capture the social behavior and interactions of energy consumers in response to cyberattacks.The preparatory stage entails day-ahead operational decisions,leveraging insights from social computing to model and predict the behaviors of individuals and communities affected by potential cyberattacks.The mitigation stage generates responses designed to contain the consequences of the attack by directing and optimizing energy use from the demand side,taking into account the social context and preferences of energy consumers,to ensure resilient,economically efficient CPES operations.Our method can determine optimal schemes in both stages,accounting for the social dimensions of the problem.An original disaster mitigation model uses an abstract formulation to develop a risk-neutral model that characterizes cyberattacks through KDR,incorporating social computing techniques to enhance the understanding and response to cyber threats.This approach can mitigate the impacts more effectively than several existing methods,even

关键词： Cyberattacks Cyber-physical energy systems Distributionally robust optimization False data injections Two-stage modeling Social computing

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The Black American Church: A Reactionary and Ideological Apparatus of Slavery

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Philosophy Study 2024年第1期14卷 30-41页

作者： paul C.Mocombe West Virginia State University West VirginiaUSA The Mocombeian Foundation Inc.FloridaUSA

This work argues that Denmark Vesey,Nat Turner,Gabriel Prosser,david Walker,Henry Highland Garnet,amongst a few others were the reactionary(dialectical)exceptions to the black church,not the norm,an(ideological)institution established to interpellate and indoctrinate blacks to accept their conditions in slavery.In other words,the aforementioned were the enslaved who used Christian dogma to(negative dialectically)respond to the barbarity of slavery by violently convicting white Christian society for not living up to its values,ideas,and ideals given the treatment of African people by so-called Christians.In the latter sense it was reactionary;in the former,it was an ideological apparatus of domination and control for the institution of slavery.The contemporary attempt to racially vindicate the black church as a sui generis revolutionary institution overflowing with Africanisms is ahistorical and ideological reaped in pseudoscientific propositions stemming from postmodern and post-structural theories.

关键词： Black Church African-Americanization racial identity religiosity black diaspora spiritualism phenomenological structuralism

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