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Theory and classification of mass extinction causation

National Science Review 2024年第1期11卷 16-36页

作者： thomas j.Algeo jun Shen State Key Laboratory of Biogeology and Environmental Geology China University of Geosciences—Wuhan State Key Laboratory of Geological Processes and Mineral Resources China University of Geosciences—Wuhan Department of Geosciences University of Cincinnati

Theory regarding the causation of mass extinctions is in need of systematization, which is the focus of this contribution. Every mass extinction has both an ultimate cause, i.e. the trigger that leads to various climato-environmental changes, and one or more proximate cause(s), i.e. the specific climato-environmental changes that result in elevated biotic mortality. With regard to ultimate causes, strong cases can be made that bolide(i.e. meteor) impacts, large igneous province(LIP) eruptions and bioevolutionary events have each triggered one or more of the Phanerozoic Big Five mass extinctions, and that tectono-oceanic changes have triggered some second-order extinction events. Apart from bolide impacts, other astronomical triggers(e.***.solar flares, gamma bursts and supernova explosions) remain entirely in the realm of speculation. With regard to proximate mechanisms, most extinctions are related to either carbon-release or carbon-burial processes, the former being associated with climatic warming, ocean acidification, reduced marine productivity and lower carbonate δ13C values, and the latter with climatic cooling, increased marine productivity and higher carbonate δ13C values. Environmental parameters such as marine redox conditions and terrestrial weathering intensity do not show consistent relationships with carbon-cycle changes.In this context, mass extinction causation can be usefully classified using a matrix of ultimate and proximate factors. Among the Big Five mass extinctions, the end-Cretaceous biocrisis is an example of a bolide-triggered carbon-release event, the end-Permian and end-Triassic biocrises are examples of LIP-triggered carbon-release events, and the Late Ordovician and Late Devonian biocrises are examples of bioevolution-triggered carbon-burial events. Whereas the bolide-impact and LIP-eruption mechanisms appear to invariably cause carbon release, bioevolutionary triggers can result in variable carbon-cycle changes, e.g. carbon burial during the Late Ordovician and Late Devonian events,

关键词： biocrisis ultimate cause proximate cause bolide large igneous province bioevolutionary event

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Stimulation of in vitro bone formation by canine prostate cancer

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journal of Cancer Metastasis and Treatment 2021年第1期7卷 511-523页

作者： Shiyu Yuan Noriko Kantake Daniel E.Hellmann Said M.Elshafae Thomas J.Rosol Department of Biomedical Sciences Heritage College of Osteopathic MedicineOhio UniversityAthensOH 45701USA Molecular and Cellular Biology Program Ohio UniversityAthensOH 45701USA Faculty of Veterinary Medicine Benha UniversityTukhQalyobiya 13736Egypt Ohio Musculoskeletal and Neurological Institute Ohio UniversityAthensOH 45701USA

Aim:Patients with prostate cancer frequently develop osteoblastic bone metastases.Canine models are important because dogs are the only mammal to develop spontaneous prostate cancer with osteoblastic bone metastases similar to men.The mechanism by which prostate cancer induces bone formation is unclear;however,it depends on the complex interaction between prostate cancer cells and bone microenvironment.This study investigated the effects of three canine prostate cancer cell lines(Ace-1,LuMa,and Probasco)on bone formation and resorption in vitro.Methods:Mouse calvaria were treated with conditioned medium(CM)from cell lines.Calvaria were evaluated by histology,fluorescent calcein uptake at sites of bone mineralization,medium calcium assay,and alkaline phosphatase activity.The expression of bone-related genes was measured using quantitative reverse transcription PCR.Results:A novel calcein uptake assay was developed to measure bone formation and mineralization in vitro.Ace-1 CM induced predominantly bone resorption in calvaria,while Probasco CM induced marked bone formation,mineralization,and healing of calvaria defects.The expression of osteoblast-related genes in calvaria showed that Probasco CM stimulated the maturation and differentiation of osteoblasts and inhibited osteoclastogenesis.Both bone modeling and remodeling were involved in Probasco CM-induced bone formation and mineralization by inhibiting remodeling with zoledronic acid.Inhibition of WNT activity by DKK-1 decreased the osteoblastic activity of Probasco cells.Conclusion:Probasco cells induced bone formation and mineralization in vitro that depended on the WNT signaling pathway.Probasco cells will serve as a valuable model for studying the mechanisms of osteoblastic bone metastasis in prostate cancer.

关键词： Bone canine dog metastasis osteoblast prostate cancer zoledronic acid DKK-1

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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell jun Okabe Ishant Khurana thomas Karagiannis julia j.Liang Lina Mariana thomas Loudovaris thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release insulin.In type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-cells.Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.Consequently,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell function.We and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation capacity.Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase.In the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell identity.The transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification.Targeting EZH2 is fundamental toβ-cell regenerative potential.Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo.These pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Examining the“revisability”benefit of hip resurfacing arthroplasty

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World journal of Orthopedics 2024年第6期15卷 554-559页

作者： jose George Adam j Taylor thomas P Schmalzried Department of Orthopedics Harbor UCLA Medical CenterTorranceCA 90509United States

BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves bone.However,the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes.AIM To compare patient reported outcomes for conversion THA after HRA failure to primary THA.METHODS A retrospective review of 36 patients(37 hips)that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed.Patient reported outcomes[modified Harris Hip Score(mHHS),University of California Los Angeles(UCLA)activity score]were obtained via an email-based responder-anonymous survey.Outcomes were compared to normative data of a primary THA cohort with similar demographics.Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction(ALTR)vs all other causes for failure.RESULTS The study group had a lower mHHS than the control group(81.7±13.8 vs 90.2±11.6,P<0.01);however,both groups had similar UCLA activity levels(7.5±2.3 vs 7.2±1.6,P=0.51).Patients that underwent conversion for non-ATLR causes had similar mHHS(85.2±11.5 vs 90.2±11.6,P=0.11)and higher UCLA activity levels(8.5±1.8 vs 7.2±1.6,P<0.01)compared to the control group.Patients that underwent conversion for ATLR had worse mHHS(77.1±14.5 vs 90.2±11.6,P<0.01)and UCLA activity levels(6.1±2.3 vs 7.2±1.6,P=0.05)when compared to the control group.CONCLUSION Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA.However,inferior outcomes were demonstrated for ALTR-related HRA failure.Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

关键词： Total hip arthroplasty Hip resurfacing arthroplasty Conversion total hip arthroplasty Adverse local tissue reaction Patient reported outcome measures

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Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： jiang-Hui Wang Dominic j.Gessler Wei Zhan thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues.Recombinant AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various diseases.However,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing methods.Seven rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and neurotoxicity.In this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies.We discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as cancers.We outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these reactions.We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

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Bone Research 2018年第1期6卷 83-94页

作者： Heather A.Carey Blake E.Hildreth III jennifer A.Geisler Mara C.Nickel jennifer Cabrera Sankha Ghosh Yue jiang jing Yan james Lee Sandeep Makam Nicholas A.Young Giancarlo R.Valiente Wael N.jarjour Kun Huang Thomas J.Rosol Ramiro E.Toribio julia F.Charles Michael C.Ostrowski Sudarshana M.Sharma Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State University Wexner Medical Center College of Veterinary Medicine The Ohio State University Department of Biochemistry and Molecular Biology and Hollings Cancer Center Medical University of South Carolina Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Division of Rheumatology and Immunology Department of Internal Medicine The Ohio State University Wexner Medical Center Department of Biomedical Informatics The Ohio State University Wexner Medical Center

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

关键词： Genome-wide GWASs MITF

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Development of sustainable thermal insulation based on bio-polyester filled with date pits

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journal of Bioresources and Bioproducts 2024年第1期9卷 74-89页

作者： Amal Mlhem thomas Teklebrhan Evenezer Bokuretsion Basim Abu-jdayil Chemical&Petroleum Engineering Department United Arab Emirates UniversityPO Box 15551United Arab Emirates National Water and Energy Center United Arab Emirates UniversityPO Box 15551United Arab Emirates

Date palm pit(DPP)-filled poly(-hydroxybutyrate)(PHB)composites were prepared,evaluated,and characterized to determine their thermal insulation ability.Thermal conductivity values ranged between 0.086 and 0.100 W/(m·K).At a maximum filler concentration(50%(w)),the specific heat capacity and thermal diffusivity were 1183 j/(kg·K)and 0.0689 mm^(2)/s,respec-tively.The DPP increased the thermal stability,and the highest compressive strength obtained was 80 MPa at 30%filler content.The PHB-DPP composites exhibited promising water absorption(less than 6%)and tensile strength(6-14 MPa).Date-pit-based PHB composites could be used in sustainable building engineering and cleaner production.

关键词： Green construction material Sustainable thermal insulator Date pit Polyhydroxybutyrate

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Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 29-36页

作者： jorge A.Gutierrez III jeremy L.Barth Rodney j.Schlosser thomas S.Edwards Timothy L.Smith Zachary M.Soler Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedP value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP.This study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

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Comparison of trigeminal lateralization with differing stimulants

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World journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 66-69页

作者： Tiffany Chen Nicolas S.Poupore Michael C.Shih thomas S.Edwards Shaun A.Nguyen Zachary M.Soler Rodney j.Schlosser Department of Otolaryngology‐Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory perception.It is unclear whether trigeminal sensitivity is similar across different transient receptor potential(TRP)receptors or if dysfunction of different receptors results in differing patient symptoms.Therefore,a prospective cohort study was conducted,consisting of trigeminal lateralization testing with three different stimulants(eucalyptol,isothiocyanate,acetic acid),olfaction testing with Sniffin'Sticks,and measurement of various patient‐reported outcome measures(PROMs).A total of 50 participants were enrolled across the olfactory spectrum.Mean TDI score was 27.1±8.3(range 7.0–39.5)with 38%normosmic and 62%dysosmic.Mean trigeminal lateralization scores out of 20 in the overall cohort were 16.18(2.78)for eucalyptol,14.94(3.49)for mustard oil,and 15.28(3.68)for vinegar.Eucalyptol showed a significant correlation with threshold scores of Sniffin'Sticks.A significant correlation was found between acetic acid and various PROMs.None of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to age.The lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other receptors.Additional investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

关键词： chemosensory olfaction trigeminal TRP receptor

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Alexa,let's train now!——A systematic review and classification approach to digital and home-based physical training interventions aiming to support healthy cognitive aging

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journal of Sport and Health Science 2024年第1期13卷 30-46页

作者： Fabian Herold Paula Theobald thomas Gronwald Navin Kaushal Liye Zou Eling D.de Bruin Louis Bherer Notger GMüller Research Group Degenerative and Chronic Diseases MovementFaculty of Health Sciences BrandenburgUniversity of PotsdamPotsdam 14476Germany Body-Brain-Mind Laboratory Shenzhen UniversityShenzhen 518060China Institute of Interdisciplinary Exercise Science and Sports Medicine MSH Medical School HamburgHamburg 20457Germany Department of Health Sciences School of Health&Human SciencesIndiana UniversityIndianapolisIN 46202USA Department of Health Sciences and Technology Institute of Human Movement Sciences and SportETH ZurichZurich 8093Switzerland Department of Neurobiology Care Sciencesand SocietyKarolinska InstituteStockholm 17177Sweden Department of Health OST-Eastern Swiss University of Applied SciencesSt.Gallen 9001Switzerland Montreal Heart Institute MontrealQC H1T 1C8Canada Department of Medicine Universite de MontrealMontrealQC H3T 1J4Canada Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal MontrealQC H3W 1W5Canada

Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions.In this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention programs.Thus,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance.Methods:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults.The systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered relevant.Two reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older adults.Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence(≤85%)and monitoring of t

关键词： Brain Cognition Digital health Exercise-cognition Physical activity

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