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Integrated Single-cell multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

Genomics, Proteomics & Bioinformatics 2024年第1期22卷 67-88页

作者： manickam Ashokkumar Wenwen mei Jackson J.Peterson Yuriko Harigaya david m.murdoch david m.margolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao Jiang Edward P.Browne Department of medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of medicine Duke UniversityDurhamNC 27708USA Department of Computer Science Duke UniversityDurhamNC 27708USA Department of Statistics Texas A&M UniversityCollege StationTX 77843USA Department of Biology Texas A&M UniversityCollege StationTX 77843USA Department of Biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Primary CD4þT cell Single-cell multiomics HIV-regulating factor machine learning

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The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin david m.Lubman Department of Surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer *** play an important role in medicine and are involved in various human disease conditions including ***-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and *** N-glycosylation significantly impacts cancer processes and targeted therapies in ***,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and *** review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and ***,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are *** and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been ***,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

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Evaluation of hand infections in the emergency department using point-of-care ultrasound

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World Journal of Emergency medicine 2024年第4期15卷 283-288页

作者： david Ahmad Haidar david mintz Brandon m Wubben Omar Rizvi Srikar Adhikari Department of Emergency medicine Michigan MedicineAnn Arbor 48109-1382USA University of Arizona College of medicine Tucson 85724USA Department of Emergency medicine University of IowaIowa City 52242-1009USA Department of Surgery University of Arizona College of MedicineTucson 85724USA Department of Emergency medicine University of Arizona College of MedicineTucson 85724USA

BACKGROUND:We aimed to evaluate the utility of point-of-care ultrasound(POCUS)in the assessment of hand infections that present to the emergency department(ED)and its impact on medical decision making and patient ***:We conducted a retrospective review of patients who presented to two urban academic EDs with clinical presentations concerning for skin and soft tissue infections(SSTI)of the hand between December 2015 and December *** trained POCUS fellowship physicians reviewed an ED POCUS database for POCUS examinations of the *** then reviewed patients’electronic health records(EHR)for demographic characteristics,history,physical examination findings,ED course,additional imaging studies,consultations,impact of POCUS on patient care and final ***:We included a total of 50 cases(28 male,22 female)in the final *** most common presenting symptoms and exam findings were pain(100%),swelling(90%),and erythema(74%).The most common sonographic findings were edema(76%),soft tissue swelling(78%),and fluid surrounding the tendon(57%).POCUS was used in medical decision making 68%of the time(n=34),with the use of POCUS leading to changes in management 38%of the time(n=19).POCUS use led to early antibiotic use(11/19),early consultation(10/19),and led to the performance of a required procedure(8/19).The POCUS diagnosis was consistent with the discharge diagnosis of flexor tenosynovitis 8/12 times,abscess 12/16 times,and cellulitis 14/20 ***:POCUS is beneficial for evaluating of hand infections that present to the ED and can be used as an important part of medical decision making to expedite patient care.

关键词： Ultrasound Point-of-care ultrasound Cellulitis Abscess Flexor tenosynovitis

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mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-david m.Gothié Timothy E.Kennedy Department of Neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by *** is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered *** is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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A computational framework for improving genetic variants identification from 5,061 sheep sequencing data

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2332-2344页

作者： Shangqian Xie Karissa Isaacs Gabrielle Becker Brenda m.murdoch Department of Animal Veterinary&Food SciencesUniversity of IdahoMoscowIDUSA Superior Farms CaliforniaUSA

Background Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic *** calling is routinely used to combine identified variants across multiple related ***,the improvement of variants identification using the mutual support information from mul-tiple samples remains quite limited for population-scale *** In this study,we developed a computational framework for joint calling genetic variants from 5,061 sheep by incorporating the sequencing error and optimizing mutual support information from multiple samples’*** variants were accurately identified from multiple samples by using four steps:(1)Probabilities of variants from two widely used algorithms,GATK and Freebayes,were calculated by Poisson model incorporating base sequencing error potential;(2)The variants with high mapping quality or consistently identified from at least two samples by GATK and Freebayes were used to construct the raw high-confidence identification(rHID)variants database;(3)The high confidence variants identified in single sample were ordered by probability value and controlled by false discovery rate(FDR)using rHID database;(4)To avoid the elimination of potentially true variants from rHID database,the vari-ants that failed FDR were reexamined to rescued potential true variants and ensured high accurate identification *** results indicated that the percent of concordant SNPs and Indels from Freebayes and GATK after our new method were significantly improved 12%-32%compared with raw variants and advantageously found low frequency variants of individual sheep involved several traits including nipples number(GPC5),scrapie pathology(PAPSS2),sea-sonal reproduction and litter size(GRm1),coat color(RAB27A),and lentivirus susceptibility(TmEm154).Conclusion The new method used the computational strategy to reduce the number of false positives,and simulta-neously improve the identifi

关键词： Computational framework Genetic variants multiple samples Sheep

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Synthetic polymers:A review of applications in drilling fluids

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Petroleum Science 2024年第1期21卷 475-518页

作者： Shadfar Davoodi mohammed Al-Shargabi david A.Wood Valeriy S.Rukavishnikov Konstantin m.minaev School of Earth Sciences&Engineering Tomsk Polytechnic UniversityLenin AvenueTomskRussia DWA Energy Limited LincolnUnited Kingdom

With the growth of deep drilling and the complexity of the well profile,the requirements for a more complete and efficient exploitation of productive formations increase,which increases the risk of various ***,reagents based on modified natural polymers(which are naturally occurring compounds)and synthetic polymers(SPs)which are polymeric compounds created industrially,are widely used to prevent emerging complications in the drilling ***,compared to modified natural polymers,SPs form a family of high-molecular-weight compounds that are fully synthesized by undergoing chemical polymerization *** provide substantial flexibility in their ***,their size and chemical composition can be adjusted to provide properties for nearly all the functional objectives of drilling *** can be classified based on chemical ingredients,type of reaction,and their responses to ***,some of SPs,due to their structural characteristics,have a high cost,a poor temperature and salt resistance in drilling fluids,and degradation begins when the temperature reaches 130℃.These drawbacks prevent SP use in some medium and deep ***,this review addresses the historical development,the characteristics,manufacturing methods,classification,and the applications of SPs in drilling *** contributions of SPs as additives to drilling fluids to enhance rheology,filtrate generation,carrying of cuttings,fluid lubricity,and clay/shale stability are explained in *** mechanisms,impacts,and advances achieved when SPs are added to drilling fluids are also *** typical challenges encountered by SPs when deployed in drilling fluids and their advantages and drawbacks are also *** issues also impact the applications of SPs in drilling ***,the cost of the most relevant SPs,and the monomers used in their synthesis,are *** impacts of SPs when deployed in drilling fluids,and t

关键词： Synthetic versus natural polymers Nanopolymers Drilling fluid additives Lubricity Clay swelling Hole cleaning

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Late Ordovician mass Extinction: Earth, fire and ice

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National Science Review 2024年第1期11卷 51-65页

作者： david A.T.Harper Palaeoecosystems Group Department of Earth SciencesDurham University

The Late Ordovician mass Extinction was the earliest of the ‘big’ five extinction events and the earliest to affect the trajectory of metazoan life. Two phases have been identified near the start of the Hirnantian period and in the middle. It was a massive taxonomic extinction, a weak phylogenetic extinction and a relatively benign ecological extinction. A rapid cooling, triggering a major ice age that reduced the temperature of surface waters, prompted a drop in sea level of some 100 m and introduced toxic bottom waters onto the shelves. These symptoms of more fundamental planetary processes have been associated with a range of factors with an underlying driver identified as volcanicity. Volcanic eruptions, and other products, may have extended back in time to at least the Sandbian and early Katian, suggesting the extinctions were more protracted and influential than hitherto documented.

关键词： Ordovician LOmE paleoecology palaeobiogeography biotas

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Development of T cell antigen-based human coronavirus vaccinesagainst nAb-escaping SARS-CoV-2 variants

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Science Bulletin 2024年第15期69卷 2456-2470页

作者： Hao Zhou Ping Leng Yang Wang Kaiwen Yang Chen Li david m.Ojcius Pengfei Wang Shibo Jiang College of medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400016China Shanghai Pudong Hospital Fudan University Pudong Medical CenterShanghai Institute of Infectious Disease and BiosecuritySchool of Life SciencesFudan UniversityShanghai 200438China Department of Biomedical Sciences University of the PaciﬁcArthur Dugoni School of DentistrySan FranciscoCA 94115USA Key Laboratory of medical molecular Virology of ministry of Education/ministry of Health/Chinese Academy of medical Sciences Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghai 200032China

Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses;however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus,raising serious concerns about their efficacy. Additionally, while neutralizing antibodies(nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus(HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to n Abs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCo Vs based on different vaccine platforms.

关键词： COVID-19 Immune escape Omicron variant SARS-CoV-2 T cell antigen-based vaccine

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multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

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Journal of Animal Science and Biotechnology 2024年第3期15卷 987-1007页

作者： mengqi Wang Naisu Yang mario Laterriere david Gagne Faith Omonijo Eveline m.Ibeagha‑Awemu Agriculture and Agri‑Food Canada Sherbrooke Research and Development CentreSherbrookeQCCanada Department of Animal Science Universite LavalQuebec CityQCCanada Quebec Research and Development Centre Agriculture and Agri-Food CanadaQuebec CityQCCanada

Background mastitis caused by multiple factors remains one of the most common and costly disease of the dairy ***-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease ***,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus *** Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical *** abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dmHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEms),***,5 factors presenting the principal variation of differential multi-omics signatures were *** important roles of Factor 1(DEG,DEm and DEL)and Factor 2(dmHB and DEm),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were *** of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical ***,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regu

关键词： Candidate discriminant multi-omics signature Gene Long non-coding RNA methylation haplotype block microRNA multi-omics integration Natural killer cell mediated cytotoxicity pathway Staphylococcus aureus infection pathway

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Rational molecular design of efficient yellow-red dendrimer TADF for solution-processed OLEDs: a combined effect of substitution position and strength of the donors

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Science China Chemistry 2024年第5期67卷 1613-1623页

作者： Changfeng Si Dianming Sun Tomas matulaitis david B.Cordes Alexandra m.Z.Slawin Eli Zysman-Colman Organic Semiconductor Centre EaStCHEM School of ChemistryUniversity of St AndrewsSt AndrewsKY169STUK

The development of high-performance solution-processed red organic light-emitting diodes(OLEDs) remains a challenge,particularly in terms of maintaining efficiency at high luminance. Here, we designed and synthesized four novel orange-red thermally activated delayed fluorescence(TADF) dendrimers that are solution-processable: 2GCz BP, 2DPACz BP, 2FBP2GCz and 2FBP2DPACz. We systematically investigated the effect of substitution position and strength of donors on the optoelectronic properties. The reverse intersystem crossing rate constant(kRISC) of the emitters having donors substituted at positions 11and 12 of the dibenzo[a,c]phenazine(BP) is more than 10-times faster than that of compounds substituted having donors substituted at positions 3 and 6. Compound 2DPACz BP, containing stronger donors than 2GCz BP, exhibits a red-shifted emission and smaller singlet-triplet energy splitting, ΔE_(ST), of 0.01 e V. The solution-processed OLED with 10 wt% 2DPACz BP doped in m CP emitted at 640 nm and showed a maximum external quantum efficiency(EQE_(max)) of 7.8%, which was effectively maintained out to a luminance of 1,000 cd m-2. Such a device's performance at relevant display luminance is among the highest for solution-processed red TADF OLEDs. The efficiency of the devices was improved significantly by using 4Cz IPN as an assistant dopant in a hyperfluorescence(HF) configuration, where the 2DPACz BP HF device shows an EQEmaxof 20.0% at λEL of 605 nm and remains high at 11.8% at a luminance of 1,000 cd m-2, which makes this device one of the highest efficiency orange-to-red HF SP-OLEDs to date.

关键词： thermally activated delayed fluorescence solution-processing red OLEDs dibenzo[a,c]phenazine dendrimers

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