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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 glycoproteome.Glycoproteins play an important role in medicine and are involved in various human disease conditions including cancer.Glycan-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and metastasis.Aberrant N-glycosylation significantly impacts cancer processes and targeted therapies in clinic.Therefore,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and diagnosis.This review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and corefucosylation.Also,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are discussed.Glycoproteins and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been introduced.Collectively,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

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 oligodendrocytes.myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.myelin 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

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

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 industry.multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,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 chromogenes.Results 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 mastitis.The 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),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The 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 revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,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 regulatory mechanisms underlying subclinical mastiti

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

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 management.mETHODS: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 2021.Two trained POCUS fellowship physicians reviewed an ED POCUS database for POCUS examinations of the hand.We 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 disposition.RESULTS:We included a total of 50 cases(28 male,22 female)in the final analysis.The 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 times.CONCLUSION: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

Driving factors behind multiple populations

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Science China(Physics,mechanics & Astronomy) 2024年第5期67卷 172-181页

作者： Ruoyun Huang Baitian Tang Chengyuan Li Doug Geisler mario mateo Ying-Yi Song Holger Baumgardt Julio A.carballo-Bello Yue Wang Jundan Nie Bruno Dias JoséG.Fernández-Trincado School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China CSST Science Center for the Guangdong-Hong Kong-macao Greater Bay Area Zhuhai 519082China Departamento de Astronomía Universidad de ConcepcionConcepcionChile Instituto de Investigación multidisciplinario en Ciencia y Tecnología Universidad de La SerenaLa SerenaChile Departamento de Astronomía Facultad de CienciasUniversidad de La SerenaChile Department of Astronomy University of MichiganAnn Arbor 48109USA david A.Dunlap Department of Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada Dunlap Institute for Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada School of mathematics and Physics The University of QueenslandSt.Lucia QLD 4072Australia Instituto de Alta Investigación Universidad de TarapacáAricaChile CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Instituto de Astrofísica Departamento de Ciencias FísicasFacultad de Ciencias ExactasUniversidad Andres BelloSantiagoChile Instituto de Astronomía Universidad Católica del NorteAntofagastaChile

Star clusters were historically considered simple stellar populations,with all stars sharing the same age and initial chemical composition.However,the presence of chemical anomalies in globular clusters(GCs),called multiple stellar populations(mPs),has challenged star formation theories in dense environments.Literature studies show that mass,metallicity,and age are likely controlling parameters for the manifestation of mPs.Identifying the limit between clusters with/without mPs in physical parameter space is crucial to reveal the driving mechanism behind their presence.In this study,we look for mP signals in Whiting 1,which is traditionally considered a young GC.Using the magellan telescope,we obtained low-resolution spectra withinλλ=3850-5500?for eight giants of Whiting 1.We measured the C and N abundances from the CN and CH spectral indices.C and N abundances have variations comparable with their measurement errors(~0.1 dex),suggesting that mPs are absent from Whiting 1.Combining these findings with literature studies,we propose a limit in the metallicity vs.cluster compactness index parameter space,which relatively clearly separates star clusters with/without mPs(GCs/open clusters).This limit is physically motivated.On a larger scale,the galactic environment determines cluster compactness and metallicity,leading to metal-rich,diffuse,old clusters formed ex situ.Our proposed limit also impacts our understanding of the formation of the Sagittarius dwarf galaxy:star clusters formed after the first starburst(age≤8-10 Gyr).These clusters are simple stellar populations because the enriched galactic environment is no longer suitable for mP formation.

关键词： stellar galactic galaxy

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 complications.Currently,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 process.However,compared to modified natural polymers,SPs form a family of high-molecular-weight compounds that are fully synthesized by undergoing chemical polymerization reactions.SPs provide substantial flexibility in their design.moreover,their size and chemical composition can be adjusted to provide properties for nearly all the functional objectives of drilling fluids.They can be classified based on chemical ingredients,type of reaction,and their responses to heating.However,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 wells.Thus,this review addresses the historical development,the characteristics,manufacturing methods,classification,and the applications of SPs in drilling fluids.The 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 detail.The mechanisms,impacts,and advances achieved when SPs are added to drilling fluids are also described.The typical challenges encountered by SPs when deployed in drilling fluids and their advantages and drawbacks are also discussed.Economic issues also impact the applications of SPs in drilling fluids.Consequently,the cost of the most relevant SPs,and the monomers used in their synthesis,are assessed.Environmental impacts of SPs when deployed in drilling fluids,and their manufacturing processes are identified,toge

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

Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World Journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee J Dufault Katherine m Adler david O Carpenter Steven G Gilbert Raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIm To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.mETHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

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Journal of Sport and Health Science 2024年第4期13卷 521-536页

作者： Helder S.Lopes marina C.Waiteman Liliam B.Priore Neal R.Glaviano david m.Bazett-Jones Ronaldo V.Briani Fabio m.Azevedo School of Science and Technology Physical Therapy DepartmentSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Department of Kinesiology College of AgricultureHealth and Natural ResourcesUniversity of ConnecticutStorrsCT 06269USA School of Exercise and Rehabilitation Sciences College of Health and Human ServicesUniversity of ToledoToledoOH 43606USA

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and function.Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation.This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders.methods:Five databases(mEDLINE,Embase,CINAHL,SPORTDiscus,and Web of Science)were searched from inception to September 2022.Only studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included.meta-analyses for each knee disorder were performed.Outcome-level certainty was assessed using the Grading of Recommendations Assessment,Development,and Evaluation,and evidence gap maps were created.Results:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were included.Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SmD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SmD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SmD=-0.48,95%CI:-0.82 to-0.14),concentric(SmD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SmD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar tendinopathy.Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SmD=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-

关键词： Chondromalacia patellae Knee flexors Knee osteoarthritis Patellar tendinopathy Patellofemoral pain