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Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy 2024年第3期9卷 872-912页

作者： Mudasir A.Kumar Sadaf K.Baba Hana Q.Sadida Sara Al.Marzooqi Jayakumar Jerobin Faisal H.Altemani Naseh Algehainy Mohammad A.Alanazi Abdul-Badi Abou-Samra Rakesh Kumar Ammira S.Al-Shabeeb Akil Muzafar A.Macha Rashid Mir Ajaz A.Bhat Watson-Crick Centre for Molecular Medicine Islamic University of Science and TechnologyAwantiporaKashmir 192122India Department of Human Genetics-Precision Medicine in Diabetes Obesity and Cancer ProgramSidra MedicineDohaQatar Qatar Metabolic Institute Academic Health SystemHamad Medical CorporationDohaQatar Department of Medical Laboratory Technology Prince Fahad Bin Sultan Chair for Biomedical ResearchFaculty of Applied Medical SciencesUniversity of TabukTabukSaudi Arabia School of Biotechnology Shri Mata Vaishno Devi UniversityKatraIndia

Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular *** exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological *** serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses *** vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease *** in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic ***,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical *** need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains *** into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the *** this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.

关键词： diseases sized sizes

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SV2B defines a subpopulation of synaptic vesicles

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Journal of Molecular Cell Biology 2023年第9期15卷 1-13页

作者： Isabelle Paulussen Hannes Beckert Timothy FMusial Lena J.Gschossmann Julia Wolf Mathieu Schmitt Jérôme Clasadonte Georges Mairet-Coello Christian Wolff Susanne Schoch Dirk Dietrich Synaptic Neuroscience Team Department of NeurosurgeryUniversity Hospital BonnBonn 53127Germany Synaptic Neuroscience Team Department of NeuropathologyUniversity Hospital BonnBonn 53127Germany Microscopy core Facility Medical FacultyUniversity of BonnBonn 53127Germany UCB Pharma Braine l’Alleud 1420Belgium

Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein ***,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron ***2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active *** contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active ***2B and SV2A were found on the membrane in the peri-active zone,suggesting the recycling from both clusters of ***2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency *** data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial *** almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.

关键词： 3D electron microscopy synaptic vesicles synaptic vesicle proteins endocytosis trafficking spatial organization

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Comparison of carotenoid,chlorophyll concentrations and their biosynthetic transcript levels in different coloured cauliflower

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Horticultural Plant Journal 2024年第3期10卷 743-754页

作者： Fatemeh Izadpanah Katja Frede Forouzandeh Soltani Susanne Baldermann Food Chemistry and Human Nutrition Leibniz Institute of Vegetable and Ornamental CropsTheodor-Echtermeyer-Weg 114979 GroßbeerenGermany Department of Food Chemistry Institute of Nutritional SciencesUniversity of PotsdamArthur-Scheunert-Allee 114-11614558 NuthetalGermany Department of Horticultural Science University of TehranDaneshkade Ave31587-77871KarajIran faculty of Life Sciences:Food Nutrition and HealthFood MetabolomeUniversity of BayreuthFritz-Hornschuch-Straße1395326 KulmbachGermany

Carotenoids and chlorophylls are among the most widely distributed pigments in nature that play essential roles in the photosynthetic apparatus and confer diverse colours in *** all vegetables,cauliflower(Brassica oleracea ***)is rich in phytochemicals and is an important crop grown all over the *** study investigates carotenoid and chlorophyll concentrations in differently pigmented cultivars and elucidates the role of transcriptional regulation of carotenoid accumulation including lutein andβ-***,we characterised changes in pigments by UHPLC-DAD-ToF-MS and changes in transcript levels of carotenoid metabolic genes by qRT-PCR in florets and leaves of orange(‘Jaffa'and‘Sunset'),purple(‘Di Sicilia Violetto'and‘Graffiti'),green(‘Trevi')and white(‘Clapton')*** levels of all carotenoid metabolic genes showed different transcript level patterns in the leaves and *** to the other cultivars,the orange cultivars had the highest levels ofβ-carotene in the florets and lutein in the leaves resulting in changes lutein/β-carotene *** the green cultivar,higher transcript levels were also found,especially for phytoene synthase and phytoene desaturase genes of the core biosynthesis ***,no increased carotenoid concentrations were observed,possibly due to a higher carotenoid turnover induced by the carotenoid cleavage dioxygenase 4 in the green *** the white(‘Clapton')and purple(‘Di Sicilia Violetto'and‘Graffiti')cultivars the phytoene desaturase transcript levels as well as carotenoid concentrations were *** concentrations changed in trend comparable to the carotenoid concentrations and were only significantly lower in the leaves of the orange cultivar‘Jaffa'.Also,the chlorophyll a/b ratio changed in‘Jaffa'.In florets the highest chlorophylls concentrations were observed for the green cultivar(‘Trevi')and the purple cultivar(‘Di Sicilia Violetto').Taken together,the study dem

关键词： Brassica oleracea L.var.botrytis Carotenoid Lutein β-Carotene Biosynthesis qRT-PCR

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Population genetic insights into the conservation of common walnut(Juglans regia)in Central Asia

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Plant Diversity 2024年第5期46卷 600-610页

作者： Linjiang Ye Robabeh Shahi Shavvon Hailing Qi Hongyu Wu Pengzhen Fan Mohammad Nasir Shalizi Safiullah Khurram Mamadzhanov Davletbek Yerlan Turuspekov Jie Liu CAS Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanChina Key Laboratory of Plant Resources and Biodiversity of Jiangxi Province Jingdezhen UniversityJingdezhen 333400JiangxiChina Germplasm Bank of Wild Species&Yunnan Key Laboratory of Crop Wild Relatives Omics Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanChina Department of Biology Faculty of ScienceYasouj UniversityYasouj 75918-74934Iran University of Chinese Academy of Sciences Beijing 100049China Department of Forestry and Environmental Resources North Carolina State UniversityRaleighNC 27695United States Department of Forestry and Natural Resources Faculty of AgricultureKabul UniversityKabul D-1006Afghanistan National Academy of Science of the Kyrgyz Republic Jalal-Abad Scientific CenterJalal-Abad 715600Kyrgyzstan Laboratory of Molecular Genetics Institute of Plant Biology and BiotechnologyAlmaty 050040Kazakhstan

The common walnut(Juglans regia)is one of the most economically important nut trees cultivated *** its importance,no comprehensive evaluation of walnut tree population genetics has been undertaken across the range where it originated,Central *** this study,we investigated the genetic diversity and population structure of 1082 individuals from 46 populations across Central *** found moderate genetic diversity of *** across Central Asia,with 46 populations clustered into three groups with a weak relationship between genetic and geographic *** findings reveal that the western Himalaya might be the core region of common walnut genetic diversity in Central Asia and that,except for two populations in Gongliu Wild Walnut Valley,humans might have introduced walnut populations to Xinjiang,*** observed distribution of the genetic landscape has probably been affected by historical climate fluctuation,breeding system,and prolonged anthropogenic *** propose the conservation of the core genetic diversity resources in the western Himalaya and pay special attention to populations from Gongliu in *** findings enhance our understanding of the genetic variation throughout the distribution range of *** in Central Asia,which will provide a key prerequisite for evidence-based conservation and management.

关键词： Central Asia Genetic diversity Germplasm management Gongliu wild walnut valley Juglans regia Western Himalaya

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Performance of the Enhanced Liver Fibrosis Score,Comparison with Vibration-controlled Transient Elastography Data,and Development of a Simple Algorithm to Predict Significant Liver Fibrosis in a Community-based Liver Service:A Retrospective Evaluation

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 800-808页

作者： Tina Reinson Janisha Patel Mead Mathews Derek Fountain Ryan M.Buchanan Christopher DByrne Nutrition and Metabolism Faculty of MedicineUniversity of SouthamptonSouthamptonUK National Institute for Health and Care Research Southampton Biomedical Research CenterUniversity Hospital SouthamptonSouthamptonUK Hepatology Department University Hospital SouthamptonSouthamptonUK St Mary’s Surgery SouthamptonUK core Minutes Ltd RingwoodUK Clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthamptonUK

Background and Aims:Liver fibrosis is a key risk factor for cirrhosis,hepatocellular carcinoma and end stage liver *** National Institute for Health and Care Excellence guidelines for assessment for advanced(≥F3)liver fibrosis in people with nonalcoholic fatty liver disease recommend the use of enhanced liver fibrosis(ELF)test,followed by vibration-controlled transient elastography(VCTE).Performance of ELF at predicting significant(≥F2)fibrosis in real-world practice is *** assess the accuracy of ELF using VCTE;investigate the optimum ELF cutoff value to identify≥F2and≥F3;and develop a simple algorithm,with and without ELF score,for detecting≥***:Retrospective evaluation of patients referred to a Community Liver Service for VCTE,Jan-Dec *** included:body mass index(BMI),diabetes status,alanine aminotransferase(ALT)levels,ELF score and biopsy-validated fibrosis stages according to ***:Data from 273 patients were available.n=110 patients had *** showed fair performance for≥F2 and≥F3,area under the curve(AUC)=0.70,95%confidence interval(CI)0.64-0.76 and AUC=0.72,95%CI:0.65-0.79 ***≥F2 Youden's index for ELF=9.85 and for≥F3,ELF=*** ALT,BMI,and HbA1c(ALBA algorithm)to predict≥F2 showed good performance(AUC=0.80,95%CI:0.69-0.92),adding ALBA to ELF improved performance(AUC=0.82,95%CI:0.77-0.88).Results were independently ***:Optimal ELF cutoff for≥F2 is 9.85 and 9.95 for≥***,BMI,and HbA1c(ALBA algorithm)can stratify patients at risk of≥*** is improved by adding ALBA.

关键词： Primary health care Retrospective evaluation Liver disease Diabetes Nonalcoholic fatty liver disease

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Coaxial Wet Spinning of Boron Nitride Nanosheet‑Based Composite Fibers with Enhanced Thermal Conductivity and Mechanical Strength

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Nano-Micro Letters 2024年第2期16卷 126-138页

作者： Wenjiang Lu Qixuan Deng Minsu Liu Baofu Ding Zhiyuan Xiong Ling Qiu Tsinghua Shenzhen International Graduate School(TSIGS) Tsinghua UniversityShenzhen 518055People’s Republic of China Monash Suzhou Research Institute(MSRI) Monash UniversitySuzhou 215000People’s Republic of China faculty of Materials Science and Engineering/Institute of Technology for Carbon Neutrality Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055People’s Republic of China Shenzhen Key Laboratory of Energy Materials for Carbon Neutrality Shenzhen 518055People’s Republic of China School of Light Industry and Engineering South China University of TechnologyGuangzhou 510614People’s Republic of China

Hexagonal boron nitride nanosheets(BNNSs)exhibit remarkable thermal and dielectric ***,their self-assembly and alignment in macroscopic forms remain challenging due to the chemical inertness of boron nitride,thereby limiting their performance in applications such as thermal *** this study,we present a coaxial wet spinning approach for the fabrication of BNNSs/polymer composite fibers with high nanosheet *** composite fibers were prepared using a superacid-based solvent system and showed a layered structure comprising an aramid core and an aramid/BNNSs ***,the coaxial fibers exhibited significantly higher BNNSs alignment compared to uniaxial aramid/BNNSs fibers,primarily due to the additional compressive forces exerted at the core-sheath interface during the hot drawing *** a BNNSs loading of 60 wt%,the resulting coaxial fibers showed exceptional properties,including an ultrahigh Herman orientation parameter of 0.81,thermal conductivity of 17.2 W m^(-1)K^(-1),and tensile strength of 192.5 *** results surpassed those of uniaxial fibers and previously reported BNNSs composite fibers,making them highly suitable for applications such as wearable thermal management *** findings present a promising strategy for fabricating high-performance composite fibers based on BNNSs.

关键词： Boron nitride nanosheets Coaxial fiber Interfacial compression Nanosheet aligning Wearable thermal management

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Single-cell trajectories of melanoma cell resistance to targeted treatment

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Cancer Biology & Medicine 2022年第1期19卷 56-73页

作者： Maria Schmidt Lena Sünke Mortensen Henry Loeffler-Wirth Corinna Kosnopfel Knut Krohn Hans Binder Manfred Kunz Interdisciplinary Centre for Bioinformatics University of LeipzigLeipzig 04107Germany Department of Dermatology Venereology and AllergologyUniversity of WürzburgWürzburg 97074Germany core Unit DNA Technologies Medical FacultyUniversity of LeipzigLeipzig 04103Germany Department of Dermatology Venereology and AllergologyUniversity of Leipzig Medical CenterLeipzig 04103Germany

Objective:Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant *** developments in single-cell sequencing technology have provided deeper insights into these ***:Here,we analyzed a BRAFV600 E-mutant melanoma cell line by single-cell RNA-seq under various conditions:cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or *** reduction by t-distributed stochastic neighbor embedding and self-organizing maps identified distinct trajectories of resistance development clearly separating the 4 treatment conditions in cell and gene state ***:Trajectories associated with resistance to single-agent treatment involved cell cycle,extracellular matrix,and de-differentiation *** contrast,shifts detected in double-resistant cells primarily affected translation and mitogen-activated protein kinase pathway reactivation,with a small subpopulation showing markers of *** findings were validated in pseudotime analyses and RNA velocity ***:The single-cell transcriptomic analyses reported here employed a spectrum of bioinformatics methods to identify mechanisms of melanoma resistance to single-and double-agent *** study deepens our understanding of treatmentinduced cellular reprogramming and plasticity in melanoma cells and identifies targets of potential relevance to the management of treatment resistance.

关键词： Melanoma single-cell transcriptome sequencing treatment response

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Determination of Parameters Affecting the Estimation of Iceberg Draft

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China Ocean Engineering 2023年第1期37卷 62-72页

作者： Hamed AZIMI Masoud MAHDIANPARI Hodjat SHIRI Civil Engineering Department Faculty of Engineering and Applied ScienceMemorial University of NewfoundlandA1B 3X5St.John’sNLCanada Department of Electrical and Computer Engineering Faculty of Engineering and Applied ScienceMemorial University of NewfoundlandA1B 3X5St.John’sNLCanada C-core A1B 3X5St.John’sNLCanada

Recent offshore oil and gas loading facilities developed in the Arctic area have led to a considerable awareness of the iceberg draft approximation, where deep keel icebergs may gouge the ocean floor, and these submarine infrastructures would be damaged in the shallower waters. Developing reliable solutions to estimate the iceberg draft requires a profound understanding of the problem’s dominant parameters. As such, the dimensionless groups of the parameters affecting the iceberg draft estimation were determined for the first time in the present study. Using the dimensionless groups recognized and the linear regression(LR) analysis, nine LR models(i.e., LR 1 to LR 9) were developed and then validated using a comprehensive dataset, which has been constructed in this study. A sensitivity analysis distinguished the premium LR models and important dimensionless groups. The best LR model, as a function of all dimensionless parameters, was able to estimate the iceberg draft with the highest level of precision and correlation along with the lowest degree of complexity. The ratio of iceberg length to iceberg height as the “iceberg length ratio” and the ratio of iceberg width to iceberg height as the “iceberg width ratio” was detected as the important dimensionless groups in the estimation of the iceberg draft. An uncertainty analysis demonstrated that the best LR model was biased towards underestimating the iceberg drafts. The premium LR model outperformed the previous empirical ***, a set of LR-based relationships were derived for estimating the iceberg drafts for practical engineering applications, e.g., the early stages of the iceberg management projects.

关键词： dimensional analysis iceberg draft subsea assets linear regression(LR) sensitivity analysis

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Effect of Cadmium on the Developmental Instability of Anabas testudineus through Evaluation of Fluctuating Asymmetry of Eye Diameter

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Journal of Environmental Protection 2023年第5期14卷 392-403页

作者： Fazlin Hazirah Mohd Sharifah Nadrah Syed Idrus Mohd Riduan Abdullah Mohd Sham Othman Center for Toxicology & Health Risk Studies (core) Faculty of Health Sciences Universiti Kebangsaan Malaysia Kuala Lumpur Malaysia

Biomonitoring using fish has been a popular method of assessing the toxic effects of cadmium concentrations of cadmium in water bodies and has led to bioaccumulation in fish contributing to various morphological alterations. Among the known effects of these alterations is developmental instability via fluctuating asymmetry (FA). The utilization of FA data is a simple yet effective method to evaluate the toxic effects of cadmium on the stability of development. This study used climbing perch (Anabas testudieneus) to assess the FA in the diameter of the eye because of low-level cadmium exposure. The left and right sides of the traits were measured once every four weeks for 16 weeks. The average measurements from both sides of the traits were used to calculate the FA value. Results found that the highest mean FA for the diameter of the eye was obtained in the highest treatment group, 0.015 mg/L. The results also indicate that increasing concentrations of cadmium exposure had a statistically significant effect on the FA of eye diameter. There was also a statistically significant interaction between the duration of exposure and treatment groups in FA of the diameter of the eye. The results from the study indicate that prolonged exposure to sub-lethal concentrations of cadmium can cause significant effects on the normal development of eyes in Anabas testudineus. This study can add to the body of research regarding fluctuating asymmetry as a tool to study developmental toxicants and assess other bilateral organs.

关键词： Biomonitoring Cadmium Eye Fluctuating Asymmetry Anabas testudineus

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Hepatosomatic and Renosomatic Indices of <i>Anabas testudineus</i>Exposed to Various Levels of Cadmium

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Journal of Environmental Protection 2022年第1期13卷 161-170页

作者： Sharifah Nadrah Syed Idrus Mohd Riduan Abdullah Fazlin Hazirah Mohd Mohd Sham Othman Center for Toxicology & Health Risk Studies (core) Faculty of Health Sciences Universiti Kebangsaan Malaysia Kuala Lumpur Malaysia

Cadmium has a high level of toxicity and can have adverse health effects on living organisms including fish. This study is conducted to identify the effects of cadmium exposure on the Hepatosomatic Index (HSI) and Renosomatic Index (RSI) of Anabas testudineus. Anabas testudineus is exposed to four different cadmium treatment groups. The fishes were exposed to four treatment groups of different cadmium concentrations (0.000 mg/L, 0.005 mg/L, 0.010 mg/L and 0.015 mg/L) for 16 weeks. The results showed a decreasing trend of HSI value increasing cadmium concentration and exposure time. However, the opposite trend was observed with RSI where the higher the cadmium concentration over an increased exposure time, the higher the RSI. In conclusion, the study outcome shows significant changes in the value of HSI and RSI between different treatment groups with exposure time.

关键词： Cadmium Anabas testudineus Hepatosomatic Index Renosomatic Index

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