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1.
Glia ; 72(7): 1304-1318, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38546197

RESUMO

Oligodendrocyte differentiation and myelination in the central nervous system are controlled and coordinated by a complex gene regulatory network that contains several transcription factors, including Zfp488 and Nkx2.2. Despite the proven role in oligodendrocyte differentiation little is known about the exact mode of Zfp488 and Nkx2.2 action, including their target genes. Here, we used overexpression of Zfp488 and Nkx2.2 in differentiating CG4 cells to identify aspects of the oligodendroglial expression profile that depend on these transcription factors. Although both transcription factors are primarily described as repressors, the detected changes argue for an additional function as activators. Among the genes activated by both Zfp488 and Nkx2.2 was the G protein-coupled receptor Gpr37 that is important during myelination. In agreement with a positive effect on Gpr37 expression, downregulation of the G protein-coupled receptor was observed in Zfp488- and in Nkx2.2-deficient oligodendrocytes in the mouse. We also identified several potential regulatory regions of the Gpr37 gene. Although Zfp488 and Nkx2.2 both bind to one of the regulatory regions downstream of the Gpr37 gene in vivo, none of the regulatory regions was activated by either transcription factor alone. Increased activation by Zfp488 or Nkx2.2 was only observed in the presence of Sox10, a transcription factor continuously present in oligodendroglial cells. Our results argue that both Zfp488 and Nkx2.2 also act as transcriptional activators during oligodendrocyte differentiation and cooperate with Sox10 to allow the expression of Gpr37 as a modulator of the myelination process.


Assuntos
Diferenciação Celular , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio , Oligodendroglia , Receptores Acoplados a Proteínas G , Fatores de Transcrição SOXE , Fatores de Transcrição , Animais , Feminino , Masculino , Camundongos , Diferenciação Celular/fisiologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Fatores de Transcrição SOXE/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
2.
BMC Genomics ; 25(1): 346, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580907

RESUMO

BACKGROUND: The yak (Bos grunniens) is a large ruminant species that lives in high-altitude regions and exhibits excellent adaptation to the plateau environments. To further understand the genetic characteristics and adaptive mechanisms of yak, we have developed a multi-omics database of yak including genome, transcriptome, proteome, and DNA methylation data. DESCRIPTION: The Yak Genome Database ( http://yakgenomics.com/ ) integrates the research results of genome, transcriptome, proteome, and DNA methylation, and provides an integrated platform for researchers to share and exchange omics data. The database contains 26,518 genes, 62 transcriptomes, 144,309 proteome spectra, and 22,478 methylation sites of yak. The genome module provides access to yak genome sequences, gene annotations and variant information. The transcriptome module offers transcriptome data from various tissues of yak and cattle strains at different developmental stages. The proteome module presents protein profiles from diverse yak organs. Additionally, the DNA methylation module shows the DNA methylation information at each base of the whole genome. Functions of data downloading and browsing, functional gene exploration, and experimental practice were available for the database. CONCLUSION: This comprehensive database provides a valuable resource for further investigations on development, molecular mechanisms underlying high-altitude adaptation, and molecular breeding of yak.


Assuntos
Multiômica , Proteoma , Animais , Bovinos/genética , Proteoma/genética , Genoma , Transcriptoma , Anotação de Sequência Molecular
3.
J Exp Zool B Mol Dev Evol ; 340(4): 316-328, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36148637

RESUMO

Yak has evolved specific adaptative mechanisms to high-altitude environment. Up to date, only a few studies reported the DNA methylation in yak. In the present study, genome-wide DNA methylome and transcriptome profiles in lung, mammary, and biceps brachii muscle tissues were compared between yak and three cattle breeds (Tibetan cattle, Sanjiang cattle, and Holstein cattle). The association between differentially expressed genes (DEGs) and differentially methylated regions (DMRs) was analyzed, and the biological functions of DEGs potentially driven by DMRs were explored by KEGG enrichment analysis. Finally, we found that yak-specific DMRs-driven DEGs were mainly involved in neuromodulation, respiration, lung development, blood pressure regulation, cardiovascular protection, energy metabolism, DNA repair, and immune functions. The higher levels of the key genes associated with these functions were observed in yak than in cattle, suggesting that DNA methylation might regulate these genes. Overall, the present study contributes basic data at the DNA methylation level to further understand the physiological metabolism in yak.


Assuntos
Metilação de DNA , Transcriptoma , Animais , Bovinos/genética , Genoma , Pulmão , RNA Mensageiro
4.
Physiol Genomics ; 54(12): 514-525, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342051

RESUMO

Rumen microorganisms play important roles in the healthy growth of yaks. This study investigated changes in yak rumen microbiome during natural grazing at the warm seasons and supplementary feeding at cold seasons. High-throughput sequencing of 16S rRNA and metagenome analysis were conducted to investigate the structures and functions of yak rumen microbial communities. The results indicated that Bacteroidetes and Firmicutes were the most abundant phyla. In addition, Bacteroidetes might play a more important role than Firmicutes during the supplementary feeding stage (spring and winter), but less during natural grazing stage (summer and autumn). KEGG analysis showed that the amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, starch and sucrose metabolism, and fructose and mannose metabolism were the main pathways in the microbial community, which were significantly different between seasons. The carbohydrate-active enzymes (CAZyme) annotation revealed that cellulose was an important carbon source for microorganisms in yak rumen. Glycoside hydrolases (GHs) were the most abundant class of CAZymes, followed by glycosyl transferases (GTs), which were important to digestion of oil, cellulose, and hemicellulose in food. These results contribute to the understanding of microbial components and functions in yak rumen.


Assuntos
Microbiota , Rúmen , Animais , Bovinos , RNA Ribossômico 16S/genética , Microbiota/fisiologia , Dieta , Bacteroidetes/genética , Celulose
5.
BMC Genomics ; 23(1): 833, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36522700

RESUMO

BACKGROUND: The yak is the most important livestock in the Qinghai-Tibet Plateau, and body weight directly affects the economic values of yak. Up to date, the genome-wide profiling of single-nucleotide polymorphisms (SNPs) associating with body weight has not been reported in yak. In the present study, the SNPs in 480 yaks from three breeds were analyzed using the commercial high-density (600 K) yak SNP chips. RESULTS: The results identified 12 and 4 SNPs potentially associated with body weight in male and female yaks, respectively. Among them, 9 and 2 SNPs showed significant difference in yak body weight between different genotypes at each locus in male and female yaks, respectively. Further exploration found 33 coding genes within the 100 kbp upstream or downstream to the SNP loci, which might be potentially affected by the variation of SNPs. Among them, G protein-coupled receptor kinase 4 (GRK4) might be potentially affected by the SNP AX-174555047, which has been reported to affect the functioning of two body-weight associated hormones (parathyroid hormone, PTH, and adrenomedullin, ADM). Determination of PTH and ADM levels in yak revealed positive relationship between PTH level and body weight, negative relationship between ADM level and body weight along with the variation of AX-174555047 mutation. CONCLUSIONS: These results suggested that the SNP AX-174555047 might potentially affect body weight through mediating GRK4 expression and then PTH and ADM functioning. Thus, the SNP AX-174555047 might be used as a biomarker for molecular breeding of yak. More investigations are required to validate this point.


Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Animais , Masculino , Bovinos/genética , Feminino , Peso Corporal/genética , Genótipo , Tibet
6.
J Anim Physiol Anim Nutr (Berl) ; 106(3): 485-493, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34494310

RESUMO

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.


Assuntos
Altitude , Proteômica , Adaptação Fisiológica , Animais , Bovinos , Genoma , Proteoma
7.
J Biol Chem ; 295(7): 1879-1888, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31932307

RESUMO

The homeodomain protein NK2 homeobox 2 (NKX2-2) is a transcription factor that plays a critical role in the control of cell fate specification and differentiation in many tissues. In the developing central nervous system, this developmentally important transcription factor functions as a transcriptional repressor that governs oligodendrocyte (OL) differentiation and myelin gene expression, but the roles of various NKX2-2 structural domains in this process are unclear. In this study, using in situ hybridization, immunofluorescence, and coimmunoprecipitation, we determined the structural domains that mediate the repressive functions of murine NKX2-2 and identified the transcriptional corepressors that interact with it in OL cells. Through in ovo electroporation in embryonic chicken spinal cords, we demonstrate that the N-terminal Tinman domain and C-terminal domain synergistically promote OL differentiation by recruiting distinct transcriptional corepressors, including enhancer of split Groucho 3 (GRG3), histone deacetylase 1 (HDAC1), and DNA methyltransferase 3 α (DNMT3A). We also observed that the NK2-specific domain suppresses the function of the C-terminal domain in OL differentiation. These findings delineate the distinct NKX2-2 domains and their roles in OL differentiation and suggest that NKX2-2 regulates differentiation by repressing gene expression via multiple cofactors and molecular mechanisms.


Assuntos
Diferenciação Celular/genética , Proteínas de Homeodomínio/genética , Neurogênese/genética , Proteínas de Peixe-Zebra/genética , Animais , Embrião de Galinha , Proteínas Correpressoras/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Regulação da Expressão Gênica no Desenvolvimento/genética , Histona Desacetilase 1/genética , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/química , Camundongos , Oligodendroglia/metabolismo , Regiões Promotoras Genéticas/genética , Domínios Proteicos/genética , Fatores de Transcrição/genética
8.
BMC Evol Biol ; 20(1): 137, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109104

RESUMO

BACKGROUND: On the Qinghai-Tibet Plateau, known as the roof ridge of the world, the yak is a precious cattle species that has been indispensable to the human beings living in this high-altitude area. However, the origin of domestication, dispersal route, and the divergence of domestic yaks from different areas are poorly understood. RESULTS: Here, we resequenced the genome of 91 domestic yak individuals from 31 populations and 1 wild yaks throughout China. Using a population genomics approach, we observed considerable genetic variation. Phylogenetic analysis suggested that the earliest domestications of yak occurred in the south-eastern QTP, followed by dispersal to the west QTP and northeast to SiChuang, Gansu, and Qinghai by two routes. Interestingly, we also found potential associations between the distribution of some breeds and historical trade routes such as the Silk Road and Tang-Tibet Ancient Road. Selective analysis identified 11 genes showing differentiation between domesticated and wild yaks and the potentially positively selected genes in each group were identified and compared among domesticated groups. We also detected an unbalanced pattern of introgression among domestic yak, wild yak, and Tibetan cattle. CONCLUSIONS: Our research revealed population genetic evidence for three groups of domestic yaks. In addition to providing genomic evidence for the domestication history of yaks, we identified potential selected genes and introgression, which provide a theoretical basis and resources for the selective breeding of superior characters and high-quality yak.


Assuntos
Bovinos/genética , Evolução Molecular , Variação Genética , Filogenia , Sequenciamento Completo do Genoma , Animais , China , Domesticação , Genoma , Genômica , Tibet
9.
BMC Genomics ; 21(1): 731, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081725

RESUMO

BACKGROUND: Domestic yaks play an indispensable role in sustaining the livelihood of Tibetans and other ethnic groups on the Qinghai-Tibetan Plateau (QTP), by providing milk and meat. They have evolved numerous physiological adaptations to high-altitude environment, including strong blood oxygen transportation capabilities and high metabolism. The roles of DNA methylation and gene expression in milk production and high-altitudes adaptation need further exploration. RESULTS: We performed genome-wide DNA methylome and transcriptome analyses of breast, lung, and biceps brachii muscle tissues from yaks of different ages. We identified 432,350 differentially methylated regions (DMRs) across the age groups within each tissue. The post-mature breast tissue had considerably more differentially methylated regions (155,957) than that from the three younger age groups. Hypomethylated genes with high expression levels might regulate milk production by influencing protein processing in the endoplasmic reticulum. According to weighted gene correlation network analysis, the "hub" gene ZGPAT was highly expressed in the post-mature breast tissue, indicating that it potentially regulates the transcription of 280 genes that influence protein synthesis, processing, and secretion. The tissue network analysis indicated that high expression of HIF1A regulates energy metabolism in the lung. CONCLUSIONS: This study provides a basis for understanding the epigenetic mechanisms underlying milk production in yaks, and the results offer insight to breeding programs aimed at improving milk production.


Assuntos
Metilação de DNA , Epigenoma , Animais , Bovinos , Leite , Fatores de Transcrição , Transcriptoma
10.
BMC Genomics ; 21(1): 347, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381004

RESUMO

BACKGROUND: The Intramuscular fat (IMF) content in meat products, which is positively correlated with meat quality, is an important trait considered by consumers. The regulation of IMF deposition is species specific. However, the IMF-deposition-related mRNA and non-coding RNA and their regulatory network in yak (Bos grunniens) remain unknown. High-throughput sequencing technology provides a powerful approach for analyzing the association between transcriptome-related differences and specific traits in animals. Thus, the whole transcriptomes of yak muscle and adipose tissues were screened and analyzed to elucidate the IMF deposition-related genes. The muscle tissues were used for IMF content measurements. RESULTS: Significant differences were observed between the 0.5- and 2.5-year-old yaks. Several mRNAs, miRNAs, lncRNAs and circRNAs were generally expressed in both muscle and adipose tissues. Between the 0.5- and 2.5-year-old yaks, 149 mRNAs, 62 miRNAs, 4 lncRNAs, and 223 circRNAs were differentially expressed in muscle tissue, and 72 mRNAs, 15 miRNAs, 9 lncRNAs, and 211 circRNAs were differentially expressed in adipose tissue. KEGG annotation revelved that these differentially expressed genes were related to pathways that maintain normal biological functions of muscle and adipose tissues. Moreover, 16 mRNAs, 5 miRNAs, 3 lncRNAs, and 5 circRNAs were co-differentially expressed in both types of tissue. We suspected that these co-differentially expressed genes were involved in IMF-deposition in the yak. Additionally, LPL, ACADL, SCD, and FASN, which were previously shown to be associated with the IMF content, were identified in the competing endogenous RNA (ceRNA) regulatory network that was constructed on the basis of the IMF deposition-related genes. Three ceRNA subnetworks also revealed that TCONS-00016416 and its target SIRT1 "talk" to each other through the same miR-381-y and miR-208 response elements, whereas TCONS-00061798 and its target PRKCA, and TCONS-00084092 and its target LPL "talk" to each other through miR-122-x and miR-499-y response elements, respectively. CONCLUSION: Taken together, our results reveal the potential mRNA and noncoding RNAs involved in IMF deposition in the yak, providing a useful resource for further research on IMF deposition in this animal species.


Assuntos
Tecido Adiposo/metabolismo , Redes Reguladoras de Genes , Músculos/metabolismo , RNA Mensageiro/genética , RNA não Traduzido/genética , Tecido Adiposo/crescimento & desenvolvimento , Animais , Bovinos , Regulação da Expressão Gênica no Desenvolvimento , Metabolismo dos Lipídeos/genética , Lipogênese/genética , Carne/análise , Transcriptoma
11.
J Exp Zool B Mol Dev Evol ; 334(6): 362-372, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32779369

RESUMO

Yak is the unique Bovidae species in the Qinghai-Tibetan Plateau. A previous proteomic study has compared the yak muscle tissue to one cattle strain using the isobaric tags for relative and absolute quantification approach. In this study, to further investigate the molecular mechanisms underlying yak adaptation, the proteomic profiles of gluteus were compared between yak and one moderate-altitude cattle strain (Tibetan cattle) and two low-altitude cattle strains (Holstein and Sanjiang cattle) using a label-free quantitative method. The comparisons identified 20, 364, 143 upregulated proteins and 4, 6, 37 downregulated proteins in yak, compared with Tibetan, Holstein, and Sanjiang cattle, respectively. Protein-protein interaction analysis indicated that these differentially expressed proteins were mainly related to "oxidative phosphorylation" and "electron transport chain." Further analysis revealed that NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4, cytochrome C oxidase subunit 6A2, mitochondrial and cytochrome c oxidase subunit NDUFA4 were all increased in the yak, suggesting that yak might increase mitochondrial capacity to sustain metabolic rates under high altitude conditions, which might be a long-term adaptive mechanism underlying adaptation to high altitude environments. Yak increased the level of thioredoxin reductase 2 to protect themselves from oxidative damages. Moreover, the increased expression levels of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform and caveolin-1 in yak suggested that yaks promoted glucose uptake for adaptation to high altitude. These results provided more information to better understand the molecular mechanisms underlying yak adaption.


Assuntos
Adaptação Fisiológica/fisiologia , Altitude , Bovinos/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Animais , Regulação da Expressão Gênica/fisiologia , Proteínas Musculares/genética , Estresse Oxidativo , Mapas de Interação de Proteínas
12.
BMC Genomics ; 20(1): 61, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658572

RESUMO

BACKGROUND: Genomic structural variation represents a source for genetic and phenotypic variation, which may be subject to selection during the environmental adaptation and population differentiation. Here, we described a genome-wide analysis of copy number variations (CNVs) in 16 populations of yak based on genome resequencing data and CNV-based cluster analyses of these populations. RESULTS: In total, we identified 51,461 CNV events and defined 3174 copy number variation regions (CNVRs) that covered 163.8 Mb (6.2%) of yak genome with more "loss" events than both "gain" and "both" events, and we confirmed 31 CNVRs in 36 selected yaks using quantitative PCR. Of the total 163.8 Mb CNVR coverage, a 10.8 Mb region of high-confidence CNVRs directly overlapped with the 52.9 Mb of segmental duplications, and we confirmed their uneven distributions across chromosomes. Furthermore, functional annotation indicated that the CNVR-harbored genes have a considerable variety of molecular functions, including immune response, glucose metabolism, and sensory perception. Notably, some of the identified CNVR-harbored genes associated with adaptation to hypoxia (e.g., DCC, MRPS28, GSTCD, MOGAT2, DEXI, CIITA, and SMYD1). Additionally, cluster analysis, based on either individuals or populations, showed that the CNV clustering was divided into two origins, indicating that some yak CNVs are likely to arisen independently in different populations and contribute to population difference. CONCLUSIONS: Collectively, the results of the present study advanced our understanding of CNV as an important type of genomic structural variation in yak, and provide a useful genomic resource to facilitate further research on yak evolution and breeding.


Assuntos
Bovinos/genética , Variações do Número de Cópias de DNA/genética , Variação Genética/genética , Sequenciamento Completo do Genoma/métodos , Animais , Bovinos/classificação , Mapeamento Cromossômico , Cromossomos de Mamíferos/genética , Genética Populacional/métodos , Genômica/métodos , Filogenia , Especificidade da Espécie
13.
Reprod Domest Anim ; 53(5): 1168-1175, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29962058

RESUMO

The yak is one of the most important and economically useful animals for highlanders. The decline in the yak population requires effective measures for the conservation and multiplication of elite germplasm. A standardized protocol will simplify the freezing and warming of yak embryos in straw and facilitate embryo transfer. In this work, we investigated a one-step protocol that uses a stable basal medium, which comprised a warming medium (1.08 M sucrose) and a freezing medium (EFS40). We also assessed the effects of the new transfer method on embryo survival. A total of 145 yak frozen embryos were thawed in a standard medium system. The one-step protocol led to a high recovery percentage (84.93) of yak embryos that survived vitrification and warming. The in vitro survival rates of these embryos significantly different from those of embryos frozen-thawed via the conventional method. The 95 embryos frozen-thawed via our one-step protocol were then implanted in selected recipients. Thirty-six singleton pregnancies were established. In conclusion, the proposed one-step method is a simple, safe, and standardized freezing-thawing protocol that ensures embryo survival and quality under field conditions. This study establishes new possibilities for the widespread use of embryo transfer in yaks.


Assuntos
Blastocisto/fisiologia , Criopreservação/veterinária , Transferência Embrionária/veterinária , Animais , Bovinos , Feminino , Fertilização in vitro/veterinária , Gravidez , Taxa de Gravidez , Vitrificação
14.
Water Sci Technol ; 73(6): 1341-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27003074

RESUMO

Hetao Oasis is located in a typical piedmont alluvial plain bounded by the Langshan Mountain Range in the north, desert in the west, and the Yellow River in the south. Agricultural activities within the oasis significantly impact the hydrological cycle and water quality in downstream locations. The research uses the Soil and Water Assessment Tool (SWAT) for a piedmont plain by defining the watershed boundary as coinciding with the natural mountain ridge, the border between the oasis and the desert, and the Yellow River. The model simulates water discharge with coefficient of determination and a Nash-Sutcliffe model efficiency of 0.78 and 0.62 during model calibration, and 0.75 and 0.69 during model validation, suggesting that delineation of the watershed as carried out in this research is suitable for piedmont plain topography. From the results, the mountains contribute 28.4% to the water discharge at the outlet of the watershed, and water-use efficiency of irrigated water is about 40%, which is consistent with field-based measurements. Methodologies used in delineating watershed boundaries and parameterizing SWAT provide a solid foundation for water balance studies in other regions of the world with similar topography.


Assuntos
Solo/química , Movimentos da Água , Qualidade da Água , Agricultura , China , Ecossistema , Modelos Teóricos , Água , Poluentes Químicos da Água
15.
Int J Cancer ; 135(11): 2612-22, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24740596

RESUMO

This phase II/III, double-blind, randomized trial assessed the efficacy, immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in young Chinese women (ClinicalTrials.gov registration NCT00779766). Women aged 18-25 years from Jiangsu province were randomized (1:1) to receive HPV vaccine (n = 3,026) or Al(OH)3 control (n = 3,025) at months 0, 1 and 6. The primary objective was vaccine efficacy (VE) against HPV-16/18 associated 6-month persistent infection (PI) and/or cervical intraepithelial neoplasia (CIN) 1+. Secondary objectives were VE against virological and clinical endpoints associated with HPV-16/18 and with high-risk HPV types, immunogenicity and safety. Mean follow-up for the according-to-protocol cohort for efficacy (ATP-E) was ∼15 months after the third dose. In the ATP-E (vaccine = 2,889; control = 2,894), for initially HPV DNA negative and seronegative subjects, HPV-16/18 related VE (95% CI) was 94.2% (62.7, 99.9) against 6-month PI and/or CIN1+ and 93.8% (60.2, 99.9) against cytological abnormalities. VE against HPV-16/18 associated CIN1+ and CIN2+ was 100% (-50.4, 100) and 100% (-140.2, 100), respectively (no cases in the vaccine group and 4 CIN1+ and 3 CIN2+ cases in the control group). At Month 7, at least 99.7% of initially seronegative vaccine recipients had seroconverted for HPV-16/18; geometric mean antibody titres (95% CI) were 6,996 (6,212 to 7,880) EU/mL for anti-HPV-16 and 3,309 (2,942 to 3,723) EU/mL for anti-HPV-18. Safety outcomes between groups were generally similar. The HPV-16/18 AS04-adjuvanted vaccine is effective, immunogenic and has a clinically acceptable safety profile in young Chinese women. Prophylactic HPV vaccination has the potential to substantially reduce the burden of cervical cancer in China.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , China , DNA Viral/genética , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Gradação de Tumores , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Resultado do Tratamento , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
16.
Neural Regen Res ; 19(10): 2132-2143, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38488548

RESUMO

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

17.
J Mol Model ; 30(2): 56, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294566

RESUMO

CONTEXT: Two-dimensional materials are a new and promising research field in materials science. This is mainly attributed to their unique photoelectric and chemical properties. In addition to possessing unique optoelectronic and chemical properties, two-dimensional materials also have important application prospects in the field of field-effect devices. Based on density functional theory, the effects of uniaxial strain and equibiaxial strain on the mechanical properties, electronic structure, and optical properties of monolayer h-BN were studied using first principles. The results indicate that compressive strain has a significant impact on the stability of monolayer h-BN. The band gap width of monolayer h-BN decreases with increasing strain, and the optical properties of monolayer h-BN exhibit a relative trend under tensile and compressive strains. The influence of biaxial strain on the mechanical properties, electronic structure, and optical properties of monolayer h-BN is greater than that of uniaxial strain. METHODS: All the calculations were done by the VASP software based on density functional theory. The interaction between atomic nuclei and electrons is described by the projected added wave pseudopotential (PAW), using the generalized gradient approximation (GGA) to exchange the Perdew-Burke-Ernzerhof (PBE) of the functional. To avoid interlayer interactions, a 15-Å vacuum layer was set up. The Brillouin zone selects the Monkhorst-Pack method to generate 9 × 9 × 1 of k-point grid, the cut off energy is set to 500 eV, the energy convergence standard of the system is 1 × 10-5 eV, and the interaction force between atoms is 0.01 eV/Å.

18.
Heliyon ; 10(6): e28068, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533059

RESUMO

In response to the problem of excessive power consumption during the furrowing operation of orchard furrowing fertilizer machines, an optimization experiment of furrowing operation parameters for orchard furrowing fertilizer machine was conducted based on discrete element simulations. This research focused on the impact of furrowing device operation parameters on furrowing power consumption under full machine operating conditions. Firstly, a kinematics analysis of the soil granules during cutting was done. The mathematical model of soil granules through three movement processes of rising, detachment, and falling was established to determine the main factors affecting the power consumption of furrowing. Secondly, in assessing the furrowing power consumption, the stability coefficient of the furrowing depth, and the percentage of soil cover, alongside the key parameters of furrowing depth, forward propulsion velocity, and furrowing blade rotation speed, a comprehensive quadratic orthogonal rotation regression experiment was meticulously conducted. It was established that test metrics and test parameters regress. Finally, the test parameters were comprehensively optimized after analyzing each factor's impact on the test metrics. The orchard furrowing fertilizer machine's optimal operating parameters were determined, and the verification test was performed. According to the field test findings, the forward propulsion velocity was 785 m/h, and the furrowing blade rotation speed was 190 r/min when the furrowing depth was 275 mm. At this point, the furrowing power consumption was 2.39 kW, the soil cover percentage was 69.06%, and the furrowing depth stability coefficient was 95.08%. These results were in line with the requirements of orchard furrowing operation. The findings of the study can be utilized as a guide for structural changes to orchard furrowing equipment and the management of furrowing operation parameters.

19.
Yi Chuan ; 35(2): 175-84, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23448930

RESUMO

To assess the genetic diversity and relationship of the Tibetan yak breeds. The genetic diversity and phylogenies of a total of 480 individual from 11 Tibetan yak groups were analyzed using PCR and multiplex gel electrophoresis of silver staining technology with eight pairs of microsatellite markers.The result showed that these markers were highly polymorphic loci with rich genetic diversity in the Tibetan yak populations.The average polymorphic information content (PIC) in 11 groups of yak were higher than 0.5. The highest HEL13 was 0.8496, and the lowest TGLA57 was 0.7349. Among them, the PICof Dingqing yak was minimum (0.7505), indicating that the group is relatively pure.Sangri Yak had the highest PIC value (0.7949) indicating greater genetic variationwithinthe groups. Among the 11 groups examined, the order of heterozygosity size wasSangri(0.8193)>Jiangda(0.8190)>Sangsang(0.8157)>Baqing(0.8150)>Kangbu(0.8123)> Jiali(0.8087)>Gongbujiangda(0.8054)>Sibu(0.8041)>Leiwuqi(0.8033)>Pali(0.8031)>Dingqing(0.7831). The groups from eastern Tibet had grater genetic diversity than those from Western Tibet, which indicate that Tibet may be one of the cradles of the yak.According to the genetic distance, the cluster relationship constructed with UPGMA and NJ methods showed that 11 yak groups in Tibet could be divided into three forms. In summary,Tibet yak has abundant genetic diversity and the selected microsatellite markers can be used to evaluategenetic diversity of Tibetan yak.


Assuntos
Bovinos/genética , DNA Mitocondrial , Variação Genética , Repetições de Microssatélites , Alelos , Animais , Bovinos/classificação , Evolução Molecular , Frequência do Gene , Loci Gênicos , Genética Populacional , Genótipo , Filogenia , Tibet
20.
Nanomaterials (Basel) ; 13(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36770544

RESUMO

Microbial infections due to bacteria, viruses, and molds are a serious threat to both human life and the health of other organisms. To develop inexpensive, easy-to-prepare, efficient, and portable nano-antibacterial materials, as well as to explore the antibacterial prospects of cationic antibacterial agents, in this work, six different membrane materials were prepared by the electrostatic spinning method and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The materials were tested for antimicrobial properties using a modified AATCC100-200 test method. Under the most suitable spinning conditions, the doping amount of the cationic antimicrobial agent, CTAB, had the greatest influence on the antimicrobial performance. The antimicrobial performance of PCL/PEO/CS/CTAB0.4 was the highest among the prepared materials, with 83.7% effectiveness against S. aureus and 99.9% against E. coli. The antimicrobial performance was found to be stable. In our study, we determined the most suitable spinning ratio to prepare an inexpensive and efficient cationic antimicrobial agent. Biodegradable, high-antimicrobial-activity antimicrobial materials can be applied as films, and this new nanofiber material has shown great potential in wound dressings and as a mask material due to its remarkable antimicrobial efficiency.

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