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OBJECTIVES: This study delves into the association between dietary niacin intake and Helicobacter pylori seropositivity, a topic gaining prominence in academic discourse. However, the precise role of Niacin in the development and progression of Helicobacter pylori seropositivity remains inadequately understood. Thus, this research aims to investigate the connections between H. pylori seropositivity and dietary niacin intake using a nationally representative sample of adults. METHODS: A cross-sectional analysis encompassed 4,000 participants from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 1999 and 2000, all aged 20 years or older. The study employed the generalized additive model (GAM) and multivariate logistic regression to explore the potential relationship between niacin intake and Helicobacter pylori seropositivity. Subgroup analyses were performed based on gender, age, diabetes, hypertension, and hyperlipemia. RESULTS: Analyzing cross-sectional data from NHANES 1999-2000 involving individuals aged 20 years and above revealed that out of 4,000 participants, 1,842 tested positive for H. pylori via serology. Multivariate analyses unveiled a significant inverse correlation between niacin intake and H. pylori seropositivity. Adjusted odds ratios (ORs) for dietary niacin intake in quartiles Q2 (13.31-19.26 mg/d), Q3 (19.27-27.42 mg/d), and Q4 (>27.42 mg/d) compared to Q1 (<13.31 mg/d) were 0.83 (95% CI: 0.69-1.01), 0.74 (95% CI: 0.61-0.90), and 0.66 (95% CI: 0.54-0.81), respectively. Moreover, a nonlinear L-shaped relationship (P = 0.022) emerged between niacin intake and H. pylori seropositivity, indicating minimal risk of H. pylori infection at approximately 44.69 mg of niacin per day in the diet. CONCLUSION: This study suggests a potential link between increased dietary niacin intake and reduced prevalence of Helicobacter pylori seropositivity. This correlation is bolstered by plausible mechanisms involving immunomodulatory function, mitochondrial dysfunction, and cellular oxidative stress.
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Dieta , Infecções por Helicobacter , Helicobacter pylori , Niacina , Inquéritos Nutricionais , Humanos , Masculino , Niacina/administração & dosagem , Adulto , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Infecções por Helicobacter/epidemiologia , Estados Unidos/epidemiologia , Idoso , Adulto JovemRESUMO
Introduction: As a systemic autoimmune disorder, the prognosis of rheumatoid arthritis (RA) is intricately linked to inflammation. This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a comprehensive indicator of inflammation combined with nutritional status, and all-cause and cardiovascular mortality among patients diagnosed with RA. Methods: The 2,305 RA patients from NHANES (2001-2018) included in the analysis were categorized into three groups according to ALI tertiles. Weighted Kaplan-Meier and multivariate COX regression analyses evaluated the relationship between ALI and mortality. The time-dependent characteristic curve (ROC) was used to assess the prediction accuracy of ALI. Results: During a median follow-up of 7.92 years, 591 participants died from all causes, including 197 from cardiovascular diseases. Increased ALI was associated with a decreased probability of death. The full COX model revealed lower all-cause mortality hazard risks in the T2 (HR: 0.67, 95%CI: 0.54-0.83) and T3 (HR: 0.47 95%CI: 0.33-0.67, p for tend <0.001) groups compared to T1, and the risk of cardiovascular mortality was also lower in the groups of T2 (HR: 0.47, 95%CI: 0.31-0.70) and T3 (HR: 0.34, 95%CI: 0.19-0.62, p for trend <0.001). Furthermore, the ROC analysis underscored the strong predictive capability of ALI (AUC for 1-year all-cause and cardiovascular mortality were 0.73 and 0.79, respectively). Conclusion: This cohort study demonstrated the higher accuracy of ALI in predicting mortality in RA patients, highlighting the important clinical value of ALI in risk assessment and prognosis evaluation.
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Soil salinization and sodification, the primary causes of land degradation and desertification in arid and semi-arid regions, demand effective monitoring for sustainable land management. This study explores the utility of partial least square (PLS) latent variables (LVs) derived from visible and near-infrared (Vis-NIR) spectroscopy, combined with remote sensing (RS) and auxiliary variables, to predict electrical conductivity (EC) and sodium absorption ratio (SAR) in northern Xinjiang, China. Using 90 soil samples from the Karamay district, machine learning models (Random Forest, Support Vector Regression, Cubist) were tested in four scenarios. Modeling results showed that RS and Land use alone were unreliable predictors, but the addition of topographic attributes significantly improved the prediction accuracy for both EC and SAR. The incorporation of PLS LVs derived from Vis-NIR spectroscopy led to the highest performance by the Random Forest model for EC (CCC = 0.83, R2 = 0.80, nRMSE = 0.48, RPD = 2.12) and SAR (CCC = 0.78, R2 = 0.74, nRMSE = 0.58, RPD = 2.25). The variable importance analysis identified PLS LVs, certain topographic attributes (e.g., valley depth, elevation, channel network base level, diffuse insolation), and specific RS data (i.e., polarization index of VV + VH) as the most influential predictors in the study area. This study affirms the efficiency of Vis-NIR data for digital soil mapping, offering a cost-effective solution. In conclusion, the integration of proximal soil sensing techniques and highly relevant topographic attributes with the RF model has the potential to yield a reliable spatial model for mapping soil EC and SAR. This integrated approach allows for the delineation of hazardous zones, which in turn enables the consideration of best management practices and contributes to the reduction of the risk of degradation in salt-affected and sodicity-affected soils.
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Salinidade , Solo , Solo/química , China , Monitoramento Ambiental/métodos , Tecnologia de Sensoriamento Remoto , Análise dos Mínimos QuadradosRESUMO
Mounting evidence indicates a complex link between circulating saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk factors, but research on erythrocyte membrane SFA associations with metabolic markers remains limited. Our study sought to investigate the correlations between erythrocyte membrane SFAs and key metabolic markers within glycemic and lipid metabolism in a Chinese population of 798 residents aged 41 to 71 from Guangzhou. Using gas chromatography-mass spectrometry, we assessed the erythrocyte membrane saturated fatty acid profile and performed multiple linear regression to evaluate the relationship between different SFA subtypes and metabolic markers. Our findings revealed that the odd-chain SFA group (C15:0 + C17:0) exhibited negative associations with fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and triglycerides (TG). Conversely, the very-long-chain SFA group (C20:0 + C22:0 + C23:0 + C24:0) exhibited positive associations with fasting insulins (FINS), HOMA-IR, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Furthermore, there was no evidence supporting an association between the even-chain group (C14:0 + C16:0 + C18:0) and metabolic markers. Our findings suggest that different subtypes of SFAs have diverse effects on glycemic and lipid metabolic markers, with odd-chain SFAs associated with a lower metabolic risk. However, the results concerning the correlations between even-chain SFAs and very-long-chain SFAs with markers of glycemic and lipid metabolism pathways are confusing, highlighting the necessity for further exploration and investigation.
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Biomarcadores , Glicemia , Membrana Eritrocítica , Ácidos Graxos , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Ácidos Graxos/sangue , Feminino , Idoso , Glicemia/metabolismo , Biomarcadores/sangue , Membrana Eritrocítica/metabolismo , Adulto , China , Resistência à Insulina , Metabolismo dos Lipídeos/fisiologia , Povo Asiático , Triglicerídeos/sangue , Insulina/sangue , População do Leste AsiáticoRESUMO
Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.
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Infertilidade Masculina , Células Intersticiais do Testículo , Fator de Transcrição 1 de Leucemia de Células Pré-B , Testículo , Testosterona , Animais , Masculino , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Fator de Transcrição 1 de Leucemia de Células Pré-B/metabolismo , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Camundongos , Testosterona/metabolismo , Testículo/metabolismo , Testículo/patologia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Infertilidade Masculina/metabolismo , Diferenciação Celular/genética , Espermatogênese/genética , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable to or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.
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Diferenciação Celular , Análise de Célula Única , Espermatogênese , Espermatogônias , Animais , Masculino , Bovinos , Espermatogônias/citologia , Espermatogênese/genética , Testículo/citologia , MeioseRESUMO
BACKGROUND: Spermatogonial stem cells (SSCs) are the foundation cells for continual spermatogenesis and germline regeneration in mammals. SSC activities reside in the undifferentiated spermatogonial population, and currently, the molecular identities of SSCs and their committed progenitors remain unclear. RESULTS: We performed single-cell transcriptome analysis on isolated undifferentiated spermatogonia from mice to decipher the molecular signatures of SSC fate transitions. Through comprehensive analysis, we delineated the developmental trajectory and identified candidate transcription factors (TFs) involved in the fate transitions of SSCs and their progenitors in distinct states. Specifically, we characterized the Asingle spermatogonial subtype marked by the expression of Eomes. Eomes+ cells contained enriched transplantable SSCs, and more than 90% of the cells remained in the quiescent state. Conditional deletion of Eomes in the germline did not impact steady-state spermatogenesis but enhanced SSC regeneration. Forced expression of Eomes in spermatogenic cells disrupted spermatogenesis mainly by affecting the cell cycle progression of undifferentiated spermatogonia. After injury, Eomes+ cells re-enter the cell cycle and divide to expand the SSC pool. Eomes+ cells consisted of 7 different subsets of cells at single-cell resolution, and genes enriched in glycolysis/gluconeogenesis and the PI3/Akt signaling pathway participated in the SSC regeneration process. CONCLUSIONS: In this study, we explored the molecular characteristics and critical regulators of subpopulations of undifferentiated spermatogonia. The findings of the present study described a quiescent SSC subpopulation, Eomes+ spermatogonia, and provided a dynamic transcriptional map of SSC fate determination.
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Análise da Expressão Gênica de Célula Única , Testículo , Masculino , Animais , Camundongos , Testículo/metabolismo , Espermatogônias , Espermatogênese/genética , Células-Tronco , Diferenciação Celular/genética , Mamíferos/genéticaRESUMO
The development of green, renewable energy conversion and storage systems is an urgent task to address the energy crisis and environmental issues in the future. To achieve high performance, stable, and safe operation of energy conversion and storage systems, energy materials need to be modified and fabricated through rationalization. Among various modification and fabrication strategies, ion beam technology has been widely used to introduce various defects/dopants into energy materials and fabricate various nanostructures, where the structure, composition, and property of prefabricated materials can be further accurately tailored to achieve better performance. In this paper, we review the recent progress in the application of ion beam technology in material modification and fabrication, focusing on nanostructured energy materials for energy conversion and storage including photo- (electro-) water splitting, batteries (solar cells, fuel cells, and metal-ion batteries), supercapacitors, thermoelectrics, and hydrogen storage. This review first provides a brief basic overview of ion beam technology and describes the classification and technological advantages of ion beam technology in the modification and fabrication of materials. Then, modification of energy materials by ion beams is reviewed mainly concerning doping and defect introduction. Fabrication of energy materials is also discussed mainly in terms of heterojunctions, nanoparticles, nanocavities, and other nanostructures. In particular, we emphasize the advantages of ion beam technology in improving the performance of energy materials. Finally, we point out our understanding of challenges and future perspectives in applying ion beam technology for the modification and fabrication of energy materials.
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Reducing soil salinization of croplands with optimized irrigation and water management is essential to achieve land degradation neutralization (LDN). The effectiveness and sustainability of various irrigation and water management measures to reduce basin-scale salinization remain uncertain. Here we used remote sensing to estimate the soil salinity of arid croplands from 1984 to 2021. We then use Bayesian network analysis to compare the spatial-temporal response of salinity to water management, including various irrigation and drainage methods, in ten large arid river basins: Nile, Tigris-Euphrates, Indus, Tarim, Amu, Ili, Syr, Junggar, Colorado, and San Joaquin. In basins at more advanced phases of development, managers implemented drip and groundwater irrigation and thus effectively controlled salinity by lowering groundwater levels. For the remaining basins using conventional flood irrigation, economic development and policies are crucial for establishing a virtuous circle of "improving irrigation systems, reducing salinity, and increasing agricultural incomes" which is necessary to achieve LDN.
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Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.
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Background: Dilated cardiomyopathy (DCM) is a severe manifestation or intermediate stage of cardiovascular disease progression with a significantly poor prognosis. Based on a protein interaction network and molecular docking, the present study determined the genes and mechanism of action of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of DCM, providing a direction for future studies on ACEI drugs for DCM. Methods: This is a retrospective study. DCM samples and healthy controls were downloaded from the GSE42955 dataset, and the targets of the potential active ingredients were obtained from PubChem. Hub genes in ACEIs were analyzed by constructing network models and a protein-protein interaction (PPI) network using the STRING database and Cytoscape software. Molecular docking was performed using Autodock vina software. Results: Twelve DCM samples and five control samples were finally included. A total of 62 intersected genes were obtained by intersecting the differentially expressed genes with six ACEI target genes. PPI analysis identified 15 intersecting hub genes from these 62 genes. Enrichment analysis showed that the hub genes were associated with T helper type 17 (Th17) cell differentiation as well as the nuclear factor kappa-B (NF-kappa B), interleukin 17 (IL-17), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt), and Toll-like receptor signaling pathways. Molecular docking indicated that the compound Benazepril to produce favorable interactions with TNF proteins with a relatively higher score (-8.3). Conclusions: This study primarily revealed that the preventive and curative effects of ACEI treatment on DCM could be realized through multiple targets and pathways, and its mechanism of action is related to genes such as TNF, vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), Cyclin D1 (CCND1), and AKT serine/threonine kinase 1 (AKT1), with immune- and inflammation-related signaling pathways involvement.
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Cattle-yak, the interspecific hybrid between yak and taurine cattle, exhibits male-specific sterility. Massive loss of spermatogenic cells, especially spermatocytes, results in azoospermia in these animals. Currently, the mechanisms underlying meiosis block and defects in spermatocyte development remain elusive. The present study was designed to investigate the differences in the protein composition of spermatocytes isolated from 12-month-old yak and cattle-yak testes. Histological analysis confirmed that spermatocytes were the most advanced germ cells in the testes of yak and cattle-yak at this developmental stage. Comparative proteomic analysis identified a total of 452 differentially abundant proteins (DAPs) in the fluorescence-activated cell sorting (FACS) isolated spermatocytes from cattle-yak and yak. A total of 291 proteins were only present in yak spermatocytes. Gene Ontology analysis revealed that the downregulated DAPs were mostly enriched in the cellular response to DNA damage stimulus and double-strand breaks (DSBs) repair via break-induced replication, while the proteins specific for yak were related to cell division and cycle, spermatogenesis, and negative regulation of the extrinsic apoptotic signaling pathway. Ultimately, these DAPs were related to the critical process for spermatocyte meiotic events, including DSBs, homologous recombination, synapsis, crossover formation, and germ cell apoptosis. The database composed of proteins associated with spermatogenesis, including KPNA2, HTATSF1, TRIP12, STIP1, LZTFL1, LARP7, MTCH2, STK31, ROMO1, CDK5AP2, DNMT1, RBM44, and CHRAC1, is the focus of further research on male hybrid sterility. In total, these results provide insight into the molecular mechanisms underlying failed meiotic processes and male infertility in cattle-yak.
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Infertilidade Masculina , Proteômica , Animais , Humanos , Bovinos , Masculino , Testículo/metabolismo , Espermatogênese/genética , Infertilidade Masculina/genética , Infertilidade Masculina/veterinária , Infertilidade Masculina/patologia , Espermatócitos/metabolismo , Proteínas de Ligação a DNA/genética , Nucleoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Transporte/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Cattle-yak, the hybrid offspring of yak (Bos grunniens) and cattle (Bos taurus), serves as a unique model to dissect the molecular mechanisms underlying reproductive isolation. While female cattle-yaks are fertile, the males are completely sterile due to spermatogenic arrest at the meiosis stage and massive germ cell apoptosis. Interestingly, meiotic defects are partially rescued in the testes of backcrossed offspring. The genetic basis of meiotic defects in male cattle-yak remains unclear. Structure-specific endonuclease subunit (SLX4) participates in meiotic double-strand break (DSB) formation in mice, and its deletion results in defects in spermatogenesis. In the present study, we examined the expression patterns of SLX4 in the testes of yak, cattle-yak, and backcrossed offspring to investigate its potential roles in hybrid sterility. The results showed that the relative abundances of SLX4 mRNA and protein were significantly reduced in the testis of cattle-yak. The results of immunohistochemistry revealed that SLX4 was predominately expressed in spermatogonia and spermatocytes. Chromosome spreading experiments showed that SLX4 was significantly decreased in the pachytene spermatocytes of cattle-yak compared with yak and backcrossed offspring. These findings suggest that SLX4 expression was dysregulated in the testis of cattle-yak, potentially resulting in the failure of crossover formation and collapses of meiosis in hybrid males.
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Doenças dos Bovinos , Infertilidade Masculina , Animais , Bovinos , Feminino , Masculino , Camundongos , Doenças dos Bovinos/metabolismo , Infertilidade Masculina/veterinária , Espermatócitos , Espermatogênese/genética , Espermatogônias , Testículo/metabolismo , Recombinases/metabolismoRESUMO
Cattle-yak, the hybrid offspring of yak and taurine cattle, exhibits male sterility with normal female fertility. Spermatogenesis is arrested in adult cattle-yak, and apoptosis is elevated in spermatogenic cells. Currently, the mechanisms underlying these defects remain elusive. Sertoli cells are the only somatic cells that directly interact with spermatogenic cells in the seminiferous tubules and play essential roles in spermatogenesis. The present study was designed to investigate gene expression signatures and potential roles of Sertoli cells in hybrid sterility in cattle-yak. Immunohistochemical analysis showed that the 5 mC and 5hmC signals in Sertoli cells of cattle-yaks were significantly different from those of age-matched yaks (P < 0.05). Transcriptome profiling of isolated Sertoli cells identified 402 differentially expressed genes (DEGs) between cattle-yaks and yaks. Notably, niche factor glial cell derived neurotrophic factor (GDNF) was upregulated, and genes involved in retinoic acid (RA) biogenesis were changed in Sertoli cells of cattle-yak, suggesting possible impairments of spermatogonial fate decisions. Further studies showed that the numbers of proliferative gonocytes and undifferentiated spermatogonia in cattle-yak were significantly higher than those in yak (P < 0.01). Exogenous GDNF significantly promoted the proliferation of UCHL1-positive spermatogonia in yaks. Therefore, we concluded that altered GDNF expression and RA signaling impacted the fate decisions of undifferentiated spermatogonia in cattle-yak. Together, these findings highlight the role of Sertoli cells and their derived factors in hybrid sterility.
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Doenças dos Bovinos , Infertilidade Masculina , Feminino , Bovinos/genética , Masculino , Animais , Células de Sertoli/metabolismo , Testículo/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Espermatogênese/genética , Espermatogônias/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/veterinária , Infertilidade Masculina/metabolismo , Perfilação da Expressão Gênica/veterinária , Transcriptoma , Doenças dos Bovinos/metabolismoRESUMO
Continuous urban expansion has a negative impact on the potential of terrestrial vegetation. Till now, the mechanism of such impact remains unclear, and there have been no systematic investigations. In this study, we design a theoretical framework by laterally bridging urban boundaries to explain the distress of regional disparities and longitudinally quantify the impacts of urban expansion on net ecosystem productivity (NEP). The findings demonstrate that global urban expanded by 37.60 × 104 km2 during 1990-2017, which is one of the causes of vegetation carbon loss. Meanwhile, certain climatic changes (e.g., rising temperature, rising CO2, and nitrogen deposition) caused by urban expansion indirectly boosted vegetation carbon sequestration potential through photosynthetic enhancement. The direct decrease in NEP due to the urban expansion (occupying 0.25 % of the Earth's land area) offsets the 1.79 % increase due to the indirect impact. Our findings contribute to a better understanding of the uncertainty associated with urban expansion towards carbon neutrality and provide a scientific reference for sustainable urban development worldwide.
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Sertoli cells play indispensable roles in spermatogenesis by providing the advanced germ cells with structural, nutritional, and regulatory support. Lactate is regarded as an essential Sertoli-cell-derived energy metabolite that nurses various types of spermatogenic cells; however, this assumption has not been tested using genetic approaches. Here, we have reported that the depletion of lactate production in Sertoli cells by conditionally deleting lactate dehydrogenase A (Ldha) greatly affected spermatogenesis. Ldha deletion in Sertoli cells significantly reduced the lactate production and resulted in severe defects in spermatogenesis. Spermatogonia and spermatocytes did not show even mild impairments, but the spermiogenesis of Ldha conditional knockout males was severely disrupted. Further analysis revealed that 2456 metabolites were altered in the sperm of the knockout animals, and specifically, lipid metabolism was dysregulated, including choline, oleic acid, and myristic acid. Surprisingly, choline supplementation completely rescued the spermiogenesis disorder that was caused by the loss of Ldha activities. Collectively, these data have demonstrated that the interruption of Sertoli-cell-derived lactate impacted sperm development through a choline-mediated mechanism. The outcomes of these findings have revealed a novel function of lactate in spermatogenesis and have therapeutic applications in treating human infertility.
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Wild yak (Bos mutus) and domestic yak (Bos grunniens) are adapted to high altitude environment and have ecological, economic, and cultural significances on the Qinghai-Tibetan Plateau (QTP). Currently, the genetic and cellular bases underlying adaptations of yak to extreme conditions remains elusive. In the present study, we assembled two chromosome-level genomes, one each for wild yak and domestic yak, and screened structural variants (SVs) through the long-read data of yak and taurine cattle. The results revealed that 6733 genes contained high-FST SVs. 127 genes carrying special type of SVs were differentially expressed in lungs of the taurine cattle and yak. We then constructed the first single-cell gene expression atlas of yak and taurine cattle lung tissues and identified a yak-specific endothelial cell subtype. By integrating SVs and single-cell transcriptome data, we revealed that the endothelial cells expressed the highest proportion of marker genes carrying high-FST SVs in taurine cattle lungs. Furthermore, we identified pathways which were related to the medial thickness and formation of elastic fibers in yak lungs. These findings provide new insights into the high-altitude adaptation of yak and have important implications for understanding the physiological and pathological responses of large mammals and humans to hypoxia.
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Células Endoteliais , Genoma , Aclimatação/genética , Animais , Bovinos , Humanos , Mamíferos/genética , RNA , Transcriptoma/genéticaRESUMO
DNA cytosine methylation modification in the germline is of particular importance since it is a highly heritable epigenetic mark. Although cytosine methylation has been analyzed at the genome-scale for several mammalian species, our knowledge of DNA methylation patterns and the mechanisms underlying male hybrid sterility is still limited in domestic animals such as cattleyak. Here we for the first time show the genome-wide and single-base resolution landscape of methylcytosines (mC) in the primary spermatocyte (PSC) genome of yak with normal spermatogenesis and the inter-specific hybrid cattleyak with male infertility. A comparative investigation revealed that widespread differences are observed in the composition and patterning of DNA cytosine methylation between the two methylomes. Global CG or non-CG DNA methylation levels, as well as the number of mC sites, are increased in cattleyak compared to yak. Notably, the DNA methylome in cattleyak PSC exhibits promoter hypermethylation of meiosis-specific genes and piRNA pathway genes with respect to yak. Furthermore, major retrotransposonson classes are predominantly hypermethylated in cattleyak while those are fully hypomethylated in yak. KEGG pathway enrichment indicates Rap1 signaling and MAPK pathways may play potential roles in the spermatogenic arrest of cattleyak. Our present study not only provides valuable insights into distinct features of the cattleyak PSC methylome but also paves the way toward elucidating the complex, yet highly coordinated epigenetic modification during male germline development for inter-specific hybrid animals.
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Epigenoma , Infertilidade Masculina , Animais , Citosina , DNA/metabolismo , Metilação de DNA , Epigênese Genética , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Infertilidade Masculina/veterinária , Masculino , Mamíferos , Espermatócitos/metabolismoRESUMO
The potential impact of natural factors on the runoff of intermittent rivers and ephemeral streams (IRES) has been largely ignored in the Tarim Basin, China. A representative example is the Keriya River. To quantify the long-term dynamic variations in lower reach surface runoff of IRES, river length, defined as the distance between a selected fix point along the perennial river segment to its dynamic, ephemeral end, was used as an indicator. Using a total of 272 remote sensing images, we digitized and measured the distance (river length) between the center of Yutian County and the river's end point on each image, and then calculated monthly inter-annual and intra-annual variations in length of the lower Keriya River from 2000 to 2019. Hydrometeorological data were combined with descriptors of anthropogenic disturbances to assess the relative influence of natural factors and anthropogenic disturbances on lower reach river runoff. The results showed that intra-annual variations in river length fluctuated seasonally, with the minimum value occurring in June; two main peaks occurred in March and August. The minimum June value in river length was closely linked to an increase in agricultural water demand and a decrease in upper reach runoff. The August peak in river length was related to the peak values in upper reach runoff and agricultural water demand; upper reach runoff made a significant contribution because the former was about 20% more than the latter in summer. The March peak corresponded to elevated lower reach groundwater levels and to the melting of ice along river channels. Inter-annual variations in river length were due to inter-annual variations in upper reach runoff and middle reach agricultural water use which increased slightly during the study period. Inter-annual variations in frequency and amplitude of the fluctuations in river length were mainly controlled by changes in upper reach runoff. The minimum in river length in 2009 was consistent with the low in upper reach runoff of the Keriya River and other rivers in the Tarim Basin. The most significant factors controlling variations in river length are natural in origin.