Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

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.

Single-cell transcriptome analyses reveal critical regulators of spermatogonial stem cell fate transitions.

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.

Single-cell analysis identifies critical regulators of spermatogonial development and differentiation in cattle-yak bulls.

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.

Integrating proximal soil sensing data and environmental variables to enhance the prediction accuracy for soil salinity and sodicity in a region of Xinjiang Province, China.

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.

Comparative proteomic analysis identifies differentially expressed proteins associated with meiotic arrest in cattle-yak hybrids.

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.

Localization and expression of SLX4 in the testis of sterile male cattle-yak.

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.

Testis transcriptome profiling identified lncRNAs involved in spermatogenic arrest of cattleyak.

Cattleyaks are the crossbred offspring between cattle and yaks, exhibiting the prominent adaptability to the harsh environment as yaks and much higher growth performances than yaks around Qinghai-Tibet plateau. Unfortunately, cattleyak cannot be effectively used in yak breeding due to its male infertility resulted from spermatogenic arrest. In this study, we performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine the expression profiles of long noncoding RNA (lncRNA) from cattleyak and yak testis. A total of 604 differentially expressed (DE) lncRNAs (135 upregulated and 469 downregulated) were identified in cattleyak with respect to yak. Through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we identified several DE lncRNAs regulating the mitotic cell cycle processes by targeting the genes significantly associated with the mitotic cell cycle checkpoint and DNA damage checkpoint term and also significantly involved in p53 signaling pathway, mismatch repair and homologous recombination pathway (P < 0.05). The reverse transcription PCR (RT-PCR) and quantitative Real-Time PCR (qRT-PCR) analysis of the randomly selected fourteen DE lncRNAs and the seven target genes validated the RNA-seq data and their true expressions during spermatogenesis in vivo. Molecular cloning and sequencing indicated that the testis lncRNAs NONBTAT012170 and NONBTAT010258 presented higher similarity among different cattleyak and yak individuals. The downregulation of these target genes in cattleyak contributed to the abnormal DNA replication and spermatogenic arrest during the S phase of mitotic cell cycle. This study provided a novel insight into lncRNA expression profile changes associated with spermatogenic arrest of cattleyak.

Comparative RNA-Seq Analysis of Differentially Expressed Genes in the Epididymides of Yak and Cattleyak.

BACKGROUND: Cattleyak are the Fl hybrids between (♀) yak (Bos grunniens) and (♂) cattle (Bos taurus). Cattleyak exhibit higher capability in adaptability to a harsh environment and display much higher performances in production than the yak and cattle. The cattleyak, however, are females fertile but males sterile. All previous studies greatly focused on testes tissues to study the mechanism of male infer-tility in cattleyak. However, so far, no transcriptomic study has been conducted on the epididymides of yak and cattleyak. OBJECTIVE: Our objective was to perform comparative transcriptome analysis between the epididymides of yak and cattleyak and predict the etiology of male infertility in cattleyak.Methods: We performed comparative transcriptome profiles analysis by mRNA sequencing in the epidi-dymides of yak and cattleyak. RESULTS: In total 3008 differentially expressed genes (DEGs) were identified in cattleyak, out of which 1645 DEGs were up-regulated and 1363 DEGs were down-regulated. Thirteen DEGs were validated by quantitative real-time PCR. DEGs included certain genes that were associated with spermatozoal matura-tion, motility, male fertility, water and ion channels, and beta-defensins. LCN9, SPINT4, CES5A, CD52, CST11, SERPINA1, CTSK, FABP4, CCR5, GRIA2, ENTPD3, LOC523530 and DEFB129, DEFB128, DEFB127, DEFB126, DEFB124, DEFB122A, DEFB122, DEFB119 were all downregu-lated, whereas NRIP1 and TMEM212 among top 30 DEGs were upregulated. Furthermore, protein processing in endoplasmic reticulum pathway was ranked at top-listed three significantly enriched KEGG pathways that as a consequence of abnormal expression of ER-associated genes in the entire ER protein processing pathway might have been disrupted in male cattleyak which resulted in the down-regulation of several important genes. All the DEGs enriched in this pathway were downregulated ex-cept NEF. CONCLUSION: Taken together, our findings revealed that there were marked differences in the epididymal transcriptomic profiles of yak and cattleyak. The DEGs were involved in spermatozoal maturation, mo-tility, male fertility, water and ion channels, and beta-defensins. Abnormal expression of ER-associated genes in the entire ER protein processing pathway may have disrupted protein processing pathway in male cattleyak resulting in the downregulation of several important genes involved in sperm maturation, motility and defense.

Electrochemically "writing" graphene from graphene oxide.

A novel approach of patterning graphene on conductive surfaces based on local electrochemical reduction of graphene oxide is reported. Graphene is "written" from typical graphene oxide dispersion by applying negative potential on conductive surfaces vs. a micrometer-sized counter electrode "pen" with scanning electrochemical microscopy (SECM). Micrometer scaled patterns are successfully generated on gold and stainless steel surfaces.

[Association between sleep disorders and vestibular vertigo].

Sleep disorders have a high comorbidity rate with vestibular diseases. The results of some small sample clinical studies have confirmed the effect of sleep deprivation on vestibular function. However, the mechanism of the effect of sleep disorder on vestibular system is still unclear. This article analyzes the possible mechanism of the effect of sleep disorders on vestibular function from the aspects of neuroanatomy and neurotransmitters, and summarizes the relationship between sleep disorder and benign paroxysmal positional vertigo, Meniere's disease, vestibular migraine and other diseases.

Association between dietary niacin intake and Helicobacter pylori seropositivity in US adults: A cross-sectional study.

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.

Association of advanced lung cancer inflammation index with all-cause and cardiovascular mortality in US patients with rheumatoid arthritis.

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.

Differential Associations of Erythrocyte Membrane Saturated Fatty Acids with Glycemic and Lipid Metabolic Markers in a Chinese Population: A Cross-Sectional Study.

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.

Recent Progress in the Application of Ion Beam Technology in the Modification and Fabrication of Nanostructured Energy Materials.

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.

Graphene-based electrochemical sensors.

Graphene, one kind of emerging carbon nanomaterial, has attracted increasing attention recently. Due to its fascinating physical and electrochemical properties, graphene as a promising electrode material has been widely used in electrochemical sensing applications. In this review, different approaches for the fabrication of graphene and the preparation of graphene-modified electrodes for electrochemical sensors are introduced. Moreover, recent research results on different graphene-based materials as an electrochemical platform for the detection of various biomolecules and chemicals are reviewed and compared. More electrochemical studies on this novel material should show up in the near future.

Impact of global urban expansion on the terrestrial vegetation carbon sequestration capacity.

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.

Transcriptome analysis reveals dysregulated gene expression networks in Sertoli cells of cattle-yak hybrids.

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.

Mechanism of angiotensin-converting enzyme inhibitors in the treatment of dilated cardiomyopathy based on a protein interaction network and molecular docking.

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.

Single-cell transcriptomic characterization of sheep conceptus elongation and implantation.

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.