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Abstract Background Circular RNAs (circRNAs) function as essential regulatory elements with pivotal roles in various biological processes. However, their expression profiles and functional regulation during the differentiation of goat myoblasts have not been thoroughly explored. This study conducts an analysis of circRNA expression profiles during the proliferation phase (cultured in growth medium, GM) and differentiation phase (cultured in differentiation medium, DM1/DM5) of skeletal muscle satellite cells (MuSCs) in goats. Results A total of 2,094 circRNAs were identified, among which 84 were differentially expressed as determined by pairwise comparisons across three distinct groups. Validation of the expression levels of six randomly selected circRNAs was performed using reverse transcription PCR (RT-PCR) and quantitative RT-PCR (qRT-PCR), with confirmation of their back-splicing junction sites. Enrichment analysis of the host genes associated with differentially expressed circRNAs (DEcircRNAs) indicated significant involvement in biological processes such as muscle contraction, muscle hypertrophy, and muscle tissue development. Additionally, these host genes were implicated in key signaling pathways, including Hippo, TGF-beta, and MAPK pathways. Subsequently, employing Cytoscape, we developed a circRNA-miRNA interaction network to elucidate the complex regulatory mechanisms underlying goat muscle development, encompassing 21 circRNAs and 47 miRNAs. Functional assays demonstrated that circTGFβ2 enhances myogenic differentiation in goats, potentially through a miRNA sponge mechanism. Conclusion In conclusion, we identified the genome-wide expression profiles of circRNAs in goat MuSCs during both proliferation and differentiation phases, and established that circTGFβ2 plays a role in the regulation of myogenesis. This study offers a significant resource for the advanced exploration of the biological functions and mechanisms of circRNAs in the myogenesis of goats.

Abstract Background Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. Materials and methods In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. Results MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90–1.06; MR Egger, OR = 0.94, 95%CI = 0.84–1.05; Weighted median, OR = 0.93, 95%CI = 0.82–1.06; Weighted mode, OR = 0.93, 95%CI = 0.84–1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D’s protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). Conclusions This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

BackgroundRNA editing, especially A-to-I editing sites, is a common RNA modification critical for stem cell differentiation, muscle development, and disease occurrence. Unveiling comprehensive RNA A-to-I editing events associated with myogenesis of the skeletal muscle satellite cells (MuSCs) is essential for extending our knowledge of the mechanism underpinning muscle development.ResultsA total of 9,632 RNA editing sites (RESs) were screened in the myoblasts (GM), myocytes (DM1), and myotubes (DM5) samples. Among these sites, 4,559 A-to-I edits were classified and further analyzed. There were 3,266 A-to-I sites in the protein-coding region, out of which 113 missense sites recoded protein. Notably, five A-to-I sites in the 3′ UTR of four genes (TRAF6, NALF1, SLC38A1, ENSCHIG00000019092) altered their targeted miRNAs. Furthermore, a total of 370 A-to-I sites with different editing levels were detected, including FBN1, MYH10, GSK3B, CSNK1D, and PRKACB genes. These genes were predominantly enriched in the cytoskeleton in muscle cells, the hippo signaling pathway, and the tight junction. Furthermore, we identified 14 hub genes (TUFM, GSK3B, JAK2, RPSA, YARS1, CDH2, PRKACB, RUNX1, NOTCH2, CDC23, VCP, FBN1, RARS1, MEF2C) that potentially related to muscle development. Additionally, 123 stage-specific A-to-I editing sites were identified, with 43 sites in GM, 25 in DM1, and 55 in DM5 samples. These stage-specific edited genes significantly enriched essential biological pathways, including the cell cycle, oocyte meiosis, motor proteins, and hedgehog signaling pathway.ConclusionWe systematically identified the RNA editing events in proliferating and differentiating goat MuSCs, which was crucial for expanding our understanding of the regulatory mechanisms of muscle development.

Understanding the colonization and change patterns of gut microbiota is pivotal for comprehending host health. As a newly cultured breed, the studies on the gut microbiota of Tianfu goats remain limited. This study aimed to address this gap by analyzing the microbial composition and colonization patterns of fecal samples collected from goat kids from birth to weaning. Fecal samples were collected on days 0, 7, 14, 21, 28, 35, 42, 49, 53, 55, 57, and 64, and the changes and colonization patterns of microorganisms were analyzed through high-throughput 16S rRNA sequencing. The results showed that the abundance of fecal microbiota in goat kids gradually increased over time, followed by a decrease after weaning and stabilization, with reduced individual differences. The colonization of fecal microorganisms mainly presented three different stages: days 0–14, days 21–49, and days 53–64. During the suckling period, the relative abundance of Proteobacteria (72.34%) was the highest, followed by Firmicutes (21.66%). From 21 days old, the microbiota in goat kids gradually to be diverse, with Lachnospiraceae and Ruminococcaceae being dominant. During post-weaning, Ruminococcaceae (30.98–33.34%) was becoming prominence which helpful for cellulose decomposition. LEfSe analyzed three important time points (d0 vs. d7, d7 vs. d14, d49 vs. d53, LDA score > 4 and p

The clearance of apoptotic cell debris, containing professional phagocytosis and non-professional phagocytosis, is essential for maintaining the homeostasis of healthy tissues. Here, we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque. Single-cell RNA sequencing (RNA-seq) has revealed a unique endothelial cell subpopulation in atherosclerosis, which was strongly associated with vascular injury-related pathways. Moreover, integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1 (SR-B1) was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances. Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis. Furthermore, SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta. Overall, this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.

Abstract Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its “year-round estrus and multiple births” and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep’s high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (F ST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, F ST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.

Abstract Harmful components in cigarette smoke, such as nicotine, tar, and organic particulate matter, are the primary culprits behind lung diseases. While conventional filter materials based on cellulose, carbon, and molecular sieves exhibit commendable filtration capabilities, their high cost restricts their widespread applications. Based on this, the authors aim to prepare PET‐based filter materials with good adsorption properties through a simple surface functionalisation strategy. The adsorption performance of the PET‐based non‐woven fabric was enhanced by the introduction of sodium alginate (SA). The gas adsorption experiments results reveal that SA‐modified PET (SA‐PET) exhibits significantly improved filtration efficiency for nicotine, tar, and total particulate matter—increasing by 27.1%, 26.2%, and 21.3%, respectively. Moreover, SA‐PET exhibits more odour control ability than traditional activated carbon‐based filter materials. These results prove that surface‐functionalised SA‐PET has better filtration performance for harmful substances in smoke and provides a new strategy for the design of high‐performance filtration materials.

ABSTRACTPublic Map Service Platforms (PMSPs) provide embedded map services in domains such as forests and rivers. Users from different domains (Domain Users) prefer specific spatial features, and extracting the Browsing Interests of Domain Users (BIDUs) can help elucidate users’ access intentions and provide suitable recommendations. Previous research has found that access frequency of spatial features is an indicator of users’ browsing interests; however, high-frequency spatial features are sparsely distributed, resulting in inaccurate extraction of browsing interests. Our objective is to model the spatial co-occurrence of spatial features and employ BIDUs extraction to address this limitation. First, to extract spatial features in tiles, we proposed a k-nearest neighbor method for Point-of-Interest (POI) extraction and a template-based method for Land Uses/Land Covers extraction. Then, we developed the word2vec model to construct a POI semantic space to quantify spatial co-occurrence and employed multi-domain user classification to verify its effectiveness. Finally, a combined word2vec and singular value decomposition model is proposed to perform topic extraction as a representation of BIDUs. Compared with the baseline models, the proposed model integrates spatial co-occurrence from massive POIs to achieve high-accuracy BIDU extraction. Our findings can help construct domain user profiles and support the development of intelligent PMSPs.

Given the current situation that the evaluation system of the deformation and instability failure of 3DPC is immature, this study was devoted to shaping the performance of 3DPC to provide new ideas and ways for exploring the stable forming of 3DPC. The relationship between the deformation in different directions and the number of layers was analysed. The deformation regulation of 3DPC was revealed, and the controllable index was determined. Results show that the vertical and horizontal deformation in the plastic state is correlated to evaluate the overall deformation by considering only the lateral deformation. The horizontal and vertical deformation of each layer decreases as the number of layers increases, forming a trapezoidal shape. The relationship between the horizontal deformation and the number of layers varies with the shape of the printed component. This relationship follows a linear pattern in the vertical direction and remains independent of the printing shape. The deformation process of 3DPC can be divided into three stages: linear deformation, elastoplastic, and plastic failure. The elastoplastic stage is identified as the primary stage, and the horizontal deformation begins here. Comparatively, the horizontal strain is more suitable for evaluating the plasticity of 3DPC than the vertical strain.

As one of the most important economic traits for domestic animal husbandry, skeletal muscle is regulated by an intricate molecular network. Adenosine deaminase acting on RNA (ADAR1) involves various physiological processes and diseases, such as innate immunity and the development of lung adenocarcinoma, breast cancer, gastric cancer, etc. However, its role in skeletal muscle growth requires further clarification. Here, we explored the functions of ADAR1 in the myogenic process of goat skeletal muscle satellite cells (MuSCs). The ADAR1 transcripts were noticeably enriched in goat visceral tissues compared to skeletal muscle. Additionally, its levels in slow oxidative muscles like the psoas major and minor muscles were higher than in the fast oxidative glycolytic and fast glycolytic muscles. Among the two common isoforms from ADAR1, p110 is more abundant than p150. Moreover, overexpressing ADAR1 enhanced the proliferation and myogenic differentiation of MuSCs. The mRNA-seq performed on MuSCs’ knockdown of ADAR1 obtained 146 differentially expressed genes (DEGs), 87 upregulated and 59 downregulated. These DEGs were concentrated in muscle development and process pathways, such as the MAPK and cAMP signaling pathways. Furthermore, many DEGs as the key nodes defined by protein–protein interaction networks (PPI), including STAT3, MYH3/8, TGFβ2, and ACTN4, were closely related to the myogenic process. Finally, RNA immunoprecipitation combined with qPCR (RIP-qPCR) showed that ADAR1 binds to PAX7 and MyoD mRNA. This study indicates that ADAR1 promotes the myogenic development of goat MuSCs, which provides a useful scientific reference for further exploring the ADAR1-related regulatory networks underlying mammal skeletal muscle growth.

Public Map Service Platforms (PMSPs) aggregate and disseminate the earth observation data. Leveraging spatiotemporal preference patterns derived from browsing targets within complex virtual trajectories on PMSPs aids in constructing user-profiles and comprehending their intentions. However, complex virtual trajectories, characterized by numerous trajectory points and overlapping pyramidal spatial structures, introduce inefficiencies and inaccuracies during browsing target extraction. To mitigate this, we propose an Optimized Spatial Structure Segmentation (OSSS) method that divides complex virtual trajectories into sub-trajectories with simplified spatial structures, enhancing the efficiency of browsing target extraction. Spatiotemporal reconstruction of these sub-trajectories establishes sequences of browsing targets, revealing patterns of interest transitions. Moreover, recognizing the spatial uncertainty inherent in complex virtual trajectories, which results in imprecise matching between browsing targets and spatial features, we introduce a spatial co-occurrence semantic modeling approach. This involves constructing a POI semantic space and introducing a semantic similarity matching method to reduce spatial uncertainty and refine the accuracy of mining spatiotemporal preference patterns. We evaluate these methods using real-world data from Tianditu. Results demonstrate that the OSSS improves extraction efficiency by 3.45 times and accuracy by 18.84%. Additionally, the semantic similarity approach combined with spatial co-occurrence effectively mitigates spatial uncertainty. This research contributes to advancing the intelligence of PMSPs.

Abstract The Galileo navigation satellite system (Galileo) E5 Alternative Binary Offset Carrier (AltBOC) signal brings various challenges due to its complex modulation, wide bandwidth, and multi-peaked auto-correlation function. While wideband tracking needs to solve the ambiguity problem and design dedicated baseband channels, the single-sideband cannot have the outstanding performance of the AltBOC signal. We propose a new tracking method called “Double Sideband Combined Tracking” (DSCT), which can fully exploit the AltBOC signal’s code tracking accuracy without ambiguity and ensure compatibility with Binary Phase Shift Keying (BPSK) processing channels, easily implemented in hardware. The DSCT employs one phase locked loop and one delay locked loop to track the carrier and code, respectively. The double-sideband correlation results used by the two loops are recovered by coherently combining the single-sideband correlation results of the two BPSK channels. Meanwhile, the combined model, the loop discriminator, and the ambiguity detection of the DSCT are discussed. Furthermore, the code tracking error caused by thermal noise is modeled and analyzed. The test results based on real Galileo E5 signals show that the DSCT exhibits better or comparable code tracking accuracy to the AltBOC wideband tracking method. When the loop falsely locks onto a side-peak, the DSCT can quickly detect and re-lock on the main peak.

Drones are typically built with integrated cameras and inertial measurement units (IMUs). It is crucial to achieve drone attitude control through relative pose estimation using cameras. IMU drift can be ignored over short periods. Based on this premise, in this paper, four methods are proposed for estimating relative pose and focal length across various application scenarios: for scenarios where the camera’s focal length varies between adjacent moments and is unknown, the relative pose and focal length can be computed from four-point correspondences; for planar motion scenarios where the camera’s focal length varies between adjacent moments and is unknown, the relative pose and focal length can be determined from three-point correspondences; for instances of planar motion where the camera’s focal length is equal between adjacent moments and is unknown, the relative pose and focal length can be calculated from two-point correspondences; finally, for scenarios where multiple cameras are employed for image acquisition but only one is calibrated, a method proposed for estimating the pose and focal length of uncalibrated cameras can be used. The numerical stability and performance of these methods are compared and analyzed under various noise conditions using simulated datasets. We also assessed the performance of these methods on real datasets captured by a drone in various scenes. The experimental results demonstrate that the method proposed in this paper achieves superior accuracy and stability to classical methods.

The process of skeletal muscle development is intricate and involves the regulation of a diverse array of genes. Accurate gene expression profiles are crucial for studying muscle development, making it essential to choose the right reference genes for real-time quantitative PCR (RT-qPCR). In the present study, eight candidate reference genes were identified from our previous transcriptome sequencing analysis of caprine skeletal muscle satellite cells (MuSCs), and two traditional reference genes (ACTB and GAPDH) were assessed. The quantitative levels of the candidate reference genes were determined through the RT-qPCR technique, while the stability of their expression was evaluated utilizing the GeNorm, NormFinder, BestKeeper, and RefFinder programs. Furthermore, the chosen reference genes were utilized for the normalization of the gene expression levels of PCNA and Myf5. It was determined that conventional reference genes, including ACTB and GAPDH, were not appropriate for normalizing target gene expression. Conversely, RPL14 and RPS15A, identified through RNA sequencing analysis, exhibited minimal variability and were identified as the optimal reference genes for normalizing gene expression during the proliferation and differentiation of goat MuSCs. Our research offers a validated panel of optimal reference genes for the detection of differentially expressed genes in goat muscle satellite cells using RT-qPCR.

Abstract Background Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. Methods We extracted age-specific rate of cancer cases and deaths during 2007–2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007–2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). Results In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7–4.3%) during 2007–2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3–4.9%), 3.3% (95% CI: 2.6–4.1%), 2.4% (95% CI: 1.4–3.5%), 4.4% (95% CI: 2.5–6.4%), and 3.6% (95% CI: 1.4–5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007–2030, except that uterine cancer deaths and mortality were declined. Conclusions With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned.

ObjectiveNeuroendocrine carcinoma of the cervix (NECC) is extremely rare in clinical practice. This study aimed to methodologically analyze the clinicopathological factors associated with NECC patients and to develop a validated survival prediction model.MethodsA total of 535 patients diagnosed with NECC between 2004 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database, while 122 patients diagnosed with NECC at Yunnan Cancer Hospital (YCH) from 2006 to 2019 were also recruited. Patients from the SEER database were divided into a training cohort (n = 376) and a validation cohort (n = 159) in a 7:3 ratio for the construction and internal validation of the nomogram. External validation was performed in a cohort at YCH. The Kaplan-Meier method was used for survival analysis, the Log-rank method test was used for univariate analysis of prognostic influences, and the Cox regression model was used for multivariate analysis.ResultsThe 3-year and 5-year overall survival (OS) rates for patients with NECC in SEER were 43.6% and 39.7%, respectively. In the training cohort, multivariate analysis showed independent prognostic factors for NECC patients including race, tumor size, distant metastasis, stage, and chemotherapy (pConclusionWe successfully constructed a nomogram that precisely predicts the OS for patients with NECC based on the SEER database and a large single-center retrospective cohort. The visualized and practical model can distinguish high-risk patients for recurrence and death who may benefit from clinical trials of boost therapy effectively. We also found that patients who received more than 4 cycles of chemotherapy acquired survival benefits than those who received less than 4 cycles.

Background: Postpartum haemorrhage (PPH) is a serious complication and a cause of maternal mortality after delivery. This study used machine learning algorithms and new feature selection methods to build an efficient PPH risk prediction model and provided new ideas and reference methods for PPH risk management. Methods: The clinical data of women who gave birth at Wenzhou People’s Hospital from 1 January 2021, to 30 March 2022, were retrospectively analysed, and the women were divided into a high haemorrhage group (337 patients) and a low haemorrhage group (431 patients) based on the amount of blood loss. Machine learning algorithms were used to identify the features associated with postpartum haemorrhage from multiple clinical variables using feature selection methods, such as recursive feature elimination (RFE), recursive feature elimination with cross-validation (RFECV), and SelectKBest, and to establish prediction models. Results: For all women, the features associated with postpartum haemorrhage were ‘age’, ‘newborn weight’, ‘gestational week’, ‘perineal laceration’, and ‘caesarean section’. The prediction model established by the random forest classifier performed best, with an F1 score of 0.73 and an area under the curve (AUC) of 0.84. For women who underwent caesarean section or had a vaginal delivery, the features associated with postpartum haemorrhage risk were different. The risk factors for postpartum haemorrhage in women who underwent caesarean section were ‘age’, ‘parity’, ‘preterm birth’, and ‘placenta previa’. The prediction model established by the random forest classifier performed best, with an F1 value of 0.96 and an AUC of 0.95. The risk factors for postpartum haemorrhage in women with vaginal delivery were ‘age’, ‘parity’, ‘gestational week’, ‘diabetes’, ‘assisted reproduction’, ‘hypertension (preeclampsia)’, and ‘multiple pregnancy’. The prediction model established by the AdaBoost classifier performed best, with an F1 value of 0.65 and an AUC of 0.76. Conclusions: Machine learning algorithms can effectively identify the features associated with postpartum haemorrhage risk from clinical variables and establish accurate prediction models, offering a novel approach for clinicians to assess the risk of and prevent postpartum haemorrhage.

Understanding the genetic makeup of local sheep breeds is essential for their scientific conservation and sustainable utilization. The Liangshan semi-fine-wool sheep (LSS), a Chinese semi-fine-wool breed renowned for its soft wool, was analyzed using whole-genome sequencing data including 35 LSS, 84 sheep from other domestic breeds, and 20 Asiatic mouflons. We investigated the genetic composition of LSS by conducting analyses of the population structure, runs of homozygosity, genomic inbreeding coefficients, and selection signature. Our findings indicated that LSS shares greater genetic similarity with Border Leicester and Romney sheep than with Tibetan (TIB), Yunnan (YNS), and Chinese Merino sheep. Genomic analysis indicated low to moderate inbreeding coefficients, ranging from 0.014 to 0.154. In identifying selection signals across the LSS genome, we pinpointed 195 candidate regions housing 74 annotated genes (e.g., IRF2BP2, BVES, and ALOX5). We also found the overlaps between the candidate regions and several known quantitative trait loci related to wool traits, such as the wool staple length and wool fiber diameter. A selective sweep region, marked by the highest value of cross-population extended haplotype homozygosity, encompassed IRF2BP2—an influential candidate gene affecting fleece fiber traits. Furthermore, notable differences in genotype frequency at a mutation site (c.1051 + 46T > C, Chr25: 6,784,190 bp) within IRF2BP2 were observed between LSS and TIB and YNS sheep (Fisher’s exact test, p < 2.2 × 10−16). Taken together, these findings offer insights crucial for the conservation and breeding enhancement of LSS.

An imbalance in urban development in China has become a contradiction. Points of Interest (POIs) serve as representations of the spatial distribution of urban functions. Analyzing POI spatial co-occurrence patterns can reveal the agglomeration patterns of urban functions across cities at different levels, providing insights into imbalances in urban development. Using POI data from 297 cities in China, the Word2vec model was employed to model the POI spatial co-occurrence patterns, allowing for the quantification of fine-granular urban functionality. Subsequently, the cities were clustered into five tiers representing different levels of development. An urban hierarchical disparity index and graph were introduced to examine variations in urban functions across different tiers. A significant correlation between POI spatial co-occurrence patterns and the GDP of cities at different levels was demonstrated. This study revealed a notable polarization trend characterized by the development of top-tier cities and lagging tail-end cities. Top-tier cities exhibit advantages in terms of their commercial environments, such as international banks, companies, and transportation facilities. Conversely, tail-end cities face deficiencies in urban infrastructure. It is crucial to coordinate resource allocation and establish sustainable development strategies that foster mutual support between the top-tier and tail-end cities.

While light-driven water splitting offers a renewable means to produce fuel, the limited availability of high-performance materials inspires the search for new photocatalysts. Here, authors demonstrate two-dimensional NiPS3 to enhance semiconductor photocatalytic H2 evolution activities.

Abstract Background Adaptive thermogenesis by brown adipose tissue (BAT) is important to the maintenance of temperature in newborn mammals. Cold exposure activates gene expression and lipid metabolism to provide energy for BAT thermogenesis. However, knowledge of BAT metabolism in large animals after cold exposure is still limited. Results In this study, we found that cold exposure induced expression of BAT thermogenesis genes and increased the protein levels of UCP1 and PGC1α. Pathway analysis showed that cold exposure activated BAT metabolism, which involved in cGMP-PKG, TCA cycle, fatty acid elongation, and degradation pathways. These were accompanied by decreased triglyceride (TG) content and increased phosphatidylcholine (PC) and phosphatidylethanolamine (PE) content in BAT. Conclusion These results demonstrate that cold exposure induces metabolites involved in glycerolipids and glycerophospholipids metabolism in BAT. The present study provides evidence for lipid composition associated with adaptive thermogenesis in goat BAT and metabolism pathways regulated by cold exposure.

Abstract Background The pigmentation phenotype diversity is rich in domestic goats, and identification of the genetic loci affecting coat color in goats has long been of interest. Via the detections of selection signatures, a duplication upstream ASIP was previously reported to be a variant affecting the Swiss markings depigmentation phenotype in goats. Results We conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 solid black vs. 17 non-classic Swiss markings). Although a single association peak harboring the ASIP gene at 52,619,845–72,176,538 bp on chromosome 13 was obtained using a linear mixed model approach, all the SNPs and indels in this region were excluded as causal variants for the pigmentation phenotype. We then found that all 17 individuals with non-classic Swiss markings carried a 13,420-bp duplication (CHI13:63,129,198–63,142,617 bp) nearly 101 kb upstream of ASIP, and this variant was strongly associated (P = 1.48 × 10− 12) with the coat color in the 65 JT goats. The copy numbers obtained from the WGS data also showed that the duplication was present in all 53 goats from three European breeds with Swiss markings and absent in 45 of 51 non-Swiss markings goats from four other breeds and 21 Bezoars, which was further validated in 314 samples from seven populations based on PCR amplification. The copy numbers of the duplication vary in different goat breeds with Swiss markings, indicating a threshold effect instead of a dose-response effect at the molecular level. Furthermore, breakpoint flanking repeat analysis revealed that the duplication was likely to be a result of the Bov-B-mediated nonallelic homologous recombination. Conclusion We confirmed that a genomic region harboring the ASIP gene is a major locus affecting the coat color phenotype of Swiss markings in goats. Although the molecular genetic mechanisms remain unsolved, the 13,420-bp duplication upstream of ASIP is a necessary but not sufficient condition for this phenotype in goats. Moreover, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity.

Tibetan goats, Taihang goats, Jining grey goats, and Meigu goats are the representative indigenous goats in China, found in Qinghai-Tibet Plateau, Western pastoral area, Northern and Southern agricultural regions. Very few studies have conducted a comprehensive analysis of the genomic diversity and selection of these breeds. We genotyped 96 unrelated individuals, using goat 53 K Illumina BeadChip array, of the following goat breeds: Tibetan (TG), Taihang (THG), Jining grey (JGG), and Meigu (MGG). A total of 45 951 single nucleotide polymorphisms were filtered to estimate the genetic diversity and selection signatures. All breeds had a high proportion (over 95%) of polymorphic loci. The observed and excepted heterozygosity ranged from 0.338 (MGG) to 0.402 (JGG) and 0.339 (MGG) to 0.395 (JGG), respectively. Clustering analysis displayed a genetically distinct lineage for each breed, and their Fst were greater than 0.25, indicating that they had a higher genetic differentiation between groups. Furthermore, effective population size reduced in all four populations, indicating a loss of genetic diversity. In addition, runs of homozygosity were mainly distributed in 5–10 Mb. Lastly, we identified signature genes, which were closely related to high-altitude adaptation (ADIRF) and prolificity (CNTROB, SMC3, and PTEN). This study provides a valuable resource for future studies on genome-wide perspectives on the diversity and selection signatures of Chinese indigenous goats.

Abstract Background Meiotic recombination is one of the important phenomena contributing to gamete genome diversity. However, except for human and a few model organisms, it is not well studied in livestock, including cattle. Results To investigate their distributions in the cattle sperm genome, we sequenced 143 single sperms from two Holstein bulls. We mapped meiotic recombination events at high resolution based on phased heterozygous single nucleotide polymorphism (SNP). In the absence of evolutionary selection pressure in fertilization and survival, recombination events in sperm are enriched near distal chromosomal ends, revealing that such a pattern is intrinsic to the molecular mechanism of meiosis. Furthermore, we further validated these findings in single sperms with results derived from sequencing its family trio of diploid genomes and our previous studies of recombination in cattle. Conclusions To our knowledge, this is the first large-scale single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of recombination, genome instability, and male infertility.

Abstract Background MicroRNAs (miRNAs) are a family of short non-coding RNA molecules and play important roles in various biological processes. However, knowledge of the expression profiles and function of miRNAs on the regulation of brown adipose tissue (BAT) thermogenesis remains largely unknown. Results In this study, we found that brown adipose tissue (BAT) existed within the perirenal fat at 1 day after birth (D1) and transferred into white adipose tissue (WAT) at 30 days after birth (D30) by UCP1 protein expression and immunohistochemistry analysis. After that, we performed RNA sequencing on six libraries of goat BAT and WAT. A total of 238 known miRNAs and 1834 goat novel miRNAs were identified. Moreover, 395 differentially expressed miRNAs including 167 up-regulated and 228 down-regulated miRNAs were obtained in BAT. For the known BAT enriched miRNA, 30 miRNAs were enriched in goat BAT but not in mouse BAT. In addition, miR-433 was enriched in goat BAT but not in mouse BAT. Gain- and loss-of-function experiments reveal that miR-433 reduced the lipid accumulation of brown adipocytes and decreased the expression of BAT marker and mitochondrial related genes. However, miR-433 had no effect on lipid accumulation and thermogenesis in white adipocytes. In addition, miR-433 inhibited the expression of MAPK8 by targeting to the 3’UTR of MAPK8 gene. These data demonstrate that miR-433 acts as a negative regulator in controlling brown adipocytes differentiation and thermogenesis. Conclusion The present study provides a detailed miRNAs expression landscape in BAT and WAT. Furthermore, we found that miR-433, which was highly expressed on BAT had a negative regulatory function on the thermogenesis and adipogenesis in goat brown adipocytes. This study provides evidence for understanding the role of miRNAs in regulating BAT thermogenesis and energy expenditure in goats.

Abstract Background Copy number variation (CNV) has been routinely studied using bulk-cell sequencing. However, CNV is not well studied on the single-cell level except for humans and a few model organisms. Results We sequenced 143 single sperms of two Holstein bulls, from which we predicted CNV events using 14 single sperms with deep sequencing. We then compared the CNV results derived from single sperms with the bulk-cell sequencing of one bull’s family trio of diploid genomes. As a known CNV hotspot, segmental duplications were also predicted using the bovine ARS-UCD1.2 genome. Although the trio CNVs validated only some single sperm CNVs, they still showed a distal chromosomal distribution pattern and significant associations with segmental duplications and satellite repeats. Conclusion Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for CNV detection using single cell sequencing data.

Meiotic de novo mutation (DNM) is one of the important phenomena contributing to gamete genome diversity. However, except for humans and a few model organisms, they are not well studied in livestock, including cattle. Moreover, bulk sperm samples have been routinely utilized in experiments, which include millions of single sperm cells and only report high-frequency variants. In this study, we isolated and sequenced 143 single sperms from two Holstein bulls and identified hundreds of candidate DNM events in ten sperms with deep sequencing coverage. We estimated DNM rates ranging from 1.08 × 10−8 to 3.78 × 10−8 per nucleotide per generation. We further validated 12 out of 14 selected DNM events using Sanger sequencing. To our knowledge, this is the first single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of point mutations and male fertility. Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for genetic variant detection using single-cell sequencing data.

Abstract Background There is a long-term interest in investigating the genetic basis of the horned/polled phenotype in domestic goats. Here, we report a genome-wide association study (GWAS) to detect the genetic loci affecting the polled phenotype in goats. Results We obtained a total of 13,980,209 biallelic SNPs, using the genotyping-by-sequencing data from 45 Jintang Black (JT) goats, which included 32 female and nine male goats, and four individuals with the polled intersex syndrome (PIS). Using a mixed-model based GWAS, we identified two association signals, which were located at 150,334,857–150,817,260 bp (P = 5.15 × 10− 119) and 128,286,704–131,306,537 bp (P = 2.74 × 10− 15) on chromosome 1. The genotype distributions of the 14 most significantly associated SNPs were completely correlated with horn status in goats, based on the whole-genome sequencing (WGS) data from JT and two other Chinese horned breeds. However, variant annotation suggested that none of the detected SNPs within the associated regions were plausible causal mutations. Via additional read-depth analyses and visual inspections of WGS data, we found a 10.1-kb deletion (CHI1:g. 129424781_129434939del) and a 480-kb duplication (CHI1:150,334,286–150,818,098 bp) encompassing two genes KCNJ15 and ERG in the associated regions of polled and PIS-affected goats. Notably, the 10.1-kb deletion also served as the insertion site for the 480-kb duplication, as validated by PCR and Sanger sequencing. Our WGS genotyping showed that all horned goats were homozygous for the reference alleles without either the structural variants (SVs), whereas the PIS-affected goats were homozygous for both the SVs. We also demonstrated that horned, polled, and PIS-affected individuals among 333 goats from JT and three other Chinese horned breeds can be accurately classified via PCR amplification and agarose gel electrophoresis of two fragments in both SVs. Conclusion Our results revealed that two genomic regions on chromosome 1 are major loci affecting the polled phenotypes in goats. We provided a diagnostic PCR to accurately classify horned, polled, and PIS-affected goats, which will enable a reliable genetic test for the early-in-life prediction of horn status in goats.

The incidence of diarrhea in lambs is frequent in large-scale sheep farms, which greatly impacts the growth and health of lambs. The aim of this study was to assess the changes in serum biochemical and immunological parameters and gut microbiome composition in suckling lambs suffering from diarrhea or not, reared on an intensive commercial farm. We found a reduced diversity of intestinal bacteria in suckling lambs suffering from diarrhea. Firmicutes and Bacteroidetes were the dominant flora in both groups of lambs, while the Bacteroidetes decreased in diarrheic lambs, no changes were reported in Firmicutes. Compared with healthy lambs, the proportion of aerobic bacteria, facultative anaerobic bacteria, and stress tolerant bacteria increased in lambs suffering from diarrhea, while that of anaerobic bacteria and potentially pathogenic bacteria decreased slightly. In addition, the contents of total cholesterol, immunoglobulins (Ig) G, and IgM in the serum of lambs suffering from diarrhea were lower than those of healthy lambs. This study explored the association between diarrhea occurrence, intestinal microbial community structure, and metabolic and immunological status in Hu lambs.

ABSTRACT Age is an important factor that determines the physiological functions of the human body, but the changes in maternal physiology, biochemistry, and intestinal flora related to reproductive age and their impact on offspring are not clear. Here, we tested and analyzed the clinical physiological and biochemical indicators and/or intestinal flora, matching the data of 252 parturients and their newborns. We found that 4 clinical indicators, including the white blood cell count and the absolute value of monocytes, were significantly related to the reproductive age (P < 0.05). The composition of the intestinal flora also varied with age, and the intestinal flora of advanced-age women (≥35 years old) was different from that of middle-aged women (>25 and

As calcium silicate hydrate (C-S-H) is the main binding phase in concrete, understanding the doping behavior of impurity elements in it is important for optimizing the structure of cementitious materials. However, most of the current studies focus on cement clinker, and the doping mechanism of impurity elements in hydrated calcium silicate is not yet fully understood. The hydrated calcium silicate component is complex, and its structure is very similar to that of the tobermorite mineral family. In this study, the effects of three different dopants (Mg, Sr and Ba) on a representing structure of C-S-H—tobermorite—was systematically explored using densify functional theory (DFT) calculations. The calculations show that Mg doping leads to a decrease in lattice volume and causes obvious structure and coordination changes of magnesium–oxygen polyhedra. This may be the reason why high formation energy is required for the Mg-doped tobermorite. Meanwhile, doping only increases the volume of the Sr- and Ba-centered oxygen polyhedra. Specifically, the Mg-doped structure exhibits higher chemical stability and shorter interatomic bonding. In addition, although Mg doping distorts the structure, the stronger chemical bonding between Mg-O atoms also improves the compressive (~1.99% on average) and shear resistance (~2.74% on average) of tobermorillonite according to the elastic modulus and has less effect on the anisotropy of the Young’s modulus. Our results suggest that Mg doping is a promising strategy for the optimized structural design of C-S-H.

Background: The aim of this study was to evaluate the relationship and impact of D-dimer levels and preeclamptic pregnancies at different ages in women. Methods: We conducted an observational retrospective cohort study of 325 pregnant women who delivered in Wenzhou People’s Hospital from January 2018 to December 2021. Clinical data including age, neutrophils, lymphocytes, platelets, fibrinogen, gestational age, D-dimer/fibrinogen, blood pressure at admission, and fetal weight were collected from the medical record database. All measurements were made using the same methods. Data for continuous variables were expressed as X ± standard deviation (SD), and inter-group differences in continuous data were compared by independent sample t-test. Continuous variables that do not conform to the normal distribution, such as age and D-dimer, were expressed as median and quartile ranges. The relationship between D-dimer and preeclampsia pregnant women of different ages was evaluated by receiver operating characteristics (ROC) curve analysis. Results: Among the middle-aged pregnant women, the average D-dimer in the normotensive pregnancy group was (1.367 ± 0.03 mg/L), which was significantly lower than that in the preeclampsia group (2.087 ± 0.16 mg/L). The D-dimer/fibrinogen ratio was comparable between the young groups, but there was a difference between the middle-aged groups. Meanwhile, in middle-aged pregnant women, the predicted area of D-dimer for preeclampsia was 70.2% (95% confidence interval (CI) 60–80.43%, p = 0.0002) , which was significantly higher than that in the young group. Conclusions: Prenatal D-dimer levels may be associated with more accurate predictors of preeclampsia in middle-aged women than in young women.

The rumen is an essential digestive and absorption organ of ruminants. During fetal life, lactation, and post-weaning period, goat rumen undergoes drastic morphological and metabolic-functional changes triggered by potential regulated genes and non-coding RNA molecules. As the essential regulatory factors, long non-coding RNAs (lncRNAs) have vital functions in various biological activities. However, their roles during rumen development are still poorly explored in ruminants. To explore the genome-wide expression profiles of lncRNAs and mRNAs in the goat rumens, we generated 5,007 lncRNAs and 19,738 mRNAs identified during the fetal and prepubertal stages by the high-throughput RNA sequencing. Notably, 365 lncRNAs and 2,877 mRNAs were considered to be differentially expressed. The weighted gene co-expression network analysis and functional analysis were performed to explore the regulatory roles of those differentially expressed molecules. The cis-and trans-target genes of differently expressed lncRNAs were enriched for pathways related to focal adhesion, cGMP-PKG signaling pathway, alpha-linolenic acid metabolism, arachidonic acid metabolism, and fat digestion and absorption. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses showed that the differently expressed genes mainly participated in mitotic cytokinesis, desmosome, fatty acid degradation, cell adhesion molecules, and fatty acid metabolism. The prediction of lncRNA-mRNA interaction networks further revealed transcripts potentially involved in rumen development. The present study profiles a global overview of lncRNAs and mRNAs during rumen development. Our findings provide valuable resources for genetic regulation and molecular mechanisms of rumen development in ruminants.

Objective We aimed to discover potential circulating genes and non-coding molecules (micro RNA [miRNA] and circular RNA [circRNA]) in CD4 + T cells in relation to seasonal allergic rhinitis (SAR). Methods Microarray data of GSE50223 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) during and outside the pollen season were analyzed using R software and by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The protein–protein interactions, modules, miRNAs targeting DEGs, merged miRNA–DEG networks, and circRNAs targeted with miRNAs were further analyzed. Results We identified 211 DEGs during the pollen season and eight DEGs outside the season, of which only MMP12 , NR4A2 , and CD69 were differentially expressed both during and outside the pollen season. DEGs during the pollen season were enriched in the GO categories ‘neutrophil degranulation’, ‘neutrophil activation involved in immune response’, ‘neutrophil mediated immunity’, and ‘neutrophil activation’. A significant module was identified with key nodes of CDK6 and hsa-miR-29b-3p. Six significant circRNAs were also identified. Conclusions Some genes, miRNAs, and circRNAs in CD4 + T may play vital roles in SAR and may thus be potential targets for the prevention and treatment of SAR.

Early weaning and milk substitutes increase the incidence of diarrhea in young ruminants, which may modify their gut microbiota, metabolism, immunity, and health. The aim of the study was to determine if early weaning and milk substitutes affect the gut microbiota, metabolism, and immunological status of goat kids suffering from diarrhea. The 16S rRNA gene and metagenomic sequencing in feces and serum metabolomics of early-weaned and artificially reared goat kids suffering from diarrhea (DK group) and healthy goat kids reared by their mothers (HK group) were analyzed. The serum biochemistry and immunoglobulin concentration were also determined. Several probiotics, such as Streptococcus and Lactobacillus, were higher in the feces of the DK group than in feces of the HK group. Ruminococcus sp. was elevated in the feces of HKs, likely being a biomarker for goat health. Taking all the carbohydrate-active enzyme (CAZyme) families into consideration, 20 CAZyme families were different between the groups. Compared with the DK group, the relative quantity of glycoside hydrolases (GH) and glycosyltransferase (GT) families in the HK group decreased. GT70 was only identified in HK kids participating in the activity of β-glucuronosyltransferase during the carbohydrate metabolism. Overall, 24 metabolites were different between the groups, which were mainly involved in protein digestion and absorption, cyanoamino acid metabolism, and cholesterol metabolism. The concentrations of immunoglobulins G and M were significantly lower in the DK than in the HK group. In conclusion, our study characterized the fecal microbiota, metabolism, and immunological status of early-weaned and artificially reared goat kids suffering from diarrhea.

Abstract miRNAs are well known to be gene repressors. A newly identified class of miRNAs termed nuclear activating miRNAs (NamiRNAs), transcribed from miRNA loci that exhibit enhancer features, promote gene expression via binding to the promoter and enhancer marker regions of the target genes. Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression. During chromatin looping, transcribed eRNAs interact with NamiRNAs through enhancer-promoter interaction to perform similar functions. Here, we review the functional differences and similarities between eRNAs and NamiRNAs in myogenesis and disease. We also propose models demonstrating their mutual mechanism and function. We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.

Intrauterine adhesions (IUAs) are important causes of female infertility, mainly but not always caused by iatrogenic endometrial injury. The microbiome of the female reproductive tract, including the vagina and uterine cavity, plays an important role in health and disease. Immune regulation imbalance caused by reproductive tract microecological disorders can act in the formation mechanism of IUAs. Here we collected clinical laboratory indicators, the vaginal secretions and uterine secretions of 6 women with and 8 women without IUAs, with a history of curettage. Vaginal and uterine cavity microbes were detected by high-throughput sequencing technology. Compared with the women without IUAs, the proportion of Lactobacillus in vaginal microbes was decreased and the proportion of Bacteroides was increased in the IUAs. The α-diversity index in the vaginal microbiome was significantly positively correlated with the hematocrit and erythrocyte count (P ＜0.05). These clinical and microbiological indicators could be used to indicate the occurrence of IUAs, so this study has clinical guiding significance for detecting and preventing them.

Circular RNAs (circRNAs) are key regulatory factors with vital functions in various biological activities. However, little has been reported concerning the genetic regulation of circRNAs during rumen development in goats. The aim of this study was to identify the genome-wide expression profiles of circRNAs in the rumen of goats during fetal development and before and after weaning. Histological morphology showed that from the fetal period (days 60 and 135 of gestation) to the prepuberal period (days 60 and 150 of age) the rumen papilla developed gradually, and the thickness of the rumen muscular layer increased. A total of 11,149 circRNAs were identified in the four development stages by RNA-sequencing. From this, 1,518 were differentially expressed circRNAs (DECs). Fifty-eight DECs were up-regulated from 60 to 135 days of gestation, and 93 from day 135 of pregnancy to 30 days after birth. A large proportion (598) of DECs were down-regulated from day 135 of gestation to 30 days after birth. The expression levels of six randomly selected circRNAs were validated by qPCR, and their back-splicing junction (BSJ) sites were also confirmed. Ontology and pathway analyses revealed that the parental genes of DECs were mainly involved in the signaling pathways related to cell proliferation and apoptosis. The interaction network of circRNAs with their target miRNAs showed its involvement in cell proliferation and apoptosis signaling pathways. In conclusion, we identified the genome-wide expression profiles of circRNAs in the rumen of goats during fetal development and before and after weaning. These results provide a basis for further study on the regulatory effect of circRNAs on the development of rumen tissues.

Abstract Background Copy number variations (CNVs) are a major form of genetic variations and are involved in animal domestication and genetic adaptation to local environments. We investigated CNVs in the domestic goat (Capra hircus) using Illumina short-read sequencing data, by comparing our lab data for 38 goats from three Chinese breeds (Chengdu Brown, Jintang Black, and Tibetan Cashmere) to public data for 26 individuals from three other breeds (two Moroccan and one Chinese) and 21samples from Bezoar ibexes. Results We obtained a total of 2394 CNV regions (CNVRs) by merging 208,649 high-confidence CNVs, which spanned ~ 267 Mb of total length and accounted for 10.80% of the goat autosomal genome. Functional analyses showed that 2322 genes overlapping with the CNVRs were significantly enriched in 57 functional GO terms and KEGG pathways, most related to the nervous system, metabolic process, and reproduction system. Clustering patterns of all 85 samples generated separately from duplications and deletions were generally consistent with the results from SNPs, agreeing with the geographical origins of these goats. Based on genome-wide F ST at each CNV locus, some genes overlapping with the highly divergent CNVs between domestic and wild goats were mainly enriched for several immunity-related pathways, whereas the genes overlapping with the highly differentiated CNVs between highland and lowland goats were mainly related to vitamin and lipid metabolism. Remarkably, a 507-bp deletion at ~ 14 kb downstream of FGF5 on chromosome 6 showed highly divergent (F ST = 0.973) between the highland and lowland goats. Together with an enhancer activity of this sequence shown previously, the function of this duplication in regulating fiber growth deserved to be further investigated in detail. Conclusion We generated a comprehensive map of CNVs in goats. Many genetically differentiated CNVs among various goat populations might be associated with the population characteristics of domestic goat breeds.

The transport and metabolism of lipids in cerebrovascular endothelial cells (ECs) have been hypothesized to regulate blood-brain barrier (BBB) maturation and homeostasis. Long-chain polyunsaturated fatty acids (LCPUFAs) as the important lipids components of cell membranes are essential for the development and function of BBB, but the direct links of lipid metabolism and ECs barrier function remain to be established. Here, we comprehensively characterize the transcriptomic phenotype of developmental cerebrovascular ECs in single-cell resolution and firstly find that trans-2-enoyl-CoA reductase (Tecr), a very-long-chain fatty acid synthesis, is highly expressed during barriergenesis and decreased after BBB maturation. EC-specific knockout of Tecr compromises angiogenesis due to delayed vascular sprouting. Importantly, EC-specific deletion of Tecr loss restrictive quality of vascular permeability from neonatal stages to adulthood, with high levels of transcytosis, but maintains the vascular tight junctions. Moreover, lipidomic analysis shows that the expression of Tecr in ECs is associated with the containing of omega-3 fatty acids, which directly suppresses caveolae vesicles formation. These results reveal a protective role for Tecr in BBB integrity and suggest that Tecr as a novel therapeutic target in the central nervous system (CNS) diseases associated with BBB dysfunction.

The ionospheric total electron content (TEC) is susceptible to factors, such as solar and geomagnetic activities, resulting in the enhancement of its non-stationarity and nonlinear characteristics, which aggravate the impact on radio communications. In this study, based on the NeuralProphet hybrid prediction framework, a regional ionospheric TEC prediction model (multi-factor NeuralProphet model, MF-NPM) considering multiple factors was constructed by taking solar activity index, geomagnetic activity index, geographic coordinates, and IGS GIM data as input parameters. Data from 2009 to 2013 were used to train the model to achieve forecasts of regional ionospheric TEC at different latitudes during the solar maximum phase (2014) and geomagnetic storms by sliding 1 day. In order to verify the prediction performance of the MF-NPM, the multi-factor long short-term memory neural network (LSTMNN) model was also constructed for comparative analysis. At the same time, the TEC prediction results of the two models were compared with the IGS GIM and CODE 1-day predicted GIM products (COPG_P1). The results show that the MF-NPM achieves good prediction performance effectively. The RMSE and relative accuracy (RA) of MF-NPM are 2.33 TECU and 93.75%, respectively, which are 0.77 and 1.87 TECU and 1.91% and 6.68% better than LSTMNN and COPG_P1 in the solar maximum phase (2014). During the geomagnetic storm, the RMSE and RA of TEC prediction results based on the MF-NPM are 3.12 TECU and 92.86%, respectively, which are improved by 1.25 and 2.30 TECU and 2.38% and 7.24% compared with LSTMNN and COPG_P1. Furthermore, the MF-NPM also achieves better performance in low–mid latitudes.

Understanding the genetic composition of indigenous goats is essential to promote the scientific conservation and sustainable utilization of these breeds. The Jianchang Black (JC) goat, a Chinese native breed, is solid black and exhibits crude feed tolerance, but is characterized by a low growth rate and small body size. Based on the whole-genome sequencing data for 30 JC, 41 Jintang Black (JT), and 40 Yunshang Black (YS) goats, and 21 Bezoar ibexes, here, we investigated the genetic composition of JC goats by conducting analyses of the population structure, runs of homozygosity (ROH), genomic inbreeding, and selection signature. Our results revealed that JT and YS showed a close genetic relationship with a non-negligible amount of gene flows but were genetically distant from JC, apart from Bezoars. An average of 2039 ROHs were present in the autosomal genome per individual. The ROH-based inbreeding estimates in JC goats generally showed moderate values ranging from 0.134 to 0.264, mainly due to rapid declines in the effective population size during recent generations. The annotated genes (e.g., IL2, IL7, and KIT) overlapping with ROH islands were significantly enriched in immune-related biological processes. Further, we found 61 genes (e.g., STIM1, MYO9A, and KHDRBS2) under positive selection in JC goats via three complementary approaches, which may underly genetic adaptations to local environmental conditions. Our findings provided references for the conservation and sustainable utilization of JC goats.

Abstract Background As one of the important livestock species around the world, goats provide abundant meat, milk, and fiber to fulfill basic human needs. However, the genetic loci that underlie phenotypic variations in domestic goats are largely unknown, particularly for economically important traits. In this study, we sequenced the whole genome of 38 goats from three Chinese breeds (Chengdu Brown, Jintang Black, and Tibetan Cashmere) and downloaded the genome sequence data of 30 goats from five other breeds (four non-Chinese and one Chinese breed) and 21 Bezoar ibexes to investigate the genetic composition and selection signatures of the Chinese goat breeds after domestication. Results Based on population structure analysis and F ST values (average F ST = 0.22), the genetic composition of Chengdu Brown goats differs considerably from that of Bezoar ibexes as a result of geographic isolation. Strikingly, the genes under selection that we identified in Tibetan Cashmere goats were significantly enriched in the categories hair growth and bone and nervous system development, possibly because they are involved in adaptation to high-altitude. In particular, we found a large difference in allele frequency of one novel SNP (c.-253G>A) in the 5′-UTR of FGF5 between Cashmere goats and goat breeds with short hair. The mutation at this site introduces a start codon that results in the occurrence of a premature FGF5 protein and is likely a natural causal variant that is involved in the long hair phenotype of cashmere goats. The haplotype tagged with the AGG-allele in exon 12 of DSG3, which encodes a cell adhesion molecule that is expressed mainly in the skin, was almost fixed in Tibetan Cashmere goats, whereas this locus still segregates in the lowland goat breeds. The pigmentation gene KITLG showed a strong signature of selection in Tibetan Cashmere goats. The genes ASIP and LCORL were identified as being under positive selection in Jintang Black goats. Conclusions After domestication, geographic isolation of some goat breeds has resulted in distinct genetic structures. Furthermore, our work highlights several positively selected genes that likely contributed to breed-related traits in domestic goats.

The Pleosporales is the most predominant order in the Dothideomycetes class, which contains over 4700 species that function in a variety of ways. The material used in this research was previously isolated from the Chinese white wax scale insect, and it was determined to be a Paraconiothyrium genus species that belonged to the Pleosporales order. For further molecular analysis, we assembled the complete mitochondrial genome of Paraconiothyrium sp. based on short reads of BGISEQ sequencing and subreads from Pacbio sequencing. The results showed that it was 42,734 bp in length and contained 8 open reading frames, 12 protein-coding genes and 31 non-coding genes. Phylogenetic analysis showed it was affiliated to the Pleosporales order and formed a sister relationship with Pithomyces chartarum. Compared to the seven other species in the Pleosporales order, Paraconiothyrium sp. has generally conserved gene content and structure, while the homologous blocks and gene order were shown to be significantly rearranged, in accordance with the species diversity in the Pleosporales order. In this study, we presented the first mitochondrial genome of Paraconiothyrium fungi to be reported, and we also showed gene order diversity in the Pleosporales order. These findings will lay the foundation for further species studies regarding molecular diversity and our understanding of species characteristics in the Paraconiothyrium genus.

Floods threaten the sustainable development of areas with a high probability of hazard. A typical analytic hierarchy process (pixel-based AHP) based flood hazard estimation method may ignore the similar threat caused by neighborhood cells at the sub-watershed scale. This study proposed an extended watershed-based Zonal Statistical AHP for flood hazard estimation: Constraining converging related indicators by the sub-watersheds (WZSAHP-RC) model to improve this gap. Before calculating the flood hazard index, the proposed model uses the sub-watershed derived by the multiple flow direction method as a based unit to calculate the maximum zonal statistical value of runoff converging indicators. Moreover, taking the Chaohu basin of Anhui in China as the case study, the validation flooding ground-truthing was constructed from GF-3, and Landsat OLI images of the flood event from 20 July to 24 July 2020, which is the biggest flood recorded by the Zhongmiao station, which recorded a new water level, 0.82 m higher than the historical record. Compared with the validation, the results indicated the proposed method could improve the correct ratio by 38% (from 22% to 60%) and the fit ratio by 17% (from 18% to 35%) when considering the predicted flood hazard levels of “High” and “Very High” as flooded areas. Moreover, the flood hazard map derived by WZSAHP-RC demonstrated greater consistency in the flooded districts filtered by Baidu News than the pixel-based AHP. It revealed that considering two- or even multi-dimensional homogeneity may help to improve the accuracy of flood hazard maps on a catchment scale.

Skeletal myogenesis is a complicated biological event that involves a succession of tightly controlled gene expressions. In order to identify novel regulators of this process, we performed mRNA-Seq studies of goat skeletal muscle satellite cells (MuSCs) cultured under proliferation (GM) and differentiation (DM1/DM5) conditions. A total of 19,871 goat genes were expressed during these stages, 198 of which represented novel transcripts. Notably, in pairwise comparisons at the different stages, 2551 differentially expressed genes (DEGs) were identified (p < 0.05), including 1560 in GM vs. DM1, 1597 in GM vs. DM5, and 959 in DM1 vs. DM5 DEGs. The time-series expression profile analysis clustered the DEGs into eight gene groups, three of which had significantly upregulated and downregulated patterns (p < 0.05). Functional enrichment analysis showed that DEGs were enriched for essential biological processes such as muscle structure development, muscle contraction, muscle cell development, striated muscle cell differentiation, and myofibril assembly, and were involved in pathways such as the MAPK, Wnt and PPAR signaling pathways. Moreover, the expression of eight DEGs (MYL2, DES, MYOG, FAP, PLK2, ADAM, WWC1, and PRDX1) was validated. These findings offer novel insights into the transcriptional regulation of skeletal myogenesis in goats.

In livestock, a comprehensive understanding of the early-life establishment and acquisition of commensal gut microbiota allow us to develop better husbandry management operations and manipulate the gut microbiota for young animals, improving the efficiency of animal production. Here, we collected 123 microbial samples of 11 healthy goat kids and their mothers to investigate the colonization and acquisition of the gut microbiota and their correlations with volatile fatty acids (VFAs) in goat kids from birth to day 56. An age-dependent increasing and more homogeneous diversity were observed for the feces of goat kids. Overall, Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla in the fecal microbiota of goat kids, but their relative abundance varied considerably with age. Accordingly, the colonization of the fecal microbiota in goat kids was divided into three distinct stages: newborn (day 0), non-rumination stage (days 7–21), and transition stages (days 28–56). LEfSe analysis revealed a total of 49 bacterial biomarkers that are stage-specific (LDA score > 3, P < 0.05). Significant Spearman correlations (P < 0.05) were observed between the abundances of several bacterial biomarkers and the VFA concentrations. Furthermore, a substantial difference in the fecal microbiota composition was present between 56-day-old goat kids and mothers, whereas there was a moderate difference in the rumen microbiota between them. Among four body sites (i.e., feces, oral cavity, vagina, and breast milk) of mothers, the maternal vaginal and breast milk microbiota were the major source of the fecal microbiota of goat kids in the first 56 days after birth, although their contributions decreased with age and unknown sources increased after day 28. In summary, we concluded that the gut bacterial community in goat kids after birth was mainly acquired from the maternal vagina and breast milk. Its colonization showed three distinct phases with dramatic shifts of composition mainly driven by age and diet changes. Our results provide a framework for a better understanding of the roles of the gut microbiota in young ruminants.

Giant axonal neuropathy (GAN) is a very rare autosomal recessive disorder characterized by abnormally large and dysfunctional neuronal axons. Mutations in the GAN gene have been identified as the cause of this disorder. In this report, we performed a detailed phenotypic assessment of a Chinese patient with GAN. An array-based exon capture test and targeted next-generation sequencing were used to detect the suspected mutation sites. Compound heterozygous mutations of p.S79L (c.236C > T) in the BTB domain and p.T489S (c.1466C > G) in the kelch domain were identified in the proband’s genome. S79L was a known mutation, and T489S was reported for the first time. The p.S79L and p.T489S were confirmed in the proband’s mother and father, respectively. Both mutations were located in highly conserved regions and affected the predicted protein crystal structures. The proband’s sural biopsy revealed the classical GAN phenotype of swollen axons filled with closely packed neurofilaments. The combined application of the next-generation sequencing platform and bioinformatics analyses was an effective method for diagnosing GAN. The novel compound mutations of S79L and T489S in the GAN gene were likely the cause of the patient’s GAN symptoms. Our findings enrich the spectrum of mutations associated with this rare type of axonopathy.