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Meniscus-derived stem cells (MeSCs), a unique type of MSC, have outstanding advantages in meniscal cytotherapy and tissue engineering, but the effects and molecular mechanisms of PBM on MeSCs are still unclear. We used 660-nm LED light with different energy densities to irradiate six human MeSC samples and tested their proliferation rate via cell counting, chondrogenic differentiation capacity via the DMMB assay, mitochondrial activity via the MTT assay, and gene expression via qPCR. The proliferation ability, chondrogenic capacity and mitochondrial activity of the 18 J/cm2 group were greater than those of the 4 J/cm2 and control groups. The mRNA expression levels of Akt, PI3K, TGF-β3, Ki67 and Notch-1 in the 18 J/cm2 group were greater than those in the other groups in most samples. After chondrogenic induction, the expression of Col2A1, Sox9 and Aggrecan in the 18 J/cm2 group was significantly greater than that in the 4 J/cm2 and control groups in most of the samples. The variation in the MTT values and Src, PI3K, Akt, mTOR and GSK3β levels decreased with time. The results showed that 660-nm LED red light promoted proliferation and chondrogenic differentiation and affected the gene expression of MeSCs, and the effects on gene expression and mitochondrial activity decreased with time. [ABSTRACT FROM AUTHOR]

Simple Summary: Yaks are a major economic source for people in the Tibetan Plateau region. Yaks are rich in nutrients, but their low fat content is not conducive to the large-scale promotion of yak meat, so the study of the mechanism of yak lipid deposition is beneficial to the marketing of yak meat. In this paper, the results of transcriptome sequencing analysis of yak liver showed that it could be determined that the expression levels of genes associated with partial lipid deposition were significantly up-regulated during yak fattening. In addition, this study found that the tenderness of yak meat improved during this process. Fattening significantly affects fat deposition in yaks, which may be realized through its effects on lipid metabolic pathways. Therefore, studying the mechanism of lipid deposition in yaks and fattening yaks will improve the quality of yak meat. Yak meat is nutritionally superior to beef cattle but has a low fat content and is slow-growing. The liver plays a crucial role in lipid metabolism, and in order to determine whether different feeding modes affect lipid metabolism in yaks and how it is regulated, we employed RNA sequencing (RNA-seq) technology to analyze the genome-wide differential gene expression in the liver of yaks maintained under different raising systems. A total of 1663 differentially expressed genes (DEGs) were identified (|log2FC| ≥ 0 and p-value ≤ 0.05), including 698 down-regulated and 965 up-regulated genes. According to gene ontology (GO) and KEGG enrichment analyses, these DEGs were significantly enriched in 13 GO terms and 26 pathways (p < 0.05). Some DEGs were enriched in fatty acid degradation, PPAR, PI3K-Akt, and ECM receptor pathways, which are associated with lipid metabolism. A total of 16 genes are well known to be related to lipid metabolism (e.g., APOA1, FABP1, EHHADH, FADS2, SLC27A5, ACADM, CPT1B, ACOX2, HMGCS2, PLIN5, ACAA1, IGF1, FGFR4, ALDH9A1, ECHS1, LAMA2). A total of 11 of the above genes were significantly enriched in the PPAR signaling pathway. The reliability of the transcriptomic data was verified using qRT-PCR. Our findings provide new insights into the mechanisms regulating yak meat quality. It shows that fattening improves the expression of genes that regulate lipid deposition in yaks and enhances meat quality. This finding will contribute to a better understanding of the various factors that determine yak meat quality and help develop strategies to improve yield and quality. [ABSTRACT FROM AUTHOR]

Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks. Yaks have been subject to natural selection, human domestication and interspecific introgression during their evolution. Here, the authors have identified genomic structural variations and the linked genes involved in these processes in domestic yaks, to reveal new insight into genetic basis of phenotypic diversity. [ABSTRACT FROM AUTHOR]

Yaks (Bos grunniens) are a critical livestock breed in the plateau region, and changing the feeding system of yaks can significantly improve their growth performance. The effects of different feeding regimes on the growth performance and meat quality of yaks were comprehensively compared here. The transcriptome and proteome of the Longissimus dorsi muscle were determined using RNA-seq and Tandem Mass Tag (TMT) techniques. Indoor feeding significantly improved the growth performance (such as the average daily gain and carcass weight) and meat quality characteristics compared with traditional grazing feeding. In the grazing (Group G) vs. in-house fed group (Group HF) comparison, 40 differentially expressed genes/differentially abundant proteins exhibited the same mRNA and protein expression trends. These genes were associated with collagen binding, the lipoxygenase pathway, and the arachidonic acid metabolic process. Parallel reaction monitoring verified whether the TMT results were reliable. Moreover, some pathways, such as the AMPK signaling pathway, FoxO signaling pathway, PPAR signaling pathway, and fatty acid metabolism, were significantly enriched. These results expand our knowledge about meat quality in yaks and provide practical information and more evidence for further insight into the biological mechanisms underlying meat quality traits. [ABSTRACT FROM AUTHOR]

The interaction between the dermal papilla cells (DPCs) and epidermal hair matrix cells (HMCs) of hair follicles (HFs) is crucial for the growth and development of HFs, but the molecular mechanism is complex and remains unclear. MicroRNAs (miRNAs) are the key signaling molecules for cellular communication. In this study, the DPCs and HMCs of yak were isolated and cultured, and the differentially expressed mRNA and miRNA were characterized to analyze the molecular basis of the interaction between DPCs and HMCs during hair follicle (HF) development in yak. The mRNA differential expression and functional enrichment analysis revealed that there were significant differences between DPCs and HMCs, and they showed the molecular functional characteristics of dermal cells and epidermal cells, respectively. Multiple KEGG pathways related to HF development were enriched in the highly expressed genes in DPCs, while the pathways associated with microbiota and immunity were significantly enriched in the highly expressed genes in HMCs. By combining analysis with our previous 10× genomics single-cell transcriptome data, 39 marker genes of DPCs of yak were identified. A total of 123 relatively specifically expressed miRNAs were screened; among these, the miRNAs associated with HF development such as miR-143, miR-214, miR-125b, miR-31, and miR-200 were presented. In conclusion, the large changes in yak DPCs and HMCs for both mRNA and miRNA expression were revealed, and numerous specifically expressed mRNAs and miRNAs in DPCs or HMCs were identified, which may contribute to the interaction and cellular communication between DPCs and HMCs during HF development in yak. [ABSTRACT FROM AUTHOR]

Cattle-yak is a hybrid F1 generation of cattle and yak, which has a history of more than 3000 years and has shown better production performance and higher economic benefits than those of yaks. However, up to now, there has been no study on the transcriptome-wide m6A methylation profile of bovine skeletal muscle and its potential biological function during muscle development. Here, we observed significant changes in the expression levels of muscle-related marker genes and methylation-related enzymes during the development of cattle-yak, and the overall m6A content in the Longissimus dorsi muscle of 18-month-old cattle-yak decreased significantly. A total of 36,602 peaks, 11,223 genes and 8388 lncRNAs were identified in the two groups, including 2989 differential peaks (427 up-regulated peaks and 2562 down-regulated peaks), 1457 differentially expressed genes (833 up-regulated genes and 624 down-regulated genes) and 857 differentially expressed lncRNAs (293 up-regulated lncRNAs and 564 down-regulated lncRNAs). GO and KEGG analysis revealed that they were significantly enriched in some muscle-related pathways (Wnt signaling pathway and MAPK signaling pathway) and high-altitude adaptation-related pathway (HIF-1 signaling pathway). Moreover, m6A abundance was positively correlated with gene expression levels, while it was negatively correlated with lncRNA expression levels. This indicates that m6A modification played an important role in the Longissimus dorsi muscle development of cattle-yak; however, the regulation mechanism of m6A-modified mRNA and lncRNA may be different. This study was the first report of transcriptome-wide m6A-modified mRNAs and lncRNAs atlas in the Longissimus dorsi muscle development of cattle-yak, one which will provide new perspectives for genetic improvement in bovines. [ABSTRACT FROM AUTHOR]

Simple Summary: Exosomes are multivesicular bodies produced and secreted by living cells as membranous vesicles with a diameter of about 30–150 nm, density of 1.13–1.19 g/mL, and a typical "cup dish" shape. Exosomes carry proteins, miRNA, lncRNA, circRNA, and mRNA and their degradation fragments are involved in intracellular signal transduction important for regulation of cellular activities. Of these, miRNAs play an important role in the regulation of gene expression in important biological processes such as cell division, tissue development, and immune response. In this study, milk quality was determined and exosome miRNAs from yak and Jeryak milk sampled in June and December were characterized by sequencing. Differentially expressed miRNAs (DEMs) and pathways related to lactation performance were identified. In summary, this study provides data that can be used to develop alternative strategies for improving the lactation performance of yaks and Jeryaks. The Jeryak is the hybrid offspring of yaks and Jersey cattle and exhibit improved milk and meat yields. Biomolecules carried within milk exosomes are important for cell growth, development, immune regulation, and various pathophysiological processes. Previous studies showed that miRNAs regulate mammary gland development, lactation, and milk quality. This study explored the relationship between milk exosomes miRNAs and lactation performance. A comparison of the milk content showed that yak milk was of a better quality compared to Jeryak milk (casein, fat, TS, SNF, lactose). Milk collected in December was superior to that collected in June for both yak and Jeryak, except for lactose concentrations. Exosomes were extracted by density gradient centrifugation and miRNA expression profiles in milk exosomes from three yaks and three Jeryaks collected in June and December were detected by small RNA sequencing. In all, 22, 120, 78, and 62 differentially expressed miRNAs (DEMs) were identified in Jun_ JY vs. Jun_ Y (P1: Jeryak in June vs. Yak in June), Jun_ JY vs. Dec_ JY (P2: Jeryak in June vs. Jeryak in December), Dec_ JY vs. Dec_ Y (P3: Jeryak in December vs. Yak in December), and Jun_ Y vs. Dec_ Y (P4: Yak in June vs. Yak in December) groups. These DEMs were enriched in functions and signaling pathways related to lactation performance. In conclusion, these findings are a reference tool to study the molecular basis of lactation performance. [ABSTRACT FROM AUTHOR]

Simple Summary: The SOX6 (sex determining region Y-box 6) gene belongs to one of the transcription factors in the SRY (sex-determining region Y) family, which affects sex determination, embryonic and nervous system development, bone and various organ formation. In the previous study, the whole-genome sequencing was used to detect multiple genes located in the copy number variation region, including SOX6 gene. In this study, we identified the correlation between the growth traits and CNV of SOX6 in 311 Ashidan yaks. The results showed that SOX6-CNV was significantly correlated with the chest girth of the 6-months old yaks (p < 0.05) and 30-months yaks (p < 0.05), and withers height of 6 months yaks (p < 0.05) and 18-months yaks (p < 0.05), suggesting the SOX6-CNV affect growth traits in yaks, and could be new markers for the selection of yak breeding. Copy number variation (CNV) is a fundamental type of structural variation of the genome affecting the economic traits of livestock. The SOX6 gene (sex-determining region Y-box 6), as a transcription factor, has multiple functions with regard to sex determination, embryonic growth, the nervous system development, as well as bone, and various organ formation. This study employed quantitative real-time fluorescence quota PCR (qPCR) for detecting the SOX6-CNV of the 311 Ashidan yaks and analyzed the correlation of the SOX6-CNV with four phenotypes (including body weight, withers height, body length, and chest girth) of the yaks aged 6, 12, 18, and 30 months using ANOVA and multiple comparisons. Furthermore, the SOX6 gene expression was identified in seven different tissues of the yaks. The experiment results demonstrated the expression of SOX6 in each tissue, and the kidney and muscle tissue were found to have higher relative expression levels. Based on the processing by IBM SPSS software, SOX6-CNV was significantly correlated with the chest girth of the 6-months old yaks (p < 0.05) and 30-months yaks (p < 0.05), and withers height of 6 months yaks (p < 0.05) and 18-months yaks (p < 0.05), as well as the normal type of CNV, was chosen for yak breeding. In conclusion, SOX6 might be prominently involved in promoting growth and development of yaks, suggesting that the SOX6 gene can be used in breeding yaks by molecular marker-assisted selection (MAS). The study also offered some important insights into the references and clues for the genetic breeding of yaks. [ABSTRACT FROM AUTHOR]

Background: The hair coat is available for the yak to live in the harsh environment of the plateau. Besides, improving the hair production of yak is necessary for its textile industry development. Hair grows from hair follicles (HFs). The HFs undergo periodic growth after birth and are regulated by the complex gene regulatory network. However, the molecular mechanism of HFs regeneration in the Tianzhu white yak remains unclear. RNA editing is a post-transcriptional mechanism that regulates gene expression and produces new transcripts. Hence, we investigated the influence of the A-to-I RNA editing events on the HFs cycle of the Tianzhu white yak. Results: We finally identified 54,707 adenosine-to-inosine (A-to-I) RNA editing sites (RESs) from RNA sequencing data of the HFs cycle in the Tianzhu white yak. Annotation results showed RESs caused missense amino acid changes in 7 known genes. And 202 A-to-I editing sites altered 23 target genes of 140 microRNAs. A total of 1,722 differential RESs were identified during the HFs cycle of Tianzhu white yak. GO and KEGG enrichment analysis revealed several signaling pathways and GO terms involved skin development, hair growth, and HFs cycle. Such as genes with differential RNA editing levels were significantly enriched in the peroxisome, metabolic pathways, Notch signaling pathway, and PPAR signaling pathway. Besides, the editing sites in HFs development-related genes FAS, APCDD1, WWOX, MPZL3, RUNX1, KANK2, DCN, DSC2, LEPR, HEPHL1, and PTK2B were suggested as the potential RESs involving HFs development. Conclusion: This study investigated the global A-to-I RNA editing events during the HFs cycle of yak skin tissue and expanded the knowledge of A-to-I RNA editing on the HFs cycle. Furthermore, this study revealed that RNA editing-influenced genes may regulate the HFs cycle by participating in the HFs development-related pathways. The findings might provide new insight into the regulation of RNA editing in hair growth. [ABSTRACT FROM AUTHOR]

Yaks are crucial genetic resources in the Tibetan Plateau and surrounding regions. Throughout the long process of domestication, natural and artificial selection pressures have enabled yaks to demonstrate adaptive characteristics to the environment in terms of physiological structure and genetic molecules, but no systematic cell analysis has been carried out on this phenomenon of yaks. Here, the population structure and genetic diversity of yak were studied by WGRS, and the genes related to yak adaptability were excavated. Combined with scRNA-seq method, the transcription map of yak lung tissue and skin tissue was constructed, which provided a new comprehensive insight into yak adaptability. The analysis of yak population structure showed that there was obvious genetic differentiation between TZ _ yak and other seven yak populations, while there was significant genetic exchange between PL _ yak and SB _ yak at high altitude. WGRS and scRNA-seq analysis revealed that the gene HIF1A related to high altitude adaptation was expressed in various cell types, while EPAS1 was predominantly expressed in epithelial and endothelial cells of yak lung tissue. Endothelial cells play a critical role in hypoxia-adapted VEGF signaling, which correlates closely with the high expression of KDR and VEGFA genes in endothelial cells and monocytes. Furthermore, in the selection signal of High _ yak vs Low _ yak, 19.8 % of the genes overlapped with the genes screened by skin scRNA-seq, including genes related to coat color such as RORA , BNC2 , and KIT. Notably, BNC2 is a gene associated with melanin deposition and shows high expression levels in HS cells. Additionally, GRN in melanocytes and SORT1 in IRS play an important role in cell communication between melanocytes and IRS. These findings offer new insights into the natural polymorphism of yaks and provide a valuable reference for future research on high-altitude mammals, and potentially even human genetics. • This study innovatively integrates whole-genome resequencing (WGRS) with single-cell RNA sequencing (scRNA-seq) to provide a comprehensive understanding of yak adaptability. • By constructing transcription maps of yak lung and skin tissues, we uncover novel insights into the cellular mechanisms underlying yak's exceptional adaptability to high-altitude environments. • Our findings reveal that genes associated with high-altitude adaptation, such as HIF1A and EPAS1 , exhibit distinct expression patterns across cell types. • Notably, we identify a crucial role for endothelial cells in hypoxia-adapted VEGF signaling, evidenced by the co-expression of KDR and VEGFA genes. • Furthermore, our comparative analysis of high- vs low-altitude yak populations uncovers an overlap of 19.8 % of genes with skin scRNA-seq results, highlighting genes related to coat color polymorphism, including BNC2 , RORA , and KIT. [ABSTRACT FROM AUTHOR]

A previous study using next-generation sequencing illustrated and confirmed that the cholinergic receptor muscarinic 3 (CHRM3) gene resides within CNVRs of yak populations that overlap with quantitative trait loci (QTL) relating to meat quality and growth, and plays a prominent role in smooth muscle contraction. This study was conducted to determine the distribution of the CNVs of the CHRM3 gene in five Chinese domestic yak breeds and to investigate the influences of the CHRM3 gene on the gene expression and growth traits of the Datong yak. The data were analyzed by ANOVA using SPSS software. Our results revealed that a gain CNV type in the CHRM3 gene is more highly associated (P < 0.05) with various growth traits in six-month-old and five-year-old Datong yaks. The gain CNV type of the CHRM3 gene more frequently occurred than loss and normal types in all yak breeds. Nevertheless, the CHRM3 gene copy number had a highly significant (P <0.0012) and moderately negative correlation with the mRNA transcription levels were determined in the skeletal muscle of Chinese Datong yaks. Therefore, we concluded that this study provided inclusive information on the application of CNVs of the CHRM3 in growth traits and its possible function. [ABSTRACT FROM AUTHOR]

Plant viruses have been engineered to express proteins and induce gene silencing for decades. Recently, plant viruses have also been used to deliver components into plant cells for genome editing, a technique called virus-induced genome editing (VIGE). Although more than a dozen plant viruses have been engineered into VIGE vectors and VIGE has been successfully accomplished in some plant species, application of VIGE to crops that are difficult to tissue culture and/or have low regeneration efficiency is still tough. This paper discusses factors to consider for an ideal VIGE vector, including insertion capacity for foreign DNA, vertical transmission ability, expression level of the target gene, stability of foreign DNA insertion, and biosafety. We also proposed a step-by-step schedule for excavating the suitable viral vector for VIGE. • Factors to considerate when designing a virus vector are discussed. • The biosafety issue of virus-induced genome editing (VIGE) was proposed. • A procedure is proposed to select the right virus for VIGE. [ABSTRACT FROM AUTHOR]

Copy number variations (CNVs) can cause radical changes in phenotype variation, gene expression and evolutionary adaptation, through gene dosage effects, disruption of transcript arrangement and regulatory polymorphisms. Therefore, the current study was undertaken to investigate the distribution of glypican1 (GPC1) CNVs in five domestic yak breeds, and their association growth traits and gene expression. The data were analysed using real-time quantitative PCR (qPCR). Loss and normal copy number types had a significant (p <.05) associated with body height, weight and length and chest girth than gain of copy number types. Population studies indicated that loss of copy number was more frequently observed in the Tianzhu, Gannan and Plateau yaks than the Polled and Datong yaks. We elucidated a moderately negative and highly significant (p <.005) correlation among DNA copy numbers and mRNA transcription levels of GPC1. From these results, we hypothesise that GPC1 CNVs could alter mRNA transcription levels of skeletal muscles which impact on quantitative of growth traits. Our study makes data available for breeders and genomics studies focussing on the fundamental function of GPC1 CNVs in gene expression and growth traits and presents the foundation for future molecular marker application in designing yak breeding programmes. The GPC1 gene encompasses within CNVRs of yak individuals that overlap with growth traits. The copy number types of GPC1 had a significant associated with growth traits of yak breeds Negative and highly significant correlation among DNA copy numbers and mRNA transcription levels of GPC1 are obtained [ABSTRACT FROM AUTHOR]

(-)-Epigallocatechin-3-gallate (EGCG), which is the most abundant catechin in green tea, has many potential health benefits, including decreased weight gain and/or adipose tissue weight. Suggested mechanisms for body weight reduction by EGCG include: (1) a decrease in calorie intake and (2) activation of AMPK in liver, skeletal muscle, and white adipose tissue. However, only one study supports the AMPK hypothesis. To determine the role of AMPK in EGCG-induced reduction of body weight, we administrated 50 mg/kg and 100 mg/kg per day to mice, together with a high-fat diet (HFD), for 20 weeks. EGCG had a significant effect on obesity and decrease in epididymal adipose tissue weight, and also affected serum lipid characteristics, including triglyceride, cholesterol (CHOL), and high- and low-density lipoprotein CHOL (HDL-C, LDL-C) concentrations. In addition, EGCG increased the excretion of free fatty acids from feces. By measuring the mRNA expression levels of genes involved in lipid metabolism, we found that EGCG inhibited the expression of genes involved in the synthesis of de novo fatty acids (acc1 , fas , scd1 , c/ebp β, ppar γ, and srebp1) and increased the expression of genes associated with lipolysis (hsl) and lipid oxidization in white adipose tissue, in both the HFD and the EGCG groups. However, EGCG significantly increased the expression of genes involved in the synthesis of de novo fatty acids compared with the HFD group. Increased AMPK activity was found in both subcutaneous and epididymal adipose tissues. In conclusion, EGCG can decrease obesity and epididymal white adipose tissue weight in mice, only partially via activation of AMPK. [ABSTRACT FROM AUTHOR]

The energy available from the diet, which affects fat deposition in vivo, is a major factor in the expression of genes regulating fat deposition in the longissimus dorsi muscle. Providing high-energy diets to yaks might increase intramuscular fat deposition and fatty acid concentrations under a traditional grazing system in cold seasons. A total of fifteen adult castrated male yaks with an initial body weight 274.3 ± 3.14 kg were analyzed for intramuscular adipose deposition and fatty acid composition. The animals were divided into three groups and fed low-energy (LE: 5.5 MJ/kg), medium-energy (ME: 6.2 MJ/kg) and high-energy (HE: 6.9 MJ/kg) diets, respectively. All animals were fed ad libitum twice daily at 08:00–09:00 am and 17:00–18:00 pm and with free access to water for 74 days, including a 14-d period to adapt to the diets and the environment. Intramuscular fat (IMF) content, fatty acid profile and mRNA levels of genes involved in fatty acid synthesis were determined. The energy levels of the diets significantly (P<0.05) affected the content of IMF, total SFA, total MUFA and total PUFA. C16:0, C18:0 and C18:1n9c account for a large proportion of total fatty acids. Relative expression of acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid-binding protein 4 (FABP4) was greater in HE than in LE yaks (P<0.05). Moreover, ME yaks had higher (P<0.05) mRNA expression levels of PPARγ, ACACA, FASN, SCD and FABP4 than did the LE yaks. The results demonstrate that the higher energy level of the diets increased IMF deposition and fatty acid content as well as increased intramuscular lipogenic gene expression during the experimental period. [ABSTRACT FROM AUTHOR]

[Display omitted] • BPB or BPAF exposure can cause changes in mouse immune comprehensive landscape. • BPB or BPAF exposure can cause changes in mouse uterine genome expression profile. • BPB or BPAF exposure can increase the risk of uterine disease. • Srd5a1 may be a valuable signal of uterus abnormalities caused by BPB/BPAF exposure. Bisphenol A (BPA) analogs, bisphenol B (BPB) and bisphenol AF (BPAF) have been widely detected in the environment and human products with increasing frequency. However, uterine health risks caused by BPB and BPAF exposure need to be further elucidated. The study aimed to explore whether BPB or BPAF exposure will induce adverse outcomes in uterus. Female CD-1 mice were continuously exposed to BPB or BPAF for 14 and 28 days. Morphological examination showed that BPB or BPAF exposure caused endometrial contraction, decreased epithelial height, and increased number of glands. Bioinformatics analysis indicated that both BPB and BPAF disturbed the immune comprehensive landscape of the uterus. In addition, survival and prognosis analysis of hub genes and tumor immune infiltration evaluation were performed. Finally, the expression of hub genes was verified by quantitative real-time PCR (qPCR). Disease prediction found that eight of the BPB and BPAF co-response genes, which participated in the immune invasion of the tumor microenvironment, were associated with uterine corpus endometrial carcinoma (UCEC). Importantly, the gene expression levels of Srd5a1 after 28-day BPB and BPAF exposure were 7.28- and 25.24-fold higher than those of the corresponding control group, respectively, which was consistent with the expression trend of UCEC patients, and its high expression was significantly related to the poor prognosis of patients (p = 0.003). This indicated that Srd5a1 could be a valuable signal of uterus abnormalities caused by BPA analogs exposure. Our study revealed the key molecular targets and mechanisms of BPB or BPAF exposure induced uterine injury at the transcriptional level, providing a perspective for evaluating the safety of BPA substitutes. [ABSTRACT FROM AUTHOR]

The ban on bisphenol A (BPA) has led to a rapid increase in the use of BPA analogs, and they are increasingly being detected in the natural environment and biological organisms. Studies have pointed out that BPA analogs can lead to adverse health outcomes. However, their interference with ovarian tissue has not been fully elucidated. In this study, seven- to eight-week-old CD-1 mice were exposed to corn oil containing 300 μg/kg/day bisphenol B (BPB) or bisphenol AF (BPAF) through oral gavage, and ovarian tissues were collected at 14 and 28 days of exposure. Ovarian toxicity was evaluated by the ovarian index, ovarian area, and follicle number. mRNA-seq was used to identify differentially expressed genes (DEGs) and infer the association of DEGs with ovarian diseases. BPB or BPAF exposure induced morphological changes in ovarian tissue in CD-1 mice. In addition, Gene Ontology (GO) analysis revealed disturbances in biological processes (BP) associated with steroid biosynthetic process (GO:0006694) and cellular calcium ion homeostasis (GO:0006874). Subsequently, regulatory networks of BPA analogs (BPB or BPAF)-DEGs-ovarian diseases were constructed. Importantly, the expression levels of DEGs and transcription factors (TFs) associated with ovarian disease were altered. BPB or BPAF exposure causes damage to ovarian morphology through the synergistic effects of multiple biological processes and may be associated with altered mRNA expression profiles as a risk factor for ovarian diseases. [Display omitted] • BPB or BPAF exposure causes morphological changes in the ovary of CD-1 mice. • BPB or BPAF exposure alters the transcriptomic profile of ovarian tissue. • Dysregulation of DEGs and TFs is associated with ovarian disease. [ABSTRACT FROM AUTHOR]

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase (RdRp) and responsible for replicating the whole HCV genome with help of viral and cellular proteins. However, how cellular factors influence NS5B and, in turn, regulating HCV replication are still poorly defined. The well known tumor suppressor Fbw7, a component of E3 ubiquitin ligase SCF Fbw7 , targets oncoproteins or cellular regulatory proteins for ubiquitin-mediated degradation through a highly conserved binding site called a Cdc4 phosphodegron (CPD). But little is known about whether Fbw7 plays a role in regulation of viral proteins. In this study, we revealed that the conserved CPD is shared by NS5B of almost all genotype of HCV and our data demonstrated that NS5B is a bona fide substrate of Fbw7. Forced expression of Fbw7 promoted the ubiquination of NS5B and negatively regulated its turnover in the proteasome–dependent manner. We further revealed the interaction between NS5B and Fbw7, which resulted in the relocation of Fbw7 from nucleus to cytoplasm. During HCV replication, ectopic expression of Fbw7 could strongly down-regulate NS5B level and consequently inhibited the virus replication. When endogenous Fbw7 was knocked down, both NS5B protein abundance and HCV replication were remarkably up-regulated. The results provide more insights into the interplay of HCV and cellular factors and shed light on molecular mechanisms of HCV replication and pathogenesis. [ABSTRACT FROM AUTHOR]

Gestation is a sensitive window to nitrogen dioxide (NO 2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO 2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO 2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time-series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO 2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern. • Maternal NO 2 exposure induces alveolar defects in lung tissue of offspring mice. • Maternal NO 2 exposure altered lncRNAs expression profiles in a time series pattern. • Dysregulation of target gene expression involved in pulmonary vascular development. [ABSTRACT FROM AUTHOR]

Locusta migratoria is a classic hemimetamorphosis insect and has caused widespread economic damage to crops as a migratory pest. Researches on the expression pattern of functional genes in L. migratoria have drawn focus in recent years, especially with the release of genome information. Real-time quantitative PCR is the most reproducible and sensitive approach for detecting transcript expression levels of target genes, but optimal internal standards are key factors for its accuracy and reliability. Therefore, it's necessary to provide a systematic stability assessment of internal control for well-performed tests of target gene expression profile. In this study, twelve candidate genes (Ach, Act, Cht2, EF1α, RPL32, Hsp70, Tub, RP49, SDH, GAPDH, 18S, and His) were analyzed with four statistical methods: the delta Ct approach, geNorm, Bestkeeper and NormFinder. The results from these analyses aimed to choose the best suitable reference gene across different experimental situations for gene profile study in L. migratoria. The result demonstrated that for different developmental stages, EF1α, Hsp70 and RPL32 exhibited the most stable expression status for all samples; EF1α and RPL32 were selected as the best reference genes for studies involving embryo and larvae stages, while SDH and RP49 were identified for adult stage. The best-ranked reference genes across different tissues are RPL32, Hsp70 and RP49. For abiotic treatments, the most appropriate genes we identified were as follows: Act and SDH for larvae subjected to different insecticides; RPL32 and Ach for larvae exposed to different temperature treatments; and Act and Ach for larvae suffering from starvation. The present report should facilitate future researches on gene expression in L. migratoria with accessibly optimal reference genes under different experimental contexts. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the expression of GRP78 in human renal cell carcinoma (RCC) and its significance. Methods: We studied RNA and tissue section of a tumor and adjacent nontumorous renal tissues obtained from radical nephrectomy specimens of 42 patients and RCC cell lines. We used reverse transcriptase-PCR and immunohistochemistry to detect the GRP78 mRNA and protein expression, respectively. Results: Reverse transcriptase-PCR revealed that GRP78 mRNA is positively expressed in RCC cell lines (786-0, OS-RC-2, and Caki-1); the GRP78 mRNA expression in the RCC and adjacent nontumorous renal tissues was 0.88 ± 0.34 and 0.44 ± 0.15, respectively (P < .001). The GRP78 protein was found in RCC cell lines. Immunohistochemistry results also showed that the level of GRP78 protein expression of RCC tissues was significantly higher than that of the adjacent nontumorous renal tissues (P < .001). The high levels of GRP78 mRNA and protein expression were related to the large tumor size and high clinical stage (P < .001) but not to sex, age, and cell differentiate (P > .05). Conclusions: To our knowledge, the present study is the first to report the upregulated expression of GRP78 and that it is possibly involved in pathogenesis of RCC. [Copyright &y& Elsevier]

Superoxide dismutase and catalase are two major antioxidant enzymes in the fish antioxidant defense system, which can remove excess reactive oxygen species and protect fish from stress-induced oxidative damage. The present study aimed to clone the sequences of Yangtze sturgeon, Acipenser dabryanus, Cu/Zn superoxide dismutase (AdCu/Zn-SOD) and catalase (AdCAT), and to explore changes of gene expression in the liver and intestine during fasting and refeeding. A total of 120 fish were exposed to four fasting and refeeding protocols (fasting for 0, 3, 7, or 14 d and then refeeding for 14 d). The coding sequences of AdCu/Zn-SOD and AdCAT encoded 155 and 526 amino acid proteins, respectively, both of which were expressed mainly in the liver. During fasting, when compared to the control group, liver AdCu/Zn-SOD expression was significantly higher in the 3- and 14-d groups, whereas its intestinal expression increased significantly only in the 7-d group. Liver AdCAT expression increased significantly in the 3-, 7-, and 14-d groups. During refeeding, liver AdCu/Zn-SOD expression increased significantly in the 3-, 7-, and 14-d groups compared with those in the control group. Similarly, intestinal AdCu/Zn-SOD expression increased significantly in the 3- and 7-d groups. Moreover, intestinal AdCAT expression was significantly higher in the 3-d group than in the control group, but decreased significantly in the 14-d group. Our findings indicated that AdCu/Zn-SOD and AdCAT play important roles in protecting fish against starvation-induced oxidative stress. Yangtze sturgeon exhibited the potential to adapt to a starvation and refeeding regime. [ABSTRACT FROM AUTHOR]

Simple Summary: Yak (Bos grunniens) provides life materials for herdsmen in high-plateau areas. Improving their low fertility is necessary to meet the demands of the development of the yak industry. The testis is an important organ for male fertility, its development is controlled by a large number of genes. Using real-time reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to explore the quantitative expression of genes can provide insights for illuminating the molecular mechanisms of testis development, but the RT-qPCR data are influenced by the stability of reference genes (RGs). Unfortunately, no available RGs can normalize the gene expression in yak testis development. In this study, the expression stability of 13 candidate genes in yak testis at different developmental stages was evaluated using five different pieces of software. The results showed that the TATA box-binding protein (TBP) and ubiquitously expressed transcript protein (UXT) exhibited high stability across various developmental stages, TBP and hydroxymethylbilane synthase (HMBS) were the most stably expressed genes in immature stages, and mitochondrial ribosomal protein L39 (MRPL39) and TBP exhibited the most stable expression across mature stages. This study provided suitable RGs for gene expression studies in yak testis development. Testis has an important function in male reproduction. Its development is regulated by a large number of genes. The real-time reserve transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a useful tool to evaluate the gene expression levels. However, unsuitable reference genes (RGs) can cause the misinterpretation of gene expression levels. Unfortunately, the ideal RGs for yak testis development are yet to be studied. In this study, 13 commonly used RGs were selected to identify the most stable RGs in yak testis at four different developmental stages, including two immature stages (6 months and 18 months) and two mature stages (30 months and 6 years). This study used GeNorm, NormFinder, BestKeeper, ∆Ct, and RefFinder programs to evaluate the stability of 13 candidate genes. The results of RefFinder showed that the stabilities of TATA box-binding protein (TBP) and ubiquitously expressed transcript protein (UXT) were ranked the top two across all developmental stages. TBP and hydroxymethylbilane synthase (HMBS) were stably expressed in immature stages, while mitochondrial ribosomal protein L39 (MRPL39) and TBP had higher stability than other candidate genes in mature stages. This study provided valuable information for gene expression studies to assist further investigation on the molecular mechanisms in underlying yak testis development. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous studies revealed that luteinizing hormone βeta polypeptide (LHB) plays an essential role in fertilization. Therefore, we aimed to confirm the importance of LHB in the testis of yak and to determine their association with male yak fertility. Histomorphological analysis of the testes is essential for predicting the fertilizing ability of the bull. To the best our knowledge, this is the first study to evaluate the micro anatomical changes and histometric alternation in testes of Datong yak. These findings could help to predict the sperm production capacity and to understand the specific molecular mechanisms of LHB during spermatogenesis. Histological examination of testes is essential for understanding infertility, sex development, and growth. Therefore, to understand the histomorphology of testes at different developmental stages, we performed hematoxylin and eosin staining of Yak testis. Our results revealed that the diameters of spermatogenic cells and their nuclei were significantly larger (p < 0.05) in the testis at six years compared to at six and 18 months. No significant difference was noted between 30 months and six years. The study was designed to compare the expression profile of LHB in Datong yak. The expression pattern of LHB was explored using quantitative PCR, semi-quantitative PCR, molecular bioinformatic, and Western blot analysis. Our observations indicated that expression of LHB was significantly higher (p < 0.05) in the testis of Datong yak. Western blotting indicated that the molecular mass of LHB protein was 16 kDa in yak. The protein encoded by yak LHB included conserved cysteine-knot domain regions. The high expression of LHB in testis indicated that LHB may be vital for the development of male gonads and the fertility of Datong yak. [ABSTRACT FROM AUTHOR]

DNA methylation modifications are implicated in many biological processes. As the most common epigenetic mechanism DNA methylation also affects muscle growth and development. The majority of previous studies have focused on different varieties of yak, but little is known about the epigenetic regulation mechanisms in different age groups of animals. The development of muscles in the different stages of yak growth remains unclear. In this study, we selected the longissimus dorsi muscle tissue at three different growth stages of the yak, namely, 90-day-old fetuses (group E), six months old (group M), and three years old (group A). Using RNA-Seq transcriptome sequencing and methyl-RAD whole-genome methylation sequencing technology, changes in gene expression levels and DNA methylation status throughout the genome were investigated during the stages of yak development. Each group was represented by three biological replicates. The intersections of expression patterns of 7694 differentially expressed genes (DEGs) were identified (padj < 0.01, |log2FC| > 1.2) at each of the three developmental periods. Time-series expression profile clustering analysis indicated that the DEGs were significantly arranged into eight clusters which could be divided into two classes (padj < 0.05), class I profiles that were downregulated and class II profiles that were upregulated. Based on this cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs from class I profiles were significantly (padj < 0.05) enriched in 21 pathways, the most enriched pathway being the Axon guidance signaling pathway. DEGs from the class II profile were significantly enriched in 58 pathways, the pathway most strongly enriched being Metabolic pathway. After establishing the methylation profiles of the whole genomes, and using two groups of comparisons, the three combinations of groups (M-vs.-E, M-vs.-A, A-vs.-E) were found to have 1344, 822, and 420 genes, respectively, that were differentially methylated at CCGG sites and 2282, 3056, and 537 genes, respectively, at CCWGG sites. The two sets of data were integrated and the negative correlations between DEGs and differentially methylated promoters (DMPs) analyzed, which confirmed that TMEM8C, IGF2, CACNA1S and MUSTN1 were methylated in the promoter region and that expression of the modified genes was negatively correlated. Interestingly, these four genes, from what was mentioned above, perform vital roles in yak muscle growth and represent a reference for future genomic and epigenomic studies in muscle development, in addition to enabling marker-assisted selection of growth traits. [ABSTRACT FROM AUTHOR]

Simple Summary: The Ashidan yak is a new cultivated breed which has polled characteristics and a mild temperament. Improving milk yield is an important aspect of a breeding program for this breed. The mammary gland undergoes dramatic physiological and metabolic changes during the transition from lactation to dry periods, which involves the expression and regulation of a great number of genes. Quantification of gene expression levels by real-time quantitative polymerase chain reaction (RT-qPCR) is important to reveal the molecular mechanisms of mammary gland development and lactation. The accuracy of RT-qPCR is strongly influenced by the expression stability of reference genes, however, a systematic approach for selecting reference genes used for analyzing gene expression of the Ashidan yak has not been developed. In this study, we selected reference genes and analyzed their expression stability at different physiological stages (lactation and dry period). We found the hydroxymethylbilane synthase gene (HMBS) and the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide gene (YWHAZ) were the most stable genes of the mammary gland of the Ashidan yak. These results help to improve the accuracy of gene expression analysis and provide a basis for future functional studies of target gene expression in the mammary gland of the Ashidan yak. Investigating the critical genes related to milk synthesis is essential for the improvement of the milk yield of the yak. Real-time quantitative polymerase chain reaction (RT-qPCR) is a reliable and widely used method to measure and evaluate gene expression levels. Selection of suitable reference genes is mandatory to acquire accurate normalization of gene expression results from RT-qPCR. To select the most stable reference genes for reliable normalization of mRNA expression by RT-qPCR in the mammary gland of the Ashidan yak, we selected 16 candidate reference genes and analyzed their expression stability at different physiological stages (lactation and dry period). The expression stability of the candidate reference genes was assessed using geNorm, NormFinder, BestKeeper, Delta Ct, and RefFinder methods. The results showed that the hydroxymethylbilane synthase gene (HMBS) and the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide gene (YWHAZ) were the most stable genes across all treatment samples. The reliability of selected reference genes was validated by normalizing relative expression of the lactation-related 60S ribosomal protein L35 gene (RPL35). The relative expression of RPL35 varied considerably according to the different reference genes. This work provides valuable information to further promote research in the molecular mechanisms involved in lactation and mammary gland development and provides a foundation for the improvement of the milk yield and quality of the Ashidan yak. [ABSTRACT FROM AUTHOR]

Testis-specific genes play an essential part in the centromere union during meiosis in male germ cells, spermatogenesis, and in fertility. Previously, there was no research report available on the expression pattern of SYCP3 and TSEG2 genes in different ages of yaks. Therefore, the current research compared the expression profiling of SYCP3 and TSEG2 genes in testes of yaks. The expression pattern of SYCP3 and TSEG2 mRNA was investigated using qPCR, semi-quantitative PCR, western blot, immunohistochemistry, and molecular bioinformatics. Our findings displayed that SYCP3 and TSEG2 genes were prominently expressed in the testicles of yaks as compared to other organs. On the other hand, the protein encoded by yak SYCP3 contains Cor1/Xlr/Xmr conserved regions, while the protein encoded by yak TSEG2 contains synaptonemal complex central element protein 3. Additionally, multiple alignments sequences indicated that proteins encoded by Datong yak SYCP3 and TSEG2 were highly conserved among mammals. Moreover, western blot analysis specified that the molecular mass of SYCP3 protein was 34-kDa and TSEG2 protein 90-kDa in the yak. Furthermore, the results of immunohistochemistry also revealed the prominent expression of these proteins in the testis of mature yaks, which indicated that SYCP3 and TSEG2 might be essential for spermatogenesis, induction of central element assembly, and homologous recombination. [ABSTRACT FROM AUTHOR]

Simple Summary: IZUMO1 (IZUMO sperm-egg fusion) is a crucial member of the immunoglobulin superfamily, and it plays a vital part in egg sperm interaction, fusion, and in spermatogenesis. Previous studies identified the fundamental role of the IZUMO1 gene in meiosis of bovine spermatogenesis and spermatogenic cell development and fertility. The current study confirmed the significant expression of the IZUMO1 gene with testicular development and its potential role in fertilization of Datong yak. This research explained the biological role of IZUMO1 in yak reproduction; therefore in the future it might provide a novel prospect to apply data on reproduction and to understand the further regulatory mechanisms of the IZUMO1 gene during spermatogenesis of different mammalian species. The IZUMO1 gene has promising benefits for the national development of novel non-hormonal contraceptives and in the treatments of fertility. Understanding the function of IZUMO1, its mRNA, and protein expression is critical to gain insight into spermatogenesis and promote sperm-egg fusion during reproduction of Datong yak. Therefore, we estimated the IZUMO1 gene expression in different ages of Datong yak by using semi quantitative PCR, qPCR, and western blotting. The results of the qPCR, semi-quantitative PCR and western blotting revealed that the expression level of IZUMO1 mRNA was significantly (p < 0.05) higher in the testis of 30 months and 6 years old followed by 18 and 6 months old Datong yak, respectively. We also predicted secondary and tertiary protein structure of IZUMO1 by using bioinformatics software that the revealed presence of a signal peptide, Izumo domain, immunoglobulin (Ig) like domain, and transmembrane region. Moreover, immunostaining analysis also elucidated that IZUMO1 was more prominent in the testis of 30 months and 6 years old yak, which represented that the IZUMO1 gene expression might be higher during the peak breeding ages (6 to 7 years) of the yak, and play a potential role in spermatogenesis, fertility, and testicular development. [ABSTRACT FROM AUTHOR]

Plants are persistently challenged by various phytopathogens. To protect themselves, plants have evolved multilayered surveillance against all pathogens. For intracellular parasitic viruses, plants have developed innate immunity, RNA silencing, translation repression, ubiquitination-mediated and autophagy-mediated protein degradation, and other dominant resistance gene-mediated defenses. Plant viruses have also acquired diverse strategies to suppress and even exploit host defense machinery to ensure their survival. A better understanding of the defense and counter-defense between plants and viruses will obviously benefit from the development of efficient and broad-spectrum virus resistance for sustainable agriculture. In this review, we summarize the cutting edge of knowledge concerning the defense and counter-defense between plants and viruses, and highlight the unexploited areas that are especially worth investigating in the near future. [ABSTRACT FROM AUTHOR]

Simple Summary: Associating copy number variations (CNVs) with growth and gene expression are a powerful approach for identifying genomic characteristics that contribute to phenotypic and genotypic variation. A previous study using next-generation sequencing illustrated that the KLF6 gene resides within CNV regions (CNVRs) of yak populations that overlap with quantitative trait loci (QTLs) of meat quality and growth. As a result, this research aimed to assess the prevalence of KLF6 CNVs in five Chinese domestic yak breeds and to determine their association with growth and gene expression level. These results confirmed the significant function of KLF6 CNVRs in determining the mRNA expression levels of this gene in Bos grunniens skeletal muscles and the expression of this gene affects quantitative growth traits in yak populations through the negative relationship between DNA copy numbers and gene expression. This work provides the first observation of the biological role of KLF6 CNVs in Chinese Datong yak breeds and might therefore provide a novel opportunity to utilize data on CNVs in designing molecular markers for the selection of animal breeding programs for larger populations of various yak breeds. Copy number variation (CNV) is a significant marker of the genetic and phenotypic diversity among individuals that accounts for complex quantitative traits of phenotype and diseases via modulating gene dosage and disrupting coding regions in the genome. Biochemically, Kruppel-like factor 6 (KLF6) genes plays a significant role in the regulation of cell differentiation and proliferation and muscle development. The aim of this study was to detect the distributions of KLF6 copy number variations (CNVs) in five breeds of domestic yak and to explore their effect on growth traits and gene expression. The data were analyzed by real-time quantitative PCR (qPCR). Our results elucidated that a decreased CNV in the KLF6 gene is more highly associated (p < 0.05) with various growth traits than increased or normal CNVs in six-month-old and five-year-old Datong yak. Nevertheless, negative correlations between the DNA copy number and KLF6 gene expression were observed in the skeletal muscle of adult Datong yak. These results suggest that CNVs of the KLF6 gene could be crucial genomic markers for growth phenotypes of Chinese Datong yak breeds and this finding constitutes the first evidence of the biological role of KLF6 CNVs in Chinese Datong yak breeds. [ABSTRACT FROM AUTHOR]

Summary Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer. [ABSTRACT FROM AUTHOR]

The progression of early childhood caries (ECC) is caused by microbial colonized in dental plaque. However, the association framework both from 16s genus down to high resolution metagenomic strain level and from composition to genome function analysis on caries lacks. 16S rRNA sequence revealed the composition of 3–6 years dental caries (ECC, n = 29), and severe dental caries (SECC, n = 36) children are significantly different from caries-free controls (CF, n = 31). Especially, genus Neisseria is enriched in caries (P < 0.05). Metagenomics sequence of 3 ECCs, 3 SECCs, and 3 CFs reveals Neisseria bacilliformis ATCC BAA-1200 in genus Neisseria is also significantly enriched in caries (P < 0.05). Then, we recovered high-quality metagenomic assembly genomes (MAG), named bin 86, which have 99% identity with Neisseria bacilliformis ATCC BAA-1200 genome. Function analysis of Neisseria bacilliformis ATCC BAA-1200 genome shows its metabolism power of sugar and adhesion, colonization, acid production, and acid tolerance ability, which suggested Neisseria bacilliformis ATCC BAA-1200 may serve as a biomarker for childhood caries. [ABSTRACT FROM AUTHOR]

• The CNV of the HSF1 gene was detected in Ashidan yaks. • There were significant correlations between HSF1-CNV and growth traits of yaks. • The expression level of the HSF1 gene was variable in different tissues of yaks. Copy Number Variation (CNV) is the major manner for the variation of genome structure, which is associated with numerous important traits. The heat shock factor 1 (HSF1) gene is a stress response transcriptional regulator. It participates in the heat shock response, simultaneously participated in the development of tissue. The objective of this research was to explore the influence of CNV of the HSF1 gene on the growth traits of the Ashidan yak. In this study, the growth traits (withers height, body weight, chest girth, and body length) of 274 Ashidan yaks were divided into four stages (6, 12, 18, and 30 months old). Moreover, quantitative polymerase chain reaction (qPCR) was exploited for determining the HSF1 gene relative expression level, and SPSS software was utilized for the statistical analysis. The outcomes indicated that HSF1 -CNV was significantly associated with body length (p < 0.05) and was extremely significant associated with withers height (p < 0.01) of 18-month-old Ashidan yaks. Besides, the HSF1 relative expression in heart and muscle was higher than that existed in other tissues (p < 0.01). The outcomes suggested that the CNV of HSF1 gene would affect the growth and development of the Ashidan yak, which is conducive to the early breeding of yak. [ABSTRACT FROM AUTHOR]