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Abstract Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD.

Objective This study aimed to investigate the effect of Codonopsis pilosula polysaccharide (CPP) on the motility, mitochondrial integrity, acrosome integrity rate, and antioxidant ability of sheep sperm after preservation at 4°C. Methods Semen from healthy adult rams were collected and divided into four groups with separate addition of 0, 200, 400, and 1,000 mg/L CPP. Sperm motility was analyzed using the Computer-Assisted Semen Analysis software after preservation at 4°C for 24, 72, 120, and 168 h. Sperm acrosome integrity rate was analyzed by Giemsa staining at 24, 72, and 120 h, and mitochondrial membrane integrity was analyzed by Mito-Tracker Red CMXRos. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content of spermatozoa were measured after 120 h of preservation. Results The sperm viability and forward-moving sperm under 200 mg/L CPP were significantly higher than that in the control group at 72 h (61.28%±3.89% vs 52.83%± 0.70%, 51.53%±4.06% vs 42.84%±1.14%), and 168 h (47.21%±0.85% vs 41.43%±0.37%, 38.68%±0.87% vs 31.68%±0.89%). The percentage of fast-moving sperm (15.03%±1.10% vs 11.39%±1.03%) and slow-moving sperm (23.63%±0.76% vs 20.29%±1.11%) in the 200 mg/L group was significantly higher than control group at 168 h. The mitochondrial membrane integrity of the sperm in the group with 200 mg/L CPP was significantly higher than those in the control group after storage at 4°C for 120 h (74.76%±2.54% vs 65.67% ±4.51%, p

Low temperature causes rice yield losses of up to 30%–40%, therefore increasing its cold tolerance is a breeding target. Few genes in rice are reported to confer cold tolerance at both the vegetative and reproductive stages. This study revealed a rice-specific 24-nt miRNA, miR1868, whose accumulation was suppressed by cold stress. Knockdown of MIR1868 increased seedling survival, pollen fertility, seed setting, and grain yield under cold stress, whereas its overexpression conferred the opposite phenotype. Knockdown of MIR1868 increased reactive oxygen species (ROS) scavenging and soluble sugar content under cold stress by increasing the expression of peroxidase genes and sugar metabolism genes, and its overexpression produced the opposite effect. Thus, MIR1868 negatively regulated rice cold tolerance via ROS scavenging and sugar accumulation.

Abstract Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

Ferroptosis is a nonapoptotic form of regulated cell death that has been reported to play a central role in cardiac ischemia‒reperfusion (I/R) injury. N-acetyltransferase 10 (NAT10) contributes to cardiomyocyte apoptosis by functioning as an RNA ac4c acetyltransferase, but its role in cardiomyocyte ferroptosis during I/R injury has not been determined. This study aimed to elucidate the role of NAT10 in cardiac ferroptosis as well as the underlying mechanism. The mRNA and protein levels of NAT10 were increased in mouse hearts after I/R and in cardiomyocytes that were exposed to hypoxia/reoxygenation. P53 acted as an endogenous activator of NAT10 during I/R in a transcription-dependent manner. Cardiac overexpression of NAT10 caused cardiomyocyte ferroptosis to exacerbate I/R injury, while cardiomyocyte-specific knockout of NAT10 or pharmacological inhibition of NAT10 with Remodelin had the opposite effects. The inhibition of cardiomyocyte ferroptosis by Fer-1 exerted superior cardioprotective effects against the NAT10-induced exacerbation of post-I/R cardiac damage than the inhibition of apoptosis by emricasan. Mechanistically, NAT10 induced the ac4C modification of Mybbp1a, increasing its stability, which in turn activated p53 and subsequently repressed the transcription of the anti-ferroptotic gene SLC7A11. Moreover, knockdown of Mybbp1a partially abolished the detrimental effects of NAT10 overexpression on cardiomyocyte ferroptosis and cardiac I/R injury. Collectively, our study revealed that p53 and NAT10 interdependently cooperate to form a positive feedback loop that promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury, suggesting that targeting the NAT10/Mybbp1a/p53 axis may be a novel approach for treating cardiac I/R.

Abstract Background Heritable rumen microbiota is an important modulator of ruminant growth performance. However, no information exists to date on host genetics-rumen microbiota interactions and their association with phenotype in sheep. To solve this, we curated and analyzed whole-genome resequencing genotypes, 16S rumen-microbiota data, and longitudinal body weight (BW) phenotypes from 1150 sheep. Results A variance component model indicated significant heritability of rumen microbial community diversity. Genome-wide association studies (GWAS) using microbial features as traits identified 411 loci-taxon significant associations (P < 10−8). We found a heritability of 39% for 180-day-old BW, while also the rumen microbiota likely played a significant role, explaining that 20% of the phenotypic variation. Microbiota-wide association studies (MWAS) and GWAS identified four marker genera (Bonferroni corrected P < 0.05) and five novel genetic variants (P < 10−8) that were significantly associated with BW. Integrative analysis identified the mediating role of marker genera in genotype influencing phenotype and unravelled that the same genetic markers have direct and indirect effects on sheep weight. Conclusions This study reveals a reciprocal interplay among host genetic variations, the rumen microbiota and the body weight traits of sheep. The information obtained provide insights into the diverse microbiota characteristics of rumen and may help in designing precision microbiota management strategies for controlling and manipulating sheep rumen microbiota to increase productivity. Video Abstract

Abstract Chinese wild rice (Zizania latifolia) is rich in phenolic compounds, particularly flavonoids. This study identified 203 basic helix‐loop‐helix (bHLHs) in Z. latifolia and showed that ZlbHLH196 (Zla16G011250) corresponds to the ZlRc gene in Z. latifolia, with its protein product localizing to the nucleus. Notably, the pericarps of ZlRc‐overexpressing (OE) rice are brown, whereas those of wild‐type (WT) rice are nonpigmented. The total phenolic, flavonoid, and proanthocyanidin contents, antioxidant activity, as well as enzyme inhibitory effects of ZlRc‐OE rice were significantly higher than those of WT rice. Overall, 221 differential phenolic metabolites were identified between ZlRc‐OE and WT rice, among which 198 were upregulated in the former. Additionally, a total of 227 differentially expressed genes were identified between ZlRc‐OE and WT rice, with 173 upregulated. Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis of phenolic metabolites revealed enhanced isoflavonoid, flavone, flavonol, and flavonoid biosynthesis pathways in ZlRc‐OE rice, which, furthermore, showed a markedly upregulated expression and significantly higher activities of four key flavonoid biosynthesis–related enzymes (phenylalanine ammonia‐lyase, chalcone synthase, chalcone‐flavanone isomerase, and dihydroflavonol 4‐reductase). These findings show that ZlRc‐overexpression promotes phenolic compound accumulation in rice seeds and can be used to bioaugment rice phenolic content.

Using historical and SSP emission scenarios simulation results from 28 global climate models in phase 6 of the Coupled Model Intercomparison Project （CMIP6） and CN05.1 grid observation data produced by the National Climate Center， based on the evaluation of 28 global climate models over the Qinghai-Xizang Plateau（TP） extreme temperature indices simulation effect， the trend of the future extreme temperature indices of the QXP under multiple greenhouse gas emission scenarios is predicted.The evaluation results show that the multi-model ensemble average simulation results are more stable and can simulate the temporal and spatial distribution characteristics of extreme temperature indices， but compared with observations， different indices have different deviations.The estimated results show that， relative to 1995 -2014， annual maximum value of daily maximum temperature（TXx）， annual minimum value of daily minimum temperature （TNn）， and warm days （TX90p） over the QXP will increase in the future， with the number of frost days （FD）， icing days （ID）， and cold days （TN10p） showed a decreasing trend.TNn increased significantly compared with TXx over the QXP.TX90p increased significantly in the southwest of the plateau， while the FD， ID， and TN10p decreased significantly in the southeast of the plateau.Under the SSP1-1.9 scenario， the extreme temperature index has a small change in the 21st century.As the radiative forcing increases， the frequency of the index also increases.Under the SSP1-2.6 scenario， when China achieves its carbon peak before 2030， the growth of TXx， TNn， and TX90p over the QXP will not exceed 1.12 ℃， 0.84 ℃， and 8.4%， respectively， and the reduction of FD， ID， and TN10p will not exceed 9.1 days， 9.7 days and 2.6%， respectively.When China achieves carbon neutrality before 2060， the increase of TXx， TNn， and TX90p over the TP will not exceed 1.72 ℃， 1.48 ℃， and 15%， respectively， and the decrease of FD， ID， and TN10p will not exceed 15.6 days， 17Days， 3.4%， respectively.

Platelet-derived growth factor-D (PDGF-D) is abundantly expressed in ocular diseases. Yet, it remains unknown whether and how PDGF-D affects ocular cells or cell-cell interactions in the eye. In this study, using single-cell RNA sequencing (scRNA-seq) and a mouse model of PDGF-D overexpression in retinal pigment epithelial (RPE) cells, we found that PDGF-D overexpression markedly upregulated the key immunoproteasome genes, leading to increased antigen processing/presentation capacity of RPE cells. Also, more than 6.5-fold ligand-receptor pairs were found in the PDGF-D overexpressing RPE-choroid tissues, suggesting markedly increased cell-cell interactions. Moreover, in the PDGF-D-overexpressing tissues, a unique cell population with a transcriptomic profile of both stromal cells and antigen-presenting RPE cells was detected, suggesting PDGF-D-induced epithelial-mesenchymal transition of RPE cells. Importantly, administration of ONX-0914, an immunoproteasome inhibitor, suppressed choroidal neovascularization (CNV) in a mouse CNV model in vivo. Together, we show that overexpression of PDGF-D increased pro-angiogenic immunoproteasome activities, and inhibiting immunoproteasome pathway may have therapeutic value for the treatment of neovascular diseases.

The selection of testis size can improve the reproductive capacity of livestock used for artificial insemination and has been considered as an important strategy for accelerating the breeding process. Although much work has been done to investigate the mechanisms of testis development in various species, there is little information available in regard to the differences in transcriptomic profiling of sheep testes at different developmental stages. In this work, we aimed to identify differentially expressed genes (DEGs) by RNA-Seq in sheep during different growth stages, including 0 month old (infant, M0), 3 months old (puberty, M3), 6 months old (sexual maturity, M6) and 12 months old (body maturity, M12). A total of 4,606 (2,381 up and 2,225 down), 7,500 (4,368 up and 3,132 down), 15 (8 up and seven down) DEGs were identified in M3_vs_M0, M6_vs_M3, and M12_vs_M6 comparison, respectively. Of which, a number of genes were continuously up-regulated and down-regulated with testicular development, including ODF3, ZPBP1, PKDREJ, MYBL1, PDGFA, IGF1, LH, INSL3, VIM, AMH, INHBA, COL1A1, COL1A2, and INHA. GO analysis illustrated that DEGs were mainly involved in testis development and spermatogenesis. KEGG analysis identified several important pathways and verified several reproduction-associated DEGs such as COL1A1, COL1A2, PDGFA, and IGF1. In addition, two gene modules highly associated with testis development and core genes with testis size were identified using weighted gene co-expression network analysis (WGCNA), including hub genes positively associated with testis size such as RANBP9, DNAH17, SPATA4, CIB4 and SPEM1, and those negatively associated with testis size such as CD81, CSK, PDGFA, VIM, and INHBA. This study comprehensively identified key genes related to sheep testicular development, which may provide potential insights for understanding male fertility and better guide in animal breeding.

The epididymis is an organ that transports, matures and stores sperm, and has functions such as secretion and absorption. Polyunsaturated fatty acid (PUFA) compositions in sperm membrane were changed during the process of epididymis maturation and influence the male fertility. This study aimed to investigate differences in crude fat and fatty acid content in cauda epididymis between high and low fertility of Hu sheep. One hundred and seventy-nine Hu ram lambs were fed from 56 days to 6 months under the same environment. After the feeding trial, all rams were slaughtered, and the body weight, testicular weight, epididymal weight and sperm density were measured. Pearson correlation analysis showed significantly moderate positive correlation between epididymal weight and sperm density and testicular weight. Eighteen rams were selected and divided into the high fertility group (H, n = 9) and low fertility group (L, n = 9) according to the epididymal weight, sperm density and histomorphology. The crude fat content, fatty acid profile and genes related to fatty acid metabolism were detected. The crude fat content, total fatty acid, total n-3 PUFA and docosahexaenoic acid (C22:6n-3, DHA) content of cauda epididymis in high fertility group was significantly higher than those in low fertility group (p < 0.05). However, the ratio of n-6/n-3 PUFA was significantly lower than that in group L (p < 0.05). Immunohistochemistry results showed that SREBP1 and ELOVL2 were expressed in pseudostratified columnar ciliated epithelium and smooth muscle cells. The mRNA expression of SREBP1 (p = 0.09) and ELOVL2 (p < 0.05) in the high fertility group were increased. In conclusion, the high expression of SREBP1 and ELOVL2 may contribute to high n-3 PUFA content in cauda epididymis of high-fertility Hu sheep.

PRAMEY (preferentially expressed antigen in melanoma, Y-linked) belongs to the cancer-testis antigens (CTAs) gene family and is predominantly expressed in testis, playing important roles in spermatogenesis and testicular development. This study cloned the full-length cDNA sequence of ovine PRAMEY using the rapid amplification of cDNA ends (RACE) method and analyzed the expression profile and copy number variation (CNV) of PRAMEY using quantitative real-time PCR (qPCR). The results revealed that the PRAMEY cDNA was 2099 bp in length with an open reading frame (ORF) of 1536 bp encoding 511 amino acids. PRAMEY was predominantly expressed in the testis and significantly upregulated during postnatal testicular development. The median copy number (MCN) of PRAMEY was 4, varying from 2 to 25 in 710 rams across eight sheep breeds. There was no significant correlation between the CNV of PRAMEY and testicular size, while a significant positive correlation was observed between the mRNA expression and testicular size in Hu sheep. The current study suggests that the expression levels of PRAMEY were closely associated with testicular size, indicating that PRAMEY may play an important role in testicular growth.

Platelet-derived growth factor-D (PDGF-D) is highly expressed in immune cells. However, the potential role of PDGF-D in immune system remains thus far unclear. Here, we reveal a novel function of PDGF-D in activating both classical and alternative complement pathways that markedly increase chemokine and cytokine responses to promote macrophage polarization. Pharmacological targeting of the complement C3a receptor using SB290157 alleviated PDGF-D-induced neuroinflammation by blocking macrophage polarization and inhibited pathological choroidal neovascularization. Our study thus suggests that therapeutic strategies targeting both PDGF-D and the complement system may open up new possibilities for the treatment of neovascular diseases.

Objective The study was designed to determine the cytotoxic effect of gallic acid (GA), obtained by the hydrolysis of tannins, on mice TM4 Sertoli cells apoptosis. Methods In the present study, non-tumorigenic mice TM4 Sertoli cells were treated with different concentrations of GA for 24 h. After treatment, cell viability was evaluated using WST-1, mitochondrial dysfunction, cells apoptosis and necrosis was detected using JC-1, Hoechst 33342 and propidium iodide staining. The expression levels of Cyclin B1, proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (BAX), and Caspase-3 were also detected by quantitative real-time polymerase chain reaction and Western-blotting. Results The results showed that 20 to 400 μM GA inhibited viability of TM4 Sertoli cells in a dose-dependent manner. Treatment with 400 μM GA significantly inhibited PCNA and Cyclin B1 expression, however up-regulated BAX and Caspase-3 expression, caused mitochondrial membrane depolarization, activated Caspase-3, and induced DNA damage, thus, markedly increased the numbers of dead cells. Conclusion Our findings showed that GA could disrupt mitochondrial function and caused TM4 cells to undergo apoptosis and necrosis.

Background Ovine milk is a rich source of bioactive proteins that supports the early growth and development of the newborn lambs. A large number of researches had targeted to the identification of ovine milk fat globule membrane proteins (MFGMPs), caseins (CNs), mastitis milk proteins in past years, but the dynamic change tendency of milk whey proteins during postnatal development has received limited attention. This research aimed to investigate the dynamic changes of ovine milk whey proteins after delivery, and explore the functions of whey proteins on early development of the newborns. Methods In this research, Hu sheep milk samples were collected from six individuals by manual milking manner, at 0 d, 3 d, 7 d, 14 d, 28 d and 56 d after delivery, respectively. The milk whey proteins were identified and quantified by the isobaric tag for relative and absolute quantification (iTRAQ) coupled with liquid chromatography (LC)-electrospray ionization (ESI) tandem MS (MS/MS) methods. In addition, biological functions of differentially expressed proteins (DEPs) were annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results A total of 310 proteins were identified , of which 121 were differentially expressed. In detail, 30 (10 up-regulated and 20 down-regulated), 22 (11 up-regulated and 11 down-regulated), 11 (four up-regulated and seven down-regulated), 11 (eight up-regulated and three down-regulated), 10 (six up-regulated and four down-regulated) DEPs were identified in 3 d vs. 0 d, 7 d vs. 3 d, 14 d vs. 7 d, 28 d vs. 14 d, 56 d vs. 28 d comparison groups, respectively. The GO annotation analysis revealed that biological process principally involved metabolic and biological regulation, the major cellular location were organelle, cell and extracellular region, and the mainly molecular function were binding and catalytic activity. Circadian rhythm, fatty acid biosynthesis and African trypanosomiasis were enriched by KEGG annotation analysis. Conclusion The study reveals a comprehensive understanding of Hu sheep milk proteome, suggesting whey proteins change dramatically in early development of newborn lambs, which provide a potential guidance for early weaning of lambs.

The CHYR (CHY ZINC-FINGER AND RING FINGER PROTEIN) proteins have been functionally characterized in iron regulation and stress response in Arabidopsis, rice and Populus. However, their roles in soybean have not yet been systematically investigated. Here, in this study, 16 GmCHYR genes with conserved Zinc_ribbon, CHY zinc finger and Ring finger domains were obtained and divided into three groups. Moreover, additional 2–3 hemerythrin domains could be found in the N terminus of Group III. Phylogenetic and homology analysis of CHYRs in green plants indicated that three groups might originate from different ancestors. Expectedly, GmCHYR genes shared similar conserved domains/motifs distribution within the same group. Gene expression analysis uncovered their special expression patterns in different soybean tissues/organs and under various abiotic stresses. Group I and II members were mainly involved in salt and alkaline stresses. The expression of Group III members was induced/repressed by dehydration, salt and alkaline stresses, indicating their diverse roles in response to abiotic stress. In conclusion, our work will benefit for further revealing the biological roles of GmCHYRs.

The deleted in azoospermia-like (DAZL) gene encoding an RNA binding protein is pivotal in gametogenesis in lots of species and also acts as a pre-meiosis marker. The current study was conducted to detect expression profiles and single nucleotide polymorphisms (SNPs) of DAZL in sheep using qPCR, DNA-pooled sequencing, improved multiplex ligase detection reaction (iMLDR®) and restriction fragment length polymorphism (RFLP) methods. The results confirmed that ovine DAZL showed the highest expression level at six-months of age across five developmental stage. At six-month stage, DAZL expressed primarily in testis across seven tissues analyzed. The abundance of DAZL in the large-testis group is higher than that in the small-testis group although it is not significant. In addition, six SNPs (SNP1-SNP6) were identified in DAZL. Of those, SNP1 (p < 0.05) and SNP6 (p < 0.01) were significantly correlated with the variation coefficient between left and right epididymis weight (VCTW). The current study implies DAZL may play important roles in testicular development and its SNPs are associated with testicular parameters, which supply important indicators for ram selection at early stage.

Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD. Riboflavin attenuates alcoholic liver disease progression, regulates alcohol-induced changes in intestinal microbiota, and affects inflammatory cell infiltration suggesting that riboflavin may be a potentially effective agent for treating ALD [ABSTRACT FROM AUTHOR]

Due to the impact of natural disasters and public security incidents, the industrial chain is broken, and the economy has declined, especially in western resource-based cities of China where enterprises have closed down, the unemployed have increased sharply, and social contradictions have become prominent. Therefore, the resilience of the industrial structure is an urgent problem to solve in the academic circle and sustainable development. This paper identifies the spatio-temporal evolution characteristics of the resilience of the resource-based cities' industrial structure in western China from 2006 to 2021 to provide a reference for the improvement of their industrial structure resilience. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF. [ABSTRACT FROM AUTHOR]

Background: Heritable rumen microbiota is an important modulator of ruminant growth performance. However, no information exists to date on host genetics-rumen microbiota interactions and their association with phenotype in sheep. To solve this, we curated and analyzed whole-genome resequencing genotypes, 16S rumen-microbiota data, and longitudinal body weight (BW) phenotypes from 1150 sheep. Results: A variance component model indicated significant heritability of rumen microbial community diversity. Genome-wide association studies (GWAS) using microbial features as traits identified 411 loci-taxon significant associations (P < 10−8). We found a heritability of 39% for 180-day-old BW, while also the rumen microbiota likely played a significant role, explaining that 20% of the phenotypic variation. Microbiota-wide association studies (MWAS) and GWAS identified four marker genera (Bonferroni corrected P < 0.05) and five novel genetic variants (P < 10−8) that were significantly associated with BW. Integrative analysis identified the mediating role of marker genera in genotype influencing phenotype and unravelled that the same genetic markers have direct and indirect effects on sheep weight. Conclusions: This study reveals a reciprocal interplay among host genetic variations, the rumen microbiota and the body weight traits of sheep. The information obtained provide insights into the diverse microbiota characteristics of rumen and may help in designing precision microbiota management strategies for controlling and manipulating sheep rumen microbiota to increase productivity. FHBZi7VG9hPqSjx265vQ6e Video Abstract [ABSTRACT FROM AUTHOR]

Purpose: The use of digital technology in firms has drawn attention of innovation management scholars and policy-makers, especially the imitation of digital technology and competition among peer firms. Drawing on dynamic competition theory, this paper examines how firms react to their peers' digital innovation behavior and the effect of external environment mechanisms on the magnitude of peer effects. Design/methodology/approach: This paper utilizes a text mining method to construct a baseline model with a Tobit estimator using data obtained for Chinese listed firms. Findings: The findings suggest that peer effects on digital innovation behavior are robust and significant positive in China. Moreover, peer effects on digital innovation participation are positively magnified by firms' strong social network and high Fintech development. However, peer effects are relatively higher in non-state-owned enterprises (non-SOEs), low-profitability and high R&D firms. Research limitations/implications: The authors' findings contribute to the digital management literature by showing that firms need digital technological imitation and diffusion of innovations in the digital era. Practical implications: Managers should provide insights into firms' imitation of their peers' acts to preserve competitive parity. Besides, firms should integrate employees within the organization and communicate digital innovation concepts and behaviors to external peer firms. Originality/value: First, this paper contributes to explaining how firms change their digital innovation strategy through the influence of peers' digital innovation behavior. Second, this paper fills the literature gaps related to the moderating effects of external environment factors in peer effects of digital innovation behavior. [ABSTRACT FROM AUTHOR]

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Simple Summary: The Chinese Hu sheep is well-known for its high fertility and early sexual maturity. Rams reach sexual maturity at the age of six months. This study investigated differential crude fat content, fatty acid composition and related metabolism genes localization and expression in cauda epididymis between high and low fertility Hu sheep at six months old. The crude fat content was positively correlated with epididymal weight. High expression of SREBP1 and EVOVL2 in high fertility Hu sheep may lead to the higher n-3 PUFA content, especially DHA, providing a basis for understanding the relationship between fertility and sperm storage environment. The epididymis is an organ that transports, matures and stores sperm, and has functions such as secretion and absorption. Polyunsaturated fatty acid (PUFA) compositions in sperm membrane were changed during the process of epididymis maturation and influence the male fertility. This study aimed to investigate differences in crude fat and fatty acid content in cauda epididymis between high and low fertility of Hu sheep. One hundred and seventy-nine Hu ram lambs were fed from 56 days to 6 months under the same environment. After the feeding trial, all rams were slaughtered, and the body weight, testicular weight, epididymal weight and sperm density were measured. Pearson correlation analysis showed significantly moderate positive correlation between epididymal weight and sperm density and testicular weight. Eighteen rams were selected and divided into the high fertility group (H, n = 9) and low fertility group (L, n = 9) according to the epididymal weight, sperm density and histomorphology. The crude fat content, fatty acid profile and genes related to fatty acid metabolism were detected. The crude fat content, total fatty acid, total n-3 PUFA and docosahexaenoic acid (C22:6n-3, DHA) content of cauda epididymis in high fertility group was significantly higher than those in low fertility group (p < 0.05). However, the ratio of n-6/n-3 PUFA was significantly lower than that in group L (p < 0.05). Immunohistochemistry results showed that SREBP1 and ELOVL2 were expressed in pseudostratified columnar ciliated epithelium and smooth muscle cells. The mRNA expression of SREBP1 (p = 0.09) and ELOVL2 (p < 0.05) in the high fertility group were increased. In conclusion, the high expression of SREBP1 and ELOVL2 may contribute to high n-3 PUFA content in cauda epididymis of high-fertility Hu sheep. [ABSTRACT FROM AUTHOR]

Aiming at the calculation problem of bearing pressure of typical overlying strata structure, in this paper, mechanical calculation, field monitoring and other methods are used to study the influence range of abutment pressure. Recently, many major rock burst accidents in working surface show that with the increase of mining depth and the change of overlying strata structure, the abutment pressure distribution has become one of the problems of safe mining. The influence range, distribution of high stress area and peak position of working surface support pressure need to be solved urgently; and through theoretical analysis, this paper reveals (whole rock single-layer structure, whole rock layered structure, whole rock single-layer structure—without arch in soil layer, whole rock layered structure—without arch in soil layer, whole rock single-layer structure—with soil arching, whole rock layered structure—with soil arching) the stress transfer mode, transfer size, and arching conditions of overlying strata in different areas. The mechanical system of abutment pressure calculation for typical overburden structure is established, which provides theoretical basis for mine optimization design scheme, mining sequence, and limited personnel distance. [ABSTRACT FROM AUTHOR]

The Maillard reaction is a type of nonenzymatic browning process and is an important pathway for the formation of humic-like substances (HLSs). Glucose is one of the three crucial precursors for the Maillard reaction, and a change in glucose concentration can inevitably affect the humification pathway, thereby regulating the composition and quality of HLSs. To verify the scientific hypothesis, the method of liquid shake-flask culture was adopted. Both catechol and glycine with fixed concentrations were added to a phosphate buffer including δ-MnO2, and only the concentration of glucose was adjusted in the sterile culture system. The obtained supernatant fluid and dark-brown residue were collected dynamically through the centrifugation method. The E4/E6 ratio and total organic C (TOC) of the supernatant fluid, the humus composition, and FTIR spectra for the dark-brown residue, and the elemental composition of humic-like acid (HLA) extracted from the dark-brown residue were analyzed to reveal the effect of varying glucose concentrations on the abiotic humification pathways for the Maillard reaction and the characteristics of relevant products under abiotic processes. The results reveal that (1) the exogenous addition of glucose at different concentrations simplifies the molecular structure in the supernatant fluid, and the TOC content is decreased to varying degrees, among which the addition of 0.24 mol/L glucose leads to the formation of simpler organic molecules in the supernatant compared to that for the other treatments, and the addition of 0.03 mol/L glucose shows the largest decrease in TOC content; (2) Under the coexistence of glycine and catechol, CHLA treated with the addition of glucose at different concentrations shows an upward trend in the course of the culture, which is significantly higher than that obtained for the CK control. The addition of 0.12 mol/L glucose results in the largest increase in CHLA. During the culture period, the structure of HLA molecules from each treatment first become complex and then gradually become simpler. Finally, the molecular structure of HLA treated with different concentrations of glucose becomes more complex, but the structure of HLA molecules from the CK control tends to be simplified. The addition of glucose can improve the condensation degree of HLA molecules, among which the addition of 0.12 mol/L glucose shows the most significant effect. With increasing exogenous glucose concentration, the number of N-containing compounds in the HLA molecules further decreases, while the number of O-containing functional groups increases. (3) The greater the concentration of glucose added, the higher the proportion of aromatic C structures in the dark-brown residue. During this process, the Mn-O bond lattice vibration of the δ-MnO2 layered structure is greatly enhanced. The organic molecules in the dark-brown residue and δ-MnO2 are bound to each other through intermolecular hydrogen bonding. The CHLA/CFLA ratio for each treatment increases to varying degrees after the culture period, indicating that the addition of glucose is more conducive to the improvement of humus quality than the CK control, among which the addition of 0.12 mol/L glucose shows the best effect. [ABSTRACT FROM AUTHOR]

Simple Summary: PRAMEY (preferentially expressed antigen in melanoma, Y-linked) is a cancer-testis antigen and is believed to play an important role in testicular development and gametogenesis. However, the structure, expression and function of PRAMEY in sheep remain unknown. In this paper, we found that PRAMEY was extremely expressed in the testis and significantly upregulated during testicular growth. The mRNA abundance of PRAMEY was significantly correlated with testicular size traits in Hu sheep at 6 months. These results imply that PRAMEY may play an important role in testicular growth. PRAMEY (preferentially expressed antigen in melanoma, Y-linked) belongs to the cancer-testis antigens (CTAs) gene family and is predominantly expressed in testis, playing important roles in spermatogenesis and testicular development. This study cloned the full-length cDNA sequence of ovine PRAMEY using the rapid amplification of cDNA ends (RACE) method and analyzed the expression profile and copy number variation (CNV) of PRAMEY using quantitative real-time PCR (qPCR). The results revealed that the PRAMEY cDNA was 2099 bp in length with an open reading frame (ORF) of 1536 bp encoding 511 amino acids. PRAMEY was predominantly expressed in the testis and significantly upregulated during postnatal testicular development. The median copy number (MCN) of PRAMEY was 4, varying from 2 to 25 in 710 rams across eight sheep breeds. There was no significant correlation between the CNV of PRAMEY and testicular size, while a significant positive correlation was observed between the mRNA expression and testicular size in Hu sheep. The current study suggests that the expression levels of PRAMEY were closely associated with testicular size, indicating that PRAMEY may play an important role in testicular growth. [ABSTRACT FROM AUTHOR]

ZNF280BY , a bovid-specific Y chromosome gene, was firstly found to be highly expressed in bovine testis, indicating that it may play important roles in testicular development and male fertility. In this study, we firstly cloned the full-length cDNA of ovine ZNF280BY containing 1,993 bp, and with a 1,632 bp open reading frame. ZNF280BY was predominantly expressed in the testis, and its expression level was significantly higher in large testis than in small testis in Hu sheep at 6 months of age. In addition, the expression level of ZNF280BY significantly increased during testicular development, showing the highest expression level at 12 mo of age. ZNF280BY showed copy number variation (CNV) in 723 rams from eight sheep breeds, ranging from 17 to 514 copies, with a median copy number of 188. Pearson correlation analysis showed that the CNV of ZNF280BY was negatively correlated with testis size in Hu sheep. Furthermore, its mRNA expression level in testis had no significant correlation with the CNV but was significantly correlated with testis size. This study concluded that the expression of ZNF280BY was closely related to testicular development, and the CNV of ZNF280BY could be used as an important genetic marker to evaluate the ram reproductive capacity at an early stage in Hu sheep. [ABSTRACT FROM AUTHOR]

The selection of testis size can improve the reproductive capacity of livestock used for artificial insemination and has been considered as an important strategy for accelerating the breeding process. Although much work has been done to investigate the mechanisms of testis development in various species, there is little information available in regard to the differences in transcriptomic profiling of sheep testes at different developmental stages. In this work, we aimed to identify differentially expressed genes (DEGs) by RNA-Seq in sheep during different growth stages, including 0 month old (infant, M0), 3 months old (puberty, M3), 6 months old (sexual maturity, M6) and 12 months old (body maturity, M12). A total of 4,606 (2,381 up and 2,225 down), 7,500 (4,368 up and 3,132 down), 15 (8 up and seven down) DEGs were identified in M3_vs_M0, M6_vs_M3, and M12_vs_M6 comparison, respectively. Of which, a number of genes were continuously up-regulated and down-regulated with testicular development, including ODF3 , ZPBP1 , PKDREJ , MYBL1 , PDGFA , IGF1 , LH , INSL3 , VIM , AMH , INHBA , COL1A1 , COL1A2 , and INHA. GO analysis illustrated that DEGs were mainly involved in testis development and spermatogenesis. KEGG analysis identified several important pathways and verified several reproduction-associated DEGs such as COL1A1 , COL1A2 , PDGFA , and IGF1. In addition, two gene modules highly associated with testis development and core genes with testis size were identified using weighted gene co-expression network analysis (WGCNA), including hub genes positively associated with testis size such as RANBP9 , DNAH17 , SPATA4 , CIB4 and SPEM1 , and those negatively associated with testis size such as CD81 , CSK , PDGFA , VIM, and INHBA. This study comprehensively identified key genes related to sheep testicular development, which may provide potential insights for understanding male fertility and better guide in animal breeding. [ABSTRACT FROM AUTHOR]