Changes in meat quality, metabolites and microorganisms of mutton during cold chain storage.

During the cold chain storage process, changes in metabolites and microorganisms are highly likely to lead to changes in meat quality. To elucidate the changes in the composition of metabolites and microbiota during cold chain storage of mutton, this study utilized untargeted metabolome and 5R 16S rRNA sequencing analyses to investigate the changes in the longissimus dorsi under different cold chain temperatures (4 °C and -20 °C). With the extension of cold chain storage time, the meat color darkened and the content of C18:2n-6, C20:3n-6, and C23:0 were significantly increased in mutton. In this study, nine metabolites, including 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, alanylphenylala-nine, indole-3-acrylic acid and the others, were significantly altered during cold chain storage. The abundance of the dominant microorganisms, including Brachymonas, Aeromonas, Corynebacterium and Steroidobacter, was significantly altered. Furthermore, a high correlation was observed between the different metabolites and microorganisms. These findings provide an in-depth understanding of the effects of different cold chain storage temperatures and times on the quality of mutton.

Amidoxime-grafted cotton fibers with anti-microbial sludge for efficient uranium recovery.

Uranium as a nuclear fuel, its source and aftertreatment has been a hot topic of debate for developers. In this paper, amidoxime and guanidino-modified cotton fibers (DC-AO-PHMG) were synthesized by the two-step functionalization approach, which exhibited remarkable antimicrobial and high uranium recovery property. Adsorption tests revealed that DC-AO-PHMG had excellent selectivity and anti-interference properties, the maximum adsorption capacity of 609.75 mg/g. More than 85 % adsorption capacity could still be kept after 10 adsorption-desorption cycles, and it conformed to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm model as a spontaneous heat-absorbing chemical monolayer process. FT-IR, EDS and XPS analyses speculated that the amidoxime and amino synergistically increased the uranium uptake. The inhibitory activities of DC-AO-PHMG against three aquatic bacteria, BEY, BEL (from Yellow River water and lake bottom silt, respectively) and B. subtilis were significantly stronger, and the uranium adsorption was not impacted by the high bacteria content. Most importantly, DC-AO-PHMG removed up to 94 % of uranium in simulated seawater and extracted up to 4.65 mg/g of uranium from Salt Lake water, which demonstrated its great potential in the field of uranium resource recovery.

The adsorption behavior of perfluorooctane sulphonate on diamane regulated by strain.

The adsorption of per- and polyfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS), is currently a critical issue in the environmental domain, yet it is not fully understood. Diamane, as a stable monolayer adsorbent, has garnered significant research interest. Defects and strain are reported to play a crucial role in regulating its electronic structure. In this study, we employ density functional theory (DFT) calculations to investigate the adsorption of PFOS on both pristine and nitrogen-vacancy (N-V) defected diamane, respectively. Additionally, we systematically examine the effects of strain in diamane along both the a- and b-directions (two directions of a monolayer) on PFOS adsorption. This analysis involves studying the adsorption energy (Eads), electron transfer, and the partial density of states. Finally, we propose the synergistic effects of N-V defects and compression strain in diamane, which enhance PFOS adsorption. Diamane is considered a promising candidate for PFOS sensing or capture.

Comparative whole-genome resequencing to uncover selection signatures linked to litter size in Hu Sheep and five other breeds.

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

Impact of Hydrostatic Pressure on Molecular Structure and Dynamics of the Sodium and Chloride Ions in Portlandite Nanopores.

In order to address the issues of energy depletion, more resources are being searched for in the deep sea. Therefore, research into how the deep-sea environment affects cement-based materials for underwater infrastructure is required. This paper examines the impact of ocean depth (0, 500, 1000, and 1500 m) on the ion interaction processes in concrete nanopores using molecular dynamics simulations. At the portlandite interface, the local structural and kinetic characteristics of ions and water molecules are examined. The findings show that the portlandite surface hydrophilicity is unaffected by increasing depth. The density profile and coordination number of ions alter as depth increases, and the diffusion speed noticeably decreases. The main cause of the ions' reduced diffusion velocity is expected to be the low temperature. This work offers a thorough understanding of the cement hydration products' microstructure in deep sea, which may help explain why cement-based underwater infrastructure deteriorates over time.

Regulation of bone homeostasis by traditional Chinese medicine active scaffolds and enhancement for the osteoporosis bone regeneration.

ETHNOPHARMACOLOGICAL RELEVANCE: The active ingredients of traditional Chinese medicine (TCM), such as naringin (NG), Eucommiol, isopsoralen, icariin, Astragalus polysaccharides, and chondroitin sulfate, contained in Drynariae Rhizoma, Eucommiae Cortex, Psoralea corylifolia, Herba Epimedii, Astragalus radix and deer antler, are considered promising candidates for enhancing the healing of osteoporotic defects due to their outstanding bone homeostasis regulating properties. They are commonly used to activate bone repair scaffolds. AIM OF THE REVIEW: Bone repair scaffolds are inadequate to meet the demands of osteoporotic defect healing due to the lack of regulation of bone homeostasis. Therefore, selecting bone scaffolds activated with TCM to improve the therapeutic effect of repairing osteoporotic bone defects. MATERIALS AND METHODS: To gather information on bone scaffold activated by traditional Chinese medicine, we conducted a thorough search of several scientific databases, including Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed, and China National Knowledge Infrastructure (CNKI). RESULTS: This review discusses the mechanism of TCM active ingredients in regulating bone homeostasis, including stimulating bone formation and inhibiting bone resorption process and the healing mechanism of traditional bone repair scaffolds activated by them for osteoporotic defect healing. CONCLUSION: In general, the introduction of TCM active ingredients provides a novel therapeutic approach for modulating bone homeostasis and facilitating osteoporotic defect healing, and also offers a new strategy for design of other unconventional bone defect healing materials.

Cold exposure affects glucose metabolism, lipid droplet deposition and mitophagy in skeletal muscle of newborn goats.

Cold exposure is a common stressor for newborn goats. Skeletal muscle plays an important role in maintaining whole-body homeostasis of glucose and lipid metabolism. However, the molecular mechanisms underlying regulation of skeletal muscle of newborn goats by cold exposure remains unclear. In this study, we found a significant increase (P < 0.01) in serum glucagon levels after 24 h of cold exposure (COLD, 6°C), while glucose and insulin concentrations were significantly decreased (P < 0.01) compared to room temperature (RT, 25°C). Additionally, we found that cold exposure reduced glycogen content (P < 0.01) in skeletal muscle. Pathway enrichment analysis revealed that cold exposure activated skeletal muscle glucose metabolism pathways (including insulin resistance and the insulin signaling pathway) and mitophagy-related pathways. Cold exposure up-regulated the expression of genes involved in fatty acid and triglyceride synthesis, promoting skeletal muscle lipid deposition. Notably, cold exposure induced mitophagy in skeletal muscle.

An Identification of Functional Genetic Variants in B4GALNT2 Gene and Their Association with Growth Traits in Goats.

ß-1,4-N-acetylgalactosamine transferase 2 (B4GALNT2) is a vital candidate gene that affects the growth traits in sheep. However, whether it has the same function in goats remains to be investigated further. This study selected 348 Nanjiang Yellow goats, screened all exons, and conserved non-coding regions of the B4GALNT2 gene for single-nucleotide polymorphisms (SNPs). Our results revealed the presence of a synonymous mutation, rs672215506, within the exon of the B4GALNT2 gene in the Nanjiang Yellow goat population. The mutation resulted in a decrease in the mRNA stability of the B4GALNT2 gene. The results of SNP detection of the conserved non-coding region of the B4GALNT2 gene showed five potential regulatory SNPs in the Nanjiang Yellow goat population. Except for rs66095343, the ~500 bp fragments of the other four SNPs (rs649127714, rs649573228, rs652899012, and rs639183528) significantly increased the luciferase activity both in goat skeletal muscle satellite cells (MuSCs) and 293T cells. The genetic diversity indexes indicated low or intermediate levels for all six SNPs analyzed, and the genotype frequencies were in Hardy-Weinberg equilibrium. Association analysis showed that rs660965343, rs649127714, and rs649573228 significantly correlate with growth traits in the later stage of growth and development of Nanjiang Yellow goats. The haplotype combinations of H2H3 and H2H2 had higher body weight and greater body size. Moreover, H2H2 haplotype combinations significantly correlated with the litter size of the Nanjiang Yellow goats. The results of our study demonstrate the potential role of the B4GALNT2 gene as a functional genetic marker in the breeding programs of Nanjiang Yellow goats.

The Risk of Cervical Cancer in Women Among Han, Bai, Dai and Hani Ethnic Minorities in Yunnan Province of China.

Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.

Whole-Genome Resequencing Reveals Genetic Diversity and Wool Trait-Related Genes in Liangshan Semi-Fine-Wool Sheep.

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

Electroreduction of CO2 on Cu, Fe, or Ni-doped Diamane Sheets: A DFT Study.

Poor mass transfer behavior and inherent activity limit the efficiency of traditional catalysts in electrocatalyzing carbon dioxide reduction reactions. However, the development of novel nanomaterials provides new strategies to solve the above problems. Herein, we propose novel single-metal atom catalysts, namely diamane-based electrocatalysts doped with Cu, Fe, and Ni, explored through density functional theory (DFT) calculations. We thoroughly investigated the doping pattern and energetics for different dopants. Furthermore, we systematically investigated the conversion process of CO2 to C1 or C2+ products, utilizing the free energy analysis of reaction pathways. Our results reveal that dopants could only be introduced into diamane following a specific pattern. Dopants significantly enhance the CO2 adsorption ability of diamane, with Fe and Ni proving notably more effective than Cu. After CO2 adsorption, Cu- and Fe-doped diamane prefer to catalyze CO2RR, while Ni-doped diamane favors hydrogen evolution reaction (HER). The C-C coupling reaction on Cu-hollow diamane, Cu-bridge diamane, and Fe-hollow diamane tends to be from C2+ products. Among all examined catalysts, Cu-hollow diamane shows better electro-catalytic performance. Our study demonstrates the feasibility of and contributes to the development of diamane-based electro-catalysts for CO2RR.

Prognostic model for survival in patients with neuroendocrine carcinomas of the cervix: SEER database analysis and a single-center retrospective study.

OBJECTIVE: Neuroendocrine carcinoma of the cervix (NECC) is extremely rare in clinical practice. This study aimed to methodologically analyze the clinicopathological factors associated with NECC patients and to develop a validated survival prediction model. METHODS: A total of 535 patients diagnosed with NECC between 2004 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database, while 122 patients diagnosed with NECC at Yunnan Cancer Hospital (YCH) from 2006 to 2019 were also recruited. Patients from the SEER database were divided into a training cohort (n = 376) and a validation cohort (n = 159) in a 7:3 ratio for the construction and internal validation of the nomogram. External validation was performed in a cohort at YCH. The Kaplan-Meier method was used for survival analysis, the Log-rank method test was used for univariate analysis of prognostic influences, and the Cox regression model was used for multivariate analysis. RESULTS: The 3-year and 5-year overall survival (OS) rates for patients with NECC in SEER were 43.6% and 39.7%, respectively. In the training cohort, multivariate analysis showed independent prognostic factors for NECC patients including race, tumor size, distant metastasis, stage, and chemotherapy (p<0.05). For extended application in other cohorts, a nomogram including four factors without race was subsequently created. The consistency index (C-index) of the nomogram predicting survival was 0.736, which was well-validated in the validation cohorts (0.746 for the internal validation cohort and 0.765 for the external validation cohort). In both the training and validation cohorts, the 3-year survival rates predicted by the nomogram were comparable to the actual ones. We then succeeded in dividing patients with NECC into high- and low-risk groups concerning OS using the nomogram we developed. Besides, univariate analysis showed that chemotherapy ≥4 cycles may improve the OS of patients at YCH with NECC. CONCLUSION: We successfully constructed a nomogram that precisely predicts the OS for patients with NECC based on the SEER database and a large single-center retrospective cohort. The visualized and practical model can distinguish high-risk patients for recurrence and death who may benefit from clinical trials of boost therapy effectively. We also found that patients who received more than 4 cycles of chemotherapy acquired survival benefits than those who received less than 4 cycles.

OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a pregnancy complication that encompasses various pathogenic mechanisms. Shallow implantation of the placenta due to abnormal trophoblast behavior is considered an important mechanism underlying PE; however, its exact etiology remains unclear. METHODS: The expression of OLFML3 in the placenta and important clinical indicators were performed, followed by a correlation analysis. The effect of OLFML3 on the behavior of HTR-8/SVneo cells was examined, and the downstream molecular mechanisms of OLFML3 were investigated in HTR-8/SVneo cells. Additionally, a rat model of PE was generated by adenovirus injection via the tail vein to verify the role of OLFML3. RESULTS: OLFML3 is highly expressed in both syncytiotrophoblasts and cytotrophoblasts and deregulated in preeclamptic placentas. OLFML3 overexpression in HTR-8/SVneo cells promoted cell proliferation, migration, invasion, and impeded apoptosis, and triggered phosphorylation on ser473 of AKT. Conversely, OLFML3 knockdown exerted opposite effects. Furthermore, OLFML3 overexpression ameliorates CoCl2-induced apoptosis of HTR-8/SVneo cells. In a rat model, OLFML3 overexpression alleviates PE-associated maternal symptoms, leading to lower blood pressure, less severe proteinuria, improved fetal growth restriction, as well as upregulation of P-AKT and downregulation of Cleaved caspase3 and Bax. DISCUSSION: OLFML3 may alleviate PE development by inhibiting extravillous trophoblast cell apoptosis through the PI3K/AKT pathway. Our findings indicated that OLFML3 may provide a possible therapeutic target for PE.

Comparison of Chromosomal Microarray Analysis and Noninvasive Prenatal Testing in Pregnant Women with Fetal Ultrasonic Soft Markers.

Objective: This study aimed to assess the utility of chromosomal microarray analysis (CMA) and noninvasive prenatal testing (NIPT) in detecting clinically significant chromosomal abnormalities among fetuses presenting ultrasonic soft markers (USMs). Methods: A retrospective observational study, spanning from January 1, 2019, to September 30, 2022, enrolled 539 singleton pregnant women with fetal USMs at our center. Of these, 418 cases (77.6%) underwent NIPT, while 121 cases (22.4%) opted for invasive prenatal diagnosis post-appropriate genetic counseling. Cases with high-risk NIPT results proceeded to invasive prenatal diagnosis, where conventional karyotyping and CMA were concurrently performed. Further stratification was done based on the number of USMs, classifying cases into single-USM and multiple-USM groups. Results: Of the 24 cases (4.5%) exhibiting abnormal findings, 17 presented numerical chromosomal abnormalities, 2 featured clinically significant copy number variations (CNVs), 3 showed variants of unknown significance (VOUS), 1 displayed LOH, and 1 exhibited chromosome nine inversion. Notably, 18 cases (75%) theoretically detectable by karyotyping (eg, sizes above 10Mb) and 16 cases (66.7%) detectable by NIPT for five common aneuploidies were identified. Six submicroscopic findings (25%) were exclusively detectable by CMA. The predominant clinically relevant aberrations were observed in the thickened nuchal-translucency (TNT) group (9/35, 25.7%), followed by the multiple soft markers group (3/32, 9.3%). In the NIPT group, the false positive rate was 1.22%, and the false negative rate was 0%. Conclusion: The prevalence of chromosome aneuploidy exceeded that of submicroscopic chromosomal imbalance in pregnant women with fetal USMs. NIPT demonstrated efficacy, particularly for soft markers like echogenic intracardiac focus. However, for those with TNT and multiple soft markers, invasive prenatal diagnosis, including CMA testing, is recommended as the primary investigative approach.

Evaluating the Impact of Maternal Exposure to Ozone on Twin Fetal Growth in China.

Unlike singletons, twins require attention not only to the birth weight of the fetuses but also to discordance (i.e., the differences between weights) because twin growth discordance is a significant factor contributing to perinatal mortality and morbidity in twin pregnancies. However, the impact of maternal air pollution exposure on twin growth discordance has rarely been investigated. We examined the association of long-term ozone exposure during preconception and pregnancy with the birth weight of twins and twin growth discordance among 35,795 twins from the National Free Preconception Health Examination Project between January 2010 and December 2019. Linear mixed-effect models and random-effect logistic regression models were used to examine the associations of ozone exposure with the birth weight-related outcomes (i.e., birth weight of twins and within-pair birth weight difference) and risk of twin growth discordance, respectively, after adjustment for demographic characteristics and lifestyle. We found that an interquartile range (IQR) increase (15 µg/m3) in ozone exposure during the entire pregnancy was associated with a reduction (-28.96g, 95% confidence interval [CI]: -46.37, -11.56) in the total birth weight of twins, and ozone had a more pronounced impact on the birth weight of the smaller fetuses (-18.28 g, 95% CI: -27.22, -9.34) compared to the larger fetuses (-9.88 g, 95% CI: -18.84, -0.92) in twin pregnancies. An IQR increase in ozone exposure during the entire pregnancy was associated with a significant increase (8.41 g, 95% CI: 4.13, 12.69) in the within-pair birth weight difference; the odds ratio (OR) of twin growth discordance related to ozone exposure increased by 9% (OR = 1.09, 95% CI: 1.01, 1.18). However, no consistently significant associations were observed for ozone exposure during prepregnancy. Male-male twin pairs and those who were born prematurely appeared to be more susceptible to ozone exposure than their counterparts. Long-term ozone exposure during pregnancy was associated with twin growth discordance, and our findings provide reference data for future studies.

BTEX sensing potential of elemental-doped graphene: a DFT study.

Elementally-doped graphene demonstrates remarkable gas sensing capabilities as a novel 2D sensor material. In this study, we employed density functional theory calculations, we investigated the impact of various dopants on the BTEX (benzene, toluene, ethylbenzene, and xylene) sensing performance of graphene. Through the systematic analysis of electronic structures and sensitivity, we observed that both the doping method and dopant type significantly influence the interactions between graphene and BTEX molecules. Out of the 22 different elemental doped graphenes studied, N-, O-, and Pd-doped graphenes emerged as promising candidates for BTEX sensor materials. Graphene with N-doping exhibited relatively higher sensitivity towards toluene, ethylbenzene, and xylene compared to O- and Pd-doped graphenes. However, it demonstrated low sensitivity towards benzene. On the other hand, O-doped graphene displayed excellent selectivity for ethylbenzene over the other three gas molecules (benzene, toluene, and xylene). Similarly, Pd-doped graphene also exhibited significant selectivity for ethylbenzene and possessed higher sensitivity than the O-doped graphene. Their distinct characteristics and sensitivities make them potential candidates for future applications in gas sensing technology.

Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

The novel RNA-RNA activation of H19 on MyoD transcripts promoting myogenic differentiation of goat muscle satellite cells.

The elaborate interplay of coding and noncoding factors governs muscle growth and development. Here, we reported a mutual activation between long noncoding RNA (lncRNA) H19 and MyoD (myogenic determination gene number 1) in the muscle process. We successfully cloned the two isoforms of goat H19, which were significantly enriched and positively correlated with MyoD transcripts in skeletal muscles or differentiating muscle satellite cells (MuSCs). To systematically screen genes altered by H19, we performed RNA-seq using cDNA libraries of differentiating H19-deficiency MuSCs and consequently anchored MyoD as the critical genes in mediating H19 function. Intriguingly, some transcripts of MyoD and H19 overlapped in the cytoplasm, which was dramatically damaged when the core complementary nucleotides were mutated. Meanwhile, MyoD RNA successfully pulled down H19 in MS2-RIP experiments. Furthermore, HuR could bind both H19 and MyoD transcripts, while H19 or its truncated mutants successfully stabilized MyoD mRNA, with or without HuR deficiency. In turn, novel functional MyoD protein-binding sites were identified in the promoter and exons of the H19 gene. Our results suggest that MyoD activates H19 transcriptionally, and RNA-RNA hybridization is critical for H19-promoted MyoD expression, which extends our knowledge of the hierarchy of regulatory networks in muscle growth.

METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m6A-Dependent Manner.

The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m6A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m6A participates in the development of goat muscle. In this study, methyltransferase 3 (METTL3) was significantly enriched in goat longissimus dorsi (LD) tissue. In addition, the global m6A modification level and differentiation of skeletal muscle satellite cells (MuSCs) were regulated by METTL3. By performing mRNA-seq analysis, 8050 candidate genes exhibited significant changes in expression level after the knockdown of METTL3 in MuSCs. Additionally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that myocyte enhancer factor 2c (MEF2C) mRNA contained m6A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m6A levels and expression of MEF2C. Moreover, the m6A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to MEF2C mRNA. The present study reveals that METTL3 enhances myogenic differentiation in MuSCs by regulating MEF2C and provides evidence of a post-transcriptional mechanism in the development of goat skeletal muscle.

Structural and Mechanical Properties of Doped Tobermorite.

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