Search Results (22)

When jointed rock masses are in a high-stress environment, the roughness of the joints is the key factor controlling their shear strength. Their loading behavior is also different from the constant normal load (CNL) conditions controlled in conventional laboratories; rather, they follow the constant normal stiffness (CNS) conditions. To investigate the effects of normal stiffness and roughness on the shear mechanical properties of unfilled joint surfaces, shear tests were simulated using PFC3D (5.0) software under CNS conditions. The effects of normal stiffness of 0 (constant normal stress of 4 MPa), 0.028 GPa/m (low normal stiffness), 0.28 GPa/m (medium normal stiffness), and 2.8 GPa/m (high normal stiffness), and joint roughness coefficients (JRC) of 2~4 (low roughness), 10~12 (medium roughness), and 18~20 (high roughness) on the shear stress, normal stress, normal deformation, surface resistance index, and block failure characteristics of the joint surface were obtained. The results indicate that for different combinations of normal stiffness—JRC—the shear simulation process primarily exhibits three deformation stages: linear stage, yield stage, and post-peak stage. Shear stress increases initially and then decreases as shear displacement increases. When normal stiffness is no less than 0.28 GPa/m, both normal stress and JRC increase gradually with increasing JRC and normal stiffness. When the normal stiffness is no greater than 0.028 GPa/m, the normal stress shows no significant change. The normal displacement changes from “shear contraction” to “shear expansion” with increasing shear displacement and from positive to negative values while the displacement gradually increases; the maximum normal displacement decreases with increasing normal stiffness and increases with increasing JRC. The peak SRI value increases with increasing JRC and decreases with increasing normal stiffness. As normal stiffness increases, the number of tensile cracks for JRC 2~4 first decreases and then increases, while the number of shear cracks gradually increases; for JRC 10~12 and 18~20, both the number of shear cracks and tensile cracks increase with increasing normal stiffness. This paper simulates the actual mechanical environment of deep underground joints to expound the influence of normal stiffness and joint roughness on the stability of deep rock masses. The research results can provide certain theoretical references for predicting the stability of deep surrounding rocks and the stress of support structures. Full article

Adipose tissue metabolism plays a crucial role in sheep meat quality and the optimization of adipose tissue utilization. To reveal the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep, we investigated the mRNA and miRNA profiles in subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (Mth-6, Mth-18, and Mth-30). We identified 927 differentially expressed (DE) genes and 134 DE miRNAs in the SAT of sheep at different growth stages. Specifically, the expressions of ACACA, FASN, DGAT2, GPAM, SCD, ELOVL6, HSD17B12, TECR, PKM, TKT, PCK1, CD44, and THBS2S genes were significantly upregulated in Mth-18 and Mth-30 compared to that in Mth-6. These genes promoted fatty acid synthesis, triglyceride synthesis, gluconeogenesis, and extracellular matrix–receptor interaction and decreased glycolysis, leading to increased adipocyte proliferation and fat deposition. Notably, our findings suggested that the reduced activity of the AMPK signaling pathway may be regulated by CAMKK2 and PP2A during sheep growth. Furthermore, our results revealed several DE miRNAs, mml-miR-320b, chi-miR-1388-3p, bta-miR-6715, oar-miR-143, and miR-424, that potentially influence fat metabolism. Overall, this study provides a theoretical basis and new insights into the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep. Full article

Hypoxic stress causes cell damage and serious diseases in organisms, especially in aquatic animals. It is important to elucidate the changes in metabolic function caused by hypoxia and the mechanisms underlying these changes. This study focuses on the low oxygen tolerance feature of a new blunt snout bream strain (GBSBF1). Our data show that GBSBF1 has a different lipid and carbohydrate metabolism pattern than wild-type bream, with altering glycolysis and lipid synthesis. In GBSBF1, the expression levels of phd2 and vhl genes are significantly decreased, while the activation of HIF-3α protein is observed to have risen significantly. The results indicate that enhanced HIF-3α can positively regulate gpd1ab and gpam through PPAR-γ, which increases glucose metabolism and reduces lipolysis of GBSBF1. This research is beneficial for creating new aquaculture strains with low oxygen tolerance traits. Full article

Maintaining the normal biological rhythms of livestock is of great significance for reflecting the environmental suitability and welfare level of animals. Mistimed feeding can interfere with the circadian rhythms of both humans and animals, resulting in disorders of lipid metabolism, obesity, and metabolic syndrome. Low-temperature environment stimulates increased appetite and decreased physical activity, resulting in higher energy intake than consumption and thus facilitating fat deposition and even obesity. In this study, growing rabbits were randomly allocated to the daytime feeding (DF) group and nighttime restricted feeding (NRF) group. Our research demonstrated that, during winter, the DF regimen disrupted the behavioral rhythms of rabbits and accelerated weight gain without changing overall feed intake. The underlying reason was that DF disturbed the lipid metabolism rhythms, promoted hepatic lipid synthesis regulated by DGAT1 and lipid synthesis of adipose tissues regulated by GPAM, thus triggering fat deposition. In contrast, the NRF regimen enhanced thermogenesis regulated by T3 and elevated body temperature and facilitated ketogenesis mediated by HMGCS2, increasing energy consumption. However, it had no significant impact on the fat content within muscle. This study offers a theoretical foundation for the refinement of feeding management and healthy raising of rabbits. Full article

Goat milk is abundant in nutrients, particularly in milk fats, which confer health benefits to humans. Exploring the regulatory mechanism of fatty acid synthesis is highly important to understand milk composition manipulation. In this study, we used chromatin immunoprecipitation sequencing (ChIP-seq) on goat mammary glands at different lactation stages which revealed a novel lactation regulatory factor: cell death-inducing DFFA-like effector B (CIDEB). RT-qPCR results revealed that CIDEB was significantly upregulated during lactation in dairy goats. CIDEB overexpression significantly increased the expression levels of genes involved in fatty acid synthesis (ACACA, SCD1, p < 0.05; ELOVL6, p < 0.01), lipid droplet formation (XDH, p < 0.05), and triacylglycerol (TAG) synthesis (DGAT1, p < 0.05; GPAM, p < 0.01) in goat mammary epithelial cells (GMECs). The contents of lipid droplets, TAG, and cholesterol were increased (p < 0.05) in CIDEB-overexpressing GMECs, and knockdown of CIDEB led to the opposite results. In addition, CIDEB knockdown significantly decreased the proportion of C16:0 and total C18:2. Luciferase reporter assays indicated that X-box binding protein 1 (XBP1) promoted CIDEB transcription via XBP1 binding sites located in the CIDEB promoter. Furthermore, CIDEB knockdown attenuated the stimulatory effect of XBP1 on lipid droplet accumulation. Collectively, these findings elucidate the critical regulatory roles of CIDEB in milk fat synthesis, thus providing new insights into improving the quality of goat milk. Full article

As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 reached the highest expression at 60 h after the differentiation of goat intramuscular preadipocytes. Overexpression of goat NR4A1 increased the number of intracellular lipid droplets and up-regulated the expression of adipocyte-differentiation-related marker genes including AP2, SREBP1, ACC, GPAM, and DGAT2, while the relative expression levels of Pref-1 and HSL were significantly decreased. On the contrary, after NR4A1 was knocked down by siRNA, the number of intracellular lipid droplets and the relative expression levels of LPL, CEBPα, CEBPβ, ACC, and DGAT2 were significantly decreased, and the relative expression levels of Pref-1 and HSL were significantly up-regulated. These results suggest that NR4A1 promotes the differentiation of goat intramuscular preadipocytes. Transcriptome sequencing was carried out after overexpression of goat NR4A1, and the KEGG enrichment analysis result showed that the most differentially expressed genes were related to adipocyte differentiation and were enriched in the PI3K-Akt signaling pathway. LY249002, an inhibitor of the PI3K-Akt signaling pathway, was introduced and decreased the number of intracellular lipid droplets, and the relative expression levels of C/EBPα, SREBP1, AP2, C/EBPβ, GPAM, ACC, DGAT1, DGAT2, and ATGL were decreased accordingly. The above results indicate that overexpression of goat NR4A1 may promote the differentiation of intramuscular preadipocytes through the PI3K-Akt signaling pathway. Full article

The composition and metabolic profile of the ruminal microbiome have an impact on milk composition. To unravel the ruminal microbiome and metabolome affecting milk fat synthesis in dairy cows, 16S rRNA and internal transcribed spacer (ITS) gene sequencing, as well as ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) methods were used to investigate the significant differences in ruminal bacterial and fungal communities as well as metabolome among Chinese Holstein cows with contrasting milk fat contents under the same diet (H-MF 5.82 ± 0.41% vs. L-MF 3.60 ± 0.12%). Another objective was to culture bovine mammary epithelial cells (BMECs) to assess the effect of metabolites on lipid metabolism. Results showed that the acetate-to-propionate ratio and xylanase activity in ruminal fluid were both higher in H-MF. Microbiome sequencing identified 10 types of bacteria and four types of fungi differently abundant at the genus level. Metabolomics analysis indicated 11 different ruminal metabolites between the two groups, the majority of which were lipids and organic acids. Among these, lauric acid (LA) was enriched in fatty acid biosynthesis with its concentration in milk fat of H-MF cows being greater (217 vs. 156 mg per 100 g milk), thus, it was selected for an in vitro study with BMECs. Exogenous LA led to a marked increase in intracellular triglyceride (TG) content and lipid droplet formation, and it upregulated the mRNA abundance of fatty acid uptake and activation (CD36 and ACSL1), TG synthesis (DGAT1, DGAT2 and GPAM), and transcriptional regulation (SREBP1) genes. Taken together, the greater relative abundance of xylan-fermenting bacteria and fungi, and lower abundance of bacteria suppressing short-chain fatty acid-producing bacteria or participating in fatty acid hydrogenation altered lipids and organic acids in the rumen of dairy cows. In BMECs, LA altered the expression of genes involved in lipid metabolism in mammary cells, ultimately promoting milk fat synthesis. Thus, it appears that this fatty acid plays a key role in milk fat synthesis. Full article

During triacylglycerol synthesis, the acylglycerol-3-phosphate acyltransferase (AGPAT) family catalyzes the conversion of lysophosphatidic acid to phosphatidic acid and the acylation of sn-2 fatty acids. However, the catalytic activity of different AGPAT members is different. Therefore, this study aimed to investigate the mechanism through which different AGPATs affect the efficiency of TAG synthesis and fatty acid composition. The conservation of amino acid sequences and protein domains of the AGPAT family was analyzed, and the functions of AGPAT1, AGPAT3, and AGPAT4 genes in buffalo mammary epithelial cells (BMECs) were studied using RNA interference and gene overexpression. Prediction of the protein tertiary structure of the AGPAT family demonstrated that four conservative motifs (motif1, motif2, motif3, and motif6) formed a hydrophobic pocket in AGPAT proteins, except AGPAT6. According to cytological studies, AGPAT1, AGPAT3, and AGPAT4 were found to promote the synthesis and fatty acid compositions of triacylglycerol, especially UFA compositions of triacylglycerol, by regulating ACSL1, FASN, GPAM, DGAT2, and PPARG gene expression. This study provides new insights into the role of different AGPAT gene family members involved in TAG synthesis, and a reference for improving the fatty acid composition of milk. Full article

Branched-chain fatty acids (BCFAs) are natural components with a variety of biological activities. However, the regulation of lipid metabolism by BCFAs is unknown. It was dedicated to examining the impacts of BCFAs inferred from yak ghee on the expression of qualities related to lipid metabolism, natural pathways, and intestinal microbiota in mice. The treatment group (purified BCFAs from yak ghee) exhibited a decrease in cholesterol levels; a decrease in HMGCR levels; downregulation of FADS1, FADS2, ACC-α, FAS, GAPT4, GPAM, ACSL1, THRSP, A-FABP, and PPARα gene expression; and upregulation of SCD1, ACSS1, FABP1, CPT1, and DGAT-1 gene expression. Gut microbiota 16S rDNA sequencing analysis showed that the treatment group improved the gut microbiota by increasing the relative abundances and increasing the short-chain fatty acid levels produced by the genera Akkermansia, Clostridium, Lachnospiraceae, Lactobacillus, Anaerotaenia, and Prevotella. After adding BCFAs to cultured breast cancer cells, pathways that were downregulated were found to be related to fatty acid degradation and fatty acid metabolism, while 20 other pathways were upregulated. Our results suggest that BCFAs reduce body fat in mice by modulating intestinal flora and lipid metabolism and modulating fatty acid metabolism in breast cancer cells. Full article

MicroRNAs (miRNAs) are small RNA molecules consisting of approximately 22 nucleotides that are engaged in the regulation of various bio-processes. There is growing evidence that miR-29 is a key regulator of hepatic lipid metabolism. Mimics and inhibitors of bta-miRNA29d-3p were transiently transfected in bovine mammary epithelial cells (BMECs) to reveal the regulation of bta-miRNA29d-3p on lipid accumulation in BMECs. Results showed that overexpression of bta-miRNA29d-3p significantly inhibited the expression of genes related to triglyceride (TAG) synthesis, namely DGAT1 and mitochondrial glycerol-3-phosphate acyltransferase (GPAM, p < 0.01) and down-regulated TAG levels in cells (p < 0.05). The expression of fatty acid synthesis and desaturation-related genes FASN, SCD1, and ACACA, and transcription factor SREBF1 also decreased. Interference of bta-miRNA29d-3p significantly increased the expression of GPAM, DGAT1, FASN, SCD1, ACACA, and SREBF1 (p < 0.01), and significantly upregulated the concentration of TAG in cells. Furthermore, a luciferase reporter assay confirmed that GPAM is a direct target of bta-miRNA29d-3p. In summary, bta-miRNA29d-3p modulates fatty acid metabolism and TAG synthesis by regulating genes related to lipid metabolism in BMECs and targeting GPAM. Thus, bta-miRNA29d-3p plays an important role in controlling mammary lipid synthesis in cows. Full article

The development of smart hydrogel with excellent mechanical properties and photothermal conversion capability is helpful in expending its application fields. Herein, a MXene/gelatin/polyacrylamide (M/G/PAM) nanocomposite double network (NDN) hydrogel was synthesized by γ-ray radiation technology for the first time. Compared with gelatin/polyacrylamide double network hydrogel, the optimized resultant M₃/G/PAM NDN hydrogel shows better mechanical properties (tensile strength of 634 ± 10 kPa, compressive strength of 3.44 ± 0.12 MPa at a compression ratio of 90%). The M₃/G/PAM NDN hydrogel exhibits a faster heating rate of 30 °C min⁻¹, stable photothermal ability, and mechanical properties even after 20 cycles of on–off 808 nm near-infrared (NIR) laser irradiation (1.0 W cm⁻²). Furthermore, the temperature of M₃/G/PAM NDN hydrogel can be increased rapidly from 25 °C to 90 °C in 10 s and could reach 145 °C in 120 s under irradiation by focused NIR laser irradiation (56.6 W cm⁻²). The high mechanical property and photothermal properties of M/G/PAM hydrogel are ascribed to the formation of double network and uniform hydrogen bonding between MXene and gelatin and PAM polymers. This work paves the way for construction of photothermal hydrogels with excellent mechanical properties. Full article

Malonyl/acetyltransferase (MAT) is a crucial functional domain of fatty acid synthase (FASN), which plays a vital role in the de novo synthesis of fatty acids in vivo. Milk fatty acids are secreted by mammary epithelial cells. Mammary epithelial cells are the units of mammary gland development and function, and it is a common model for the study of mammary gland tissue development and lactation. This study aimed to investigate the effects of MAT deletion on the synthesis of triacylglycerol and medium-chain fatty acids. The MAT domain was knocked out by CRISPR/Cas9 in the goat mammary epithelial cells (GMECs), and in MAT knockout GMECs, the mRNA level of FASN was decreased by approximately 91.19% and the protein level decreased by 51.83%. The results showed that MAT deletion downregulated the contents of triacylglycerol and medium-chain fatty acids (p < 0.05) and increased the content of acetyl-Coenzyme A (acetyl-CoA) (p < 0.001). Explicit deletion of MAT resulted in significant drop of FASN, which resulted in downregulation of LPL, GPAM, DGAT2, PLIN2, XDH, ATGL, LXRα, and PPARγ genes in GMECs (p < 0.05). Meanwhile, mRNA expression levels of ACC, FASN, DGAT2, SREBP1, and LXRα decreased following treatment with acetyl-CoA (p < 0.05). Our data reveals that FASN plays critical roles in the synthesis of medium-chain fatty acids and triacylglycerol in GMECs. Full article

The COVID-19 pandemic has resulted in educational disruption at a global scale. Based on the United Nation’s Sustainable Development Goal 4, “achieving inclusive and quality education for all”, this study designed two feasible learning models for the solution of sustainable learning during the COVID-19 pandemic, GPAM-WATA and Paper-and-Pencil test (PPT). The GPAM-WATA, a web-based dynamic assessment, offers online learning to most of the populations impacted by the COVID-19 pandemic, while PPT makes the vulnerable groups’ access to learning possible with the aid of paper-based delivery. A quasi-experimental design was adopted, and both learning models were applied to a junior high school English reading course in Taiwan. A total of 122 seventh graders were randomly assigned to the GPAM-WATA group and PPT group for self-directed learning. The findings show that the GPAM-WATA is a sustainable educational technique that facilitates a better improvement in English reading performance. The PPT also has a positive effect on English reading performance, although not significantly if compared with the GPAM-WATA. This study suggests that GPAM-WATA is effective for English reading instruction in an online learning environment. The PPT can be an alternative approach for students stuck without access to online delivery during the COVID-19 pandemic. Full article

This study aimed to examine the effects of increasing levels of three 18-carbon fatty acids (stearate, oleate and linoleate) on mammary lipogenesis, and to evaluate their effects on the milk lipogenic pathway in porcine mammary epithelial cells (pMECs). We found that increasing the three of 18-carbon fatty acids enhanced the cellular lipid synthesis in a dose-dependent manner, as reflected by the increased (triacylglycerol) TAG content and cytosolic lipid droplets in pMECs. The increased lipid synthesis by the three 18-carbon fatty acids was probably caused by the up-regulated expression of major genes associated with milk fat biosynthesis, including CD36 (long chain fatty acid uptake); GPAM, AGPAT6, DGAT1 (TAG synthesis); PLIN2 (lipid droplet formation); and PPARγ (regulation of transcription). Western blot analysis of CD36, DGAT1 and PPARγ proteins confirmed this increase with the increasing incubation of 18-carbon fatty acids. Interestingly, the mRNA expressions of ACSL3 and FABP3 (fatty acids intracellular activation and transport) were differentially affected by the three 18-carbon fatty acids. The cellular mRNA expressions of ACSL3 and FABP3 were increased by stearate, but were decreased by oleate or linoleate. However, the genes involved in fatty acid de novo synthesis (ACACA and FASN) and the regulation of transcription (SREBP1) were decreased by incubation with increasing concentrations of 18-carbon fatty acids. In conclusion, our findings provided evidence that 18-carbon fatty acids (stearate, oleate and linoleate) significantly increased cytosolic TAG accumulation in a dose-dependent manner, probably by promoting lipogenic genes and proteins that regulate the channeling of fatty acids towards milk TAG synthesis in pMECs. Full article

cAMP response element binding protein 1 (CREB1) is a member of the leucine zipper transcription factor family of DNA binding proteins. Although studies in non-ruminants have demonstrated a crucial role of CREB1 in lipid synthesis in liver and adipose tissue, it is unknown if this transcription regulator exerts control of fatty acid synthesis in ruminant mammary cells. To address this question, we first defined the expression dynamics of CREB1 in mammary tissue during lactation. Analysis of CREB1 in mammary tissue revealed higher mRNA abundance in mammary tissue harvested at peak lactation. Overexpression of CREB1 markedly upregulated sterol regulatory element binding transcription factor 1 (SREBP1), fatty acid synthase (FASN), acetyl-coenzyme A carboxylase α (ACACA), elongase of very long chain fatty acids 6 (ELOVL6), lipoprotein lipase (LPL), fatty acid binding protein 3 (FABP3), lipin 1 (LPIN1) and diacylglycerol acyltransferase 1 (DGAT1), but had no effect on glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) or 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6). In addition, overexpressing CREB1 led to a significant increase in the concentration and desaturation index of C16:1 (palmitoleic acid) and C18:1 (oleic acid), along with increased concentration of triacylglycerol. Taken together, these results highlight an important role of CREB1 in regulating lipid synthesis in goat mammary epithelial cells. Thus, manipulation of CREB1 in vivo might be one approach to improve the quality of goat milk. Full article