Chronic heat stress upregulates pyruvate metabolic process and gluconeogenesis but downregulates immune responses in Sahiwal cattle.

Climate change and growing population and their strain on animal production are the impending challenges that the developing countries, like India, need to tackle in the coming days. This study aimed to detect and analyze the uncharacterized variation in the gene expression patterns with the change of condition, from thermoneutral to chronic hot-humid, in the Sahiwal cattle, one of the best breeds of milk-producing cattle in India, known for being heat-tolerant. Using RNA-Seq analysis on peripheral blood mononuclear cells (PBMCs), 4021 differentially expressed mRNAs (2772 upregulated, 1249 downregulated) and 1303 differentially expressed long non-coding RNAs (769 upregulated, 534 downregulated) were identified, with the thresholds of false discovery rate < 0.05 and|log2(fold change)| > 2. Significantly (p-adjusted < 0.05) overrepresented Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways were analyzed, revealing upregulation of processes like pyruvate metabolic process, gluconeogenesis, ion transmembrane transport, neuropeptide signaling pathway, and animal organ development, with genes like SHH, GRK1, CHRM3, CAMK2A, and HSPB7 were upregulated, while translation and immune responses, with genes like RPS3, EEF1A1, TNF, BoLA-DRB3, and UBB were downregulated. Analysis of cis-mRNAs of DE-lncRNAs showed presence of both up- and down-regulated cis-mRNAs for both up- and down-regulated lncRNAs indicating existence of positive and negative regulation of mRNA expression by lncRNAs. Managemental nudges that decrease metabolic heat generation, like betaine and chromium supplementation, and increase heat dissipation, like microenvironment cooling, should be utilized. This study highlights the role of pyruvate metabolism and gluconeogenesis in coping up with heat stress and offers an improved understanding of the heat stress response of Sahiwal cattle along with the genes and pathways responsible for it.

Plasma proteomic analysis reveals key pathways associated with divergent residual body weight gain phenotype in beef steers.

We utilized plasma proteomics profiling to explore metabolic pathways and key proteins associated with divergent residual body weight gain (RADG) phenotype in crossbred (Angus × Hereford) beef steers. A group of 108 crossbred growing beef steers (average BW = 282.87 ± 30 kg; age = 253 ± 28 days) were fed a high-forage total mixed ration for 49 days in five dry lot pens (20-22 beef steers per pen), each equipped with two GrowSafe8000 intake nodes to determine their RADG phenotype. After RADG identification, blood samples were collected from the beef steers with the highest RADG (most efficient; n = 15; 0.76 kg/d) and lowest RADG (least efficient; n = 15; -0.65 kg/d). Plasma proteomics analysis was conducted on all plasma samples using a nano LC-MS/MS platform. Proteins with FC ≥ 1.2 and false-discovery rate-adjusted p-values (FDR) ≤ 0.05 were considered significantly differentially abundant. The analysis identified 435 proteins, with 59 differentially abundant proteins (DAPs) between positive and negative-RADG beef steers. Plasma abundance of 38 proteins, such as macrophage stimulating 1 and peptidase D was upregulated (FC ≥ 1.2, FDR ≤ 0.05) in positive-RADG beef steers, while 21 proteins, including fibronectin and ALB protein were greater (FC < 1.2, FDR ≤ 0.05) in negative-RADG beef steers. The results of the Gene Ontology (GO) analysis of all the DAPs showed enrichment of pathways such as metabolic processes, biological regulation, and catalytic activity in positive-RADG beef steers. Results of the EuKaryotic Orthologous Groups (KOG) analysis revealed increased abundance of DAPs involved in energy production and conversion, amino acid transport and metabolism, and lipid transport and metabolism in positive-RADG beef steers. The results of this study revealed key metabolic pathways and proteins associated with divergent RADG phenotype in beef cattle which give more insight into the biological basis of feed efficiency in crossbred beef cattle.

Evolution of quorum sensing process and their regulatory role on biochemical metabolism during the organic loading rate increase in dry anaerobic digestion.

The organic loading rate (OLR) is a critical parameter affecting the stability of dry anaerobic digestion (AD) of kitchen waste (KW), and significantly impacting the variations in physicochemical parameters and microbial communities. However, the evolution of quorum sensing (QS) and their role on anaerobic biochemical metabolism during the increase in OLR in dry AD remain unknown. Therefore, this study systematically elucidated the matter through multi-omics analysis based on a pilot-scale dry AD of KW. The results demonstrated that fluctuations in the OLR significantly influenced the microbial QS in dry AD. When the OLR ≤4.0 g·VS/L·d, the system operated stably, and methane production increased. The enrichment of Proteobacteria was crucial for sustaining high levels of functional genes associated with various types of QS, including acyl-homoserine lactones (AI-1), autoinducer-2 (AI-2), autoinducer-3 (AI-3), and gamma-aminobutyric acid (GABA). This enabled cooperative communication among microbes under low OLR. Furthermore, most genes associated with these QS processes positively affected hydrolysis, acidogenesis, and methanogenesis. When the OLR increased to 6.0 g·VS/L·d, the fatty acids and hydrogen partial pressure increased significantly. The autoinducing peptides (AIP)-type became the predominant QS and was positively correlated with fatty acids abundance. Syntrophaceticus and Syntrophomonas may promote syntrophic oxidation of acetate at high OLR through AIP-type QS. These findings provided new insights into the QS processes of microbes during dry AD of KW and a theoretical foundation for optimizing biochemical metabolic processes in dry AD through QS.

Genome-wide screening and characterization of phospholipase A (PLA)-like genes in sorghum (Sorghum bicolor L.).

MAIN CONCLUSION: The characterisation of PLA genes in the sorghum genome using in-silico methods revealed their essential roles in cellular processes, providing a foundation for further detailed studies. Sorghum bicolor (L.) Moench is the fifth most cultivated crop worldwide, and it is used in many ways, but it has always gained less popularity due to the yield, pest, and environmental constraints. Improving genetic background and developing better varieties is crucial for better sorghum production in semi-arid tropical regions. This study focuses on the phospholipase A (PLA) family within sorghum, comprehensively characterising PLA genes and their expression across different tissues. The investigation identified 32 PLA genes in the sorghum genome, offering insights into their chromosomal localization, molecular weight, isoelectric point, and subcellular distribution through bioinformatics tools. PLA-like family genes are classified into three groups, namely patatin-related phospholipase A (pPLA), phospholipase A1 (PLA1), and phospholipase A2 (PLA2). In-silico chromosome localization studies revealed that these genes are unevenly distributed in the sorghum genome. Cis-motif analysis revealed the presence of several developmental, tissue and hormone-specific elements in the promoter regions of the PLA genes. Expression studies in different tissues such as leaf, root, seedling, mature seed, immature seed, anther, and pollen showed differential expression patterns. Taken together, genome-wide analysis studies of PLA genes provide a better understanding and critical role of this gene family considering the metabolic processes involved in plant growth, defence and stress response.

Recent advances in design and application of synthetic membraneless organelles.

Membraneless organelles (MLOs) formed by liquid-liquid phase separation (LLPS) have been extensively studied due to their spatiotemporal control of biochemical and cellular processes in living cells. These findings have provided valuable insights into the physicochemical principles underlying the formation and functionalization of biomolecular condensates, which paves the way for the development of versatile phase-separating systems capable of addressing a variety of application scenarios. Here, we highlight the potential of constructing synthetic MLOs with programmable and functional properties. Notably, we organize how these synthetic membraneless compartments have been capitalized to manipulate enzymatic activities and metabolic reactions. The aim of this review is to inspire readerships to deeply comprehend the widespread roles of synthetic MLOs in the regulation enzymatic reactions and control of metabolic processes, and to encourage the rational design of controllable and functional membraneless compartments for a broad range of bioengineering applications.

Liver transcriptome analysis reveal the metabolic and apoptotic responses of Trachinotus ovatus under acute cold stress.

Trachinotus ovatus is an economically important fish and has been recommended as a high-quality aquaculture fish breed for the high-quality development of sea ranches in the South China Sea. However, T. ovatus shows intolerance to low temperature, greatly limiting the extension of farming scale, reducing production efficiency in winter, and increasing farming risks. In this study, liver transcriptome analysis was investigated in T. ovatus under acute low temperature conditions (20 and 15 °C) using RNA sequencing (RNA-Seq) technology. Inter-groups differential expression analysis and trend analysis screened 1219 DEGs and four significant profiles (profiles 0, 3, 4, and 7), respectively. GO enrichment analysis showed that these DEGs were mainly related to metabolic process and cell growth and death process. KEGG enrichment analysis found that DEGs were mainly associated with lipid metabolism, carbohydrate metabolism, and cell growth and death, such as gluconeogenesis, glycolysis, fatty acid oxidation, cholesterol biosynthesis, p53 signaling pathway, cell cycle arrest, and apoptotic cell death. Moreover, protein-protein interaction networks identified two hub genes (FOS and JUNB) and some important genes related to metabolic process and cell growth and death process, that corresponding to enrichment analysis. Overall, gluconeogenesis, lipid mobilization, and fatty acid oxidation in metabolic process and cell cycle arrest and apoptotic cell death in cell growth and death process were enhanced, while glycolysis, liver glycogen synthesis and cholesterol biosynthesis in metabolic process were inhibited. The enhancement or attenuatment of metabolic process and cell growth and death process is conducive to maintain energy balance, normal fluidity of cell membrane, normal physiological functions of liver cell, enhancing the tolerance of T. ovatus to cold stress. These results suggested that metabolic process and cell growth and death process play important roles in response to acute cold stress in the liver of T. ovatus. Gene expreesion level analysis showed that acute cold stress at 15 °C was identified as a critical temperature point for T. ovatus in term of cellular metabolism alteration and apoptosis inducement, and rewarming intervention should be timely implemented above 15 °C. Our study can provide theoretical support for breeding cold-tolerant cultivars of T. ovatus, which is contributed to high-quality productions fish production.

Diversity, composition, metabolic characteristics, and assembly process of the microbial community in sewer system at the early stage.

Sewer systems play vital roles in wastewater treatment facilities, and the microbial communities contribute significantly to the transformation of domestic wastewater. Therefore, this study conducted a 180-day experiment on a sewer system and utilized the high-throughput sequencing technology to characterize the microbial communities. Additionally, community assembly analysis was performed to understand the early-stage dynamics within the sewer system. The results demonstrated that the overall diversity of microbial communities exhibited fluctuations as the system progressed. The dominant phyla observed were Chloroflexi, Bacteroidetes, Firmicutes, and Proteobacteria, accounting for over 85.4% of the total relative abundances. At the genus level, bacteria associated with fermentation displayed a high relative abundance, particularly during days 75 to 180. A random-forest machine-learning model identified a group of microbes that confirmed the substantial contribution of fermentation. During the process of fermentation, microorganisms predominantly utilized propionate formation as the main pathway for acidogenesis, followed by acetate and butyrate formation. In terms of nitrogen and sulfur cycles, dissimilatory nitrate reduction and assimilatory sulfate reduction played significant roles. Furthermore, stochastic ecological processes had a dominant effect during the experiment. Dispersal limitation primarily governed the assembly process almost the entire experimental period, indicating the strong adaptability and metabolic plasticity of microorganisms in response to environmental variations. This experiment provides valuable insights into the metabolic mechanisms and microbial assembly associated with sewer systems.

Rapid identification of chemical constituents and dynamic metabolic profile of Shenqi-Tiaoshen formula in rat plasma based on UPLC-Q-TOF/MSE.

Shenqi-Tiaoshen formula (SQTSF) is a traditional Chinese medicine (TCM) prescription that has been employed in the treatment of chronic obstructive pulmonary disease (COPD). Clinical practice has demonstrated that SQTSF is an effective prescription for stable COPD. However, owing to the complexity of TCM prescription, there is a lack of in-depth understanding of the chemical components of SQTSF and its in vivo metabolism studies. In this study, a comprehensive analytical strategy based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was established to identify the chemical components, the absorbed components, and the metabolites of SQTSF given by gavage in rats, and analyze their dynamic changes. As a result, 86 chemical components of SQTSF were characterized, which were mainly categorized into flavonoids, saponins, organic acids, terpenoids, etc. Among them, 13 compounds were confirmed unambiguously by reference standards. Furthermore, 20 prototype components and 46 metabolites were detected in rat plasma at different time points. It was found that one prototype component and thirteen metabolites could be detected during the entire 24 h, indicating that these compounds were slowly eliminated and thus accumulated in vivo over a prolonged duration. Interestingly, the phenomenon that three prototype components and fourteen metabolites reappeared after a period of disappearance from the plasma was found. It was also observed that different prototype components may generate the same metabolite. The metabolic processes of SQTSF in rats mainly included oxidation, reduction, hydration, demethylation, deglycosylation, methylation, acetylation, glucuronidation, glutathionylation, and associated combination reactions. Overall, the present study identified the chemical components of SQTSF and their dynamic metabolic profile in rat plasma, which provided a systematic and applicable strategy for screening and characterization of the prototype components and metabolites of TCM compound preparations.

ABCB11 accumulated in immature tertiary lymphoid structures participates in xenobiotic metabolic process and predicts resistance to PD-1/PD-L1 inhibitors in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are at a high risk of recurrence and multimodal therapy have not significantly improved survival in recent decades. Although immune checkpoint inhibitors (ICIs) are effective in a small proportion of HNSCC patients, the majority do not respond. In this study, we for the first time revealed that xenobiotic metabolic process was significantly associated with resistance to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in HNSCC and found that ATP binding cassette subfamily B member 11 (ABCB11) accumulated in immature tertiary lymphoid structures (TLSs) predicted worse progression-free survival (PFS) and overall survival (OS) after PD-1/PD-L1 inhibitors therapy. Moreover, the expression of cytochrome P450 1A2 (CYP1A2), a cytochrome P450 (CYP) enzyme that participates in xenobiotic metabolic process, was significantly upregulated in CD45+ABCB11+ tumor-infiltrating lymphocytes (TILs) compared with CD45+ABCB11-TILs in HNSCC tissues. Whole slide scans of 110 HNSCC tissues with hematoxylin-eosin (HE) and multispectral immuno-fluorescent (mIF) staining revealed that ABCB11 had a high co-expression with CYP1A2 in immature TLSs, and colocalization of ABCB11 and CYP1A2 in immature TLs significantly associated with high infiltration of immunosuppressive T-regulatory (Treg). Our study revealed that ABCB11 accumulated in immature TLSs might upregulate CYP1A2 to mediate xenobiotic metabolic process, thus increase the immunosuppressive Treg infiltration, and induce resistance to PD-1/PD-L1 inhibitors in HNSCC.

Low KCNQ1 expression is associated with unfavorable outcome and metabolism of gastric cancer.

BACKGROUND: Potassium voltage-gated channel subfamily Q member 1 (KCNQ1), is implicated in the onset and progression of gastric carcinoma (GC), one of the most common types of stomach malignancies. This research aims to investigate the potential prognostic implications of KCNQ1 mRNA in GC using various databases such as The Cancer Genome Atlas (TCGA), The Human Protein Atlas (HPA), LinkedOmics, TISIDB, ESTIMATE, and TIMER. METHODS: We searched the HPA database to obtain information on KCNQ1 levels in human normal tissues, organs, and cell lines as well as in pan-cancer tissues. Then, we used TIMER and UALCAN to comparatively analyze the KCNQ1 mRNA levels in different types of cancers relative to their adjacent normal counterparts. Based on TCGA and Gene Expression Omnibus, the correlation of clinical information with KCNQ1 expression was analyzed using logistic regression model. Univariable and Multivariate Cox analyses were then carried out to compare differences in survival among patients with different clinical characteristics. The multivariate methods, such as Kaplan-Meier plotter and GEPIA survival curves, were further employed to identify the correlation of KCNQ1 expression with overall survival (OS). Besides, LinkedOmics was used to identify differentially expressed genes for functional enrichment analysis. RESULTS: KCNQ1 exhibited tissue-specific imprinting and expression in human normal tissues, organs and cell lines, while it was aberrantly expressed in pan-cancer tissues. Lower KCNQ1 mRNA expression was determined in GC tissue samples versus normal counterparts. In GC cases, elevated KCNQ1 levels were strongly linked to a longer OS and strongly correlated with invasion depth (χ2=12.631, P=0.006), TNM stage (χ2=8.750, P=0.033), differentiation grade (χ2=7.426, P=0.024), and vital status (χ2=5.676, P=0.017). Furthermore, KCNQ1 was identified by univariable and multivariate Cox analyses as an independent risk factor for GC. Based on Gene Ontology analysis, digestion as well as tricarboxylic acid metabolic, carbohydrate catabolic, and small molecule catabolic processes were differentially enriched in the up-regulated KCNQ1 phenotypic pathway. While carbon metabolism, fatty acid degradation, peroxisome, and citrate cycle (TCA cycle) were identified by the Kyoto Encyclopedia of Genes and Genomes-based analysis as pathways with differential enrichment. CONCLUSION: Being a prognostic biomarker, KCNQ1 may play an inhibitory role and involve in the metabolic process of GC.

Anaerobic biodegradation of pyrene and benzo[a]pyrene by a new sulfate-reducing Desulforamulus aquiferis strain DSA.

The study of anaerobic high molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) biodegradation under sulfate-reducing conditions by microorganisms, including microbial species responsible for biodegradation and relative metabolic processes, remains in its infancy. Here, we found that a new sulfate-reducer, designated as Desulforamulus aquiferis strain DSA, could biodegrade pyrene and benzo[a]pyrene (two kinds of HMW-PAHs) coupled with the reduction of sulfate to sulfide. Interestingly, strain DSA could simultaneously biodegrade pyrene and benzo[a]pyrene when they co-existed in culture. Additionally, the metabolic processes for anaerobic pyrene and benzo[a]pyrene biodegradation by strain DSA were newly proposed in this study based on the detection of intermediates, quantum chemical calculations and analyses of the genome and RTqPCR. The initial activation step for anaerobic pyrene and benzo[a]pyrene biodegradation by strain DSA was identified as the formation of pyrene-2-carboxylic acid and benzo[a]pyrene-11-carboxylic acid by carboxylation Thereafter, CoA ligase, ring reduction through hydrogenation, and ring cracking occurred, and short-chain fatty acids and carbon dioxide were identified as the final products. Additionally, DSA could also utilize benzene, naphthalene, anthracene, phenanthrene, and benz[a]anthracene as carbon sources. Our study can provide new guidance for the anaerobic HMW-PAHs biodegradation under sulfate-reducing conditions.

Transcriptome Analysis Reveals the Effect of Stocking Density on Energy Metabolism in the Gills of Cherax quadricarinatus under Rice-Crayfish Co-Culture.

Stocking density is a crucial factor affecting productivity in aquaculture, and high stocking density is a stressor for aquatic animals. In this study, we aimed to investigate the effects of stocking densities on oxidative stress and energy metabolism in the gills of Cherax quadricarinatus under rice-crayfish farming. The C. quadricarinatus were reared at low density (LD), medium density (MD), and high density (HD) for 90 days. The results showed that the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) levels were higher in the HD group than those in the LD group. Transcriptomic analysis revealed 1944 upregulated and 1157 downregulated genes in the gills of the HD group compared to the LD group. Gene ontology (GO) enrichment analysis indicated that these differentially expressed genes (DEGs) were significantly associated with ATP metabolism. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis also showed that high stocking density resulted in the dysregulation of oxidative phosphorylation. Furthermore, high stocking density upregulated six lipid metabolism-related pathways. Overall, our findings, despite the limited number of samples, suggested that high stocking density led to oxidative stress and dysregulation of energy metabolism in the gills of C. quadricarinatus under rice-crayfish co-culture. Alteration in energy metabolism may be an adaptive response to adverse farming conditions.

Microbial degradation and transformation of PPCPs in aquatic environment: A review.

The Pharmaceuticals and Personal Care Products (PPCPs) presence at harmful levels has been identified in aquatic ecosystems all over the world. Currently, PPCPs are more common in aquatic regions and have been discovered to be extremely harmful to aquatic creatures. Waste-water treatment facilities are the primary cause of PPCPs pollution in aquatic systems due to their limited treatment as well as the following the release of PPCPs. The degree of PPCPs elimination is primarily determined by the method applied for the remediation. It must be addressed in an eco-friendly manner in order to significantly improve the environmental quality or, at the very least, to prevent the spread as well as effects of toxic pollutants. However, when compared to other methods, environmentally friendly strategies (biological methods) are less expensive and require less energy. Most biological methods under aerobic conditions have been shown to degrade PPCPs effectively. Furthermore, the scientific literature indicates that with the exception of a few extremely hydrophobic substances, biological degradation by microbes is the primary process for the majority of PPCPs compounds. Hence, this review discusses about the optimistic role of microbe concerned in the degradation or transformation of PPCPs into non/less toxic form in the polluted environment. Accordingly, more number of microbial strains has been implicated in the biodegradation/transformation of harmful PPCPs through a process termed as bioremediation and their limitations.

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.

BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

Upregulation of LPGAT1 Enhances Lung Adenocarcinoma Proliferation.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related mortality. Lysophosphatidylglycerol acyltransferase (LPGAT1) regulates the biosynthesis of triacylglycerol, which is essential for maintaining phospholipid homeostasis and modulating the structural integrity of mitochondrial membranes. LPGAT1 has been demonstrated to be differentially expressed in normal lung tissue and LUAD tissues, and can serve as a metabolically relevant gene with potential prognostic value. However, the potential role of LPGAT1 in LUAD is still unknown. This study sought to determine the role of LPGAT1 in LUAD progression. METHODS: LPGAT1 expression was examined in LUAD cells and tumor tissues from LUAD patients. The effect of LPGAT1 was then assessed in both cell and animal models after LPGAT1 was knocked down by RNA interference. RESULTS: LPGAT1 was upregulated in LUAD tissues. Overexpression of LPGAT1 was associated with an unfavorable prognosis in LUAD patients, as revealed by univariate and multivariate Cox analyses. Knockdown of LPGAT1 abrogated tumor growth and proliferation in both cell and animal models. CONCLUSIONS: This study demonstrates that LPGAT1 promotes proliferation and inhibits apoptosis in LUAD. Hence, LPGAT1 may provide new treatment strategies for LUAD.

Family with Sequence Similarity 72 (FAM72) - A prospective biomarker for poor prognosis in patients with oral squamous cell carcinoma.

OBJECTIVE: To study the effect of FAM72 on the prognosis of patients with oral squamous cell carcinoma (OSCC) and to explore the relationship between FAM72 and OSCC. DESIGN: We used a vast array of databases and analytical vehicles to assess the relation between FAM72 and OSCC, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. We made a preliminary verification of OSCC lines and tissues by real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: FAM72 was higher in OSCC than in normal tissues. Analysis of univariate COX data indicated that elevated expression of FAM72A, FAM72B, and FAM72C in OSCC was related to poor overall survival. Moreover, FAM72B and FAM72C were independent of overall survival in multiple COX regression. FAM72A-D and its coexpressed genes in Metascape were analyzed by Gene Ontology (GO), they were enriched in cellular cycle, mitotic and DNA metabolism. Gene set enrichment analysis (GSEA) demonstrated an enrichment in pathways related to cell metabolism. Additionally, high FAM72 expression related to a worse prognosis in OSCC patients. FAM72A-D linked to the infiltration of tumor immune cell in OSCC patients. We found that methylation levels are likely linked to prognosis in OSCC patients. We used RT-qPCR to ascertain the differential FAM72B and FAM72C expression levels in cancer and paracancerous tissues of OSCC, human normal oral keratinocytes (HOK), and human tongue squamous cell carcinoma (Cal-33). CONCLUSION: Our findings indicate that FAM72B and FAM72C are potential molecular markers of poor prognosis in OSCC and may act as novel targets for OSCC treatment strategies.

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction.

Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs-miRNAs-mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.

Congener-Specific Uptake and Metabolism of Bisphenols in Carrot Cells: Dissipation Kinetics, Biotransformation, and Enzyme Responses.

Food consumption has been considered a key pathway of bisphenol compound (BP) exposure for humans. However, there is a lack of evidence concerning their congener-specific behavior and metabolism in plants. Herein, we examined the uptake and metabolism of five BPs in plants using carrot cells. Bisphenol S (BPS) and bisphenol AF (BPAF) exhibited substantially lower dissipation rates in the cells than the other BPs, indicating a strong selectivity in the uptake and metabolism among bisphenol congeners. For a total of 23 metabolites of BPs, the predominant biotransformation pathways were found to be glycosylation, methoxylation, and conjugation, while hydroxylation, methylation, and glutathionylation were only observed for some BPs. The changes in the mRNA expression of cytochrome P450 (P450) and the activities of glycosyltransferase and glutathione S-transferase were remarkably higher in cells exposed to bisphenol F, bisphenol A, and bisphenol B than in cells exposed to BPS and BPAF, indicating congener specificity in their effects on enzymes and the associated biotransformation processes. Consequently, the potential congener-specific differences in plant uptake, metabolism, and accumulation must be considered when assessing the environmental risks posed by these commonly used plasticizers.

Fetal Programming of the Endocrine Pancreas: Impact of a Maternal Low-Protein Diet on Gene Expression in the Perinatal Rat Pancreas.

In rats, the time of birth is characterized by a transient rise in beta cell replication, as well as beta cell neogenesis and the functional maturation of the endocrine pancreas. However, the knowledge of the gene expression during this period of beta cell expansion is incomplete. The aim was to characterize the perinatal rat pancreas transcriptome and to identify regulatory pathways differentially regulated at the whole organ level in the offspring of mothers fed a regular control diet (CO) and of mothers fed a low-protein diet (LP). We performed mRNA expression profiling via the microarray analysis of total rat pancreas samples at embryonic day (E) 20 and postnatal days (P) 0 and 2. In the CO group, pancreas metabolic pathways related to sterol and lipid metabolism were highly enriched, whereas the LP diet induced changes in transcripts involved in RNA transcription and gene regulation, as well as cell migration and apoptosis. Moreover, a number of individual transcripts were markedly upregulated at P0 in the CO pancreas: growth arrest specific 6 (Gas6), legumain (Lgmn), Ets variant gene 5 (Etv5), alpha-fetoprotein (Afp), dual-specificity phosphatase 6 (Dusp6), and angiopoietin-like 4 (Angptl4). The LP diet induced the downregulation of a large number of transcripts, including neurogenin 3 (Neurog3), Etv5, Gas6, Dusp6, signaling transducer and activator of transcription 3 (Stat3), growth hormone receptor (Ghr), prolactin receptor (Prlr), and Gas6 receptor (AXL receptor tyrosine kinase; Axl), whereas upregulated transcripts were related to inflammatory responses and cell motility. We identified differentially regulated genes and transcriptional networks in the perinatal pancreas. These data revealed marked adaptations of exocrine and endocrine in the pancreas to the low-protein diet, and the data can contribute to identifying novel regulators of beta cell mass expansion and functional maturation and may provide a valuable tool in the generation of fully functional beta cells from stem cells to be used in replacement therapy.

Denitrification performance and characteristics of untreated corncob for enhanced nitrogen removal of municipal sewage with low C/N ratio.

Unpretreated corncob was applied in denitrification bio-filter (DNBF) and anoxic tank of AAO system, respectively, to treat sewage with low C/N ratio, and both two approaches achieved good denitrification performance. Although shorter HRT could effectively decrease effluent chroma and COD of corncob-DNBF, nitrogen removal efficiency declined unexpectedly. Higher internal reflux ratio was beneficial for corncob-AAO without damage to anoxic environment for denitrification, while there was no risk of effluent chroma and excessive COD. Different supplement modes could realize same denitrification effect with distinct advantages, which were higher specific denitrification rate and biomass amount, respectively. The latter mode, applying corncob at secondary treatment, was preferable for its operational stability and convenience. Stoichiometry analysis indicated the unit COD demand of AAO decreased from 5.70 to 5.04 g COD/g N after adding corncob, and the oxygen demand (or energy consumption of aeration) decreased as well. The dominant substrates decomposer in corncob-AAO altered to Kouleothrix (affiliated to phylum Chloroflexi), and the main denitrifying bacteria were unclassified_f__Methylophilaceae and Azospira. Accordingly, functional enzymes for degrading glucan, xylan and lignin and processing denitrification showed satisfying abundance in the integrated system, especially in the newly formed biofilm.