Cobalt-based Co3Mo3N/Co4N/Co Metallic Heterostructure as a Highly Active Electrocatalyst for Alkaline Overall Water Splitting.

Alkaline water electrolysis holds promise for large-scale hydrogen production, yet it encounters challenges like high voltage and limited stability at higher current densities, primarily due to inefficient electron transport kinetics. Herein, a novel cobalt-based metallic heterostructure (Co3Mo3N/Co4N/Co) is designed for excellent water electrolysis. In operando Raman experiments reveal that the formation of the Co3Mo3N/Co4N heterointerface boosts the free water adsorption and dissociation, increasing the available protons for subsequent hydrogen production. Furthermore, the altered electronic structure of the Co3Mo3N/Co4N heterointerface optimizes ΔGH of the nitrogen atoms at the interface. This synergistic effect between interfacial nitrogen atoms and metal phase cobalt creates highly efficient active sites for the hydrogen evolution reaction (HER), thereby enhancing the overall HER performance. Additionally, the heterostructure exhibits a rapid OH- adsorption rate, coupled with great adsorption strength, leading to improved oxygen evolution reaction (OER) performance. Crucially, the metallic heterojunction accelerates electron transport, expediting the afore-mentioned reaction steps and enhancing water splitting efficiency. The Co3Mo3N/Co4N/Co electrocatalyst in the water electrolyzer delivers excellent performance, with a low 1.58 V cell voltage at 10 mA cm-2, and maintains 100 % retention over 100 hours at 200 mA cm-2, surpassing the Pt/C||RuO2 electrolyzer.

Quantification of circadian rhythm in mitochondrial DNA copy number in whole blood, and identification of factors that influence it.

Mitochondrial DNA (mtDNA), the genetic material in mitochondria, encodes key genes related to the respiratory chain and ATP production. To accurate quantification mtDNA content in whole blood is important for various disease states. Absolute quantitative Real-time PCR and platelet contamination erase method were used for mtDNA copy number analysis in whole blood. In the quantitative study of mtDNA content, it was found that whole blood mtDNA copy number showed a fluctuating rhythm during a 24-h period due to dynamic changes in white blood cells combined with platelets. However, when isolated white blood cells were used, or absolute whole blood mtDNA was calculated, the circadian rhythm pattern of mtDNA disappeared. In this study, a feasible method that can accurately quantify mitochondrial DNA in small blood samples was established, and it was found that two factors which greatly influenced mtDNA copy number were sampling time and platelets in blood.

Ebola virus encodes a miR-155 analog to regulate importin-α5 expression.

The 2014 outbreak of Ebola virus caused more than 10,000 human deaths. Current knowledge of suitable drugs, clinical diagnostic biomarkers and molecular mechanisms of Ebola virus infection is either absent or insufficient. By screening stem-loop structures from the viral genomes of four virulence species, we identified a novel, putative viral microRNA precursor that is specifically expressed by the Ebola virus. The sequence of the microRNA precursor was further confirmed by mining the existing RNA-Seq database. Two putative mature microRNAs were predicted and subsequently validated in human cell lines. Combined with this prediction of the microRNA target, we identified importin-α5, which is a key regulator of interferon signaling following Ebola virus infection, as one putative target. We speculate that this microRNA could facilitate the evasion of the host immune system by the virus. Moreover, this microRNA might be a potential clinical therapeutic target or a diagnostic biomarker for Ebola virus.

Giant Blue Energy Harvesting in Two-Dimensional Polymer Membranes with Spatially Aligned Charges.

Blue energy between seawater and river water is attracting increasing interest, as one of the sustainable and renewable energy resources that can be harvested from water. Within the reverse electrodialysis applied in blue energy conversion, novel membranes with nanoscale confinement that function as selective ion transport mediums are currently in high demand for realizing higher power density. The primary challenge lies in constructing well-defined nanochannels that allow for low-energy barrier transport. This work proposes a concept for nanofluidic channels with a simultaneous dual electrostatic effect that can enhance both ion selectivity and flux. To actualize this, this work has synthesized propidium iodide-based two-dimensional polymer (PI-2DP) membranes possessing both skeleton charge and intrinsic space charge, which are spatially aligned along the ion transport pathway. The dual charge design of PI-2DP significantly enhances the electrostatic interaction between the translocating anions and the cationic polymer framework, and a high anion selectivity coefficient (≈0.8) is reached. When mixing standard artificial seawater and river water, this work achieves a considerable power density of 48.4 W m-2, outperforming most state-of-the-art nanofluidic membranes. Moreover, when applied between the Mediterranean Sea and the Elbe River, an output power density of 42.2 W m-2 is achieved by the PI-2DP. This nanofluidic membrane design with dual-layer charges will inspire more innovative development of ion-selective channels for blue energy conversion that will contribute to global energy consumption.

Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat.

It is important to clarify the distinct contributions of estrogen/estrogen receptor (ER) and androgen/androgen receptor (AR) signaling and their reciprocal effects on the regulation of hepatic lipid homeostasis. We studied the molecular mechanisms underlying the preventive effects of estradiol (E2), dihydrotestosterone (DHT), or E2+DHT on high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in an orchidectomized Sprague-Dawley (SD) rat model. E2 is shown to be associated with decreased fatty acid synthesis in hepatic zone 3-specific manner by increasing the phosphorylation of acetyl coenzyme-A carboxylase via an ERα-mediated pathway. DHT is shown to be associated with decreased lipid accumulation and cholesterol synthesis in a hepatic zone 1-specific manner by increasing expression of carnitine palmitotyltransferase1 and phosphorylation of 3-hydroxy-3-methyl-glutaryl-CoA reductase via an AR-mediated pathway. E2+DHT showed an additive positive effect and normalized all three impaired zones of the liver. Gene expression changes in human severe liver steatosis were similar to those of experimental rat NAFLD. Steroids reversed the histopathological NAFLD changes, likely by decreasing fatty acid and cholesterol synthesis and increasing ß-oxidation. The diverse steroid effects (ER/AR) on NAFLD prevention in male rats indicate the potential applicability of ER/AR modulators for NAFLD treatment.

Identification of Two Immune Related Genes Correlated With Aberrant Methylations as Prognosis Signatures for Renal Clear Cell Carcinoma.

Almost 75% of renal cancers are renal clear cell carcinomas (KIRC). Accumulative evidence indicates that epigenetic dysregulations are closely related to the development of KIRC. Cancer immunotherapy is an effective treatment for cancers. The aim of this study was to identify immune-related differentially expressed genes (IR-DEGs) associated with aberrant methylations and construct a risk assessment model using these IR-DEGs to predict the prognosis of KIRC. Two IR-DEGs (SLC11A1 and TNFSF14) were identified by differential expression, correlation analysis, and Cox regression analysis, and risk assessment models were established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.6907. In addition, we found that risk scores were significantly associated with 31 immune cells and factors. Our present study not only shows that two IR-DEGs can be used as prognosis signatures for KIRC, but also provides a strategy for the screening of suitable prognosis signatures associated with aberrant methylation in other cancers.

Immune-Related lncRNAs to Construct Novel Signatures and Predict the Prognosis of Rectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers. Almost 1/3 of CRC are rectal cancer, and 95% of rectal cancers are rectal adenocarcinoma (READ). Increasing evidences indicated that long noncoding RNAs (lncRNAs) have important role in the genesis and development of cancers. The purpose of our present study was to identify the differential expression lncRNAs which potentially related with immune cells infiltration and establish a risk assessment model to predict the clinical outcome for READ patients. We obtained three immune-related differential expression lncRNAs (IR-DELs) (C17orf77, GATA2-AS1, and TPT1-AS1) by differential expression analysis following correlation analysis and Cox regression analysis. A risk assessment model were constructed by integrating these analysis results. We then plotted the 1-, 3-, and 5-year ROC curves depending on our risk assessment model, which suggested that all AUC values were over 0.7. In addition, we found that the risk assessment model was correlated with several immune cells and factors. This study suggested that those three signatures (C17orf77, GATA2-AS1, and TPT1-AS1) screened by pairing IR-DELs could be prognosis markers for READ patients and might benefit them from antitumor immunotherapy.

Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. METHODS: In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. RESULTS: Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. CONCLUSION: This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

MicroRNA related prognosis biomarkers from high throughput sequencing data of kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC. METHODS: All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. RESULTS: We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year. CONCLUSION: The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.

Reducing embryonic mtDNA copy number alters epigenetic profile of key hepatic lipolytic genes and causes abnormal lipid accumulation in adult mice.

Adverse fetal environment, in particular a shortage or excess of nutrients, is associated with increased risks of metabolic diseases later in life. However, the molecular mechanisms underlying this developmental origin of adult diseases remain unclear. Here, we directly tested the role of mitochondrial stress in mediating fetal programming in mice by enzymatically depleting mtDNA in zygotes. mtDNA-targeted plasmid microinjection is used to reduce embryonic mtDNA copy number directly, followed by embryo transfer. Mice with reduced zygote mtDNA copy number were born morphologically normal and showed no accelerated body weight gain. However, at 5 months of age these mice showed markedly increased hepatic lipidosis and became glucose-intolerant. Hepatic mRNA and protein expressions of peroxisome proliferator-activated receptor α (Pparα), a key transcriptional regulator of lipid metabolism, were significantly decreased as a result of increased DNA methylation in its proximal regulatory region. These results indicate that perturbation of mitochondrial function around the periconceptional period causes hypermethylation and thus suppressed expression of PPARα in fetal liver, leading to impaired hepatic lipid metabolism. Our findings provide the first direct evidence that mitochondrial stress mediates epigenetic changes associated with fetal programming of adult diseases in a mammalian system.

Immune-Related Gene Expression Analysis Revealed Three lncRNAs as Prognostic Factors for Colon Cancer.

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy.

Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance.

In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.

MicroRNA-Related Prognosis Biomarkers from High-Throughput Sequencing Data of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors. METHODS: In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers. RESULTS: We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly. CONCLUSION: In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.

Surface-Induced 2D/1D Heterostructured Growth of ReS2/CoS2 for High-Performance Electrocatalysts.

Two-dimensional/one-dimensional (2D/1D) heterostructures have received much attention from researchers for their abundant catalytically active sites and low contact resistance due to formation of chemical bonds at the interface. The investigation of such heterostructures, however, is confined to lattice-matched materials, which severely limits the material candidates. Herein, we demonstrate a lattice-mismatched 2D/1D heterostructured electrocatalyst consisting of 2D ReS2 nanosheets and 1D CoS2 nanowires. We propose that the higher surface energy of the CoS2 nanowire and the lattice mismatch between 1D and 2D units are crucial for the growth process of ReS2 nanosheets. More importantly, the terminal S2- exposed on the surface of CoS2 nanowires serves not only as the nucleus of ReS2 nanosheets but also as a bridge to enhance electron transport efficiency. Thus, the ReS2/CoS2 heterostructures show outstanding hydrogen evolution reaction performance. This work is of general interest for the design of complex multidimensional nano-heterostructures with outstanding functionalities.

Enhanced charge transport in ReSe2-based 2D/3D electrodes for efficient hydrogen evolution reaction.

Ultra-high-density rhenium diselenide (ReSe2) nanoflakes were synthesized on a porous carbon cloth (PCC) by chemical vapor deposition (CVD). Besides the two-dimensional/three-dimensional (2D/3D) construction with more active catalytic sites, the small size effect together with the interfacial C-Se bonding facilitated the electron transport between ReSe2 and PCC. Hence, the heat-treated ReSe2@PCC with enhanced charge transport is by far the best performance electrode for the hydrogen evolution reaction (HER) among the state-of-the-art ReX2-based electrodes.

Perinatal exposure to low-dose methoxychlor impairs testicular development in C57BL/6 mice.

Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.