Recently, two Middle East respiratory syndrome coronavirus (MERS-CoV) closely related to bat merbecoviruses, NeoCoV and PDF-2180, were discovered to use angiotensin-converting enzyme 2 (ACE2) for ...entry. The two viruses cannot use human ACE2 efficiently, and their host range and cross-species transmissibility across a wide range of mammalian species remain unclear. Herein, we characterized the species-specific receptor preference of these viruses by testing ACE2 orthologues from 49 bats and 53 non-bat mammals through receptor-binding domain (RBD)-binding and pseudovirus entry assays. Results based on bat ACE2 orthologues revealed that the two viruses were unable to use most, but not all, ACE2 from Yinpterochiropteran bats (Yin-bats), which is distinct from NL63 and SARS-CoV-2. Besides, both viruses exhibited broad receptor recognition spectra across non-bat mammals. Genetic and structural analyses of bat ACE2 orthologues highlighted four crucial host range determinants, all confirmed by subsequent functional assays in human and bat cells. Notably, residue 305, participating in a critical viral receptor interaction, plays a crucial role in host tropism determination, particularly in non-bat mammals. Furthermore, NeoCoV and PDF-2180 mutants with enhanced human ACE2 recognition expanded the potential host range, especially by enhancing their interaction with an evolutionarily conserved hydrophobic pocket. Our results elucidate the molecular basis for the species-specific ACE2 usage of MERS-related viruses and shed light on their zoonotic risks.
The development of efficient, stable and low-cost electrocatalysts for the alkaline hydrogen evolution reaction (HER) is critical for large-scale, economically viable water splitting. In this work, ...we successfully prepared non-precious metal CoB@MoS
2
hybrid electrocatalysts for the HER in alkaline media by the reductive growth of cobalt boride nanoparticles (CoB NPs) on the surface of MoS
2
nanoflowers (MoS
2
NFs). The CoB@MoS
2
-0.5-300 hybrid showed an HER overpotential of only 146 mV at a current density of 10 mA cm
−2
and a Tafel slope of 80.9 mV dec
−1
in 1.0 M KOH solution. The significantly enhanced HER activity of the hybrid is primarily attributable to the ability of CoB to drive the OER in alkaline solution and improved electrical conductivity of the hybrid electrocatalyst relative to the pristine MoS
2
. Furthermore, the synthetic strategy used to prepare the CoB@MoS
2
electrocatalyst was successfully applied to prepare NiB@MoS
2
and FeB@MoS
2
hybrid electrocatalysts, which similarly showed very good HER activity in 1.0 M KOH solution. Thus, this work conclusively demonstrates that the introduction of transition metal borides is an effective approach for enhancing the HER performance of MoS
2
in alkaline media.
The CoB@MoS
2
hybrid enhanced the HER activity compared to MoS
2
in 1.0 M KOH solution (HER overpotential is 146 mV).
Background
Observational studies have shown inconsistent results of the associations between type 2 diabetes mellitus (T2DM) and blood lipid profiles, while there is also a lack of evidence from ...randomized controlled trials (RCTs) for the causal effects of T2DM on blood lipid profiles and lipoprotein subclasses.
Objectives
Our study aimed at investigating the causal effects of T2DM on blood lipid profiles and concentration of particle-size-determined lipoprotein subclasses by using the two-sample Mendelian randomization (MR) method.
Methods
We obtained genetic variants for T2DM and blood lipid profiles including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from international genome-wide association studies (GWASs). Two-sample MR method was applied to explore the potential causal effects of genetically predicted T2DM on blood lipid profiles based on different databases, respectively, and results from each MR analysis were further meta-analyzed to obtain the summary results. The causal effects of genetically predicted T2DM on the concentration of different subclasses of lipoproteins that are determined by particle size were also involved in MR analysis.
Results
Genetically predicted 1-unit higher log odds of T2DM had a significant causal effect on a higher level of TG (estimated
β
coefficient: 0.03, 95% confidence interval CI: 0.00 to 0.06) and lower level of HDL-C (estimated
β
coefficient: −0.09, 95% CI: −0.11 to −0.06). The causality of T2DM on the level of TC or LDL-C was not found (estimated
β
coefficient: −0.01, 95% CI: −0.02 to 0.01 for TC and estimated
β
coefficient: 0.01, 95% CI: −0.01 to 0.02 for LDL-C). For different sizes of lipoprotein particles, 1-unit higher log odds of T2DM was causally associated with higher level of small LDL particles, and lower level of medium HDL particles, large HDL particles, and very large HDL particles.
Conclusion
Evidence from our present study showed causal effects of T2DM on the level of TG, HDL-C, and concentration of different particle sizes of lipoprotein subclasses comprehensively, which might be particularly helpful in illustrating dyslipidemia experienced by patients with T2DM, and further indicate new treatment targets for these patients to prevent subsequent excessive cardiovascular events from a genetic point of view.
Bone, a pivotal structural organ, is susceptible to disorders with profound health implications. The investigation of gene expression in bone tissue is imperative, particularly within the context of ...metabolic diseases such as obesity and diabetes that augment the susceptibility to bone fractures. The objective of this study is to identify a set of internal control genes for the analysis of gene expression.
This study employs reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) to assess gene expression in bone tissue. We selected fourteen housekeeping genes and assessed their stability in the cortical bone of mouse models for obesity and diabetes using four well-established algorithms (GeNorm, BestKeeper, NormFinder, and the comparative Delta Ct method).
We identified
as the mostly stably expressed reference gene in cortical bone tissue from mouse models of obesity and diabetes (db/db), while
was found to be the most stable reference gene in another diabetes model, KKAy mice. Additionally,
, and
were identified as alternative genes suitable for normalizing gene expression in cortical bone from obesity and diabetes mouse models. These findings enhance RT-qPCR accuracy and reliability, offering a strategic guide to select reference gene for studying bone tissue gene expression in metabolic disorders.
In this paper, mesoporous CuO with a novel architecture was synthesized through a conventional hydrothermal approach followed by a facile sintering procedure. HR-TEM analysis found that mesoporous ...CuO with an interconnected pore structure has exposed high-energy crystal planes of (002) and (200). Theoretical calculations indicated that the high-energy crystal planes have superior adsorption capacity for H
ions, which is critical for the excellent adsorption and remarkable photocatalytic activity of the anionic dye. The adsorption capacity of CuO to methyl orange (MO) at 0.4 g/L was approximately 30% under adsorption equilibrium conditions. We propose a state-changing mechanism to analyze the synergy and mutual restraint relation among the catalyst CuO, H
ions, dye and H
O
. According to this mechanism, the degradation rate of MO can be elevated 3.5 times only by regulating the MO ratio in three states.
Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, ...genital index and serum testosterone level after continual chronic stress for 21 days. Two‐dimensional gel electrophoresis (2‐DE) and MALDI‐TOF‐MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17β‐HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.
Purpose: To study the therapeutic effects of anti-miR-24 and anti-miR-34 in cardiac diseasesMethods: H9c2 rat cardiomyocyte cell lines were transfected with the synthetic oligonucleotides antimiR-24 ...and anti-miR-34 which reduced the expressions of miR-24 and miR-34. Proliferation assay, real time-polymerase chain reaction (RT-PCR) and immunoblotting were carried out to determine the effect of the transfections on cardiomyocyte proliferation, expressions of miR-24 and miR-34, as well as expressions of the target genes, TGF-β1 and E2F3.Results: The proliferation ability of the transfected cells was decreased significantly, relative to negative control. In contrast, percentage apoptosis was higher in the negative control group than in transfected cells. The expression profiles of anti-miR-24 and anti-miR-34 were significantly reduced, when compared to negative control. These results were further confirmed using immunoblot which revealed that the expression of the target genes, TGF-β1 and E2F3, were upregulated in the transfected cells.Conclusion: These results suggest that the synthetic oligonucleotides (anti-miR-24 and anti-miR-34) might be useful in developing therapeutic drug targets for cardiac diseases by suppressing the expressions of miR-24 and miR-34.
Keywords: H9c2rat cardiomyocyte miRNA, Anti-miR-24, Anti-miR-34, Cardiac diseases
A one-pot polymerization system using tetradecyl allyldimethylammonium chloride (TADMAC) and grafting cotton with unsaturated bonds (G-cotton) was designed to synthesize novel long-chain alkylation ...polycationic cotton (LP-cotton) and the homopolymer of TADMAC (PTADMAC). The LP-cotton had a high cationic degree of substitution of 0.108. The high monomer conversion of 98.8% suggests that almost all the TADMAC monomers participated in the polymerization. It is possible that when only LP-cotton was used as the adsorbent, its long-chain alkylation cationic TADMAC unit played the role of a similar surfactant in enhancing the association between the dye and cotton surface, resulting in a great improvement in adsorption capacity. The adsorption capacities were 57.5, 531.7, 4.4, and 2.9 times higher than those of the widely used activated carbon, untreated cotton, G-cotton, and polycationic film-coated cotton (PF-cotton), respectively, reported in our previous study. Using only PTADMAC as the flocculant led to a wide range of application adaptability, removing more than 97.0% of various anionic dyes in the water by forming flocs. As a result, PTADMAC could also be used as an enhancer at a low dosage for improving the flocculation ability of some conventional flocculants. Moreover, due to the mutual associations of the long-chain tetradecyl groups, the combined use of the LP-cotton adsorbent and PTADMAC flocculant not only reduced the dosage of LP-cotton adsorbent to 30% of that required for adsorption-only treatments but also decreased the dye removal time to 10 s. The dye solution became clear almost instantly, enhancing the removal of water-soluble dyes from water more comprehensively than the use of adsorbent or flocculant alone.
Anatase TiO2 aligned arrays supported on carbon cloth (termed as ATAC) composites are successfully prepared as a high-performance anode material for Li-ion batteries. The obtained ATAC displays ...enhanced cycling performance and rate capability, which shows an initial discharge capacity of 390mAhg−1 and a remaining capacity of 188mAhg−1 for the ATAC after 500 cycles. The enhanced electrochemical performance of the ATAC is related to the synergistic effect between ATO arrays and carbon fibers.
•An anatase TiO2 arrays supported on carbon cloth composite is prepared by solvothermal method.•The initial discharge capacity of the as-synthesized composite is up to 390mAhg−1.•The remaining capacity of the as-prepared composite is 188mAhg−1 after 500 cycles.
PDF
