The community-associated methicillin-resistant
(CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are ...yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in
. The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of
in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in
-independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant
(MRSA) and methicillin-sensitive
(MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.
Cryptosporidium baileyi is the most common Cryptosporidium species in birds. However, effective prevention measures and treatment for C. baileyi infection were still not available. Long non-coding ...RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in regulating occurrence and progression of many diseases and are identified as effective biomarkers for diagnosis and prognosis of several diseases. In the present study, the expression profiles of host mRNAs, lncRNAs and circRNAs associated with C. baileyi infection were investigated for the first time.
The tracheal tissues of experimental (C. baileyi infection) and control chickens were collected for deep RNA sequencing, and 545,479,934 clean reads were obtained. Of them, 1376 novel lncRNAs were identified, including 1161 long intergenic non-coding RNAs (lincRNAs) and 215 anti-sense lncRNAs. A total of 124 lncRNAs were found to be significantly differentially expressed between the experimental and control groups. Additionally, 14,698 mRNAs and 9085 circRNAs were identified, and significantly different expressions were observed for 1317 mRNAs and 104 circRNAs between two groups. Bioinformatic analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for their targets and source genes suggested that these dysregulated genes may be involved in the interaction between the host and C. baileyi.
The present study revealed the expression profiles of mRNAs, lncRNAs and circRNAs during C. baileyi infection for the first time, and sheds lights on the roles of lncRNAs and circRNAs underlying the pathogenesis of Cryptosporidium infection.
MYO15A variants are responsible for human non-syndromic autosomal recessive deafness (DFNB3). The majority of MYO15A variants are associated with a congenital severe-to-profound hearing loss ...phenotype, except for MYO15A variants in exon 2, which cause a milder auditory phenotype, suggesting a genotype-phenotype correlation of MYO15A. However, MYO15A variants not in exon 2 related to a milder phenotype have also been reported, indicating that the genotype-phenotype correlation of MYO15A is complicated. This study aimed to provide more cases of MYO15A variation with diverse phenotypes to analyse this complex correlation.
Fifteen Chinese autosomal recessive non-syndromic hearing loss (ARNSHL) individuals with MYO15A variants (8 males and 7 females) from 14 unrelated families, identified by targeted gene capture of 127 known candidate deafness genes, were recruited. Additionally, we conducted a review of the literature to further analyses all reported MYO15A genotype-phenotype relationships worldwide.
We identified 16 novel variants and 12 reported pathogenic MYO15A variants in 15 patients, two of which presented with a milder phenotype. Interestingly, one of these cases carried two reported pathogenic variants in exon 2, while the other carried two novel variants not in exon 2. Based on our literature review, MYO15A genotype-phenotype correlation analysis showed that almost all domains were reported to be correlated with a milder phenotype. However, variants in the N-terminal domain were more likely to cause a milder phenotype. Using next-generation sequencing (NGS), we also found that the number of known MYO15A variants with milder phenotypes in Southeast Asia has increased in recent years.
Our work extended the MYO15A variant spectrum, enriched our knowledge of auditory phenotypes, and tried to explore the genotype-phenotype correlation in different populations in order to investigate the cause of the complex MYO15A genotype-phenotype correlation.
The design of novel catalysts for efficient electroreduction of CO2 into value‐added chemicals is a promising approach to alleviate the energy crisis. Herein, we successfully modify the carbon ...nanotube by a layer of mesoporous carbon shell anchored by nickel (Ni) nanoparticles. Ni species effectively enable carbon deposition derived from pyrolysis of surfactant 1‐hexadecyl trimethyl ammonium bromide to form a mesoporous carbon shell. At the same time, Ni nanoparticles can be embedded in the mesoporous carbon shell due to the confinement effect. Owing to the dispersive Ni nanoparticles and N‐doping active sites of mesoporous carbon, the as‐prepared electrocatalyst exhibits exciting catalytic performance for the selective reduction of CO2 to carbon monoxide (CO) with a maximum Faradaic efficiency of 98% at a moderate overpotential of −0.81 V (vs. reversible hydrogen electrode) and a high partial current density of 60 mA cm−2 in H‐cell with an aqueous electrolyte.
With the aid of nickel chloride, a layer of mesoporous carbon shell anchored with nickel nanoparticles was modified on the surface of carbon nanotubes by the pyrolysis deposition method to enhance the selective electrochemical reduction of carbon dioxide to carbon monoxide.
Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, ...limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.
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•Nucleotidyl lipid, oligonucleotide delivery, extrahepatic targeting, pancreatic cancer
•Cu/SiO2 can hydrogenate 5-hydroxymethylfurfural (HMF) into 97% yield of 2,5-bis-hydroxymethylfuran (BHMF).•HZSM-5 catalyzes etherification of BHMF with methanol with 70% 2,5-bis-methoxymethylfuran ...(BMMF) yield achieved.•The cetane number of BMMF (80) is much higher than that of the commercial diesel (45).
Efficient hydrogenation of 5-hydroxymethylfurfural (HMF) into 2,5-bis-hydroxymethylfuran (BHMF) was performed using a Cu/SiO2 catalyst, obtaining as high as 97% BHMF yield. In the presence of acidic ZSM-5 zeolite (HZSM-5), the synthesized BHMF further reacted with methanol, leading to 70% yield of corresponding 2,5-bis-methoxymethylfuran (BMMF). The target product BMMF was an excellent cetane number improver for diesel, proved by its cetane number of 80 (much higher than that of the commercial diesel), high flash point (90°C) and low cold filter plugging point (<−37°C).
The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and ...quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)
presentation, while cross-presentation is optimal for acid polymerase (PA)
presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
A novel approach for the simultaneous separation and indirect ultraviolet detection of chlorate and perchlorate using pyridinium ionic liquids as mobile phase additives in reversed‐phase liquid ...chromatography was developed. Pyridinium ionic liquids and imidazolium ionic liquids as the mobile phase additives were compared. The effects of pyridinium ionic liquids, methanol, column temperature, and detection wavelength on the separation and detection of chlorate and perchlorate were investigated. The role of ionic liquids, retention rules and relevant mechanisms were discussed. Pyridinium ionic liquids mainly acted as ultraviolet absorption reagent and ion‐pair reagent. The successful separation and indirect ultraviolet detection of chlorate and perchlorate were achieved by using a common reversed‐phase column, 0.2 mmol/L N‐octylpyridinium bromide aqueous solution/methanol (90/10, v/v) as mobile phase and at the detection wavelength of 210 nm. The retention times of chlorate and perchlorate were 30.51 and 37.06 min, respectively. The detection limits of chlorate and perchlorate were 0.16 and 0.29 mg/L, respectively. The linearity and repeatability of the method were satisfactory. The approach was used to the analysis of river water samples with accurate and reliable results. This method is easy to popularize due to the use of common reversed‐phase column and ultraviolet detector in liquid chromatography.
Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been ...well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD.
We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells.
After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation.
Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.
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