Suppressing photoinduced charge recombination at the BiVO4||NiOOH junction by sandwiching an oxygen vacancy layer for efficient photoelectrochemical water oxidation

Nickel oxyhydroxide (NiOOH) is regarded as one of the promising cocatalysts to enhance the catalytic performance of photoanodes but suffers from serious interfacial charge-carrier recombination at the photoanode|| NiOOH interface. In this work, surface-engineered BiVO4 photoanodes are fabricated by sandwiching an oxygen vacancy (Ovac) interlayer between BiVO4 and NiOOH. The surface Ovac interlayer is introduced on BiVO4 by a chemical reduction treatment using a mild reducing agent, sodium hypophosphite. The induced Ovac can alleviate the interfacial charge-carrier recombination at the BiVO4||NiOOH junction, resulting in efficient charge separation and transfer efficiencies, while an outer NiOOH layer is coated to prevent the Ovac layer from degradation. As a result, the as-prepared NiOOH-P-BiVO4 photoanode exhibits a high photocurrent density of 3.2 mA cm�2 at 1.23 V vs. RHE under the irradiatio

Enhanced Hardness-Toughness Balance Induced by Adaptive Adjustment of the Matrix Microstructure in In Situ Composites

With the development of high-speed and heavy-haul railway transportation, the surface failure of rail turnouts has become increasingly severe due to insufficient high hardness-toughness combination. In this work, in situ bainite steel matrix composites with WC primary reinforcement were fabricated via direct laser deposition (DLD). With the increased primary reinforcement content, the adaptive adjustments of the matrix microstructure and in situ reinforcement were obtained at the same time. Furthermore, the dependence of the adaptive adjustment of the composite microstructure on the composites’ balance of hardness and impact toughness was evaluated. During DLD, the laser induces an interaction among the primary composite powders, which leads to obvious changes in the phase composition and morphology of the composites. With the increased WC primary reinforcement content, the dominant sheaves of the lath-like bainite and the few island-like retained austenite are changed into needle-like lower bainite and plenty of block-like retained austenite in the matrix, and the final reinforcement of Fe3W3C and WC is obtained. In addition, with the increased primary reinforcement content, the microhardness of the bainite steel matrix composites increases remarkably, but the impact toughness decreases. However, compared with conventional metal matrix composites, the in situ bainite steel matrix composites manufactured via DLD possess a much better hardness-toughness balance, which can be attributed to the adaptive adjustment of the matrix microstructure. This work provides a new insight into obtaining new materials with a good combination of hardness and toughness

A label-free strategy for immobilization of GPCRs using site-specific encoded non-natural amino acids to develop a selectively chromatographic approach for pursuing potential ligands binding to 5-hydroxytryptamine 1A receptor

G protein-coupled receptors (GPCRs) are one of the most prominent targets for drug discovery. Immobilizing GPCRs has proven to be an effective strategy for expanding the utility of GPCRs into nonbiological contexts. However, traditional strategies of immobilizing GPCRs have been severely challenged due to the loss of receptor function. Here, we reported a novel and general approach to realize the label-free and site-selective immobilization of 5-hydroxytryptamine 1A receptor (5-HT1AR) and the application in developing a chromatographic method with improved specificity for pursuing 5-HT1AR ligands from natural products. This method involved the use of a clickable non-natural amino acid, O-allyl-L-tyrosine (O-ALTyr) to immobilize the receptor onto thiol-functionalized silica gels through a 'thiol-ene' click chemistry, which allowed us to avoid the purification step and directly immobilize 5-HT1AR on silica gels. The immobilized receptor was characterized using immunofluorescence assay, and receptor-ligand interaction analysis was conducted through frontal analysis. To test the feasibility of the immobilized 5-HT1ARO-ALTyr in complex matrices, bioactive compounds in Ziziphi Spinosae Semen (ZSS) were screened and their interaction with the receptor was assessed using zonal elution. Our findings indicated that immobilizing the receptor through nnAAs effectively minimizes the chromatographic peak tailing and broadening of specific ligands, leading to a significant improvement in chromatographic performance. The association constants of the three ligands to 5-HT1AR were approximately one order of magnitude greater than those of Halo-tag attachment. These results demonstrated that the immobilized 5-HT1AR exhibits high specificity and the ability to recognize receptor ligands from complex matrices. This allowed us to identify magnoflorine (Mag) as a potential ligand of 5-HT1AR from ZSS extract. In vivo assay also proved that Mag presented a promising anxiolytic effect by promoting the expression of 5-HT1AR in mice brain. The above findings pointed to the fact that the immobilized 5-HT1AR affinity chromatographic strategy relying on the site-specific encoded non-natural amino acid is a powerful alternative for precisely determining the drug-protein interaction and discovering the specific ligand of GPCRs from complex matrixes

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia

Abstract Background A previous study has demonstrated a significantly increased CD3ζ gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3ζ mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3ζ, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775 in the CTLA-4 gene, and the distribution of the CD3ζ 3′-UTR splice variant in AA patients. Methods CD3ζ 3′-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67 patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non-sever aplastic anemia (NSAA)] by RT-PCR. CD3ζ, CD28, CTLA-4, and Cbl-b gene expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4 gene was analyzed by PCR-RFLP. Results CD3ζ and CD28 expression was significantly higher, while CTLA-4 and Cbl-b expression was significantly lower in AA patients compared with healthy individuals. Significantly higher CD3ζ expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of the AA samples had the same genotype (WT+AS+CD3ζ 3′-UTR); 22 % of the AA patients had a WT+AS−CD3ζ 3′-UTR genotype, and 14 % of the AA patients had a WT−AS+CD3ζ 3′-UTR genotype. The CD3ζ expression level of WT−AS+ subgroup was the highest in the SAA patients. A significantly higher frequency of the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene expression levels was found in healthy individuals with the AA and AG genotypes, but not in the AA patients. Conclusions This is the first study analyzing the expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our results suggest that aberrant T cell activation may be related to the first and second signals of T cell activation in AA. The GG genotype of SNP rs231775 in CTLA-4 gene might be associated with AA risk in the Chinese population. The characteristics of CD3ζ 3′-UTR alternative splicing may be an index for evaluating the T cell activation status in AA patients, particularly in SAA patients

Table1_Early Late Triassic retro-foreland basin in response to flat subduction of the Paleo-Tethyan oceanic plate, SE Tibet.DOCX

Syn-subduction basins bear significant implications to understand tectonic evolution of any fossil subduction zone. The late Paleozoic to early Mesozoic (Paleo-Tethyan) tectonics of the eastern and southeastern Tibetan Plateau (i.e., the Sanjiang Orogenic Belt) is featured by ocean-continent subduction systems. A huge pile of volcanic-absent sedimentary succession developed in the middle segment of the Sanjiang orogenic belt, its age and tectonic nature remain unclear. Detailed geological mapping and zircon U-Pb dating results demonstrate that the early Late Triassic volcanic-absent succession comprises the nonmarine Maichuqing Formation in the lower part and the shallow marine Sanhedong Formation in the upper part. The Maichuqing Formation consists of coarse to fine-grained sandstone, siltstone and mudstone with abundant basal erosional surfaces, trough and planar cross-beddings, ripples, mudcracks, and plant fragments. The Sanhedong Formation comprises predominantly bioclastic limestones interlayered with marl, calcareous-muddy siltstone, and calcareous sandstone with abundant bivalve fossils. Syn-sedimentation deformation structures, such as slump folds and associated normal faults are common, suggesting intense tectonism during deposition. Synthesizing sedimentary data, paleocurrent and provenance results, combined with other available data, demonstrate that the volcanic-absent succession deposited within a retro-foreland basin along the rear part of the Permian-Triassic Jomda-Weixi-Yunxian arc in response to flat-subduction of the Paleo-Tethyan Ocean during the early Late Triassic time.</p

A Shigella sonnei clone with extensive drug resistance associated with waterborne outbreaks in China.

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health

Characterization of a Salmonella enterica serovar Typhimurium lineage with rough colony morphology and multidrug resistance

Abstract Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (−44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype