Microwave-Assisted Synthesis of Few-Layer Ti3C2Tx Loaded with Ni0.5Co0.5Se2 Nanospheres for High-Performance Supercapacitors.

Transition metal selenides have high theoretical capacities, making them attractive candidates for energy storage applications. Here, using the microwave-absorbing properties of the materials, we designed a simple and efficient microwave-assisted synthesis method to produce a composite made of nanospheres Ni0.5Co0.5Se2 (NCSe) and highly conductive, stable Ti3C2Tx MXene. The Ni0.5Co0.5Se2/Ti3C2Tx composites are characterized via scanning electron microscopy, X-ray diffraction, cyclic voltammetry, and electrochemical impedance spectroscopy. The findings indicate that 3D Ni0.5Co0.5Se2 bimetallic selenide nanospheres were uniformly loaded within the few-layer Ti3C2Tx MXene wrapper in a short period. The optimal NCSe/Ti3C2Tx-2 electrode can demonstrate a specific capacitance of 752.4 F g-1 at 1 A g-1. Furthermore, the asymmetric supercapacitor combined with activated carbon maintains a capacitance retention of 110% even after 5000 cycles. The method of directly growing active substances on few-layer Ti3C2Tx MXene will provide inspiration for the manufacture of high-pseudocapacitance supercapacitors.

Whole exome sequencing identified a homozygous novel variant in DOP1A gene in the Pakistan family with neurodevelopmental disabilities: case report and literature review.

Background: Hereditary neurodevelopmental disorders (NDDs) are prevalent in poorly prognostic pediatric diseases, but the pathogenesis of NDDs is still unclear. Irregular myelination could be one of the possible causes of NDDs. Case presentation: Here, whole exome sequencing was carried out for a consanguineous Pakistani family with NDDs to identify disease-associated variants. The co-segregation of candidate variants in the family was validated using Sanger sequencing. The potential impact of the gene on NDDs has been supported by conservation analysis, protein prediction, and expression analysis. A novel homozygous variant DOP1A(NM_001385863.1):c.2561A>G was identified. It was concluded that the missense variant might affect the protein-protein binding sites of the critical MEC interaction region of DOP1A, and DOP1A-MON2 may cause stability deficits in Golgi-endosome protein traffic. Proteolipid protein (PLP) and myelin-associate glycoprotein (MAG) could be targets of the DOP1A-MON2 Golgi-endosome traffic complex, especially during the fetal stage and the early developmental stages. This further supports the perspective that disorganized myelinogenesis due to congenital DOP1A deficiency might cause neurodevelopmental disorders (NDDs). Conclusion: Our case study revealed the potential pathway of myelinogenesis-relevant NDDs and identified DOP1A as a potential NDDs-relevant gene in humans.

Blue light-mediated gene expression as a promising strategy to reduce antibiotic resistance in Escherichia coli.

The discovery of antibiotics has noticeably promoted the development of human civilization; however, antibiotic resistance in bacteria caused by abusing and overusing greatly challenges human health and food safety. Considering the worsening situation, it is an urgent demand to develop emerging nontraditional technologies or methods to address this issue. With the expanding of synthetic biology, optogenetics exhibits a tempting prospect for precisely regulating gene expression in many fields. Consequently, it is attractive to employ optogenetics to reduce the risk of antibiotic resistance. Here, a blue light-controllable gene expression system was established in Escherichia coli based on a photosensitive DNA-binding protein (EL222). Further, this strategy was successfully applied to repress the expression of ß-lactamase gene (bla) using blue light illumination, resulting a dramatic reduction of ampicillin resistance in engineered E. coli. Moreover, blue light was utilized to induce the expression of the mechanosensitive channel of large conductance (MscL), triumphantly leading to the increase of streptomycin susceptibility in engineered E. coli. Finally, the increased susceptibility of ampicillin and streptomycin was simultaneously induced by blue light in the same E. coli cell, revealing the excellent potential of this strategy in controlling multidrug-resistant (MDR) bacteria. As a proof of concept, our work demonstrates that light can be used as an alternative tool to prolong the use period of common antibiotics without developing new antibiotics. And this novel strategy based on optogenetics shows a promising foreground to combat antibiotic resistance in the future.

Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation.

INTRODUCTION: The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. METHODS: Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. RESULTS: The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. CONCLUSIONS: Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

Fine mapping and breeding application of two brown planthopper resistance genes derived from landrace rice.

The Brown planthopper (Nilaparvata lugens Stål; BPH) is known to cause significant damage to rice crops in Asia, and the use of host-resistant varieties is an effective and environmentally friendly approach for controlling BPH. However, genes limited resistance genes that are used in insect-resistant rice breeding programs, and landrace rice varieties are materials resources that carry rich and versatile genes for BPH resistance. Two landrace indica rice accessions, CL45 and CL48, are highly resistant to BPH and show obvious antibiosis against BPH. A novel resistance locus linked to markers 12M16.983 and 12M19.042 was identified, mapped to chromosome 12 in CL45, and designated Bph46. It was finely mapped to an interval of 480 kb and Gene 3 may be the resistance gene. Another resistance locus linked to markers RM26567 and 11MA104 was identified and mapped to chromosome 11 in CL48 and designated qBph11.3 according to the nominating rule. It was finely mapped to an interval of 145 kb, and LOC_Os11g29090 and LOC_Os11g29110 may be the resistance genes. Moreover, two markers, 12M16.983 and 11MA104, were developed for CL45 and CL48, respectively, using marker-assisted selection (MAS) and were confirmed by backcrossing individuals and phenotypic detection. Interestingly, we found that the black glume color is closely linked to the BPH resistance gene in CL48 and can effectively assist in the identification of positive individuals for breeding. Finally, several near-isogenic lines with a 9311 or KW genetic background, as well as pyramid lines with two resistance parents, were developed using MAS and exhibited significantly high resistance against BPHs.

Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage.

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.

Engineering a Lactobacillus Lysine Riboswitch to Dynamically Control Metabolic Pathways for Lysine Production in Corynebacterium glutamicum.

Knock-out of genes of metabolic pathways is conventionally used in the metabolic engineering of microorganisms, but it is not applicable for genes of essential pathways. In order to avoid undesirable effects caused by gene deletion, it is attractive to develop riboswitches to dynamically control the metabolic pathways of microbial cell factories. In this regard, the aim of this study is to utilize the lysine riboswitch to control gene expressions of the biosynthetic pathways and by-pathways and thus improve lysine production in Corynebacterium glutamicum. To achieve this, a natural lysine riboswitch from Lactobacillus plantarum (LPRS) was first detected and then fused with RFP to test its functionality. After that, engineered lysine-activated (Lys-A) and lysine-repressed (Lys-R) riboswitches were successfully screened by dual genetic selection. Furthermore, the optimized A263 and R152 were applied to control the expression of aspartate kinase III and homoserine dehydrogenase in the lysine-producing strain C. glutamicum QW45, respectively. In contrast with QW45, the growth of the resulting A263-lysC mutant QW48 was similar to that of QW45; however, the growth of the resulting R357-hom mutant QW54 was slightly inhibited, indicating an inhibition of threonine biosynthesis caused by the riboswitch upon binding of intracellular lysine. Importantly, the lysine production of QW48 and QW54 was, respectively, 35% and 43% higher than that of the parent strain QW45, implying more metabolic flux directed into the lysine synthesis pathway. Finally, the engineered A263 and R357 were simultaneously applied to the same mutant QW55, which greatly improved lysine production. Thus, the approach demonstrated in this work could be principally used as a powerful tool to dynamically control any other undesired metabolic pathways.

Defects in the cell wall and its deposition caused by loss-of-function of three RLKs alter root hydrotropism in Arabidopsis thaliana.

Root tips can sense moisture gradients and grow into environments with higher water potential. This process is called root hydrotropism. Here, we report three closely related receptor-like kinases (RLKs) that play critical roles in root hydrotropism: ALTERED ROOT HYDROTROPIC RESPONSE 1 (ARH1), FEI1, and FEI2. Overexpression of these RLKs strongly reduce root hydrotropism, but corresponding loss-of-function mutants exhibit an increased hydrotropic response in their roots. All these RLKs show polar localization at the plasma membrane regions in root tips. The biosynthesis of the cell wall, cutin, and wax (CCW) is significantly impaired in root tips of arh1-2 fei1-C fei2-C. A series of known CCW mutants also exhibit increased root hydrotropism and reduced osmotic tolerance, similar to the characteristics of the triple mutant. Our results demonstrat that the integrity of the cell wall, cutin, and root cap wax mediate a trade-off between root hydrotropism and osmotic tolerance.

Effects of flora deficiency on the structure and function of the large intestine.

The significant anatomical changes in large intestine of germ-free (GF) mice provide excellent material for understanding microbe-host crosstalk. We observed significant differences of GF mice in anatomical and physiological involving in enlarged cecum, thinned mucosal layer and enriched water in cecal content. Furthermore, integration analysis of multi-omics data revealed the associations between the structure of large intestinal mesenchymal cells and the thinning of the mucosal layer. Increased Aqp8 expression in GF mice may contribute to enhanced water secretion or altered hydrodynamics in the cecum. In addition, the proportion of epithelial cells, nutrient absorption capacity, immune function and the metabolome of cecum contents of large intestine were also significantly altered. Together, this is the first systematic study of the transcriptome and metabolome of the cecum and colon of GF mice, and these findings contribute to our understanding of the intricate interactions between microbes and the large intestine.

Translation and psychometric testing of the Chinese version of the Perinatal Missed Care Survey.

Objective: This study aimed to translate and evaluate the psychometric properties of the Perinatal Missed Care Survey in China. Methods: The Perinatal Missed Care Survey was translated according to the guidelines of the cross-cultural debugging scale recommended by the American Academy of Orthopaedic Surgeons Evidence-Based Medicine Committee, including forward translation, back translation, cultural adaption, and content validation, and its Chinese version was used in a cross-sectional study conducted from February to April in 2023. A total of 491 midwives from 14 different level hospitals in southwest China were recruited through a convenience sampling method. The discrimination ability of the items was tested through item analysis, and construct validity was assessed through exploratory factory and confirmatory factor analyses. The content validity index and Cronbach's α coefficients evaluated content validity and reliability, respectively. Results: The Chinese version's item-total correlation coefficients ranged from 0.641 to 0.866 in part A and from 0.644 to 0.819 in part B (P < 0.001). Parts A and B's scale-level content validity indexes were 0.95, and the item-level content validity indexes were from 0.86 to 1.00. The three common factors of part A (necessary care, basic care, and postnatal care) and part B (communication, labor resources, and material resources) were extracted, accounting for 70.186% and 71.984% of the total variance, respectively. Confirmatory factor analysis indicated that the good fit of the three-factor models was acceptable. The Cronbach's α coefficients were 0.968 (part A) and 0.940 (part B). Conclusion: The Chinese version of the Perinatal Missed Care Survey is a reliable and valid instrument for assessing nursing care missed by midwives during labor and birth and the reasons it was missed. Studies with large sample sizes are needed to verify the instrument's applicability in China.

Prevention of high-fat-diet-induced obesity in mice by soluble dietary fiber from fermented and unfermented millet bran.

Obesity-related diabetes, cardiovascular disease, and hypertension pose many risks to human health. Thus, mice on a high-fat diet were gavaged with millet bran (unfermented/fermented) soluble dietary fiber (RSDF/FSDF, 500 mg·kg-1) for 10 weeks in current research, and then evaluated the various biological indicators. These findings revealed that RSDF and FSDF supplements could prevent fat synthesis by inhibiting sterol regulatory element-binding protein-1c gene expression. The RSDF supplements can also accelerate fat catabolism through enhanced the mRNA expression levels of adipose triglyceride lipase and peroxisome proliferator-activated receptor α. FSDF supplements can prevent obesity by decreasing 3-hydroxy-3-methyl-glutaryl-CoA reductase expression and increasing cholesterol 7α-hydroxylase expression. Moreover, FSDF also controls obesity development by lowering total cholesterol and low-density lipoprotein cholesterol levels in the blood, triglyceride, total cholesterol, and bile acid levels in the liver. Notably, FSDF supplements can promote Bacteroides and Prevotella propagation; excretive propionic acid binds to free fatty acid receptor 2/3 and then stimulates intestinal epithelial cells to generate glucagon-like-peptide-1 and peptide YY, which can reduce food and energy intake and ultimately prevent obesity. All evidence suggests that FSDF supplements play a crucial role in preventing obesity.

The role of tertiary lymphoid structure and B cells in nasopharyngeal carcinoma: Based on bioinformatics and experimental verification.

OBJECTIVE: Transcriptomic characteristics and prognosis of tertiary lymphoid structures (TLS) and infiltrating B cells in nasopharyngeal carcinoma (NPC) remain unclear. Here, NPC transcriptomic data and clinical samples were used to investigate the role of infiltrating B cells and TLS in NPC. METHODS: We investigated the gene expression and infiltrating immune cells of NPC patients and further investigated the clinical relevance of B cell and TLS signatures. Transcriptional features of infiltrating B cell subsets were revealed by single-cell RNA sequencing (scRNA-seq) analysis. Immunohistochemical (IHC) and HE staining were performed to validate the clinical relevance of infiltrating B cells and TLS in NPC samples. RESULTS: 27 differentially expressed immune-related genes (IRGs) associated with prognosis were identified, including B cell marker genes CD19 and CD79B. The higher B cells and TLS signature scores were associated with better outcomes and early pathological staging in 88 NPC patients. ScRNA-seq identified five distinct B cell subsets in NPC, including the BC-4 cluster associated with poor outcomes and the BC-0 cluster associated with better outcomes. EBV infection was positively associated with the formation of TLS. Furthermore, experimental results showed that the infiltration of B cells in NPC tissues was higher than that of normal tissues, and the density of TLS in an early stage of NPC was higher than that in advanced-stage TLS. CONCLUSION: Our findings demonstrate the functional importance of distinct B cell subsets in the prognosis of NPC. Additionally, we confirmed that B cells and TLS may serve as prognostic biomarkers of survival for NPC patients.

Characteristics of splenic PD-1+ γδT cells in Plasmodium yoelii nigeriensis infection.

Although the functions of programmed death-1 (PD-1) on αß T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in the Plasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, SR3335, was used to investigate the role of RORα in regulating PD-1+ γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1+ γδT cells from infected mice than in PD-1- γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1+ γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1+ γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα following Plasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1+ γδT cells after treatment with a RORα selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis-infected C57BL/6 mice, and it requires further investigation.

Rational engineering and insight for a L-glutaminase activity reduced type II L-asparaginase from Bacillus licheniformis and its antileukemic activity in vitro.

Type II L-asparaginase (ASNase) has been approved by the FDA for treating acute lymphoid leukemia (ALL), but its therapeutic effect is limited by low catalytic efficiency and L-glutaminase (L-Gln) activity. This study utilized free energy based molecular dynamics calculations to identify residues associated with substrate binding in Bacillus licheniformis L-asparaginase II (BLASNase) with high catalytical activity. After saturation and combination mutagenesis, the mutant LGT (74 L/75G/111 T) with intensively reduced l-glutamine catalytic activity was generated. The l-glutamine/L-asparagine activity (L-Gln/L-Asn) of LGT was only 6.6 % of parent BLASNase, whereas the L-asparagine (L-Asn) activity was preserved >90 %. Furthermore, structural comparison and molecular dynamics calculations indicated that the mutant LGT had reduced binding ability and affinity towards l-glutamine. To evaluate its effect on acute leukemic cells, LGT was supplied in treating MOLT-4 cells. The experimental results demonstrated that LGT was more cytotoxic and promoted apoptosis compared with commercial Escherichia coli ASNase. Overall, our findings firstly provide insights into reducing l-glutamine activity without impacting L-asparagine activity for BLASNase to possess remarkable potential for anti-leukemia therapy.

Structure-Guided Steric Hindrance Engineering of Devosia Strain A6-243 Quinone-Dependent Dehydrogenase to Enhance Its Catalytic Efficiency.

Deoxynivalenol (DON), the most widely distributed mycotoxin worldwide, causes severe health risks for humans and animals. Quinone-dependent dehydrogenase derived from Devosia strain A6-243 (DADH) can degrade DON into less toxic 3-keto-DON and then aldo-keto reductase AKR13B3 can reduce 3-keto-DON into relatively nontoxic 3-epi-DON. However, the poor catalytic efficiency of DADH made it unsuitable for practical applications, and it has become the rate-limiting step of the two-step enzymatic cascade catalysis. Here, structure-guided steric hindrance engineering was employed to enhance the catalytic efficiency of DADH. After the steric hindrance engineering, the best mutant, V429G/N431V/T432V/L434V/F537A (M5-1), showed an 18.17-fold increase in specific activity and an 11.04-fold increase in catalytic efficiency (kcat/Km) compared with that of wild-type DADH. Structure-based computational analysis provided information on the increased catalytic efficiency in the directions that attenuated steric hindrance, which was attributed to the reshaped substrate-binding pocket with an expanded catalytic binding cavity and a favorable attack distance. Tunnel analysis suggested that reshaping the active cavity by mutation might alter the shape and size of the enzyme tunnels or form one new enzyme tunnel, which might contribute to the improved catalytic efficiency of M5-1. These findings provide a promising strategy to enhance the catalytic efficiency by steric hindrance engineering.