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Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross‐contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy‐modified carbon nitride nanosheets (g‐C3N4‐VC Ns) coated on the non‐woven fabrics of the out layer of the mask, offering effective and long‐term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy‐disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron‐hole pairs, thus promoting the electron‐hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as‐prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self‐protection. [ABSTRACT FROM AUTHOR]

The precise synthesis of chiral small molecules is a core research area in chemical science. Deracemization, an appealing technology that converts racemate to its single enantiomer with the same constitution in theoretical 100 % yield, appears as a straightforward and efficient strategy in asymmetric synthesis. A cascading redox sequence was the most employed approach to drive deracemization through destroy and recreate the stereocenter in a given molecule. This review mainly focuses on the progress of redox deracemization driven by respective biocatalysis and chemo–catalysis. In particular, each section will be subdivided according to the action modes, the respective substrate classes and perspectives on future development. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a prominent malignancy that poses a significant threat to human well‐being worldwide. Despite advancements in chemotherapy and immunotherapy, which have effectively augmented patient survival rates, the mortality rate associated with GC remains distressingly high. This can be attributed to the elevated proliferation and invasive nature exhibited by GC. Our current understanding of the drivers behind GC cell proliferation remains limited. Hence, in order to reveal the molecular biological mechanism behind the swift advancement of GC, we employed single‐cell RNA‐sequencing (scRNA‐seq) to characterize the tumour microenvironment in this study. The scRNA‐seq data of 27 patients were acquired from the Gene Expression Omnibus database. Differential gene analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were employed to investigate 38 samples. The copy number variation level exhibited by GC cells was determined using InferCNV. The CytoTRACE, Monocle and Slingshot analysis were used to discern the cellular stemness and developmental trajectory of GC cells. The CellChat package was utilized for the analysis of intercellular communication crosstalk. Moreover, the findings of the data analysis were validated through cellular functional tests conducted on the AGS cell line and SGC‐7901 cell line. Finally, this study constructed a risk scoring model to evaluate the differences of different risk scores in clinical characteristics, immune infiltration, immune checkpoints, functional enrichment, tumour mutation burden and drug sensitivity. Within the microenvironment of GC, we identified the presence of 8 cell subsets, encompassing NK_T cells, B_Plasma cells, epithelial cells, myeloid cells, endothelial cells, mast cells, fibroblasts, pericytes. By delving deeper into the characterization of GC cells, we identified 6 specific tumour cell subtypes: C0 PSCA+ tumour cells, C1 CLDN7+ tumour cells, C2 UBE2C+ tumour cells, C3 MUC6+ tumour cells, C4 CHGA+ tumour cells and C5 MUC2+ tumour cells. Notably, the C2 UBE2C+ tumour cells demonstrated a close association with cell mitosis and the cell cycle, exhibiting robust proliferative capabilities. Our findings were fortified through enrichment analysis, pseudotime analysis and cell communication analysis. Meanwhile, knockdown of the transcription factor CREB3, which is highly active in UBE2C+ tumour cells, significantly impedes the proliferation, migration and invasion of GC cells. And the prognostic score model constructed with CREB3‐related genes showcased commendable clinical predictive capacity, thus providing valuable guidance for patients' prognosis and clinical treatment decisions. We have identified a highly proliferative cellular subgroup C2 UBE2C+ tumour cells in GC for the first time. The employment of a risk score model, which is based on genes associated with UBE2C expression, exhibits remarkable proficiency in predicting the prognosis of GC patients. In our investigation, we observed that the knockdown of the transcription factor CREB3 led to a marked reduction in cellular proliferation, migration and invasion in GC cell line models. Implementing a stratified treatment approach guided by this model represents a judicious and promising methodology. [ABSTRACT FROM AUTHOR]

Dendrocalamus brandisii (Munro) Kurz is a sympodial bamboo species with inimitable taste and flavorful shoots. Its rapid growth and use as high‐quality material make this bamboo species highly valued for both food processing and wood applications. However, genome information for D. brandisii is lacking, primarily due to its polyploidy and large genome size. Here, we assembled a high‐quality genome for hexaploid D. brandisii, which comprises 70 chromosomes with a total size of 2,756 Mb, using long‐read HiFi sequencing. Furthermore, we accurately separated the genome into its three constituent subgenomes. We used Oxford Nanopore Technologies long reads to construct a transcriptomic dataset covering 15 tissues for gene annotation to complement our genome assembly, revealing differential gene expression and post‐transcriptional regulation. By integrating metabolome analysis, we unveiled that well‐balanced lignin formation, as well as abundant flavonoid and fructose contents, contribute to the superior quality of D. brandisii shoots. Integrating genomic, transcriptomic, and metabolomic datasets provided a solid foundation for enhancing bamboo shoot quality and developing efficient gene‐editing techniques. This study should facilitate research on D. brandisii and enhance its use as a food source and wood material by providing crucial genomic resources. [ABSTRACT FROM AUTHOR]

Background: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. Methods: Analysis of multi‐omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co‐immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual‐luciferase reporter, chromatin immunoprecipitation, western blotting and real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log‐rank test. Results: c‐Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate‐aspartate shuttle (MAS) in NB cells. Mechanistically, c‐Myc directly promoted the expression of glutamyl‐prolyl‐tRNA synthetase (EPRS) and leucyl‐tRNA synthetase (LARS), resulting in translational up‐regulation of glutamic‐oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c‐Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre‐clinically, lobeline was discovered as a LMNA‐binding compound to facilitate its interaction with c‐Myc, which inhibited aminoacyl‐tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c‐Myc knock‐in mice. Low levels of LMNA or elevated expression of c‐Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. Conclusions: These results suggest that targeting c‐Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression. [ABSTRACT FROM AUTHOR]

SUMMARY: Drought stress caused by global warming has resulted in significant tree mortality, driving the evolution of water conservation strategies in trees. Although phytohormones have been implicated in morphological adaptations to water deficits, the molecular mechanisms underlying these processes in woody plants remain unclear. Here, we report that overexpression of PtoMYB142 in Populus tomentosa results in a dwarfism phenotype with reduced leaf cell size, vessel lumen area, and vessel density in the stem xylem, leading to significantly enhanced drought resistance. We found that PtoMYB142 modulates gibberellin catabolism in response to drought stress by binding directly to the promoter of PtoGA2ox4, a GA2‐oxidase gene induced under drought stress. Conversely, knockout of PtoMYB142 by the CRISPR/Cas9 system reduced drought resistance. Our results show that the reduced leaf size and vessel area, as well as the increased vessel density, improve leaf relative water content and stem water potential under drought stress. Furthermore, exogenous GA3 application rescued GA‐deficient phenotypes in PtoMYB142‐overexpressing plants and reversed their drought resistance. By suppressing the expression of PtoGA2ox4, the manifestation of GA‐deficient characteristics, as well as the conferred resistance to drought in PtoMYB142‐overexpressing poplars, was impeded. Our study provides insights into the molecular mechanisms underlying tree drought resistance, potentially offering novel transgenic strategies to enhance tree resistance to drought. Significance Statement: Here we demonstrate that PtoMYB142, a transcription factor, modulates gibberellin catabolism by directly regulating the expression of PtoGA2ox4, a key enzyme involved in gibberellin degradation. This regulatory pathway leads to a reduction in leaf size and an improvement in vessel features, which enhances water transport and reduces water loss in response to water stress. These novel insights into the molecular mechanisms underlying drought‐induced morphological changes in trees have significant implications for improving ecosystem resilience in water‐limited environments. [ABSTRACT FROM AUTHOR]

Antibiotic residues in water represent an urgent environmental challenge. To efficiently remove these residues, a low‐carbon integrated biochar synthesis method was proposed, and an optimized typha biochar (TBIK) was prepared. Compared with the biochar prepared by a conventional two‐step carbonization and activation method (TBTK), the TBIK preparation process reduced energy consumption by 43849.58 J and cut carbon dioxide emissions by 32.80%. TBIK exhibited a large surface area of 1252.40 m2/g and rapidly achieved an equilibrium removal efficiency of 99.95% within 20 min for simulated antibiotics wastewater. Furthermore, TBIK possessed more number of functional groups than TBTK, especially O‐H and C‐S groups. The adsorption stability and tolerance of TBIK in solutions with different ionic strengths and coexisting anions were examined. Characterization techniques such as scanning electron microscopy (SEM), Fourier transform infrared (FT‐IR), and X‐ray photoelectron spectroscopy (XPS) as well as Brunauer, Emmett and Teller (BET) analyses were employed to elucidate the morphology and adsorption mechanism of the adsorbent. The microporous structure and abundance of functional groups are key to the excellent adsorption capabilities of TBIK. Thus, this integrated method for biochar production, optimized for treating antibiotic wastewater, holds significant potential for future applications. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer‐related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single‐cell RNA sequencing (scRNA‐seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co‐localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha‐smooth muscle actin (α‐SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis‐associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC. [ABSTRACT FROM AUTHOR]

Immediate oral implant placement is a widely accepted technique, known for its efficacy in reducing treatment duration, surgical visits, and overall healing time. One of the primary challenges associated with immediate implant placement is the attainment of initial stability. The inevitable loss of bone and soft tissue after extraction poses a risk to implant osseointegration in both vertical and horizontal dimensions. Guided tissue regeneration/guided bone regeneration (GTR/GBR) is a well‐established method for periodontal regeneration. However, current GTR/GBR membranes lack tissue inherent regeneration properties and necessitate combination with grafts to enhance tissue recovery. In this context, biomaterials have emerged as a promising option due to their good biocompatibility, biodegradability, and bioactive properties. They present a potential alternative to standard autologous/allograft procedures. The field of biomaterials for bone regeneration has rapidly evolved, developing new guiding materials and engineering techniques. These advances have become integral in addressing tissue defects at the immediate implant site. Various materials such as bioceramics, natural polymers, and synthetic polymers have been used for tissue repair. This article undertakes an etiological examination of tissue deficiency associated with immediate implant placement. Additionally, it reviews the advantages and disadvantages of a variety of biomaterials, aiming to provide references for clinical treatment and areas for further investigation. [ABSTRACT FROM AUTHOR]

Summary: Auxin signaling provides a promising approach to controlling root system architecture and improving stress tolerance in plants. However, how the auxin signaling is transducted in this process remains unclear.The Aux indole‐3‐acetic acid (IAA) repressor IAA17.1 is stabilized by salinity, and primarily expressed in the lateral root (LR) primordia and tips in poplar. Overexpression of the auxin‐resistant form of IAA17.1 (IAA17.1m) led to growth inhibition of LRs, markedly reduced salt tolerance, increased reactive oxygen species (ROS) levels, and decreased flavonol content. We further identified that IAA17.1 can interact with the heat shock protein HSFA5a, which was highly expressed in roots and induced by salt stress. Overexpression of HSFA5a significantly increased flavonol content, reduced ROS accumulation, enhanced LR growth and salt tolerance in transgenic poplar. Moreover, HSFA5a could rescue the defective phenotypes caused by IAA17.1m.Expression analysis showed that genes associated with flavonol biosynthesis were altered in IAA17.1m‐ and HAFA5a‐overexpressing plants. Furthermore, we identified that HSFA5a directly activated the expression of key enzyme genes in the flavonol biosynthesis pathway, while IAA17.1 suppressed HSFA5a‐mediated activation of these genes.Collectively, the IAA17.1/HSFA5a module regulates flavonol biosynthesis, controls ROS accumulation, thereby modulating the root system of poplar to adapt to salt stress. [ABSTRACT FROM AUTHOR]

Soft tissue damage stimulates sympathetic nerves to release large amounts of catecholamine hormones which bind to β‐adrenergic receptors (β‐ARs) on the cell membrane surface. It activates the downstream effector molecules and impairs soft tissue wound healing. β‐blockers specifically inhibit β‐ARs activation in acute/chronic skin lesions and ulcerative hemangiomas. They also accelerate soft tissue wound healing by shortening the duration of inflammation, speeding keratinocyte migration and reepithelialization, promoting wound contraction and angiogenesis, and inhibiting bacterial virulence effects. In addition, β‐blockers shorten wound healing periods in patients with severe thermal damage by reducing the hypermetabolic response. While β‐blockers promote/inhibit corneal epithelial cell regeneration and restores limbal stem/progenitor cells function, it could well accelerate/delay corneal wound healing. Given these meaningful effects, a growing number of studies are focused on examining the efficacy and safety of β‐blockers in soft tissue wound repair, including acute and chronic wounds, severe thermal damage, ulcerated infantile hemangioma, corneal wounds, and other soft tissue disorders. However, an intensive investigation on their acting mechanisms is imperatively needed. The purpose of this article is to summerize the roles of β‐blockers in soft tissue wound healing and explore their clinical applications. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) pathogenesis is largely associated with intestinal epithelial barrier dysfunction. A therapeutic approach to UC involves the repair of damaged intestinal barrier. Our study aimed to investigate whether aryl hydrocarbon receptor (AhR) mediated the intestinal barrier repair effects of quercetin to ameliorate UC. 3% dextran sulfate sodium was used to induce colitic mice, and quercetin (25, 50, and 100 mg/kg) was administered orally for 10 days to assess the therapeutic effects. In vitro, Caco‐2 cells were used to explore the effect of quercetin on tight junction protein expression and AhR activation. The results showed that quercetin alleviated colitic mice by restoring tight junctions (TJs) integrity via an AhR‐dependent manner (p < 0.05). In vitro, quercetin dose‐dependently elevated the expressions of TJs protein ZO‐1 and Claudin1, and activated AhR by enhancing the expression of CYP1A1 and facilitating AhR nuclear translocation in Caco‐2 cells (p < 0.05). While AhR antagonist CH223191 reversed the therapeutic effects of quercetin (p < 0.05) and blocked quercetin‐induced AhR activation and enhancement of TJs protein (p < 0.05). In conclusion, quercetin repaired intestinal barrier dysfunction by activating AhR‐mediated enhancement of TJs to alleviate UC. Our research offered new perspectives on how quercetin enhanced intestinal barrier function. [ABSTRACT FROM AUTHOR]

Despite extensive characterization of the state and function of haematopoietic stem cells (HSCs), the use of transcription factors to define the HSC population is still limited. We show here that the HSC population in mouse bone marrow can be defined by the distinct expression levels of Spi1 and Gata1. By using a double fluorescence knock‐in mouse model, PGdKI, in which the expression levels of PU.1 and GATA‐1 are indicated by the expression of GFP and mCherry, respectively, we uncover that the HSCs with lymphoid and myeloid repopulating activity are specifically enriched in a Lin−PU.1dimGATA‐1− (LPG) cell subset. In vivo competitive repopulation assays demonstrate that bone marrow cells gated by LPG exhibit haematopoietic reconstitution activity which is comparable to that of classical Lin−Sca1+c‐kit+ (LSK). The integrated analysis of single‐cell RNA sequence data from LPG and LSK‐gated cells reveals that a transcriptional network governed by core TFs contributes to regulation of HSC multipotency. These discoveries provide new clues for HSC characterization and functional study. [ABSTRACT FROM AUTHOR]

Background: What is highlighted in this study refers to the role and molecular mechanism of long noncoding RNA (lncRNA) X‐inactive specific transcript (XIST) in cells with insulin resistance (IR). Methods: In this study, LX‐2 cells were applied to establish IR model in vitro. The expressions of lncRNA XIST, phosphoenolpyruvate carboxykinase (PEPCK,) and glucose‐6‐phosphatase (G6Pase) were quantified by quantitative reverse transcription polymerase chain reaction. The 2‐deoxy‐d‐glucose‐6‐phosphate (2‐DG6P) level was detected utilizing 2‐deoxy‐d‐glucose (2‐DG) uptake measurement kit. Western blot was adopted to measure the protein expressions of insulin‐like growth factor‐1 receptor (IGF‐1R), G6Pase, PEPCK, and phosphatidylinositol 3‐kinase (PI3K)/Akt pathway‐related genes. StarBase was used to predict the targeting relationship between lncRNA XIST or IGF‐1R with miR‐182‐5p, the results of which were verified by dual‐luciferase reporter, RNA pull‐down, and RNA immunoprecipitation assays. Rescue experiments were conducted to investigate the effect of miR‐182‐5p on IR cells. Next, low‐expressed lncRNA XIST and high‐expressed miR‐182‐5p were observed in IR cells. Results: Upregulation of lncRNA XIST increased IGF‐1R and 2‐DG6P levels, decreased G6Pase and PEPCK expressions, and promoted PI3K/Akt pathway activation in IR cells. LncRNA XIST sponged miR‐182‐5p which targeted IGF‐1R. MiR‐182‐5p mimic reversed the above effects of lncRNA XIST overexpression on IR cells. Conclusions: In conclusion, lncRNA XIST/miR‐182‐5p axis alleviates hepatic IR in vitro via IGF‐1R/PI3K/Akt signaling pathway, which could be the promising therapeutic target. [ABSTRACT FROM AUTHOR]

Background & Aims: Various intracellular pathways regulate inflammation in NASH. Cyclic GMP‐AMP synthase (cGAS) is a DNA sensor that activates STING and plays a role in inflammatory diseases. Here, we explored the role of cGAS in hepatic damage, steatosis, inflammation, and liver fibrosis in mouse models of NASH. Methods: cGAS deficient (cGAS‐KO) and STING deficient (STING‐KO) mice received high fat‐high cholesterol‐high sugar diet (HF‐HC‐HSD) or relevant control diets. Livers were evaluated after 16 or 30 weeks. Results: HF‐HC‐HSD diet, both at 16 and 30 weeks, resulted in increased cGAS protein expression as well as in increased ALT, IL‐1β, TNF‐α and MCP‐1 in wild‐type (WT) mice compared to controls. Surprisingly, liver injury, triglyceride accumulation, and inflammasome activation were greater in HF‐HC‐HSD cGAS‐KO compared to WT mice at 16 and to a lesser extent at 30 weeks. STING, a downstream target of cGAS was significantly increased in WT mice after HF‐HC‐HSD. In STING‐KO mice after HF‐HC‐HSD feeding, we found increased ALT and attenuated MCP1 and IL‐1β expression compared to WT mice. Markers of liver fibrosis were increased in cGAS‐ and STING‐KO mice compared to WT on HF‐HC‐HSD. We discovered that cGAS‐KO mice had a significant increase in circulating endotoxin levels on HF‐HC‐HSD that correlated with changes in intestinal morphology which was exacerbated by HF‐HC‐HSD compared to WT mice. Conclusion: Our findings indicate that cGAS or STING deficiency exacerbate liver damage, steatosis, and inflammation in HF‐HC‐HSD diet‐induced NASH, which might be linked to the disruption of the gut barrier. [ABSTRACT FROM AUTHOR]

The ongoing epidemic of SARS‐CoV‐2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS‐CoV‐2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3‐, 6‐, 12‐, and 18‐month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID‐19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long‐term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient‐weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long‐term antibody prediction (LTAP) model could predict long‐term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1‐score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long‐term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus‐infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hyperlipidemia. In discovery of novel small molecules that interfere PCSK9/LDLR protein–protein interaction (PPI), structural modification was performed based on our previously derived compounds. A series of [5,5′‐bibenzo[d][1,3]dioxol]‐6‐amine analogs were designed and synthesized for the activity evaluation. In the PCSK9/LDLR PPI impairing test, molecules D28 and D29, exhibited remarkable inhibitory potency with IC50 values of 8.30 and 6.70 μM compared with SBC‐115337 (17.89 μM), respectively. Molecular docking predicted the binding pattern of compounds D28 and D29 in the LDLR binding site of PCSK9. Hydrophobic interactions play an important role in the binding of aromatic molecular fragments to the pockets in the PCSK9/LDLR binding interface. Further LDLR expression and LDL uptake studies revealed that both D28 and D29 restored LDLR expression on the surface of hepatic HepG2 cells and improved extracellular LDL uptake in the presence of PCSK9. It is significant that molecules D28 and D29 exhibited potential for the treatment of hyperlipidemia in current in vitro investigations. Generally, lead compounds with novel structures were developed in the present study for further design of lipid‐lowering molecules by targeting PCSK9/LDLR PPI. [ABSTRACT FROM AUTHOR]

With the integration of wind, electricity and heat, the combined heat and power system has the characteristic of multi‐time scales, in which the wind power has high uncertainty, the thermal system is difficult to synchronize with the power system for the large inertia and delay. Therefore, the fixed time‐scale dispatching is unable to guarantee the reliability of the system. Given the above problems, this paper proposes a time‐scale adaptive dispatching strategy of the combined heat and power system considering thermal inertia. This strategy analyzes the time characteristics of wind power forecasting error and the thermal inertia, while later establishing time‐scale adaptive dispatching sub‐main model of combined heat and power system. Specifically, in the time‐scale adaptive method, the system available reserve model is improved due to the power support of the thermal inertia. Based on the existing fixed time‐scale dispatching, this method dynamically adjusts the steps of forecasting and the time‐scales of dispatching when the system available reserve is inadequate to compensate for the wind power forecasting error. Taking the 4‐h fixed time‐scale dispatching as an example, the simulation results suggest that the proposed strategy achieves the dynamic dispatching of the combined heat and power system, while improving its reliability and stability. [ABSTRACT FROM AUTHOR]

Low crystalline photocatalysts with unsaturated active sites, such as oxygen vacancy (Ov), is reported to exhibit enhanced adsorption and activation of oxygen‐containing small molecules, such as H2O and CO2, thus boosting the activity in photocatalytic H2 evolution and CO2 reduction. However, numerous low‐crystalline photocatalysts show unsatisfactory stability due to the easily repaired surface Ov. Herein, three SnNb2O6 with different crystallinity were prepared by hydrothermal approach with similar precursors. Compared with bulk SnNb2O6 and ultra‐thin layered SnNb2O6, low‐crystalline SnNb2O6 (SNA) exhibits optimal visible‐light‐driven evolution rates of H2 (86.04 μmol g−1 h−1) and CO from CO2 (71.97 μmol g−1 h−1), which is mainly ascribed to the fast separation of the photogenerated carriers and enhanced photoreduction power caused by the surface Ov. More importantly, the sharp decrease of photocatalytic activity of SNA after seven cycles is well restored by the hydrothermal treatment of recycled SNA, ascribed to the reactivated surface Ov with the recovered low‐crystalline structure. These works thus offer a promising strategy for developing low‐crystalline and amorphous photocatalysts with high activity and stability. [ABSTRACT FROM AUTHOR]

Exosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis‐ease progression, treatment effects and prognosis. Here, we report an efficient target recycling amplification process (TRAP) for the digital detection of miRNAs using photonic resonator absorption microscopy. We achieve multiplex digital detection with sub‐attomolar sensitivity in 20 minutes, robust selectivity for single nucleotide variants, and a broad dynamic range from 1 aM to 1 pM. Compared with traditional qRT‐PCR, TRAP showed similar accuracy in profiling exosomal miRNAs derived from cancer cells, but also exhibited at least 31‐fold and 61‐fold enhancement in the limits of miRNA‐375 and miRNA‐21 detection, respectively. The TRAP approach is ideal for exosomal or circulating miRNA biomarker quantification, where the miRNAs are present in low concentrations or sample volume, with potentials for frequent, low‐cost, and minimally invasive point‐of‐care testing. [ABSTRACT FROM AUTHOR]

In the current literature on latent variable models, much effort has been put on the development of dichotomous and polytomous cognitive diagnostic models (CDMs) for assessments. Recently, the possibility of using continuous responses in CDMs has been brought to discussion. But no Bayesian approach has been developed yet for the analysis of CDMs when responses are continuous. Our work is the first Bayesian framework for the continuous deterministic inputs, noisy, and gate (DINA) model. We also propose new interpretations for item parameters in this DINA model, which makes the analysis more interpretable than before. In addition, we have conducted several simulations to evaluate the performance of the continuous DINA model through our Bayesian approach. Then, we have applied the proposed DINA model to a real data example of risk perceptions for individuals over a range of health‐related activities. The application results exemplify the high potential of the use of the proposed continuous DINA model to classify individuals in the study. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) is the most common extracranial malignancy in childhood; however, the mechanisms underlying its aggressive characteristics still remain elusive. Methods: Integrative data analysis was performed to reveal tumour‐driving transcriptional regulators. Co‐immunoprecipitation and mass spectrometry assays were applied for protein interaction studies. Real‐time reverse transcription‐polymerase chain reaction, western blotting, sequential chromatin immunoprecipitation and dual‐luciferase reporter assays were carried out to explore gene expression regulation. The biological characteristics of NB cell lines were examined via gain‐ and loss‐of‐function assays. For survival analysis, the Cox regression model and log‐rank tests were used. Results: Cellular nucleic acid‐binding protein (CNBP) was found to be an independent factor affecting NB outcome, which exerted oncogenic roles in ribosome biogenesis, tumourigenesis and aggressiveness. Mechanistically, karyopherin subunit beta 1 (KPNB1) was responsible for nuclear transport of CNBP, whereas liquid condensates of CNBP repressed the activity of switch/sucrose‐nonfermentable (SWI/SNF) core subunits (SMARCC2/SMARCC1/SMARCA4) via interaction with SMARCC2, leading to alternatively increased activity of SMARCC1/SMARCA4 binary complex in facilitating gene expression essential for 18S ribosomal RNA (rRNA) processing in tumour cells, extracellular vesicle‐mediated delivery of 18S rRNA and subsequent M2 macrophage polarisation. A cell‐penetrating peptide blocking phase separation and interaction of CNBP with SMARCC2 inhibited ribosome biogenesis and NB progression. High KPNB1, CNBP, SMARCC1 or SMARCA4 expression or low SMARCC2 levels were associated with poor survival of NB patients. Conclusions: These findings suggest that CNBP phase separation is a target for inhibiting ribosome biogenesis and tumour progression in NB via modulating SWI/SNF complex activity. [ABSTRACT FROM AUTHOR]

To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)‐induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg−1·d−1, i.g.) for 10 days, meanwhile, in order to induce colitis, the mice were free to drink 3% DSS for 6 days. We found that wogonin could obviously ameliorate DSS‐induced colitis, including preventing colon shortening and inhibiting pathological damage. In addition, wogonin could increase the expression of PPARγ, which not only restores intestinal epithelial hypoxia but also inhibits iNOS protein to reduce intestinal nitrite levels. All these effects facilitated a reduction in the abundance of Enterobacteriaceae in DSS‐induced colitis mice. Therefore, compared with the DSS group, the number of Enterobacteriaceae in the intestinal flora was significantly reduced after administration of wogonin or rosiglitazone by 16s rDNA technology. We also verified that wogonin could promote the expression of PPARγ mRNA and protein in Caco‐2 cells, and this effect disappeared when PPARγ signal was inhibited. In conclusion, our study suggested that wogonin can activate the PPARγ signal of the Intestinal epithelium to ameliorate the Intestinal inflammation caused by Enterobacteriaceae bacteria expansion. [ABSTRACT FROM AUTHOR]

The practical application of lithium–sulfur (Li–S) batteries has been handicapped by the notorious polysulfide shuttling and sluggish sulfur conversion kinetics. Although the functional modification of separator is readily proposed as an effective strategy to optimize the Li–S redox reactions, the excessive material dosage and invalid structural design still result in inferior electrocatalyst utilization. Herein, generic graphene‐metal selenide heterostructures (Gr‐MxSey, M = Mo, W, Mn, Cu and Zn) are controllably grown on commercial glass fiber (GF) separator employing a sequential low‐temperature chemical vapor deposition procedure. Such a tailored reservoir can not only render ample active sites but also realize the synergy of polar and catalytic framework, which maximizes the electrochemical functions in alleviating shuttle effect and guiding Li2S nucleation/decomposition. The thus‐derived Gr‐MxSey/GF separator affording favorable heatproof feature endows the Li–S battery with an outstanding cycling stability (100% capacity retention over 100 cycles at 0.2 C). Furthermore, the flexible Li–S pouch cell based on this new separator delivers good device performance (with a capacity decay of 0.25% per cycle over 100 cycles). This study offers comprehensive insight into the reliable separator design toward working Li–S batteries. [ABSTRACT FROM AUTHOR]

Hybrid heterostructures are promising neurotransmitter platforms for photonic synapses in bioinspired optoelectronics. Organic–inorganic heterostructures have the features of a wide photoresponse and wet synthesis but still face poor stability and limited comprehensive performance. Here, it has been reported ultrastable and broadband photonic synaptic behaviors from solution‐processed cross‐linked conjugated polymer/zinc oxide nanorod heterostructures, which can be formed by in situ polymerization and hydrothermal methods. Light‐tunable synaptic function enables neuromorphic behaviors, such as high paired‐pulse facilitation, short‐ and long‐term plasticity, over the UV‐to‐visible spectral range. Impressively, the heterosynapse can maintain clear synaptic plasticity after being annealed in ambient air at 300 °C, showing robust thermal stability in harsh conditions. Moreover, visual perception and recognition can be mimicked with our synapse arrays, providing a reliable pathway to construct stable neurotransmitters toward practical neuromorphic optoelectronics. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) therapy is a promising treatment for hepatocellular carcinoma (HCC). However, it is limited by low response rates. Tumour‐infiltrating immune cells (TIICs), specifically CD8+ T cells, in the tumour microenvironment (TME) are related to tumour immune responses and are potential predictors for immunotherapeutic and survival outcomes. Therefore, we established a new CD8+ T cell‐related genes prognostic index (CD8T‐RGPI) for evaluating immune responses and prognostic outcomes for HCC. Using the TCGA databases, we evaluated the RNA‐seq data of CD8+ T cell‐related genes with gene co‐expression network. Then, the CD8T‐RGPI model was built by combining univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The nomogram exhibited a good prediction ability for HCC patients' prognosis in either TCGA or ICGC databases. The CD8T‐RGPI was elevated in patients with high T, M and TNM stages. Functional enrichment analyses revealed that in CD8T‐RGPI high‐risk group, tumour‐related and immunosuppressive pathways, such as focal adhesion, aerobic glycolysis, HIF1 transcription factor pathway, IL‐4 and IL‐13 signalling were significantly enriched. Moreover, for CD8T‐RGPI high‐risk HCC patients, immune tolerance and immunosurveillance escape was associated with poor therapeutic outcomes for ICB therapy. The CD8T‐RGPI low‐risk HCC patients with elevated immune infiltration levels were associated with good immunotherapeutic responses to ICB. Our findings provide prospective prognostic biomarkers and elucidate on HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Due to its strong randomness and volatility, the modes of wind power are complex. After decomposing wind power time series into three subseries, the complex modes are deconstructed and each subseries maintain unique characteristics. Aiming at the characteristics of each subseries, a wind power forecast method based on Broad Learning System (BLS) and Simplified Long Short Term Memory (SLSTM) is proposed. Firstly, the decomposed subseries is analysed. The first layer subseries reflects the main amplitude changes caused by ramp events and the second represents the local fluctuations accompanying ramp events. Due to the randomness of ramp events, new modes appear frequently in the two subseries. The third layer subseries consists of continuous irregular jitter. Then, the BLS is introduced to forecast the first and second layer subseries. By adjusting its structure dynamically, various modes of ramp events can be learned from amplitude change and accompanying fluctuation. Additionally, according to the characteristics of the third layer subseries, continuous jitter needn't be transmitted in long‐term memory. Setting the forget gate to 0, SLSTM is proposed to forecast the third layer subseries. Finally, the wind power data from the Belgian ELIA website is used to verify the superiority of the proposed method. [ABSTRACT FROM AUTHOR]

In recent years, the experiments have revealed that plants raise the cytotoxicity and anticancer potentials of iron nanoparticles against several cell lines especially tumor cell lines. In the present study, we formulated a modern drug by iron nanoparticles (FeNPs) containing Glycyrrhiza glabra L leaf for the treatment of acute lymphoblastic leukemia. Characterization of FeNPs was done by TEM, FE‐SEM, UV–Vis, and FT‐IR. FE‐SEM and TEM images revealed an average diameter of 11–18 nm for the nanoparticles. UV–Vis revealed an absorption band at 298 nm that is related to the surface plasmon resonance of FeNPs. FT‐IR results offered antioxidant compounds in the nanoparticles were the sources of reducing power, reducing iron ions to FeNPs. MTT assay was used on normal (HUVEC) and acute lymphoblastic leukemia (MOLT‐3, CEM/C2, TALL‐104, and CCRF‐CEM) cell lines for comparing the anti‐acute lymphoblastic leukemia properties of FeCl3, G. glabra, and FeNPs. Iron nanoparticles had very low cell viability dose‐dependently against MOLT‐3, CEM/C2, TALL‐104, CCRF‐CEM cell lines without any cytotoxicity on the HUVEC cell line. The best result of cytotoxicity property of FeNPs against the above cell lines was seen in the case of CCRF‐CEM cell line. These nanoparticles can be administrated in humans for the treatment of acute lymphoblastic leukemia after confirming in the in vivo and clinical trials. [ABSTRACT FROM AUTHOR]

HLA‐C*06:02:96 differs from HLA‐C*06:02:01:01 (924C → A, I284I), resulting in a synonymous change in exon 5. [ABSTRACT FROM AUTHOR]

We report the bi‐polaron transport and magnetic field induced Pauli spin‐blockade in solid‐state molecular junctions (MJs) evidenced by a positive magnetoresistance (MR). The junction was made of thin layers of redox‐active ruthenium polypyridyl‐oligomers Ru(tpy)2 sandwiched between conducting amorphous carbon (a‐C) electrodes. The redox‐active Ru(tpy)2 molecule, which enables small polaron and deep traps in the charge transport of the Ru(tpy)2 MJ as revealed by the temperature‐dependent current–voltage response, leads to the formation of the bi‐polaron and magnetic field induced Pauli spin blockade, resulting into the MR. At the meantime, the reliable and controllable device performance renders a rigid thickness‐dependent MR evolution. The bi‐polaron transport revealed in our study underscores the importance of the multi‐particle transport by molecular design in MJs and laid the foundation for magnetic‐electronic function in molecular‐scale devices. [ABSTRACT FROM AUTHOR]

DNA G‐quadruplexes (G4s) have been identified as critical elements in modulating genomic functions and many other biological processes. Their functions are highly dependent on the primary nucleotides and secondary folding structures. Therefore, to understand their functions, methods to identify and differentiate structures of G4 with speed and accuracy are required but limited. In this report, we have applied a synthetic G4 DNA‐encoded nanoparticle approach to identify and differentiate G4 DNA molecules with different topologies and nucleotide residues. We found that the resulting plasmonic properties of the gold nanoparticles, monitored by UV/Vis spectroscopy, are quite sensitive to different G4 structures, including stacking layers, loop sequences, capping bases on G4s, and topological structures. Through these systematic investigations, we demonstrate that this G4‐encoded gold nanoparticle approach can be used to profile the G4 structures and distinguish G4s from human telomeres. Such a method may have wide applications in G4 research. [ABSTRACT FROM AUTHOR]

METTL3 was known to run through the whole cycle of RNA. It relied on m6A modification in the mRNAs of cancer‐related genes to regulate tumour progression. The development of prostate cancer cells could be promoted by METTL3 via hedgehog pathway. Recent studies had shown that the effect of METTL3 on non‐coding RNA was mainly dependent on the modification of m6A. However, it is still unknown whether METTL3 promotes tumour development through this mechanism in prostate cancer. The expression of METTL3 in prostate cancer tissues and cells was analysed by qRT‐PCR and Western blot assays. CCK‐8 assay, colony formation assay, wound‐healing assay and transwell assays were conducted to detect the impact of METTL3 on cell proliferation, migration and invasion. Nude mice tumour models were built to evaluate the role of METTL3 in tumorigenesis. N6‐methyladenosine (m6A) RNA immunoprecipitation assay (MeRIP) and co‐immunoprecipitations assays were performed to verified that METTL3 upregulated the m6A level, interacted with microprocessor protein DGCR8, recognized the m6A modification of pre‐miR‐182 to regulate its maturation.METTL3 was highly expressed in prostate cancer, and knockdown of METTL3 significantly inhibited cell proliferation, migration, invasion and tumorigenesis, while overexpression of METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. In addition, we found that METTL3 upregulating the level of m6A, and interacted with DGCR8 to recognize the m6A modification of pre‐miR‐182 to regulate its splicing and maturation and promote the high expression of miRNA. Our study suggests that METTL3 could be used in targeted therapies for PCa. [ABSTRACT FROM AUTHOR]

The selective hydrogenation of nitroarenes bearing competitive reducible groups to produce functionalized amino compounds has wide application in industrial production. However, to control only reducing the target group is still a challenge. Here, Cu2O/M2Ta2O6 (M=H, Li, Na, K, Ag, Bi) catalysts were prepared to evaluate their catalytic performance using 3‐nitrostyrene (3‐NS) as a model reaction. The results confirm pristine Cu2O has a highly activity to hydrogenate 3‐NS but low selectivity with the coexisted products of 3‐vinylaniline (3‐VA), 3‐ethylaniline(3‐EA) and 1‐ethyl‐3‐nitrobenzene (3‐NE), whereas the independent tantalate can converse 3‐NS to sole product 3‐VA via absolutely preferential reduction of −NO2 moiety but with a low conversion rate. Importantly, if combining Cu2O and tantalate, the activity and selectivity of the appointed product were all obviously increased. Furthermore, the hydrogenation activity of 3‐NS to generate 3‐VA is positively related with the catalysts' intrinsic basicity and the preferential adsorption toward −NO2 group. [ABSTRACT FROM AUTHOR]

Background and Aims: Evidence suggests that interferon alpha (IFNα) plays an essential role in decreasing the HBsAg quantification and elevating the rate of clinical cure in chronic hepatitis B (CHB). However, the mechanisms underlying the effects of the exosomes on the expression of host genes in IFNα treatment remain unclear. Methods: CHB patients with IFNα treatment were divided into responders and non‐responders according to the degree of HBsAg decline. Through microRNA sequencing and a series of molecular biology methods, the key microRNAs in serum exosomes associated with clinical antiviral response of Peg‐IFNα treatment in nucleotide analogue‐treated CHB patients were investigated. The roles of exosomal miRNAs on the IFNα signal pathway were explored in macrophages. Results: MicroRNA sequencing and RT‐qPCR assays confirmed six distinctly declined miRNAs in serum exosomes of responders at week 12 compared with levels at baseline. Exosomes with declined miR27b‐3p in the serum of Peg‐IFNα‐treated responders activated phosphorylation of interferon regulatory factor 3/7 (IRF3/7) in IFNα synthesis pathway in macrophages. However, miR27b‐3p overexpression in HepAD38 cells suppressed IFNα synthesis in macrophages, resulting in insufficient ability to eliminate HBV, whereas the inhibitory effect could be blocked by inhibitors of exosomes release. Luciferase assay showed miR‐27b‐3p directly suppressed retinoic acid‐inducible gene I (RIG‐I) and TANK‐binding kinase 1 (TBK1) expressions, and these effects could be abrogated in mutation experiments. Conclusions: In IFNα treatment, exosomes with declined miR‐27b‐3p triggered activation of RIG‐I/TBK1 signalling in macrophages against HBV. Serum exosomal miR‐27‐3p might represent a potential biomarker for patients with CHB. [ABSTRACT FROM AUTHOR]

HLA‐B*15:01:75 differs from HLA‐B*15:01:01:01 by a single synonymous change in exon 2. [ABSTRACT FROM AUTHOR]

Summary: The role of abscisic acid (ABA) receptors, PYR1/PYL/RCAR (PYLs), is well established in ABA signalling and plant drought response, but limited research has explored the regulation of wheat PYLs in this process, especially the effects of their allelic variations on drought tolerance or grain yield. Here, we found that the overexpression of a TaABFs‐regulated PYL gene, TaPYL1‐1B, exhibited higher ABA sensitivity, photosynthetic capacity and water‐use efficiency (WUE), all contributed to higher drought tolerance than that of wild‐type plants. This heightened water‐saving mechanism further increased grain yield and protected productivity during water deficit. Candidate gene association analysis revealed that a favourable allele TaPYL1‐1BIn‐442, carrying an MYB recognition site insertion in the promoter, is targeted by TaMYB70 and confers enhanced expression of TaPYL1‐1B in drought‐tolerant genotypes. More importantly, an increase in frequency of the TaPYL1‐1BIn‐442 allele over decades among modern Chinese cultivars and its association with high thousand‐kernel weight together demonstrated that it was artificially selected during wheat improvement efforts. Taken together, our findings illuminate the role of TaPYL1‐1B plays in coordinating drought tolerance and grain yield. In particular, the allelic variant TaPYL1‐1BIn‐442 substantially contributes to enhanced drought tolerance while maintaining high yield, and thus represents a valuable genetic target for engineering drought‐tolerant wheat germplasm. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the main cause of cardiovascular diseases. The Fat‐1 gene can express the n‐3 fatty acid desaturase, which converts n‐6 polyunsaturated fatty acids (PUFA) to n‐3 PUFAs. The role of n‐3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n‐3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat‐1 transgenic rabbits and their littermate (WT) rabbits by feeding a high‐cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n‐3 PUFAs increased and n‐6 PUFAs decreased in the Fat‐1 group. Plasma high‐density lipoprotein cholesterol (HDL‐C) levels were significantly increased in the Fat‐1 group, and the atherosclerotic lesion area of the aortic arch in Fat‐1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly. In conclusion, n‐3 PUFAs improve atherosclerosis in Fat‐1 transgenic rabbits, and this process may depend on the increase in plasma HDL‐C and the decrease in the amount of SMCs in atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

Although the concomitance of nonalcoholic fatty liver disease (NAFLD) and viral hepatitis is soaring, there is not much knowledge about the impact of NAFLD on viral hepatitis. Here, we aimed to investigate how NAFLD influences the pathogenesis of viral hepatitis. Wild‐type C3H/HeN mice with NAFLD induced by high‐fat diet were infected with murine hepatitis virus 3 (MHV‐3) and sacrificed at Days 4, 8, 12, and 16 post infection. Although there was no difference in the survival rate between mice with and without NAFLD, individuals with steatosis suffered more severe and prolonged liver injury demonstrated by transaminases and histology examination. The intrahepatic viral load was higher in NAFLD group during early infection, although it declined ultimately. On the contrary, the serum antiviral antibody titer remained in a lower level in mice with NAFLD throughout the investigation. In NAFLD group, the production of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, interleukin 6, and interleukin 17A) and the frequencies of antiviral immune cells (NKG2D+ NK cells and CD69+ cytotoxic T lymphocytes [CTLs]) were profoundly increased. Parallelly, the production of anti‐inflammatory cytokine (interleukin 10) and inhibitory checkpoint expression (NKG2A on NK cells and programmed cell death‐1 on CTLs) were also significantly elevated to maintain homeostasis. However, the upregulation of interleukin 22, a protective cytokine was deficient in NAFLD group post MHV‐3 infection. Conclusively, hepatic lipid metabolic abnormalities disturb antiviral immunity and increase the vulnerability to and severity of viral hepatitis. [ABSTRACT FROM AUTHOR]

Background: As a metabolic reprogramming feature, cancer cells derive most of their energy from aerobic glycolysis, while its regulatory mechanisms and therapeutic strategies continue to be illusive. Methods: Integrative analysis of publically available expression profile datasets was used to identify critical transcriptional regulators and their target glycolytic enzymes. The functions and acting mechanisms of transcriptional regulators in cancer cells were investigated by using in vitro and in vivo assays. The Kaplan–Meier curve and log‐rank assay were used to conduct the survival study. Results: Salmonella pathogenicity island 1 (SPI1/PU.1), a haematopoietic transcription factor, was identified to facilitate glycolytic process, tumourigenesis, invasiveness, as well as metastasis of colon cancer cells, which was interplayed by tumour‐associated neutrophils. Mechanistically, neutrophils delivered SPI1 mRNA via extracellular vesicles, resulting in enhanced SPI1 expression of cancer cells. Through physical interaction with SPI1‐related protein (SPIB), SPI1 drove expression of glycolytic genes within cancer cells, which in turn induced polarization of neutrophils via glycolytic metabolite lactate. Depletion of neutrophils or SPIB–SPI1 interaction in cancer cells significantly inhibited glycolytic process, tumourigenesis and aggressiveness. Upregulation of SPI1 or SPIB was found to be associated with poor prognosis in patients suffering from colon cancer. Conclusions: Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Daptomycin is an effective clinical drug for treating Staphylococcus aureus bacteraemia. Daptomycin and its derivatives are essential resources for antimicrobial screening and drug development. The daptomycin nucleus is a critical intermediate for producing daptomycin and its derivatives; it is catalysed by deacylase from Actinoplanes utahensis. However, the yield of the daptomycin nucleus was low by the original strain. RESULTS: In this study, the deacylase gene was overexpressed in the heterologous hosts of three different Streptomyces strains, and the efficiency of recombinant Streptomyces coelicolor was higher than that of the other two strains. Daptomycin and its nucleus were isolated, their structures were identified by nuclear magnetic resonance (NMR) and liquid chromatography‐mass spectrometry (LC–MS), and its bioconversion was confirmed by high‐performance liquid chromatography (HPLC). The optimal conditions were a phosphate buffer with 0.2 mol L−1 KCl, pH 7.0, and temperature of 40 °C, with a reaction time >4 h; in these conditions, the bioconversion efficiency increased from 71.04% to 85.02%, which is an increase of 16.44%. In addition, daptomycin nucleus yield could reach 4.36 g L−1 when 8 g L−1 daptomycin was added to the 200 mL reaction system by recombinant S. coelicolor, and the yield was 1.23 g L−1 when 6 g L−1 of daptomycin was introduced into wild‐type strain in a preliminary study for further industrialization applications. CONCLUSION: These results are helpful for enhancing daptomycin nucleus production in recombinant Streptomyces. Our work could make it possible to commercialise the daptomycin nucleus‐overproducing stains and provide a library of chemical substances for antibacterial screening and drug development. © 2021 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]