Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

Uniform Nanoscale Ion-Selective Membrane Prepared by Precision Control of Solution Spreading and Evaporation.

Ion-selective membrane has broad application in various fields, while the present solution-processed techniques can only prepare uniform membrane with microscale thickness. Herein, a high-quality polymer membrane with nanoscale thickness and uniformity is precisely prepared by controlling solution spreading and solvent evaporation stability/rate. With the arrayed capillaries, the stable spreading of polymer solution with volume of microliter induces the formation of solution film with micrometers thickness. Moreover, the fast increase of solution dynamic viscosity during solvent evaporation inhibits nonuniform Marangoni flow and capillary flow in solution film. Consequently, the uniform Nafion-Li membranes with ∼200 nm thickness are prepared, while their Li+ conductivity is 2 orders of magnitude higher than that of commercially Nafion-117 membrane. Taking lithium-sulfur battery as a model device, the cells (capacities of 8-10 mAh cm-2) can stably operate for 150 cycles at a S loading of 12 mg cm-2 and an electrolyte/sulfur ratio of ∼7.

Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

HLA-A+ tertiary lymphoid structures with reactivated tumor infiltrating lymphocytes are associated with a positive immunotherapy response in esophageal squamous cell carcinoma.

BACKGROUND: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance. METHODS: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses. We systematically assessed the tumor microenvironment using the NanoString GeoMx digital spatial profiler, single-cell RNA-seq and multiplex immunohistochemistry in ESCC. Finally, we evaluated the associations between HLA-A-positive tertiary lymphoid structures (TLSs) and patients' responses to ICB in 60 ESCC patients. RESULTS: Tumor infiltrating B lymphocytes and several immune-related gene signatures, such as the antigen presenting machinery (APM) signature, are significantly elevated in ICB treatment responders. Multiplex immunohistochemistry identified the presence of HLA-A+ TLSs and showed that TLS-resident cells increasingly express HLA-A as TLSs mature. Most TLS-resident HLA-A+ cells are tumor-infiltrating T (TIL-T) or tumor-infiltrating B (TIL-B) lymphocytes. Digital spatial profiling of spatially distinct TIL-T lymphocytes and single-cell RNA-seq data from 60 ESCC tumor tissues revealed that CXCL13-expressing exhausted TIL-Ts inside TLSs are reactivated with elevated expression of the APM signature as TLSs mature. Finally, we demonstrated that HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, are associated with a clinical benefit from ICB treatment for ESCC. CONCLUSIONS: HLA-A+ TLSs are present in ESCC tumor tissues. TLS-resident TIL-Ts with elevated expression of the APM signature may be reactivated. HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, may serve as biomarkers for ICB-treated ESCC patients.

Revitalizing gut barrier integrity: role of miR-192-5p in enhancing autophagy via Rictor in enteritis.

Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis.NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis.

AlgU mediates hyperosmotic tolerance in Pseudomonas protegens SN15-2 by regulating membrane stability, ROS scavenging, and osmolyte synthesis.

Pseudomonas protegens can serve as an agricultural biocontrol agent. P. protegens often encounters hyperosmotic stress during industrial production and field application. The ability of P. protegens to withstand hyperosmotic stress is important for its application as a biocontrol agent. AlgU is a global regulator responsible for stress response and biocontrol ability. However, the specific regulatory role of AlgU in the hyperosmotic adaptation of P. protegens is poorly understood. In this study, we found that the AlgU mutation disrupted the hyperosmotic tolerance of P. protegens. Many genes and metabolites related to cell envelope formation were significantly downregulated in ΔalgU compared with that in the wild-type (WT) strain under hyperosmotic conditions, and we found that the algU mutation caused membrane integrity to be compromised and increased membrane permeability. Further experiments revealed that the cell envelope integrity protein TolA, which is regulated by AlgU, contributes to cell membrane stability and osmotic tolerance in P. protegens. In addition, several genes related to oxidative stress response were significantly downregulated in ΔalgU, and higher levels of intracellular reactive oxygen species were found in ΔalgU. Furthermore, we found that the synthesis of N-acetyl glutaminyl glutamine amide is directly regulated by AlgU and contributes to the hyperosmotic adaptation of P. protegens. This study revealed the mechanisms of AlgU's participation in osmotic tolerance in P. protegens, and it provides potential molecular targets for research on the hyperosmotic adaptation of P. protegens.IMPORTANCEIn this study, we found that the extracytoplasmic function sigma factor AlgU is essential for the survival of P. protegens under hyperosmotic conditions. We provided evidence supporting the roles of AlgU in influencing cell membrane stability, intracellular reactive oxygen species (ROS) accumulation, and dipeptide N-acetylglutaminylglutamine amide (NAGGN) synthesis in P. protegens under hyperosmotic conditions. Our findings revealed the mechanisms of AlgU's participation in hyperosmotic stress tolerance in P. protegens, and they provide potential molecular targets for research on the hyperosmotic adaptation of P. protegens, which is of value in improving the biocontrol ability of P. protegens.

Stereoselective Synthesis of ß, γ-Fused Bicyclic γ-Ureasultams via an Intramolecular Mannich and aza-Michael Addition Cascade.

A novel approach has been developed for the synthesis of bicyclic ß, γ-fused bicyclic γ-ureasultams containing two consecutive chiral centers through an intramolecular Mannich and aza-Michael addition cascade of alkenyl sulfamides. The straightforward practical procedure and readily available starting materials enable the synthesis of variously substituted ureasultams. In addition, bicyclic γ-ureasultams is a class of potential biotin analogues.

Engineering a Ce Promoter into a Three-Dimensional Porous Mo2C@NC Heterostructure for Hydrogen Evolution Electrocatalysis via Weakening the Mo-H Bond Strength.

The pursuit of highly efficient electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of paramount importance for water splitting. However, it is still a formidable task in Mo2C-based materials because of the agglomeration and strong Mo-H binding of Mo2C units. Herein, a novel CeOCl-CeO2/Mo2C heterostructure nesting within a three-dimensional porous nitrogen-doped carbon matrix has been designed and used for catalyzing HER via simultaneous morphology and heterointerface engineering. As expected, the optimal CeOCl-CeO2(0.2)/Mo2C@3DNC exhibits impressive HER activity, with a low overpotential of 156 mV at a current density of 10 mA cm-2 coupled with a slight Tafel slope of 62.20 mV dec-1. Introducing a Ce promoter, that is CeOCl and CeO2, would endow the interface with an internal electric field and electron redistribution between CeOCl-CeO2 and Mo2C induced by the heterogeneous work function difference. Moreover, experimental investigation and density functional calculations confirm that the CeOCl-CeO2/Mo2C heterointerface can downshift the d-band center of the active Mo center, weakening the strength of the Mo-H coupling. This proposed concept, engineering Ce-based promoters into active entities involved in the heterostructure to modulate intermediate adsorption, offers a great opportunity for the design of superior electrocatalysts for energy conversion.

Calf circumference was negatively associated with all-cause mortality among the Chinese centenarians: a prospective study with a 5-year follow-up.

BACKGROUND: Sarcopenia is an aging-related disorder characterized by a loss of muscle mass and function. Calf circumference (CC) is a useful surrogate marker of muscle mass and function. This prospective study was designed to investigate the association between CC and all-cause mortality during a follow-up for 5 years in the Chinese centenarians. METHODS: The China Hainan Centenarian Cohort Study (CHCCS) is conducted in 18 cities and counties of Hainan, China. RESULTS: All 231 centenarians had a mean age of 103.03 years. Survival participants had a longer CC and were often living alone compared with others (P<0.05 for all). Multivariate Cox regression models showed that CC was negatively associated with all-cause mortality (P < 0.05 for all). Participants with a longer CC had a lower mortality risk compared with others [Exp(ß): 0.918; 95%confidence interval: 0.863-0.977]. Participants with a longer CC had a lower mortality risk whether they were males or females and lived with family members or alone. CONCLUSION: CC was negatively associated with all-cause mortality and could be an indicator of future mortality among the Chinese centenarians. Further researches should focus on preventing a decline in the CC in order to promote human longevity.

Ratiometric electrochemical determination of hydroxyl radical based on graphite paper modified with metal-organic frameworks and impregnated with salicylic acid.

Hydroxyl radical (•OH) detection is pivotal in medicine, biochemistry and environmental chemistry. Yet, electrochemical method-specific detection is challenging because of hydroxyl radicals' high reactivity and short half-life. In this study, we aimed to modify the electrode surface with a specific recognition probe for •OH. To achieve this, we conducted a one-step hydrothermal process to fabricate a CoZnMOF bimetallic organic framework directly onto conductive graphite paper (Gp). Subsequently, we introduced salicylic acid (SA) and methylene blue (MB), which easily penetrated the pores of CoZnMOF. By selectively capturing •OH by SA and leveraging the electrochemical signal generated by the reaction product, we successfully developed an electrochemical sensor Gp/CoZnMOF/SA + MB. The prepared sensor exhibited a good linear relationship with •OH concentrations ranging from 1.25 to 1200 nM, with a detection limit of 0.2 nM. Additionally, the sensor demonstrated excellent reproducibility and accuracy due to the incorporation of an internal reference. It exhibited remarkable selectivity for •OH detection, unaffected by other electrochemically active substances. The establishment of this sensor provides a way to construct MOF-modified sensors for the selective detection of other reactive oxygen species (ROS), offering a valuable experimental basis for ROS-related disease research and environmental safety investigations.

New Insights into the Genetic Basis of Lysine Accumulation in Rice Revealed by Multi-Model GWAS.

Lysine is an essential amino acid that cannot be synthesized in humans. Rice is a global staple food for humans but has a rather low lysine content. Identification of the quantitative trait nucleotides (QTNs) and genes underlying lysine content is crucial to increase lysine accumulation. In this study, five grain and three leaf lysine content datasets and 4,630,367 single nucleotide polymorphisms (SNPs) of 387 rice accessions were used to perform a genome-wide association study (GWAS) by ten statistical models. A total of 248 and 71 common QTNs associated with grain/leaf lysine content were identified. The accuracy of genomic selection/prediction RR-BLUP models was up to 0.85, and the significant correlation between the number of favorable alleles per accession and lysine content was up to 0.71, which validated the reliability and additive effects of these QTNs. Several key genes were uncovered for fine-tuning lysine accumulation. Additionally, 20 and 30 QTN-by-environment interactions (QEIs) were detected in grains/leaves. The QEI-sf0111954416 candidate gene LOC_Os01g21380 putatively accounted for gene-by-environment interaction was identified in grains. These findings suggested the application of multi-model GWAS facilitates a better understanding of lysine accumulation in rice. The identified QTNs and genes hold the potential for lysine-rich rice with a normal phenotype.

How is work-family conflict linked to nurse-assessed patient safety among intensive care unit nurses? A serial multiple mediation analysis.

AIM: The aim of this study was to test whether rumination and negative affectivity mediate the relationship between work-family conflict and nurse-assessed patient safety among intensive care unit nurses. BACKGROUND: Most intensive care unit nurses experience work-family conflicts that jeopardise patient safety. Although prior studies have explored the effect of work-family conflict on patient safety, few have investigated whether work-family conflict is associated with patient safety through rumination and negative affectivity among intensive care unit nurses. DESIGN: Cross-sectional study. METHODS: This study included 209 intensive care unit nurses from five general hospitals. The Work-Family Conflict Scale, the Ruminative Response Scale, the Positive and Negative Affect Schedule-Negative Affectivity, and three items indicating nurses' perception of overall patient safety were used to gather data. Associations between work-family conflict, rumination, negative affectivity, and nurse-assessed patient safety were assessed using correlation and serial multiple mediation analysis. RESULTS: Work-family conflict, rumination, negative affectivity, and nurse-assessed patient safety were significantly correlated (p < 0.01). Work-family conflict can have not only a direct negative impact on the nurse-assessed patient safety (effect = -0.0234; standard error [SE] = 0.0116; 95% confidence interval [CI]: lower limit [LL] = -0.0464, upper limit [UL] = -0.0005) but also an indirect impact on nurse-assessed patient safety through three paths: the independent mediating role of rumination (effect = -0.0118; SE = 0.0063; 95% CI: LL = -0.0251, UL = -0.0006), the independent mediating role of negative affectivity (effect = -0.0055; SE = 0.0039; 95% CI: LL = -0.0153, UL = -0.0001), and the chain-mediating role of rumination and negative affectivity (effect = -0.0078; SE = 0.0031; 95% CI: LL = -0.0152, UL = -0.0027). CONCLUSION: Our findings indicated that work-family conflict could influence nurse-assessed patient safety through increasing rumination and negative affectivity among intensive care unit nurses. Based on the results, interventions aimed at decreasing work-family conflict would be beneficial for intensive care unit nurses' emotional stability and patient safety.

Unlocking Mechanism of Anion and Cation Interaction on Ion Conduction of Polymer Based Electrolyte in Metal Batteries.

Polymer based electrolyte shows advantages in compatibly improving safety and interface stability of batteries, while its limited ion conductivity and transfer number make it difficult to apply it in batteries with high energy density. Herein, by designing four crosslinking polyesters with different electron withdrawing group (EWG), it is found that strengthening the binding of EWG to anion for weakening the binding of anion to Li+ is critical for high Li+ transfer number (tLi+) and ionic conductivity of electrolyte. As a result, poly(2,2,3,3-tetrafluoropropyl methacrylate) (PTFM) based gel polymer electrolyte (GPE) shows an ionic conductivity of 0.78 mS cm-1 and a tLi+ of 0.85, much higher than those of poly(methyl methacrylate) (PMMA) without EWG. Moreover, PTFM based GPE shows excellent flame retardancy property. Li||PTFM||NCM811 batteries with an ultrahigh capacity of 5.5 mAh cm-2 show stable cycles of 5 times to that of Li||PMMA||NCM811. Moreover, the assembled graphite||PTFM||NCM811 pouch cell shows a capacity retention rate of 92% after 500 cycles. This work clarifies the mechanism of cation||anion interaction on ionic conductivity of GPE, which is important to develop high-performance devices with good safety and flexibility.

Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers.

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

Bioinspired Electrode for the Production and Timely Separation of Nitrile and Hydrogen.

Replacing electrocatalytic oxygen evolution reaction (OER) with amine oxidation reaction is adopted to boost clean and environment-friendly energy source hydrogen (H2 ) in water. However, the electrocatalytic reaction is severely restricted by the strong adsorption of product on the catalyst surface. Inspired by the cooperation of flavin adenine dinucleotide and mitochondria membrane in biological system, the catalysis-separation complex electrodes are introduced to promote the desorption of product and hinder its readsorption by applying polytetrafluoroethylene (PTFE)-separation membrane on the one side of electrode, which is benefit for the cleanness of active sites on the catalyst surface for the continuous production and timely separation of nitrile and hydrogen. With the intermolecular force between PTFE and nitrile, the nitrile droplets can be quickly desorbed and separated from catalyst surface of anode, and the size of nitrile droplets on the catalyst surface is only 0.23% to that without PTFE. As a result, the current at 1.49 VRHE from the catalyst with PTFE membrane is about 33 times to that of catalyst without PTFE after long-term operation. Moreover, the cathode with PTFE membrane also achieves the rapid desorption of H2 bubbles and stable cathodic current because of the strong absorption of PTFE to H2 .

Increased RNA editing sites revealed as potential novel biomarkers for diagnosis in primary Sjögren's syndrome.

BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy. CONCLUSION: These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.

Multistage Modulation Formation of Hydrophilic-Hydrophobic Boron Carbon Nitride Nanomaterials.

Boron carbon nitride (BCN) ternary compounds are attractive due to their wide applications in adsorption, catalysis, protective coatings, etc. A simple way is provided to synthesize BCN materials with multistage modulation of hydrophilic-hydrophobic properties. Hydrophilic BCN nanoparticles with a contact angle of 31° and nearly superhydrophobic BCN sheets with a contact angle of 145° are obtained. The participation of a CuO additive in the synthesis process has the role of tuning morphologies, components, and properties of BCN materials. The addition of CuO would improve the hydrophobicity of BCN due to its microstructure with enhanced surface roughness. The interaction between melamine and boric acid on the surface of CuO(111) is investigated by first-principles calculations based on density functional theory (DFT). The tuned BCN materials have different photoelectric properties also, and their performance as photocatalysts has been verified in photocatalytic reactions for hydrogen from water. The achieved uniform hydrophilic BCN nanoparticles and hydrophobic BCN sheets have the potential for further practical applications.

Hollow Starlike Ag/CoMo-LDH Heterojunction with a Tunable d-Band Center for Boosting Oxygen Evolution Reaction Electrocatalysis.

It is a challenging task to utilize efficient electrocatalytic metal hydroxide-based materials for the oxygen evolution reaction (OER) in order to produce clean hydrogen energy through water splitting, primarily due to the restricted availability of active sites and the undesirably high adsorption energies of oxygenated species. To address these challenges simultaneously, we intentionally engineer a hollow star-shaped Ag/CoMo-LDH heterostructure as a highly efficient electrocatalytic system. This design incorporates a considerable number of heterointerfaces between evenly dispersed Ag nanoparticles and CoMo-LDH nanosheets. The heterojunction materials have been prepared using self-assembly, in situ transformation, and spontaneous redox processes. The nanosheet-integrated hollow architecture can prevent active entities from agglomeration and facilitate mass transportation, enabling the constant exposure of active sites. Specifically, the powerful electronic interaction within the heterojunction can successfully regulate the Co3+/Co2+ ratio and the d-band center, resulting in rational optimization of the adsorption and desorption of the intermediates on the site. Benefiting from its well-defined multifunctional structures, the Ag0.4/CoMo-LDH with optimal Ag loading exhibits impressive OER activity, the overpotential being 290 mV to reach a 10 mA cm-2 current density. The present study sheds some new insights into the electron structure modulation of hollow heterostructures toward rationally designing electrocatalytic materials for the OER.

Design, synthesis and mechanism studies of dual EZH2/BRD4 inhibitors for cancer therapy.

Aberrant expression of EZH2 is frequently observed in cancers, and the EZH2 inhibitors are only effective in hematological malignancies and almost noneffective against solid tumors. It has been reported that the combination of EZH2 and BRD4 inhibitors may be a promising strategy to treat solid tumors being insensitive to EZH2 inhibitors. Thus, a series of EZH2/BRD4 dual inhibitors were designed and synthesized. The optimized compound 28, encoded as KWCX-28, was the most potential compound by the SAR studies. Further mechanism studies showed that KWCX-28 inhibited HCT-116 cells proliferation (IC50 = 1.86 µM), induced HCT-116 cells apoptosis, arrested cell cycle arrest at G0/G1 phase and resisted the histone 3 lysine 27 acetylation (H3K27ac) upregulation. Therefore, KWCX-28 was a potential dual EZH2/BRD4 inhibitors for treating solid tumors.