Phaser-Trim: A Phase Separation Based Genetically Encoded Reporter for H3K9 Trimethylation in Living Cells.

Histone methylation is a key epigenetic modification that regulates the chromatin structure and gene expression for proper cellular and physiological processes. Aberrant histone methylation patterns are implicated in many diseases. Therefore, monitoring histone methylation dynamics in living cells and species is essential for elucidating its regulatory mechanisms and identifying potential therapeutic targets. However, current methods for detecting histone methylation are limited by their low sensitivity and specificity. To overcome this challenge, we have developed a genetically encoded biosensor named Phaser-Trim (Phase separation based genetically encoded reporter for H3K9 Trimethylation) to detect the dynamic changes of H3K9me3 in living cells and species through the generation and disappearance of phase-separated droplets. Phaser-Trim demonstrates advantages of clear phenotypic characteristics, convenient operation, quantitative accuracy, biocompatibility, high specificity, and superior imaging performance with high signal-to-background ratio (SBR) for in vivo animal imaging. Using Phaser-Trim, we have successfully detected the dynamics of the H3K9me3 level during the differentiation of neural stem cells in Drosophila. Furthermore, Phaser-Trim also holds promise for application in high-throughput screening systems to facilitate the discovery of novel anticancer drugs.

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma.

Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03-333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43-34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.

Clinical diagnostic value of targeted next­generation sequencing for infectious diseases (Review).

As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next­generation sequencing (mNGS) is increasingly used. This shift underscores the growing need for more cost­effective and universally accessible sequencing assays to improve patient care and public health. Therefore, targeted NGS (tNGS) is gaining prominence. tNGS involves enrichment of target pathogens in patient samples based on multiplex PCR amplification or probe capture with excellent sensitivity. It is increasingly used in clinical diagnostics due to its practicality and efficiency. The present review compares the principles of different enrichment methods. The high positivity rate of tNGS in the detection of pathogens was found in respiratory samples with specific instances. tNGS maintains high sensitivity (70.8­95.0%) in samples with low pathogen loads, including blood and cerebrospinal fluid. Furthermore, tNGS is effective in detecting drug­resistant strains of Mycobacterium tuberculosis, allowing identification of resistance genes and guiding clinical treatment decisions, which is difficult to achieve with mNGS. In the present review, the application of tNGS in clinical settings and its current limitations are assessed. The continued development of tNGS has the potential to refine diagnostic accuracy and treatment efficacy and improving infectious disease management. However, further research to overcome technical challenges such as workflow time and cost is required.

Platinum nanowires/MXene nanosheets/porous carbon ternary nanocomposites for in situ monitoring of dopamine released from neuronal cells.

Dopamine is an important neurotransmitter in the body and closely related to many neurodegenerative diseases. Therefore, the detection of dopamine is of great significance for the diagnosis and treatment of diseases, screening of drugs and unraveling of relevant pathogenic mechanisms. However, the low concentration of dopamine in the body and the complexity of the matrix make the accurate detection of dopamine challenging. Herein, an electrochemical sensor is constructed based on ternary nanocomposites consisting of one-dimensional Pt nanowires, two-dimensional MXene nanosheets, and three-dimensional porous carbon. The Pt nanowires exhibit excellent catalytic activity due to the abundant grain boundaries and highly undercoordinated atoms; MXene nanosheets not only facilitate the growth of Pt nanowires, but also enhance the electrical conductivity and hydrophilicity; and the porous carbon helps induce significant adsorption of dopamine on the electrode surface. In electrochemical tests, the ternary nanocomposite-based sensor achieves an ultra-sensitive detection of dopamine (S/N = 3) with a low limit of detection (LOD) of 28 nM, satisfactory selectivity and excellent stability. Furthermore, the sensor can be used for the detection of dopamine in serum and in situ monitoring of dopamine release from PC12 cells. Such a highly sensitive nanocomposite sensor can be exploited for in situ monitoring of important neurotransmitters at the cellular level, which is of great significance for related drug screening and mechanistic studies.

Atomic-level tailoring of single-atom tungsten catalysts for optimized electrochemical nitrate-to-ammonia conversion.

Nitrate contamination of water resources poses significant health and environmental risks, necessitating efficient denitrification methods that produce ammonia as a desirable product. The electrocatalytic nitrate reduction reaction (NO3RR) powered by renewable energy offers a promising solution, however, developing highly active and selective catalysts remains challenging. Single-atom catalysts (SACs) have shown impressive performance, but the crucial role of their coordination environment, especially the next-nearest neighbor dopant atoms, in modulating catalytic activity for NO3RR is underexplored. This study aims to optimize the NO3RR performance of tungsten (W) single atoms anchored on graphene by precisely engineering their coordination environment through first and next-nearest neighbor dopants. The stability, reaction paths, activity, and selectivity of 43 different nitrogen and boron doping configurations were systematically studied using density functional theory. The results reveal W@C3, with W coordinated to three carbon atoms, exhibits outstanding NO3RR activity with a low limiting potential of -0.36 V. Intriguingly, introducing next-nearest neighbor B and N dopants further enhances the performance, with W@C3-BN achieving a lower limiting potential of -0.26 V. This exceptional activity originates from optimal nitrate adsorption strengths facilitated by orbital hybridization and charge modulation effects induced by the dopants. Furthermore, high energy barriers for NO2 and NO formation on W@C3 and W@C3-BN ensure their selectivity towards NO3RR products. These findings provide crucial atomic-level insights into rational design strategies for high-performance single-atom NO3RR catalysts via coordination environment engineering.

Cascade CRISPR/Cas12a and DSN for the electrochemical biosensing of miR-1246 in BC-derived exosomes.

MiR-1246 in breast cancer-derived exosomes was a promising biomarker for early diagnosis of breast cancer(BC). However, the low abundance, high homology and complex background interference make the accurate quantitative detection of miR-1246 facing great challenges. In this study, we developed an electrochemical biosensor based on the subtly combined of CRISPR/Cas12a, double-stranded specific nuclease(DSN) and magnetic nanoparticles(MNPs) for the detection of miR-1246 in BC-derived exosomes. Ascribed to the good synergistic effect of DSN, Cas12a and MNPs, the developed electrochemical biosensor exhibited excellent performance with the linear range from 500 aM to 5 pM, and the detection limit as low down to about 50 aM. The target-specific triggered enzyme-digest activity of DSN and Cas12a system, as well as the powerful separation ability of MNPs ensure the high specificity of developed electrochemical biosensor which can distinguish single base mismatches. In addition, the developed electrochemical biosensor has been successfully applied to detect miR-1246 in blood-derived exosomes and realize distinguishing the BC patients from the healthy individuals. It is expected that the well-designed biosensing platform will open up new avenues for clinical liquid biopsy and early screening of breast cancer, as well as provide deeper insights into clinical oncology treatment.

Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.

Schistosomiasis is a neglected disease of poverty that affects over 200 million people worldwide and relies on a single drug for therapy. The cathepsin B1 cysteine protease (SmCB1) of Schistosoma mansoni has been investigated as a potential target. Here, a structure-based pharmacophore virtual screening (VS) approach was used on a data set of approved drugs to identify potential antischistosomal agents targeting SmCB1. Pharmacophore (PHP) models underwent validation through receiver operating characteristics curves achieving values >0.8. The data highlighted riboflavin (RBF) as a compound of particular interest. A 1 µs molecular dynamics simulation demonstrated that RBF altered the conformation of SmCB1, causing the protease's binding site to close around RBF while maintaining the protease's overall integrity. RBF inhibited the activity of SmCB1 at low micromolar values and killed the parasite in vitro. Finally, in a murine model of S. mansoni infection, oral administration of 100 mg/kg RBF for 7 days significantly decreased worm burdens by ∼20% and had a major impact on intestinal and fecal egg burdens, which were decreased by ∼80%.

Berberine alleviates diabetic retinopathy by regulating the Th17/Treg ratio.

BACKGROUND: Diabetic retinopathy (DR) stands as a prominent complication of diabetes. Berberine (BBR) has reported to be effective to ameliorate the retinal damage of DR. Studying the potential immunological mechanisms of BBR on the streptozotocin (STZ) induced DR mouse model will explain the therapeutic mechanisms of BBR and provide theoretical basis for the clinical application of this drug. METHODS: C57BL/6 J mice were induced into a diabetic state using a 50 mg/(kg·d) dose of STZ over a 5-day period. Subsequently, they were subjected to a high-fat diet (HFD) for one month. Following a 5-week treatment with 100 mg/(kg·d) BBR, the concentrations of inflammatory factors in the mice's peripheral blood were determined using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin staining was employed to scrutinize pathological changes in the mice's retinas, while flow cytometry assessed the proportions of T-lymphocyte subsets and the activation status of dendritic cells (DCs) in the spleen and lymph nodes. CD4+T cells and DC2.4 cell lines were utilized to investigate the direct and indirect effects of BBR on T cells under high glucose conditions in vitro. RESULTS: Following 5 weeks of BBR treatment in the streptozotocin (STZ) mouse model of DR, we observed alleviation of retinal lesions and a down-regulation in the secretion of inflammatory cytokines, namely TNF-α, IL-1ß, and IL-6, in the serum of these mice. And in the spleen and lymph nodes of these mice, BBR inhibited the proportion of Th17 cells and promoted the proportion of Treg cells, thereby down-regulating the Th17/Treg ratio. Additionally, in vitro experiments, BBR directly inhibited the expression of the transcription factor RORγt and promoted the expression of the transcription factor Foxp3 in T cells, resulting in a down-regulation of the Th17/Treg ratio. Furthermore, BBR indirectly modulated the Th17/Treg ratio by suppressing the secretion of TNF-α, IL-1ß, and IL-6 by DCs and enhancing the secretion of indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-ß) by DCs. This dual action inhibited Th17 cell differentiation while promoting Treg cells. CONCLUSION: Our findings indicate that BBR regulate T cell subpopulation differentiation, reducing the Th17/Treg ratio by directly or indirectly pathway. This represents a potential therapeutic avenue of BBR for improving diabetic retinopathy.

Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

p53 exerts anticancer effects by regulating enhancer formation and activity.

The abnormality of p53 tumor suppressor is crucial in lung cancer development, and p53 may regulate target gene promoters to combat cancer. Recent studies have shown extensive p53 binding to enhancer elements. However, whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood. In the current study, we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout human bronchial epithelial cells (BEAS-2B). A total of 943 active regular enhancers and 370 super-enhancers (SEs) disappeared upon the deletion of p53, indicating that p53 modulates the activity of hundreds of enhancer elements. We found that one p53-dependent SE, located on chromosome 9 and designated as KLF4-SE, regulated the expression of the Krüppel-like factor 4 ( KLF4) gene. Furthermore, deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression, but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model. Subsequently, in TP53 knockout cells, the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency. Consistently, KLF4 expression also decreased in lung cancer tissues and cell lines. Overexpression of KLF4 significantly suppressed lung cancer cell proliferation and migration. Collectively, our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function. Therefore, our findings offer novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

Understanding the removal of heavy metals from stormwater runoff in permeable pavement system.

Understanding the removal of heavy metals (HMs) in permeable pavement systems is of great significance for controlling urban runoff pollution and optimizing structural design. However, few studies have systematically investigated the mechanism of permeable pavement systems in removing HMs from stormwater runoff. In this study, we adopted a hierarchical strategy to understand the efficiency of individual structural layers on HMs removal in a permeable interlocking concrete pavement (PICP) system. Experimental results illuminated that the surface layer exhibited the highest uptakes of HMs, which can remove up to 64 % of Pb2+, 50 % of Cu2+, 28 % of Cd2+ and 13 % of Zn2+. Meanwhile, as the rainfall return period increased, the removal rates of HMs in PICP was gradually decreased. In addition, batch experiments were conducted and the adsorption results were in accordance with the rainfall filtration experiments. More importantly, X-ray Photoelectron Spectroscopy (XPS) and leaching results were investigated to understand the HMs removal mechanism, which found that the ion exchange is the main mechanism in the surface layer to remove HMs, whereas the chemical adsorption play a crucial role in the base and sub-base layers. Overall, these findings provided new insights into the transport patterns of HMs in the internal structural layers of the PICP.

5-Heptadecylresorcinol Improves Aging-Associated Hepatic Fatty Acid Oxidation Dysfunction via Regulating Adipose Sirtuin 3.

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.

Maternal Brown Rice Diet during Pregnancy Promotes Adipose Tissue Browning in Offspring via Reprogramming PKA Signaling and DNA Methylation.

SCOPE: Brown rice, the most consumed food worldwide, has been shown to possess beneficial effects on the prevention of metabolic diseases. However, the way in which maternal brown rice diet improves metabolism in offspring and the regulatory mechanisms remains unclear. The study explores the epigenetic regulation of offspring energy metabolic homeostasis by maternal brown rice diet during pregnancy. METHODS AND RESULTS: Female mice are fed brown rice during pregnancy, and then body phenotypes, the histopathological analysis, and adipose tissues biochemistry assay of offspring mice are detected. It is found that maternal brown rice diet significantly reduces body weight and fat mass, increases energy expenditure and heat production in offspring. Maternal brown rice diet increases uncoupling protein 1 (UCP1) protein level and upregulates the mRNA expression of thermogenic genes in adipose tissues. Mechanistically, protein kinase A (PKA) signaling is likely responsible in the induced thermogenic program in offspring adipocytes, and the progeny adipocytes browning program is altered due to decreased level of DNA methyltransferase 1 protein and hypomethylation of the transcriptional coregulator positive regulatory domain containing 16 (PRDM16). CONCLUSIONS: These findings demonstrate that maternal brown rice during pregnancy improves offspring mice metabolic homeostasis via promoting adipose browning, and its mechanisms may be mediated by DNA methylation reprogramming.

Regioselective hydroformylation of propene catalysed by rhodium-zeolite.

Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

Elevating the significance of legume intake: A novel strategy to counter aging-related mitochondrial dysfunction and physical decline.

Mitochondrial dysfunction increasingly becomes a target for promoting healthy aging and longevity. The dysfunction of mitochondria with age ultimately leads to a decline in physical functions. Among them, biogenesis dysfunction and the imbalances in the metabolism of reactive oxygen species and mitochondria as signaling organelles in the aging process have aroused our attention. Dietary intervention in mitochondrial dysfunction and physical decline during aging processes is essential, and greater attention should be directed toward healthful legume intake. Legumes are constantly under investigation for their nutritional and bioactive properties, and their consumption may yield antiaging and mitochondria-protecting benefits. This review summarizes mitochondrial dysfunction with age, discusses the benefits of legumes on mitochondrial function, and introduces the potential role of legumes in managing aging-related physical decline. Additionally, it reveals the benefits of legume intake for the elderly and offers a viable approach to developing legume-based functional food.

Electrocatalytic Hydrogenation Using Palladium Membrane Reactors.

Hydrogenation is a crucial chemical process employed in a myriad of industries, often facilitated by metals such as Pd, Pt, and Ni as catalysts. Traditional thermocatalytic hydrogenation usually necessitates high temperature and elevated pressure, making the process energy intensive. Electrocatalytic hydrogenation offers an alternative but suffers from issues such as competing H2 evolution, electrolyte separation, and limited solvent selection. This Perspective introduces the evolution and advantages of the electrocatalytic Pd membrane reactor (ePMR) as a solution to these challenges. ePMR utilizes a Pd membrane to physically separate the electrochemical chamber from the hydrogenation chamber, permitting the use of water as the hydrogen source and eliminating the need for H2 gas. This setup allows for greater control over reaction conditions, such as solvent and electrolyte selection, while mitigating issues such as low Faradaic efficiency and complex product separation. Several representative hydrogenation reactions (e.g., hydrogenation of C=C, C≡C, C=O, C≡N, and O=O bonds) achieved via ePMR over the past 30 years were concisely discussed to highlight the unique advantages of ePMR. Promising research directions along with the advancement of ePMR for more challenging hydrogenation reactions are also proposed. Finally, we provide a prospect for future development of this distinctive hydrogenation strategy using hydrogen-permeable membrane electrodes.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Bifunctional Electrocatalysts for Overall and Hybrid Water Splitting.

Electrocatalytic water splitting driven by renewable electricity has been recognized as a promising approach for green hydrogen production. Different from conventional strategies in developing electrocatalysts for the two half-reactions of water splitting (e.g., the hydrogen and oxygen evolution reactions, HER and OER) separately, there has been a growing interest in designing and developing bifunctional electrocatalysts, which are able to catalyze both the HER and OER. In addition, considering the high overpotentials required for OER while limited value of the produced oxygen, there is another rapidly growing interest in exploring alternative oxidation reactions to replace OER for hybrid water splitting toward energy-efficient hydrogen generation. This Review begins with an introduction on the fundamental aspects of water splitting, followed by a thorough discussion on various physicochemical characterization techniques that are frequently employed in probing the active sites, with an emphasis on the reconstruction of bifunctional electrocatalysts during redox electrolysis. The design, synthesis, and performance of diverse bifunctional electrocatalysts based on noble metals, nonprecious metals, and metal-free nanocarbons, for overall water splitting in acidic and alkaline electrolytes, are thoroughly summarized and compared. Next, their application toward hybrid water splitting is also presented, wherein the alternative anodic reactions include sacrificing agents oxidation, pollutants oxidative degradation, and organics oxidative upgrading. Finally, a concise statement on the current challenges and future opportunities of bifunctional electrocatalysts for both overall and hybrid water splitting is presented in the hope of guiding future endeavors in the quest for energy-efficient and sustainable green hydrogen production.

Regulation mechanism of EBV-encoded EBER1 and LMP2A on YAP1 and the impact of YAP1 on the EBV infection status in EBV-associated gastric carcinoma.

This study aims to explore the role and regulatory mechanism of Yes-associated protein 1 (YAP1) in the development of Epstein-Barr virus-associated gastric cancer (EBVaGC). Here we showed that EBV can upregulate the expression and activity of YAP1 protein through its encoded latent products EBV-encoded small RNA 1 (EBER1) and latent membrane protein 2A (LMP2A), enhancing the malignant characteristics of EBVaGC cells. In addition, we also showed that overexpression of YAP1 induced the expression of EBV encoding latent and lytic phase genes and proteins in the epithelial cell line AGS-EBV infected with EBV, and increased the copy number of the EBV genome, while loss of YAP1 expression reduced the aforementioned indicators. Moreover, we found that YAP1 enhanced EBV lytic reactivation induced by two known activators, 12-O-tetradecanoylhorbol-13-acetate (TPA) and sodium butyrate (NaB). These results indicated a bidirectional regulatory mechanism between EBV and YAP1 proteins, providing new experimental evidence for further understanding the regulation of EBV infection patterns and carcinogenic mechanisms in gastric cancer.