Nuclear factor Y-A3b binds to the SINGLE FLOWER TRUSS promoter and regulates flowering time in tomato.

The control of flowering time is essential for reproductive success and has a major effect on seed and fruit yield and other important agricultural traits in crops. Nuclear factors Y (NF-Ys) are transcription factors that form heterotrimeric protein complexes to regulate gene expression required for diverse biological processes, including flowering time control in plants. However, to our knowledge, there has been no report on mutants of individual NF-YA subunits that promote early flowering phenotype in plants. In this study, we identified SlNF-YA3b, encoding a member of the NF-Y transcription factor family, as a key gene regulating flowering time in tomato. Knockout of NF-YA3b resulted in an early flowering phenotype in tomato, whereas overexpression of NF-YA3b delayed flowering in transgenic tomato plants. NF-YA3b was demonstrated to form heterotrimeric protein complexes with multiple NF-YB/NF-YC heterodimers in yeast three-hybrid assays. Biochemical evidence indicated that NF-YA3b directly binds to the CCAAT cis-elements of the SINGLE FLOWER TRUSS (SFT) promoter to suppress its gene expression. These findings uncovered a critical role of NF-YA3b in regulating flowering time in tomato and could be applied to the management of flowering time in crops.

Xiaoer-Feire-Qing granules alleviate pyretic pulmonary syndrome induced by Streptococcus pneumoniae in young rats by affecting the lungs and intestines: An in vivo study based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. PURPOSE: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. METHODS: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1ß, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. RESULTS: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. CONCLUSION: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application.

Estimation of linezolid exposure in patients with hepatic impairment using machine learning based on a population pharmacokinetic model.

PURPOSE: To investigate the pharmacokinetic changes of linezolid in patients with hepatic impairment and to explore a method to predict linezolid exposure. METHODS: Patients with hepatic impairment who received linezolid were recruited. A population pharmacokinetic model (PPK) was then built using NONMEM software. And based on the final model, virtual patients with rich concentration values was constructed through Monte Carlo simulations (MCS), which were used to build machine learning (ML) models to predict linezolid exposure levels. Finally, we investigated the risk factors for thrombocytopenia in patients included. RESULTS: A PPK model with population typical values of 3.83 L/h and 34.1 L for clearance and volume of distribution was established, and the severe hepatic impairment was identified as a significant covariate of clearance. Then, we built a series of ML models to predict the area under 0 -24 h concentration-time curve (AUC0-24) of linezolid based on virtual patients from MCS. The results showed that the Xgboost models showed the best predictive performance and were superior to the methods for estimating linezolid AUC0-24 based on though concentration or daily dose. Finally, we found that baseline platelet count, linezolid AUC0-24, and combination with fluoroquinolones were independent risk factors for thrombocytopenia, and based on this, we proposed a method for calculating the toxicity threshold of linezolid. CONCLUSION: In this study, we successfully constructed a PPK model for patients with hepatic impairment and used ML algorithm to estimate linezolid AUC0-24 based on limited data. Finally, we provided a method to determine the toxicity threshold of linezolid.

[Research progress in pharmacological effects of Gypsum Fibrosum and material basis for its heat-clearing effect].

Gypsum Fibrosum, as a classic heat-clearing medicine, is widely used in the clinical practice of traditional Chinese medicine(TCM). However, debates exist about the material basis and mechanism of its efficacy. Therefore, this paper reviewed the recent research progress in the heat-clearing effect and mechanism of Gypsum Fibrosum and discussed the material basis for the heat-clearing effect of this medicine. Ca~(2+) may inhibit the upward movement of temperature set point by regulating the Na~+/Ca~(2+) level in the heat-regulating center. Moreover, trace elements may inhibit the rise of body temperature by regulating the immune system, promoting the absorption of Ca~(2+), and affecting the synthesis of prostaglandin E2(PGE2). This review aims to enrich the knowledge about the mechanism of Gypsum Fibrosum in clearing heat and provides a scientific basis for the clinical application and further development of Gypsum Fibrosum.

Defective mutations in STAY-GREEN 1, PHYTOENE SYNTHASE 1, and MYB12 genes lead to formation of green ripe fruit in tomato.

Modern tomatoes produce colorful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. Here, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci responsible for fruit development. The colorless peel of LBS fruits was caused by a 603 bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as STAY-GREEN 1 (SlSGR1) and PHYTOENE SYNTHASE 1 (SlPSY1). SGR1 and PSY1 co-suppression by RNAi converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were also identified in several wild tomatoes bearing green or gray ripe fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS, and transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii also failed to convert purple-flesh into red-flesh fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1, and SlSGR1 control fruit color in cultivated and some wild tomato species.

Variations in root architecture traits and their association with organ mass fraction of common annual ephemeral species in the desert of northern Xinjiang.

The variation of plant traits is closely related to the trade-offs between resource acquisition and conservation, as well as the accumulation of biomass. However, there has been a lack of comprehensive insights into the variation patterns, phylogenetic conservatism, and covariation with biomass allocation of root system architecture in desert areas. We examined the root systems of 47 annual ephemeral species and evaluated their biomass allocation and six key root system architecture traits. Our results indicated that the variation in root traits mainly originated from interspecific variation (48.78%-99.76%), but intraspecific variation should not be ignored as to why the contribution rate of root tissue density (RTD) reached 51.22%. The six root traits were mainly loaded on the first and second axes of the principal component analysis (PCA), these traits mainly vary along two dimensions. The highest interspecific variation is in RTD (51.63%) and the lowest in topological index (TI; 5.92%). The intraspecific variation value and range of specific root length (SRL), specific root area (SRA), and RTD were significantly higher than TI (p < .05), and they are not limited by phylogenetic relationships (0< K < 1, p > .05). The SRA is positively correlated with SRL (r = .72, p < .001) and negatively correlated with RTD (r = -.57, p < .05). The LMF is positively correlated with SRL, and SRA demonstrated the coordination between water consumption and acquisition. The positive correlation between RMF and MRD indicated the coordination of root carbon investment with exploring soil vertical space. The multi-dimensional variation of root traits, divergence of RTDs, and convergence of TI are important ecological strategies for annual short-lived plants to adapt to heterogeneous desert habitats. Meanwhile, these plants achieve optimal access to scarce resources through the high plasticity of resource acquisition (e.g., SRL and SRA) and conservation traits (e.g., RTD), as well as the trade-offs between them and organ mass fraction.

High-quality assembled and annotated genomes of Nicotiana tabacum and Nicotiana benthamiana reveal chromosome evolution and changes in defense arsenals.

Nicotiana tabacum and Nicotiana benthamiana are widely used models in plant biology research. However, genomic studies of these species have lagged. Here we report the chromosome-level reference genome assemblies for N. benthamiana and N. tabacum with an estimated 99.5% and 99.8% completeness, respectively. Sensitive transcription start and termination site sequencing methods were developed and used for accurate gene annotation in N. tabacum. Comparative analyses revealed evidence for the parental origins and chromosome structural changes, leading to hybrid genome formation of each species. Interestingly, the antiviral silencing genes RDR1, RDR6, DCL2, DCL3, and AGO2 were lost from one or both subgenomes in N. benthamiana, while both homeologs were kept in N. tabacum. Furthermore, the N. benthamiana genome encodes fewer immune receptors and signaling components than that of N. tabacum. These findings uncover possible reasons underlying the hypersusceptible nature of N. benthamiana. We developed the user-friendly Nicomics (http://lifenglab.hzau.edu.cn/Nicomics/) web server to facilitate better use of Nicotiana genomic resources as well as gene structure and expression analyses.

Efficacy, Safety, and Cost-effectiveness Analysis of Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with higher non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). But the preferred drug for preventing cytomegalovirus infection is still controversial. We evaluate the efficacy, safety, and cost-effectiveness of antiviral agents based on the most recent studies. METHODS: A pairwise and network meta-analysis was conducted to obtain direct and indirect evidence of antivirals. The cost of allo-HSCT recipients in a teaching hospital was collected, and a cost-effectiveness analysis using a decision tree combined with Markov model was completed from the perspective of allo-HSCT recipients over a lifetime horizon. RESULTS: A total of 19 RCTs involving 3565 patients (8 antivirals) were included. In the network meta-analysis, relative to placebo, letermovir, valacyclovir, and ganciclovir significantly reduced CMV infection incidence; ganciclovir significantly reduced CMV disease incidence; ganciclovir significantly increased the incidence of serious adverse event; none of antivirals significantly reduced all-cause mortality. Based on meta-analysis and Chinese medical data, the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) saved for maribavir, acyclovir, valacyclovir, ganciclovir, and letermovir relative to placebo corresponded to US$216 635.70, US$11 590.20, US$11 816.40, US$13 049.90, and US$12 189.40, respectively. One-way sensitivity analysis showed the most influential parameter was discount rate. The probabilistic sensitivity analysis indicated a 53.0% probability of letermovir producing an ICER below the willingness-to-pay threshold of US$38 824.23/QALY. The scenario analysis demonstrated prophylaxis with letermovir is considered cost-effective in the United States. CONCLUSIONS: Currently, letermovir is an effective and well-tolerated treatment for preventing CMV infection, and it might be a cost-effective choice in allo-HSCT recipients in China.

EARLY FLOWERING is a dominant gain-of-function allele of FANTASTIC FOUR 1/2c that promotes early flowering in tomato.

Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.

QiShenYiQi pill inhibits atherosclerosis by promoting TTC39B-LXR mediated reverse cholesterol transport in liver.

BACKGROUND: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice. PURPOSE: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice. STUDY DESIGN AND METHODS: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis. RESULTS: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-ß, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/ß, CYP7A1 and ABCG5 in rat hepatocyte. CONCLUSION: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function.

(-)-Epigallocatechin-3-Gallate Reduces Perfluorodecanoic Acid-Exacerbated Adiposity and Hepatic Lipid Accumulation in High-Fat Diet-Fed Male C57BL/6J Mice.

Perfluorodecanoic acid (PFDA), an enduring and harmful organic pollutant, is widely employed in diverse food-related sectors. Our previous studies have provided evidence that PFDA has the potential to facilitate obesity and hepatic fat accumulation induced by high-fat diet (HFD) intake. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, has been suggested to possess potential preventive effects against metabolic abnormalities and fatty liver. The purpose of this research was to investigate the effects of EGCG on PFDA-exacerbated adiposity and hepatic lipid accumulation in HFD-fed mice. The results showed that EGCG reduced body weight gain; tissue and organ weights; blood glucose, serum insulin, HOMA-IR, leptin, and lipid parameters; serum inflammatory cytokines (IL-1ß, IL-18, IL-6, and TNF-α); and hepatic lipid accumulation in PFDA-exposed mice fed an HFD. Further work showed that EGCG improved liver function and glucose homeostasis in mice fed an HFD and co-exposed to PFDA. The elevated hepatic mRNA levels of SREBP-1 and associated lipogenic genes, NLRP3, and caspase-1 in PFDA-exposed mice fed an HFD were significantly decreased by EGCG. Our work provides evidence for the potential anti-obesity effect of EGCG on co-exposure to HFD and PFDA and may call for further research on the bioactivity of EGCG to attenuate the endocrine disruption effects of long-term exposure to pollutants.

Metallo-ß-lactamases immobilized by magnetic zeolitic imidazolate frameworks-8 for degradation of ß-lactam antibiotics in an aqueous environment.

Residual antibiotics in nature are an important cause of antimicrobial drug resistance, and how to deal with residual ß-lactam antibiotics in aqueous environments has become an urgent issue. In this work, magnetic zeolitic imidazolate frameworks-8 (ZIF-8) for immobilizing metallo-ß-lactamases (MBLs), or Fe3O4@ZIF-8@MBLs, were successfully synthesized using the one-pot method in aqueous solution. The morphology and chemical structure of Fe3O4@ZIF-8@MBLs were characterized by scanning electron microscopy, energy dispersive spectra, X-ray diffraction, infrared spectra, physical adsorption, and zeta potential. Further, the degradation performance of Fe3O4@ZIF-8@MBLs for ß-lactam antibiotics (penicillin G, cefoperazone, meropenem) in an aqueous environment was investigated by UV-visible absorption spectrophotometry. The results indicated that Fe3O4@ZIF-8@MBLs, compared to control ZIF-8, exhibited superior degradation ability, excellent reusability, and better stability under several harsh conditions. The strategy of combining ZIF-8 and MBLs to form magnetic porous polymers may be suitable for removing ß-lactam antibiotics from an aqueous environment. This work provided an original insight into future studies on the degradation of ß-lactam antibiotics employing MBLs immobilized by magnetic metal-organic frameworks.

A novel strategy for therapeutic drug monitoring: application of biosensors to quantify antimicrobials in biological matrices.

Over the past few years, therapeutic drug monitoring (TDM) has gained practical significance in antimicrobial precision therapy. Yet two categories of mainstream TDM techniques (chromatographic analysis and immunoassays) that are widely adopted nowadays retain certain inherent limitations. The use of biosensors, an innovative strategy for rapid evaluation of antimicrobial concentrations in biological samples, enables the implementation of point-of-care testing (POCT) and continuous monitoring, which may circumvent the constraints of conventional TDM and provide strong technological support for individualized antimicrobial treatment. This comprehensive review summarizes the investigations that have harnessed biosensors to detect antimicrobial drugs in biological matrices, provides insights into the performance and characteristics of each sensing form, and explores the feasibility of translating them into clinical practice. Furthermore, the future trends and obstacles to achieving POCT and continuous monitoring are discussed. More efforts are necessary to address the four key 'appropriateness' challenges to deploy biosensors in clinical practice, paving the way for personalized antimicrobial stewardship.

Metabolic characteristics of voriconazole - Induced liver injury in rats.

Voriconazole (VOR) - induced liver injury is a common adverse reaction, and can lead to serious clinical outcomes. It is of great significance to describe the metabolic characteristics of VOR - induced liver injury and to elucidate the potential mechanisms. This study investigated the changes of plasma metabolic profiles in a rat model of VOR - induced liver injury by non - targeted metabolomics. Correlation analysis was performed between differentially expressed metabolites and plasma liver function indexes. The metabolites with strong correlation were determined for their predictive performance for liver injury using receiver operating characteristic (ROC) curve analysis. Potential biomarkers were then screened combined with liver pathological scores. Finally, the expression level of genes that involved in lipid metabolism were determined in rat liver to verify the mechanism of VOR - induced liver injury we proposed. VOR - induced liver injury in rats was characterized by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, the lipid droplets accumulation in liver, as well as inflammation and fibrosis. Significant changes of plasma metabolites were observed, with a decrease in lipid metabolites accounting for over 50% of all changed metabolites, and alterations of cholesterol and bile acids metabolites. The decrease of 3 phosphatidylcholine (PC) in plasma could indicate the occurrence of VOR - induced liver injury. Decreased fatty acids (FA) oxidation and bile acid excretion might be the potential mechanisms of VOR - induced liver injury. This study provided new insights into the molecular characterization of VOR - induced liver injury.

TurboID-based proximity labelling reveals a connection between VPS34 and cellular homeostasis.

Unlike animals, plants and yeasts only have a class III phosphatidylinositol 3-kinase (PI3KC3). Its lipid product, phosphatidylinositol 3-phosphate (PtdIns-3-P, PI3P), organizes intracellular trafficking routes such as autophagosome formation, multivesicular body (MVB) formation, retro-transport from trans-Golgi network (TGN) to late Golgi, and the fusion events between autophagosomes and MVBs and the vacuole. The catalytic subunit of plant PI3KC3 is encoded by the essential gene Vacuolar Protein Sorting 34 (VPS34). Despite the importance of VPS34 in cellular homeostasis and plant development, a VPS34 interactome is lacking. Here we employed TurboID, an enzyme-catalyzed proximity labelling (PL) method, to describe a proximal interactome of Arabidopsis VPS34. TurboID catalyzed spatially restricted biotinylation and enabled VPS34-specific enrichment of 273 proteins from affinity purification coupled with mass spectrometry. The interactome confirmed known functions of VPS34 in endo-lysosomal trafficking. Intriguingly, carbohydrate metabolism was the most enriched Gene Ontology (GO) term, including glycolytic enzymes in the triose portion and enzymes functioning in chloroplast triose export and sucrose biosynthesis. The interaction between VPS34 and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH, GAPC1/2) was validated in planta. Also verified was the interaction between VPS34 and the plasma membrane H+-ATPase AHA2, a primary determinant of membrane potential. Our study links PI3KC3 to carbohydrate metabolism and membrane potential, two key processes that maintain cellular homeostasis.

SlTCP24 and SlTCP29 synergistically regulate compound leaf development through interacting with SlAS2 and activating transcription of SlCKX2 in tomato.

The complexity of compound leaves results primarily from the leaflet initiation and arrangement during leaf development. However, the molecular mechanism underlying compound leaf development remains a central research question. SlTCP24 and SlTCP29, two plant-specific transcription factors with the conserved TCP motif, are shown here to synergistically regulate compound leaf development in tomato. When both of them were knocked out simultaneously, the number of leaflets significantly increased, and the shape of the leaves became more complex. SlTCP24 and SlTCP29 could form both homodimers and heterodimers, and such dimerization was impeded by the leaf polarity regulator SlAS2, which interacted with SlTCP24 and SlTCP29. SlTCP24 and SlTCP29 could bind to the TCP-binding cis-element of the SlCKX2 promoter and activate its transcription. Transgenic plants with SlTCP24 and SlTCP29 double-gene knockout had a lowered transcript level of SlCKX2 and an elevated level of cytokinin. This work led to the identification of two key regulators of tomato compound leaf development and their targeted genes involved in cytokinin metabolic pathway. A model of regulation of compound leaf development was proposed based on observations of this study.

Few-Layer Fullerene Network for Photocatalytic Pure Water Splitting into H2 and H2 O2.

A few-layer fullerene network possesses several advantageous characteristics, including a large surface area, abundant active sites, high charge mobility, and an appropriate band gap and band edge for solar water splitting. Herein, we report for the first time that the few-layer fullerene network shows interesting photocatalytic performance in pure water splitting into H2 and H2 O2 in the absence of any sacrificial reagents. Under optimal conditions, the H2 and H2 O2 evolution rates can reach 91 and 116 µmol g-1 h-1 , respectively, with good stability. This work demonstrates the novel application of the few-layer fullerene network in the field of energy conversion.

Perfluorodecanoic acid promotes high-fat diet-triggered adiposity and hepatic lipid accumulation by modulating the NLRP3/caspase-1 pathway in male C57BL/6J mice.

Perfluorodecanoic acid (PFDA), a chemical contaminant, may casue became obesity, which makes it a public health concern. In this study, we investigated the effects of PFDA on adiposity development and hepatic lipid accumulation in mice fed with a high-fat diet (HFD). Animals were assigned to two diet treatments (low-fat and high-fat); and PFDA was administered through drinking water for 12 weeks. The contaminant promoted body weight gain and adiposity in HFD-fed mice. Moreover, HFD-fed mice exposed to PFDA had impaired glucose metabolism, inflammation and hepatic lipid accumulation compared to mice fed HFD alone. PFDA activated the expression of hepatic NLRP3 and caspase-1, and induced that of SREBP-1c expression in the liver of HFD-fed mice. PFDA exposure in HFD-fed mice significantly inhibited hepatic AMPK expression than animals fed HFD without PFDA exposure. Furthermore, MCC950, an NLRP3 inhibitor, suppressed the upregulation of NLRP3 and caspase-1 expression, and inhibited the expression of SREBP-1c and the accumulation of hepatic lipid in mice exposed to PFDA. Thus, PFDA may enhance HFD-induced adiposity and hepatic lipid accumulation through the NLRP3/caspase-1 pathway. This contaminant may be a key risk factor for obesity development in individuals consuming high-fat foods, particularly Western diet.

Mechanisms Underlying the Effects of the Green Tea Polyphenol EGCG in Sarcopenia Prevention and Management.

Sarcopenia is prevalent among the older population and severely affects human health. Tea catechins may benefit for skeletal muscle performance and protect against secondary sarcopenia. However, the mechanisms underlying their antisarcopenic effect are still not fully understood. Despite initial successes in animal and early clinical trials regarding the safety and efficacy of (-)-epigallocatechin-3-gallate (EGCG), a major catechin of green tea, many challenges, problems, and unanswered questions remain. In this comprehensive review, we discuss the potential role and underlying mechanisms of EGCG in sarcopenia prevention and management. We thoroughly review the general biological activities and general effects of EGCG on skeletal muscle performance, EGCG's antisarcopenic mechanisms, and recent clinical evidence of the aforesaid effects and mechanisms. We also address safety issues and provide directions for future studies. The possible concerted actions of EGCG indicate the need for further studies on sarcopenia prevention and management in humans.

QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/ß-ABCA1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: QiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. AIM OF STUDY: The aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. MATERIALS AND METHODS: Eight-week-old male apoE-/- mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. RESULTS: After eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/ß-ABCA1 in atherosclerotic plaque. CONCLUSION: The anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque.