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Abstract GCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.

Obesity is a major public health concern globally. Plant-based ingredients have been proposed as alternative treatments for obesity. L-Theanine (THE), a unique nutraceutical component of tea, is known for its neuroprotective and cognitive benefits. However, there are few reports on THE’s effects and mechanisms in improving obesity and its complications. In this study, the alleviating effects and potential mechanisms of THE on obesity-related complications (ORCs) induced by a high-fat diet(HFD) in mice were explored by performing biochemical, hepatic transcriptomics, and plasma metabolomics analyses. The results indicated THE (900 mg/kg of body weight) was effective in mitigating ORCs by decreasing body weight gain and fat deposition, improving glycolipid metabolism disorders, inflammation dysregulation, and alleviating fatty liver formation due to long-term HFD. The hepatic transcriptomics data suggested that THE intervention suppresses the lipid metabolism and inflammation pathways in HFD-fed mice, thereby inhibiting hepatic steatosis and inflammation. Moreover, plasma metabolomics analysis revealed that THE exhibited positive effects on the homeostasis of plasma metabolite balance, such as phosphatidylcholine (PC(14:0/18:1)), phosphatidylethanolamine (Lyso-PE(14:0)), phosphatidic acid (PA(16:0e/18:0)), stigmasterol, and deoxycholic acid glycine conjugate. These metabolites were strongly correlated with ORC-related indicators. Our results indicated that THE, as a functional food additive, possesses potential for ORC alleviation. However, the exact molecular mechanism of how THE alleviates ORCs needs to be investigated in the future.

Photodynamic therapy (PDT), a promising treatment modality, employs photosensitizers to generate cytotoxic reactive oxygen species (ROS) within localized tumor regions. This technique involves administering a photosensitizer followed by light activation in the presence of oxygen (O2), resulting in cytotoxic ROS production. PDT’s spatiotemporal selectivity, minimally invasive nature, and compatibility with other treatment modalities make it a compelling therapeutic approach. However, hypoxic tumor microenvironment (TME) poses a significant challenge to conventional PDT. To overcome this hurdle, various strategies have been devised, including in-situ O2 generation, targeted O2 delivery, tumor vasculature normalization, modulation of mitochondrial respiration, and photocatalytic O2 generation. This review aims to provide a comprehensive overview of recent developments in designing tumor-oxygenated nanomaterials to enhance PDT efficacy. Furthermore, we delineate ongoing challenges and propose strategies to improve PDT’s clinical impact in cancer treatment.

This research uses difference-in-difference (DID) and other empirical methods to analyze firm-level real estate data to discover how heterogeneous firm characteristics affect managers’ decision-making about development expansion when a firm faces a temporary negative sales shock in the Chinese housing market. The manager’s decision is a utility maximization problem under uncertainty, determined by their risk aversion levels, which managers choose to optimize by considering other factors of interest, including career risk and personal wealth. Also, the advance payment rule encourages real estate developers to maintain high turnover, since new projects allow developers to collect cash first. The results show that state-owned enterprises (SOEs) are much more conservative than other types of developers. SOEs tend to focus on current developing projects. Firms with more concentrated management pursue expansion and seek to use new project sales to compensate for their slower growth. Larger developers with headquarters in large cities tend to slow their development speed when they observe negative signals, as they can quickly engage in new projects given these firms’ easy access to financial resources such as bank loans. This study makes a novel contribution to the literature since previous research has tended to focus on the macro market level rather than the firm level. The findings also have strong policy and regulation value. The results indicate that higher cashflow monitoring needs, especially to monitor family-owned developers, to prevent misuse and excessive project expansion.

Tea has been used medicinally and dietarily for thousands of years. Tea polysaccharides (TPS), considered one of the main bioactive components of tea, show diverse health benefits. Yet it has received far less attention than tea polyphenols. During recent decades, considerable researches have been dedicated to TPS, including extraction, structural characteristics, and potential bioactivity. Recent studies suggested that the biological effects of dietary TPS are subjected to gut microbiota (GM) modulation. Thus, this review focuses on recent research advance on the structure characteristics of TPS, TPS degradation in the gut, TPS modulation on the diversity of GM and production of short chain fatty acids (SCFAs), and the health benefits of TPS through targeting GM. Furthermore, some future research directions were also proposed. The purpose of this review is to enhance our understanding the health-promoting properties of TPS and to promote further researches on the TPS.

To fulfill the design goal of acceleration performance of a power-split hybrid vehicle，constraint matrices of all possible configurations of power-split hybrid powertrain system that can be constructed by two-planetary-gear system are derived and screened. A systematic solution to the maximum output torque of all types of two planetary gear power-split systems is introduced. Base on the solution，the 100 km acceleration performance of the derived configurations are simulated，so that the optimal configuration is found.

Abstract Background Genetic analysis of gene expression level is a promising approach for characterizing candidate genes that are involved in complex economic traits such as meat quality. In the present study, we conducted expression quantitative trait loci (eQTL) and allele-specific expression (ASE) analyses based on RNA-sequencing (RNAseq) data from the longissimus muscle of 189 Duroc × Luchuan crossed pigs in order to identify some candidate genes for meat quality traits. Results Using a genome-wide association study based on a mixed linear model, we identified 7192 cis-eQTL corresponding to 2098 cis-genes (p ≤ 1.33e-3, FDR ≤ 0.05) and 6400 trans-eQTL corresponding to 863 trans-genes (p ≤ 1.13e-6, FDR ≤ 0.05). ASE analysis using RNAseq SNPs identified 9815 significant ASE-SNPs in 2253 unique genes. Integrative analysis between the cis-eQTL and ASE target genes identified 540 common genes, including 33 genes with expression levels that were correlated with at least one meat quality trait. Among these 540 common genes, 63 have been reported previously as candidate genes for meat quality traits, such as PHKG1 (q-value = 1.67e-6 for the leading SNP in the cis-eQTL analysis), NUDT7 (q-value = 5.67e-13), FADS2 (q-value = 8.44e-5), and DGAT2 (q-value = 1.24e-3). Conclusions The present study confirmed several previously published candidate genes and identified some novel candidate genes for meat quality traits via eQTL and ASE analyses, which will be useful to prioritize candidate genes in further studies.

Huangshan Maofeng green tea (HMGT) is one of the most well-known green teas consumed for a thousand years in China. Research has demonstrated that consumption of green tea effectively improves metabolic disorders. However, the underlying mechanisms of obesity prevention are still not well understood. This study investigated the preventive effect and mechanism of long-term intervention of Huangshan Maofeng green tea water extract (HTE) on obesity-associated metabolic disorders in leptin receptor knockout (Lepr−/−) rats by using gut microbiota and hepatic lipidomics data. The Lepr−/− rats were administered with 700 mg/kg HTE for 24 weeks. Our results showed that HTE supplementation remarkably reduced excessive fat accumulation, as well as ameliorated hyperlipidemia and hepatic steatosis in Lepr−/− rats. In addition, HTE increased gut microbiota diversity and restored the relative abundance of the microbiota responsible for producing short chain fatty acids, including Ruminococcaceae, Faecalibaculum, Veillonellaceae, etc. Hepatic lipidomics analysis found that HTE significantly recovered glycerolipid and glycerophospholipid classes in the liver of Lepr−/− rats. Furthermore, nineteen lipid species, mainly from phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and triglycerides (TGs), were significantly restored increases, while nine lipid species from TGs and diglycerides (DGs) were remarkably recovered decreases by HTE in the liver of Lepr−/− rats. Our results indicated that prevention of obesity complication by HTE may be possible through maintaining homeostasis of gut microbiota and certain hepatic lipid classes.

The circadian rhythm regulates the daily cycles of various physiological activities. Accumulating evidences revealed that circadian rhythm plays an important role in regulating metabolic homeostasis, and disruptions of circadian rhythms resulting in metabolic disorder. Peripheral clocks are not only controlled by the central clock but also entrained by external cues. Dietary pattern and compounds derived from food are found to play multiple roles in regulating metabolic processes through resetting peripheral clocks. Here we review the recent advance of effects and mechanisms of dietary pattern and compounds modulating peripheral clocks and regulating metabolic processes. Multiple molecular mechanisms linked dietary pattern and compounds with circadian rhythm and metabolism were summarized. Elaboration of crosstalk between diet and circadian rhythm may provide targets for the prevention of metabolic disorder. The exact mechanisms that feeding pattern and dietary compounds linked metabolic process and circadian rhythm need to be further investigated.

Metabolic syndrome is a chronic metabolic disorder that has turned into a severe health problem worldwide. A previous study reported that large yellow tea exhibited better anti-diabetic and lipid-lowering effects than green tea. Nevertheless, the potential mechanisms are not yet understood. In this study, we examined the prevention effects and mechanisms of large yellow tea water extract (LWE) on metabolic syndrome using leptin receptor knockout (Lepr−/−) rats. Seven-week-old male Lepr−/− and wild type (WT) littermate rats were divided into Lepr−/− control group (KO) (n = 5), Lepr−/− with LWE-treated group (KL) (n = 5), WT control group (WT) (n = 6), and WT with LWE intervention group (WL) (n = 6). Then, the rats were administered water or LWE (700 mg/kg BW) daily by oral gavage for 24 weeks, respectively. The results showed that the administration of LWE significantly reduced the serum concentrations of random blood glucose, total cholesterol, triglyceride, and free fatty acids, and increased glucose tolerance in Lepr−/− rats. Moreover, LWE remarkably reduced hepatic lipid accumulation and alleviated fatty liver formation in Lepr−/− rats. A mechanistic study showed that LWE obviously activated SIRT6 and decreased the expression of key lipogenesis-related molecules SREBP1, FAS, and DGAT1 in the livers of Lepr−/− rats. Furthermore, LWE significantly improved microbiota dysbiosis via an increase in gut microbiota diversity and an abundance of the microbiota that produce short chain fatty acids (SCFAs), such as Ruminococcaceae, Faecalibaculum, Intestinimonas, and Alistipes. Finally, LWE supplementation increased the concentrations of SCFAs in the feces of Lepr−/− rats. These results revealed that LWE attenuated metabolic syndrome of Lepr−/− rats via the reduction of hepatic lipid synthesis through the SIRT6/SREBP1 pathway and the modulation of gut microbiota.

Summary: Yellow fever virus (YFV), a deadly human pathogen, is the prototype of the genus Flavivirus. Recently, YFV re-emerged in Africa and Brazil, leading to hundreds of deaths, with some cases imported to China. Prophylactic or therapeutic countermeasures are urgently needed. Previously, several human monoclonal antibodies against YFV were screened out by phage display. Here, we find that one of them, 5A, exhibits high neutralizing potency and good protection. Crystallographic analysis of the YFV envelope (E) protein in its pre- and post-fusion states shows conformations similar to those observed in other E proteins of flaviviruses. Furthermore, the structures of 5A in complex with the E protein in both states are resolved, revealing an invariant recognition site. Structural analysis and functional data suggest that 5A has high neutralization potency because it interferes with virus entry by preventing both virus attachment and fusion. These findings will be instrumental for immunogen or inhibitor design. : Yellow fever virus (YFV) is a deadly flavivirus. Lu et al. report the structures of YFV envelope protein in its pre- and post-fusion states and a potent neutralizing monoclonal antibody bound to both states. Structural and functional analyses reveal the double lock of the antibody to neutralize YFV infection. Keywords: yellow fever virus, neutralizing monoclonal antibody, envelope protein, flavivirus, crystal structure, epitope, prefusion, postfusion

The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.

Objective: To observe the safety and short-term efficacy of apatinib in the treatment of recurrent, metastatic cervical cancer in patients who have already received more than two kinds of comprehensive treatment. Methods: Forty-eight patients with recurrent or metastatic cervical cancer after radiotherapy or surgery who received apatinib between June 2016 and June 2017 were involved in this study. These patients experienced progression after first-line or second-line chemotherapy. There were 38 patients with cervical squamous cell carcinoma, 8 with adenocarcinoma, and 2 with adenosquamous carcinoma. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and evaluated. Results: All patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5-20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31-5.26) and OS was 13.9 months (95% CI=8.37-17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1-2, and no drug-related death occurred. Conclusions: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients. [ABSTRACT FROM AUTHOR]

Background: Polar overdominance at the ovine callipyge (CLPG) locus involves the post-transcriptional trans-inhibition of DLK1 in skeletal muscle of CLPG/CLPG sheep. The abundant maternally expressed microRNAs (miRNAs) mapping to the imprinted DLK1-GTL2 domain are prime candidate mediators of this trans-effect. Results: We have tested the affinity of 121 miRNAs processed from this locus for DLK1 by co-transfecting COS1 cells with a vector expressing the full-length ovine DLK1 with corresponding mimic miRNAs. None of the tested miRNAs was able to down regulate DLK1 to the extent observed in vivo. Conclusions: This suggests that other factors, with or without these miRNAs, are involved in mediating the observed trans-effect. [ABSTRACT FROM AUTHOR]

A unique autothermal thermophilic aerobic digestion (ATAD) process has been used to convert human excreta to liquid fertilizer in Japan. This study investigated the changes in physicochemical and bacterial community characteristics during the full-scale ATAD process operated for approximately 3 weeks in 2 different years. After initiating simultaneous aeration and mixing using an air-inducing circulator (aerator), the temperature autothermally increased rapidly in the first 1 to 2 days with exhaustive oxygen consumption, leading to a drastic decrease and gradual increase in oxidation-reduction potential in the first 2 days, reached >50°C in the middle 4 to 6 days, and remained steady in the final phase. Volatile fatty acids were rapidly consumed and diminished in the first 2 days, whereas the ammonia nitrogen concentration was relatively stable during the process, despite a gradual pH increase to 9.3. Principal-coordinate analysis of 16S rRNA gene amplicons using next-generation sequencing divided the bacterial community structures into distinct clusters corresponding to three phases, and they were similar in the final phase in both years despite different transitions in the middle phase. The predominant phyla (closest species, dominancy) in the initial, middle, and final phases were Proteobacteria (Arcobacter trophiarum, 19 to 43%; Acinetobacter towneri, 6.3 to 30%), Bacteroidetes (Moheibacter sediminis, 43 to 54%), and Firmicutes (Thermaerobacter composti, 11 to 28%; Heliorestis baculata, 2.1 to 16%), respectively. Two predominant operational taxonomic units (OTUs) in the final phase showed very low similarities to the closest species, indicating that the process is unique compared with previously published ones. This unique process with three distinctive phases would be caused by the aerator with complete aeration. [ABSTRACT FROM AUTHOR]