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•Moringa-Fu brick tea extract improved obesity in rats induced by high-fat diet.•Moringa-Fu brick tea extract reduced cholesterol accumulation by regulating bile acid ...metabolism.•Moringa-Fu brick tea extract effectively regulated the structure and relative abundance of microbioa associated with bile salt hydrolase (BSH) activity.
Obesity is regarded to be correlated with disorders of lipid metabolism, bile acid metabolism and dysbiosis of the gut microbiota. Moringa-Fu brick tea (MFBT), a functional food, has a significant anti-obesity effect. However, the effectiveness and mechanisms of MFBT in preventing obesity require further investigation. Here, our results show that moringa-Fu brick tea extract (MFTE) displays anti-obesity effects by reducing high-fat diet-induced weight gain and adipose tissue accumulation in rats, and attenuating visceral adiposity index, oxidative stress and inflammation. In addition, MFTE could regulate gut microbiota diversity, reduce the relative abundance of microbioa associated with bile salt hydrolase (BSH) activity, such as Blautia, Ruminococcaceae, Coprococcus and Roseburia. Moreover, MFTE could improve the expression of the main rate-limiting enzymes CYP7A1 and CYP27A1 in the process of bile acid synthesis, downregulate the expression of intestinal FXR protein, promote the serum bile acid level, and reduce the accumulation of cholesterol in serum and liver. Taken together, these results suggested that MFBT could serve as a functional food for prevention of obesity and hyperlipidemia in association with regulating bile acid metabolism and gut microbiota.
Summary
Jasmonic acid (JA) and gibberellin (GA) coordinately regulate plant developmental programs and environmental cue responses. However, the fine regulatory network of the cross‐interaction ...between JA and GA remains largely elusive. In this study, we demonstrate that MdNAC72 together with MdABI5 positively regulates anthocyanin biosynthesis through an exquisite MdNAC72‐MdABI5‐MdbHLH3 transcriptional cascade in apple.
MdNAC72 interacts with MdABI5 to promote the transcriptional activation of MdABI5 on its target gene MdbHLH3 and directly activates the transcription of MdABI5.
The MdNAC72‐MdABI5 module regulates the integration of JA and GA signals in anthocyanin biosynthesis by combining with JA repressor MdJAZ2 and GA repressor MdRGL2a. MdJAZ2 disrupts the MdNAC72–MdABI5 interaction and attenuates the transcriptional activation of MdABI5 by MdNAC72. MdRGL2a sequesters MdJAZ2 from the MdJAZ2‐MdNAC72 protein complex, leading to the release of MdNAC72.
The E3 ubiquitin ligase MdSINA2 is responsive to JA and GA signals and promotes ubiquitination‐dependent degradation of MdNAC72. The MdNAC72‐MdABI5 interface fine‐regulates the integration of JA and GA signals at the transcriptional and posttranslational levels by combining MdJAZ2, MdRGL2a, and MdSINA2. In summary, our findings elucidate the fine regulatory network connecting JA and GA signals with MdNAC72‐MdABI5 as the core in apple.
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•Inhibition of RIP1K produces neuroprotection against focal cerebral ischemia.•Inhibition of RIP1K directly protects ischemic neurons and astrocytes.•Inhibition of RIP1K decreases ...RIP1K–RIP3K complex formation.•Inhibition of RIP1K reduces LC3II and active cathepsin B levels and lysosomal membrane permeability.
Although the receptor-interacting protein 1 kinase (RIP1K)-regulated necroptosis can be evoked by cerebral ischemia, the effects of RIP1K in mediating neuronal and astrocytic cell death and the underlying mechanisms remain poorly understood. This study evaluates the contribution of RIP1K to ischemic stroke-induced neuronal and astrocytic cell death, and the activation of autophagic-lysosomal pathway. Using an in vitro oxygen and glucose deprivation (OGD) in primary cultured neurons or astrocytes and a permanent middle cerebral artery occlusion (pMCAO) model in rats or mice, we observed the role of RIP1K in the ischemic neuronal and astrocytic cell death and the underlying mechanisms by pharmacological or genetic inhibition of RIP1K. pMCAO or OGD condition led to an increase in RIP1K, RIP3K and RIP1K–RIP3K complex. RIP1K knockdown or necrostatin-1 (Nec-1, a specific inhibitor of RIP1K) treatment reduced infarct volume, improved neurological deficits, increased microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) levels, and attenuated neuronal or astrocytic necrotic cell death in the ischemic cortex. RIP1K knockdown decreased RIP1K–RIP3K complex formation, light chain 3 II (LC3II) and active cathepsin B levels and lysosomal membrane permeability (LMP). Furthermore, a combination of Nec-1 and an inhibitor of autophagy or cathepsin B produced an enhancement of protective effect on neuronal or astrocytic cell death. RIP1K-mediated necroptosis may play important roles in ischemia-induced neuronal and astrocytic cell death through the activation of autophagic-lysosomal pathway.
Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes ...can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 MSH5, cilia- and flagella-associated protein 54 CFAP54, MAP7 domain containing 3 MAP7D3, and coiled-coil domain containing 33 CCDC33) and three novel risk genes (coiled-coil domain containing 168 CCDC168, chromosome 16 open reading frame 96 C16orf96, and serine protease 48 PRSS48) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as ...a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr
) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.
•Lipids in materials affect the fresh tea leaves quality and thus the finished tea.•Plucking rounds and appropriate pruning intervals affect flavor index through lipids composition.•Lipid oxidation ...functions in tea flavor formation of postharvest stages.
New shoots from tea plants (Camellia sinensis) are changed into finished tea after the process, which endows the products with a characteristic flavor. Tea quality is reflected in all aspects, from new shoots to the finished tea that are affected by cultivar, cultivation condition, harvest season, manufacturing methods, and quality of fresh tea leaves. Lipids are hydrophobic metabolites connected with tea flavor quality formation. Herein, we emphasize that the lipids composition in preharvest tea leaves is crucial for materials quality and hence tea flavor. The characterization of lipids in preharvest tea leaves provides a reference to obtain better tea quality. Lipids transformation in postharvest stages of tea leaves differs from varieties of tea types, and lipid oxidations functions in the tea flavor formation. A comprehensive overview of the lipids in tea leaves of preharvest and postharvest stages is necessary to improve tea quality.
Abstract
Background
It is important to recognize the coronavirus disease 2019 (COVID-19) patients in severe conditions from moderate ones, thus more effective predictors should be developed.
Methods
...Clinical indicators of COVID-19 patients from two independent cohorts (Training data: Hefei Cohort, 82 patients; Validation data: Nanchang Cohort, 169 patients) were retrospected. Sparse principal component analysis (SPCA) using Hefei Cohort was performed and prediction models were deduced. Prediction results were evaluated by receiver operator characteristic curve and decision curve analysis (DCA) in above two cohorts.
Results
SPCA using Hefei Cohort revealed that the first 13 principal components (PCs) account for 80.8% of the total variance of original data. The PC1 and PC12 were significantly associated with disease severity with odds ratio of 4.049 and 3.318, respectively. They were used to construct prediction model, named Model-A. In disease severity prediction, Model-A gave the best prediction efficiency with area under curve (AUC) of 0.867 and 0.835 in Hefei and Nanchang Cohort, respectively. Model-A’s simplified version, named as LMN index, gave comparable prediction efficiency as classical clinical markers with AUC of 0.837 and 0.800 in training and validation cohort, respectively. According to DCA, Model-A gave slightly better performance than others and LMN index showed similar performance as albumin or neutrophil-to-lymphocyte ratio.
Conclusions
Prediction models produced by SPCA showed robust disease severity prediction efficiency for COVID-19 patients and have the potential for clinical application.
l-theanine, the most represented non-proteinogenic amino acid in tea plants (Camellia sinensis), is extensively utilized as a food supplement and a pharmaceutical, nutraceutical, and cosmetic ...ingredient. Tea plants are major sources of l-theanine, however, successfully extracting l-theanine from plants is limited by environmental conditions. Furthermore, the chemical synthesis of l-theanine is inefficient owing to the coproduction of undesirable stereoisomers that affect downstream applications. To overcome these problems, microbial engineering processes based on enzymatic catalysis and fermentation have emerged as sustainable manufacturing approaches for l-theanine biosynthesis. Advantages of these processes include the availability of well-established microbial engineering tools and strategies and high production rates.
In this review, we first introduced the natural biosynthetic pathway of l-theanine production and discussed the detailed microbial or enzymatic processes involved in l-theanine production. We then summarized the information from recently published studies on the production of l-theanine using microbial platforms, emphasizing the latest advances and most relevant process parameters in l-theanine biosynthesis.
As an alternative approach to the non-environmentally friendly and largely energy-consuming traditional methods, the microbial production of l-theanine is expected to be successfully utilized in various industrial applications.
•Recent advances of the l-theanine biosynthesis pathway in nature were introduced.•Several microbial enzymes with l-theanine biocatalysis ability were characterized.•The main three host strains for the production of l-theanine were discussed.•Fermentation plays an important role for improving the production of l-theanine.
Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective ...mechanisms based on the “gut microbiota-barrier-liver axis” are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman’s correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.
Developing polymer-based organic afterglow materials with switchable ultralong organic phosphorescence (UOP) that are insensitive to moisture remains challenging. Herein, two organic luminogens, BBCC ...and BBCS, were synthesized by attaching 7H-benzoccarbazole (BBC) to benzophenone and diphenyl sulfone. These two emitters were employed as guest molecules and doped into epoxy polymers (EPs), which were constructed by in situ polymerization to achieve polymer materials BBCC-EP and BBCS-EP. It was found that BBCC-EP and BBCS-EP films exhibited significant photoactivated UOP properties. After light irradiation, they could produce a conspicuous organic afterglow with phosphorescence quantum yields and lifetimes up to 5.35% and 1.91 s, respectively. Meanwhile, BBCS-EP also presented photochromic characteristics. Upon thermal annealing, the UOP could be turned off, and the polymer films recovered to their pristine state, showing switchable organic afterglow. In addition, BBCC-EP and BBCS-EP displayed excellent water resistance and still produced obvious UOP after soaking in water for 4 weeks. Inspired by the unique photoactivated UOP and photochromic properties, BBCC and BBCS in the mixtures of diglycidyl ether of bisphenol A (DGEBA) and 1,3-propanediamine were employed as security inks for light-controlled multilevel anticounterfeiting. This work may provide helpful guidance for developing photostimuli-responsive polymer-based organic afterglow materials, especially those with stable UOP under ambient conditions.
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