Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats

Obesity is associated with gut dysbiosis and metabolic endotoxin.Junshanyinzhen tea extract(JSTE)reduced fat accumulation and body weight in obese mice.However,the effects and mechanism of JSTE in preventing obesity were unclear.Therefore,we used different doses of JSTE(75,150 and 300 mg/(kg·day))to evaluate the effect on high-fat diet(HFD)-induced rats under 8 weeks of intervention.Here,our results showed that JSTE could significantly reduce body weight gain,blood lipid levels and fat accumulation,improve fatty damage in liver tissue(P<0.05).In addition,JSTE increased the expression of intestinal tight junction proteins(P<0.05),relieved metabolic endotoxemia(P<0.05)and chronic low-grade inflammation in HFD rats.Sequencing of fecal samples showed that JSTE could effectively reverse the microbial diversity and the ratio of Firmicutes to Bacteroidetes to normal levels in HFD-fed rats.Desulfovibrioceae and Erysipelotrichaceae,which are positively related to obesity,were decreased by JSTE intervention(P<0.05).while Bifidobacteriaceae,Bacteroidaceae,Akkermansia,and Clostridium,which are negatively related to obesity,were increased.Together,these results suggested that JSTE might effectively prevent obesity by modulating gut microbiota dysbiosis,intestinal barrier dysfunction,metabolic endotoxemia and chronic low-grade infl ammation in HFD-induced rats.

Polysaccharides of Aspergillus cristatus attenuate obesity by regulating gut microbiota and gut microbiota-related metabolites

Golden-flower fungus,the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea,is considered a potential probiotic fungus based on its anti-obesity effect.However,the classification of golden-flower fungi is still controversial;the anti-obesity effect of golden-flower fungus polysaccharides remains unknown.In this study,we identify a golden-flower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis,which resolves the controversy of classification.Moreover,we find A.cristatus polysaccharides(ACPS)attenuate obesity in rats.ACPS modulate gut bacterial composition.in which Akkermansia,Akkermansia muciniphila,Bacteroides,Romboutsia,Blautia,and Desulfovibrio are considered the core microbes regulated by ACPS.ACPS increase fecal total short-chain fatty acid content and serum,hepatic,and fecal total bile acid content.Furthermore,ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity,according to a fecal transplantation experiment.Thus,ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.

The role of cholesterol in modifying the lipid-lowering effects of Fuzhuan brick-tea in Caenorhabditis elegans via SBP-1/SREBP

Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels.We found that FZT signifi cantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet,while lipid accumulation was increased for a high cholesterol diet.Moreover,this mechanism may involve the conserved sterol regulatory element-binding protein(SREBP)/mediator-15(MDT-15)signaling pathway and the nuclear hormone receptor NHR-80.In addition,lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet.Thus,our fi ndings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level,which may help to improve the consumption of FZT.

Theasinensin A attenuated diabetic development by restoring glucose homeostasis, improving hepatic steatosis and modulating gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice

Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.

Splitting of Degenerate Superatomic Molecular Orbitals Determined by Point Group Symmetry

We first confirm an idea obtained from first-principles calculations,which is in line with symmetry theory:Although superatomic molecular orbitals(SAMOs) can be classified according to their angular momentum similar to atomic orbitals,SAMOs with the same angular momentum split due to the point group symmetry of superatoms.Based on this idea,we develop a method to quantitatively modulate the splitting spacing of molecular orbitals in a superatom by changing its structural symmetry or by altering geometric parameters with the same symmetry through expansion and compression processes.Moreover,the modulation of the position crossover is achieved between the lowest unoccupied molecular orbital and the highest occupied molecular orbital originating from the splitting of different angular momenta,leading to an effective reduction in system energy.This phenomenon is in line with the implication of the Jahn–Teller effect.This work provides insights into understanding and regulating the electronic structures of superatoms.

清代道光时期南苑内部管理的整顿风波

道光十八年(1838)三月二十七日,道光帝在南苑例行行围后,发现苑内牲兽稀少,大为恼怒":围猎之时,一无牲畜,尚复成何事体?"[1]立即命军机大臣会同管理奉宸苑大臣对南苑内部管理进行调查,随后掀起一波整顿风潮。一、制定南苑新章程时任奉宸苑管理大臣的禧恩作为直接责任人于闰四月十二日自请议处,同时向道光帝建议明确南苑现有管理人员的职责分工。

渗透率应力敏感影响下气井产能试井拟合图版的建立与应用

总结前人对变形介质的研究成果,认为变形介质中的渗流存在渗透率应力敏感性特征。针对变形介质中地层渗透率变化的初始阶段可以近似认为是线性变化的特点,从其渗流的连续性方程、运动方程和渗透率应力敏感状态方程出发,推导了渗透率线性变化条件下产能方程,进一步得到了气井无因次产能公式。在此基础上绘制了气井无因次产能试井图版,进一步分析了渗透率应力敏感性气井产能的影响。研究表明:渗透率应力敏感性对气井产能的影响不可忽略;图版的使用具有准确、方便、快捷的特点;渗透率应力敏感影响下气井无阻流量要远大于未考虑渗透率应力敏感影响下的无阻流量。

Targeting β-secretase with RNAi in neural stem cells for Alzheimer's disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.

Cold Stress-induced Glucosyltransferase CsUGT78A15 is Involved in the Formation of Eugenol Glucoside in Camellia sinensis

Eugenol is a natural phenolic compound known for its health-promoting properties and its ability to add a floral scent to tea plants.Plant eugenol glycosides have been identified and shown to make important contributions to fruit floral quality.However,the details of their biosynthesis and metabolism in tea plants are still unknown.Here,eugenol glucoside was unambiguously identified as a native metabolite in the tea plant,and its biosynthesis was shown to be induced by low temperature treatment.Through the analysis of UGTs induced by low temperature,the glycosyltransferase CsUGT78A15 was identified in tea,and its encoded protein was shown to catalyze the glucosylation of eugenol.Vmax/Km ratios showed that eugenol was the most suitable substrate for CsUGT78A15.Sugar donor preference analysis showed that CsUGT78A15 had a higher selectivity for glucose,followed by galactose and glucuronic acid.The expression of CsUGT78A15was correlatedwith the accumulation of eugenol glucoside in different tissues and genotypes of tea.Down-regulation of CsUGT78A15 led to a decreased eugenol glucoside content under cold stress,indicating that CsUGT78A15 plays an important role in the biosynthesis of eugenol glucoside under cold stress.The identification of eugenol glucoside in the tea plant and the discovery of a cold stress-induced eugenol glucosyltransferase in tea provide the foundation for the improvement of tea flavor under cold stress and the biotechnological production of eugenol glucoside.

Fermentation characteristics and probiotic activity of a purified fraction of polysaccharides from Fuzhuan brick tea

Polysaccharides from Fuzhuan brick tea(FBTPS),one of most important bioactive components in tea,showed various health-promoting functions.Our previous work demonstrated that the crude FBTPS(CFBTPS)could modulate the gut microbiota.However,which purified fraction in CFBTPS contributing to the modulation of gut microbiota remains unclear.Thus,the fermentation characteristics and probiotic activity of a purified fraction(FBTPS-2-1)of CFBTPS were evaluated in this work.The results showed that gut microbiota could utilize FBTPS-2-1 to produce short-chain fatty acids including acetic,propionic,n-butyric and n-valeric acids.FBTPS-2-1 could modulate the structure and metabolic pathways of gut microbiota.FBTPS-2-1 could increase the health-promoting gut microbiota such as Prevotellaceae and Bifidobacteriaceae,and decreased the harmful bacteria such as Enterobacteriaceae and Fusobacteriaceae.The results of metagenomics showed that Prevotella copri and Megamonas funiformis were the dominant bacteria after fermentation of FBTPS-2-1.Furthermore,FBTPS-2-1 could regulate the biosynthesis and metabolism pathways of gut microbiota.Thus,the enrichment of food with FBTPS-2-1 is expected as a potential strategy for promoting human health due to modulation of gut microbiota.

Allometry-based estimation of forest aboveground biomass combining LiDAR canopy height attributes and optical spectral indexes

Accurate estimates of forest aboveground biomass(AGB)are essential for global carbon cycle studies and have widely relied on approaches using spectral and structural information of forest canopies extracted from various remote sensing datasets.However,combining the advantages of active and passive data sources to improve estimation accuracy remains challenging.Here,we proposed a new approach for forest AGB modeling based on allometric relationships and using the form of power-law to integrate structural and spectral information.Over 60 km^(2) of drone light detection and ranging(LiDAR)data and 1,370 field plot measurements,covering the four major forest types of China(coniferous forest,sub-tropical broadleaf forest,coniferous and broadleaf-leaved mixed forest,and tropical broadleaf forest),were collected together with Sentinel-2 images to evaluate the proposed approach.The results show that the most universally useful structural and spectral metrics are the average values of canopy height and spectral index rather than their maximum values.Compared with structural attributes used alone,combining structural and spectral information can improve the estimation accuracy of AGB,increasing R^(2) by about 10%and reducing the root mean square error by about 22%;the accuracy of the proposed approach can yield a R^(2) of 0.7 in different forests types.The proposed approach performs the best in coniferous forest,followed by sub-tropical broadleaf forest,coniferous and broadleaf-leaved mixed forest,and then tropical broadleaf forest.Furthermore,the simple linear regression used in the proposed method is less sensitive to sample size and outperforms statistically multivariate machine learning-based regression models such as stepwise multiple regression,artificial neural networks,and Random Forest.The proposed approach may provide an alternative solution to map large-scale forest biomass using space-borne LiDAR and optical images with high accuracy.

Genetic diversity,population structure and core collection analysis of Hunan tea plant germplasm through genotyping-by-sequencing

Tea is considered to be a well-known and widely consumed beverage and Hunan province is rich in tea plant germplasm.In order to better conserve and utilize Hunan tea plant resources,110 tea accessions from seven geographical origins were used to assess genetic diversity of Hunan tea plant germplasm through genotyping by sequencing(GBS)technology.As a result,a total of 311,044 high-quality single nucleotide polymorphism(SNP)markers were obtained.Population structure,phylogenetic relationships and principal component analysis(PCA)divided the entire accessions into three groups.The genetic diversity and population differentiation analysis showed that the mean observed heterozygosity(Ho)ranged from 0.16 to 0.24,while the mean polymorphic information content(PIC)ranged from 0.14 to 0.17,and mean minor allele frequency(MAF)ranged from 0.11 to 0.14.Analysis of molecular variance(AMOVA)indicated that 81.38%of the total variance was derived from within populations,which suggested a rich genetic diversity in Hunan tea germplasms.Furthermore,a core tea germplasm set was developed,which was comprised of 22 tea plant accessions and maintained the whole genetic diversity of the entire collection.This work should be valuable for conservation and utilization of tea germplasm in Hunan。

Anti-inflammatory properties of Fu brick tea water extract contribute to the improvement of diarrhea in mice

Fu brick tea,a special kind of dark tea fermented dominantly by Eurotium cristatum,is traditionally used for diarrhea therapy in China.However,limited reports are available on the anti-diarrhea of Fu brick tea water extract(FTE)and its potential mechanisms.In the present study,the treatment effects of FTE on the senna-induced diarrhea in mice were investigated.We found that FTE effectively improved diarrhea index and inhibited gut peristalsis.Additionally,histopathological examination revealed that FTE protected the integrity and reduced inflammatory infiltration of the ileum mucosal barrier.Furthermore,FTE significantly decreased the levels of the pro-inflammatory factor 5-hydroxytryptamine(5-HT)and increased the expression of sodium–hydrogen exchanger 3(NHE-3).The association among both intestinal damage and electrolyte balance and inflammation has been reported by many studies.Collectively,our study showed that FTE had anti-diarrhea activity,which may be associated with anti-inflammatory properties.

Bottom-up design and assembly with superatomic building blocks

Constructing specific structures from the bottom up with artificial units is an important interdisciplinary topic involving physics,chemistry,materials,and so on.In this work,we theoretically demonstrated the feasibility of using superatoms as building blocks to assemble a complex at atomic-level precision.By using a series of actinide-based endohedral metallofullerene(EMF)superatoms that can form one,two,three and four chemical bonds,a planar complex with intra-and inter-molecular interactions was assembled on the Au(111)surface.This complex is composed of two parts,containing ten and eight superatoms,respectively.The electronic structure analysis shows that the electron density inside each part is connected and the closed-shell electronic arrangement system is designed.There is also an obvious van der Waals boundary by physical adsorption between the two parts,and a stable complex is formed.Since this complex is realized by the first-principles calculations of quantum mechanics,our results help not only achieve atomic-level precision construction with artificial superatomic units but also maintain atomic-level functional properties.

Peptide nanotube loaded with a STING agonist,c-di-GMP,enhance cancer immunotherapy against melanoma

The activation of the stimulating factor of the interferon gene(STING)pathway can enhance the immune response within the tumor.Cyclic diguanylate monophosphate(c-di-GMP)is a negatively charged,hydrophilic STING agonist,however,its effectiveness is limited due to the poor membrane permeability and low bioavailability.Herein,we introduced KL-7 peptide derived from Aβamyloid fibrils that can self-assemble to form nanotubes to load and deliver c-di-GMP,which significantly enhanced c-di-GMP’s effectiveness and then exhibited a robust“in situ immunity”to kill melanoma cells.KL-7 peptide nanotube,also called PNT,was loaded with negatively charged c-di-GMP via electrostatic interaction,which prepared a nanocomposite named c-di-GMP-PNT.Treatment of RAW 264.7 cells(leukemia cells in mouse macrophage)with c-di-GMP-PNT markedly stimulated the secretion of IL-6 and INF-βalong with phospho-STING(Ser365)protein expression,indicating the activation of the STING pathway.In the unilateral flank B16-F10(murine melanoma cells)tumor-bearing mouse model,compared to PNT and cdi-GMP,c-di-GMP-PNT can promote the expression of INF-β,TNF-α,IL-6,and IL-1β.At the same time,up-regulated CD4 and CD8 active T cells kill tumors and enhance the immune response in tumor tissues,resulting in significant inhibition of tumor growth in tumor-bearing mice.More importantly,in a bilateral flank B16-F10 tumor model,both primary and distant tumor growth can also be significantly inhibited by c-di-GMP-PNT.Moreover,c-di-GMP-PNT demonstrated no obvious biological toxicity on the main organs(heart,liver,spleen,lung,and kidney)and biochemical indexes of mice.In summary,our study provides a strategy to overcome the barriers of free c-di-GMP in the tumor microenvironment and c-di-GMP-PNT may be an attractive nanomaterial for anti-tumor immunity.

Injectable and biofunctionalized fibrin hydrogels co-embedded with stem cells induce hair follicle genesis

Fibrin-based hydrogels have been widely used in various tissue engineering because of their biocompatibility,biodegradability,tunable mechanical characteristics and nanofibrous structural properties.However,their ability to support stem cells for hair follicle neogenesis is unclear.In this study,we investigated the effect of fibrin hydrogels in supporting skin-derived precursors(SKPs)in hair follicle neogenesis.Our results showed that SKPs in fibrin hydrogels with high cell viability and proliferation,the stemness of SKPs could be maintained,and the expression of hair induction signature genes such as akp2 and nestin was enhanced.Moreover,hair follicle reconstruction experiments showed de novo hair genesis in mice and the hairs persisted for a long time without teratoma formation.More importantly,the blood vessels and sebaceous glands were also regenerated.Our study demonstrated that fibrin hydrogels are promising in hair follicle regeneration and have potential application in clinical settings for alopecia and wound healing.

Biochar addition to tea garden soils:effects on tea fluoride uptake and accumulation

Long-term consumption of tea with high fluoride(F)content has a potential threat to human health.The application of different amounts of biochar to reduce F accumulation in tea leaves has been little studied.In this study,a pot experiment was conducted to investigate the effect of biochar amounts(0,0.5%,2.5%,5.0%,8.0%,and 10.0%,w/w)on tea F content during the tea plant growth.Changes in tea quality,soil F fraction,and soil properties caused by biochar and the relationship with tea F accumulation were also considered.The results showed that the application of biochar amendment significantly reduced water-soluble F contents in tea leaves compared to CK(without biochar),especially in the 8.0%treatment(72.55%).Overall,biochar contributed to improving tea polyphenols and caffeine,but had no significant impact on free amino acids and water leachate.Compared with CK,5.0-10.0%biochar significantly increased soil water-soluble F content due to the substitution of F−with OH−under high pH.Additionally,biochar applied to tea garden soil was effective in decreasing the soil exchangeable aluminum(Ex-Al)content(46.37-91.90%)and increasing the soil exchangeable calcium(Ca^(2+))content(12.02-129.74%)compared to CK,and correlation analysis showed that this may help reduce F enrichment of tea leaves.In general,the application of 5.0-8.0%biochar can be suggested as an optimal application dose to decrease tea F contents while simultaneously improving tea quality.

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

How PD-L1 expression is regulated in cancer is poorly understood.Here,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four members of the EGF receptor family,all with protein tyrosine kinase domains.ERBB3 is a pseudokinase with a high binding affin-ity to ATP.We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines.The ERBB3 ATP-binding mutant cells dramatically reduce IFN-g-induced PD-L1 expres-sion.Mechanistically,ERBB3 regulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis.CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells.Knockin of a tumor-derived ERBB3 mutation located in the ki-nase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy,suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune check-point therapy.

Impaired dNKAP function drives genome instability and tumorigenic growth in Drosophila epithelia

Mutations or dysregulated expression of NF-kappaB-activating protein(NKAP)family genes have been found in human cancers.How NKAP family gene mutations promote tumor initiation and progression remains to be determined.Here,we characterized dNKAP,the Drosophila homolog of NKAP,and showed that impaired dNKAP function causes genome instability and tumorigenic growth in a Drosophila epithelial tumor model.dNKAP-knockdown wing imaginal discs exhibit tumorigenic characteristics,including tissue overgrowth,cell-invasive behavior,abnormal cell polarity,and cell adhesion defects.dNKAP knockdown causes both R-loop accumulation and DNA damage,indicating the disruption of genome integrity.Further analysis showed that dNKAP knockdown induces c-Jun N-terminal kinase(JNK)-dependent apoptosis and causes aberrant cell proliferation in distinct cell populations.Activation of the Notch and JAK/STAT signaling pathways contributes to the tumorigenic growth of dNKAP-knockdown tissues.Furthermore,JNK signaling is essential for dNKAP depletion-mediated cell invasion.Transcriptome analysis of dNKAP-knockdown tissues confirmed the misregulation of signaling pathways involved in promoting tumorigenesis and revealed abnormal regulation of metabolic pathways.dNKAP knockdown and oncogenic Ras,Notch,or Yki mutations show synergies in driving tumorigenesis,further supporting the tumor-suppressive role of dNKAP.In summary,this study demonstrates that dNKAP plays a tumor-suppressive role by preventing genome instability in Drosophila epithelia and thus provides novel insights into the roles of human NKAP family genes in tumor initiation and progression.

Post-translational regulation of inflammasomes

Infiammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications （PTMs） that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions.