Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Long-term drinking of green tea combined with exercise improves hepatic steatosis and obesity in male mice induced by high-fat diet.

Dietary habits and exercise play an important role in the well-being of human health. Currently, how long of drinking tea combined with exercise could efficiently ameliorate hepatic steatosis and obesity still needs to be investigated. Here, short-term and long-term green tea drinking combined with exercise were studied to improve hepatic steatosis and obesity in high-fat diet-induced (HF) mice. Our results showed that Yunkang 10 green tea (GT) combined with exercise (Ex) exhibited synergistic prevention effects on ameliorating hepatic steatosis and obesity. Especially, 22-week intervention with GT or Ex improved all symptoms of obesity, which indicated that long-term intervention exhibited profound preventive effects than the short term. Moreover, the combined intervention of 22 weeks inhibited the activation of NF-κB pathway and the expression of proinflammatory cytokines, which suggests that tea combined exercise may improve liver steatosis mainly by inhibiting inflammation. The key molecules for regulating lipid and glucose metabolism SCD1 were obviously downregulated, and GLU2 and PPARγ were significantly upregulated by GT and exercise in the liver of high-fat diet-induced mice. This study demonstrated that long-term intervention with GT and exercise effectively relieved hepatic steatosis and obesity complications by ameliorating hepatic inflammation, reducing lipid synthesis, and accelerating glucose transport.

Isolation and identification of 3,4-seco-labdane diterpenoids from Callicarpa nudiflora and investigation of their cytotoxicity against HepG2 cells.

Twenty-one previously undescribed compounds, including nineteen 3,4-seco-labdanes (nudiflopenes P-W, Y, AI-JI), one 3,4-seco-pimarane (nudiflopene X), and one labdane (nudiflopene Z), along with nine known compounds (one 3,4-seco-pimarane and eight 3,4-seco-labdanes) were isolated from the leaves of Callicarpa nudiflora Hook. Et Arn. The structures of these compounds were elucidated by high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance spectroscopy. In addition, configurations of the isolated compounds were determined by electronic circular dichroism, DP4+ probability analysis, and single-crystal X-ray diffraction experiments. All undescribed compounds were evaluated for their cytotoxicity against HepG2 cells in vitro, among which compound 12 exhibited a moderate activity with an IC50 value of 27.8 µM.

Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity.

Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER) enzyme that mediates the formation of disulfide bonds, and is also a therapeutic target for cancer treatment. Our previous studies found that PDI mediates apoptotic signaling by inducing mitochondrial dysfunction. Considering that mitochondrial dysfunction is a major contributor to autophagy, how PDI regulates autophagy remains unclear. Here, we provide evidence that high expression of PDI in colorectal cancer tumors significantly increases the risk of metastasis and poor prognosis of cancer patients. PDI inhibits radio/chemo-induced cell death by regulating autophagy signaling. Mechanistically, the combination of PDI and GRP78 was enhanced after ER stress, which inhibits the degradation of AKT by GRP78, and eventually activates the mTOR pathway to inhibit autophagy initiation. In parallel, PDI can directly interact with the mitophagy receptor PHB2 in mitochondrial, then competitively blocks the binding of LC3II and PHB2 and inhibits the mitophagy signaling. Collectively, our results identify that PDI can reduce radio/chemo-sensitivity by regulating autophagy, which could be served as a potential target for radio/chemo-therapy.

Symmetry breaking of solitons in the PT-symmetric nonlinear Schrödinger equation with the cubic-quintic competing saturable nonlinearity.

The symmetry breaking of solitons in the nonlinear Schrödinger equation with cubic-quintic competing nonlinearity and parity-time symmetric potential is studied. At first, a new asymmetric branch separates from the fundamental symmetric soliton at the first power critical point, and then, the asymmetric branch passes through the branch of the fundamental symmetric soliton and finally merges into the branch of the fundamental symmetric soliton at the second power critical point, while the power of the soliton increases. This leads to the symmetry breaking and double-loop bifurcation of fundamental symmetric solitons. From the power-propagation constant curves of solitons, symmetric fundamental and tripole solitons, asymmetric solitons can also exist. The stability of symmetric fundamental solitons, asymmetric solitons, and symmetric tripole solitons is discussed by the linear stability analysis and direct simulation. Results indicate that symmetric fundamental solitons and symmetric tripole solitons tend to be stable with the increase in the soliton power. Asymmetric solitons are unstable in both high and low power regions. Moreover, with the increase in saturable nonlinearity, the stability region of fundamental symmetric solitons and symmetric tripole solitons becomes wider.

Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis.

Ferroptosis, a type of regulated cell death brought about by lipid peroxidation, has been discovered to suppress tumor growth. Here, we report that targeting RRM1 promotes ferroptosis and affects sensitivity to radiation and chemotherapeutics in cancer cells. In vitro experiments demonstrate that RRM1 increases the accumulation of cellular reactive oxygen species (ROS) and lipid peroxidation by disrupting the activity and expression of the antioxidant enzyme GPX4. Further studies reveal the downstream mechanisms of RRM1, which can regulate the deubiquitinating enzyme USP11 and ubiquitinating enzyme MDM2 to affect the ubiquitination modification of p53. Unstable p53 then inhibited the activity and expression of GPX4 by restraining the p21 protein. Furthermore, our data reveal that targeting RRM1 also increases radiation-induced DNA damage and apoptotic signaling and causes crosstalk between ferroptosis and apoptosis. On the basis of our collective findings, we propose that RRM1 is an essential negative mediator of radiosensitivity through regulating ferroptosis, which could serve as a potential target to inhibit the tumor's antioxidant system and enhance the efficiency of radio/chemotherapy.

The Relationship Between Low-Density Lipoprotein Cholesterol and Progression of Mild Cognitive Impairment: The Influence of rs6859 in PVRL2.

Background: Genome-wide association studies have identified many Alzheimer's disease (AD) genetic-risk single nucleotide polymorphisms (SNPs) and indicated the important role of the cholesterol/lipid metabolism pathway in AD pathogenesis. This study aims to investigate the effects of cholesterol and genetic risk factors on progression of mild cognitive impairment (MCI) to AD. Methods: We prospectively followed 316 MCI participants aged ≥50 years with a baseline cholesterol profile and SNP genotyping data for 4.5 years on average in a sub-cohort of the Shanghai Aging Study. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol in serum were measured at baseline. SNP genotyping was performed using a MassARRAY system. At follow-up, consensus diagnosis of incident dementia and AD were established based on medical, neurological, and neuropsychological examinations. Cox regression models were used to assess the association of cholesterol and SNP with incident AD. Results: The AG/AA genotypes of PVRL2 rs6859 were significantly associated with increased incident AD in MCI participants, compared with GG genotype (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.32-5.76, p = .007, false discovery rate-adjusted p = .030). In PVRL2 rs6859 AG/AA carriers, each-1 mmol/L higher level of LDL-C was significantly associated with a 48% decreased risk of AD (adjusted HR 0.52, 95%CI 0.33-0.84, p = .007). Consistent results were obtained when using LDL-C as the categorical variable (P for trend = 0.016). Conclusion: The relationship between LDL-C and progression of MCI may be influenced by genetic variants.

Transformation of the sp2 Carbanion to Carbene with Subsequent 1,1-Migratory Insertion and Nucleophilic Substitution in Rare-Earth Metal Chemistry.

The development of Fischer-type electrophilic carbene chemistry with early transition metals has been a great challenge due to the fact that such metals in their high oxidation states lack the d electrons to stabilize the electrophilic carbene. Herein, we disclose the first experimental and theoretical findings of in situ transformation of an sp2 carbanion to a Fischer-type electrophilic carbene with rare-earth metals in their high oxidation state with a d0 electron via electron transfer. The carbene may undergo 1,1-migratory insertion into an adjacent RE-C(sp3) bond, and an unprecedented ring opening of the indole ring of the ligand occurs when the carbenes undergo nucleophilic substitution with a special organolithium reagent o-Me2NC6H4CH2Li. The key to success is the uniquely tailored novel ligand systems featuring a suitable conjugate building block (-C═C-C═N) bearing an sp2 carbanion connected to the rare-earth metal center.

A yellow-emitting carbon quantum dot-based fluorescent logic gate for the continuous detection of Au3+ and biothiols.

Yellow-emitting carbon quantum dots, named Y-CQDs, were synthesized from O-phenylenediamine and ethylene glycol via a one-pot hydrothermal method. A fluorescent IMPLICATION logic gate for the continuous and "on-off-on" detection of Au3+ and biothiols in tap water at the nanoscale level was constructed based on these QDs. It showed promise in real sample detection and also as a fluorescent ink.

Predictors of Willingness to Receive the COVID-19 Vaccine after Emergency Use Authorization: The Role of Coping Appraisal.

The current study aims to identify psychosocial factors based on protection motivation theory (PMT) influencing Chinese adults' willingness to receive the COVID-19 vaccine after the emergency use authorization of the New Coronavirus Inactivated Vaccine in China. A cross-sectional online survey was conducted among Chinese residents aged 18-59 years, and 2528 respondents from 31 provinces and autonomous regions were included in the current study. Based on PMT, threat appraisals and coping appraisals were measured. Hierarchical multiple regressions and multivariate logistic regressions were used to identify the relationships between the PMT constructs and vaccination willingness after other covariates were controlled for. A total of 1411 (55.8%) respondents reported being willing to receive the COVID-19 vaccine. The PMT model explained 26.6% (p < 0.001) of the variance in the vaccine willingness. The coping appraisals, including response efficacy, self-efficacy, and response costs, were significantly correlated with the willingness to receive the COVID-19 vaccine, and response efficacy was the strongest influencing factor (adjusted OR = 2.93, 95% CI: 2.42-3.54). In conclusion, the coping appraisals for vaccination, instead of threat appraisals regarding the pandemic itself, mainly influenced people's willingness to get vaccinated after the emergency use authorization of the COVID-19 vaccine in China. These findings are helpful for developing education and interventions to promote vaccination willingness and enhance public health outcomes during a pandemic.

Disturbed microbial ecology in Alzheimer's disease: evidence from the gut microbiota and fecal metabolome.

BACKGROUND: Gut microbiota (GMB) alteration has been reported to influence the Alzheimer's disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. CONCLUSIONS: These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

Health Belief Model Perspective on the Control of COVID-19 Vaccine Hesitancy and the Promotion of Vaccination in China: Web-Based Cross-sectional Study.

BACKGROUND: The control of vaccine hesitancy and the promotion of vaccination are key protective measures against COVID-19. OBJECTIVE: This study assesses the prevalence of vaccine hesitancy and the vaccination rate and examines the association between factors of the health belief model (HBM) and vaccination. METHODS: A convenience sample of 2531 valid participants from 31 provinces and autonomous regions of mainland China were enrolled in this online survey study from January 1 to 24, 2021. Multivariable logistic regression was used to identify the associations of the vaccination rate and HBM factors with the prevalence of vaccine hesitancy after other covariates were controlled. RESULTS: The prevalence of vaccine hesitancy was 44.3% (95% CI 42.3%-46.2%), and the vaccination rate was 10.4% (9.2%-11.6%). The factors that directly promoted vaccination behavior were a lack of vaccine hesitancy (odds ratio [OR] 7.75, 95% CI 5.03-11.93), agreement with recommendations from friends or family for vaccination (OR 3.11, 95% CI 1.75-5.52), and absence of perceived barriers to COVID-19 vaccination (OR 0.51, 95% CI 0.35-0.75). The factors that were directly associated with a higher vaccine hesitancy rate were a high level of perceived barriers (OR 1.63, 95% CI 1.36-1.95) and perceived benefits (OR 0.51, 95% CI 0.32-0.79). A mediating effect of self-efficacy, influenced by perceived barriers (standardized structure coefficient [SSC]=-0.71, P<.001), perceived benefits (SSC=0.58, P<.001), agreement with recommendations from authorities (SSC=0.27, P<.001), and agreement with recommendations from friends or family (SSC=0.31, P<.001), was negatively associated with vaccination (SSC=-0.45, P<.001) via vaccine hesitancy (SSC=-0.32, P<.001). CONCLUSIONS: It may be possible to increase the vaccination rate by reducing vaccine hesitancy and perceived barriers to vaccination and by encouraging volunteers to advocate for vaccination to their friends and family members. It is also important to reduce vaccine hesitancy by enhancing self-efficacy for vaccination, due to its crucial mediating function.

Continuous response fluorescence sensor for three small molecules based on nitrogen-doped carbon quantum dots from prunus lannesiana and their logic gate operation.

In this study, an environmentally friendly and water-soluble nitrogen-doped carbon quantum dots (N-CQDs) with quantum yield (QY) of 8.59% were prepared by one-step hydrothermal synthesis without any chemical reagent using the leaves of prunus lannesiana as precursors. The properties and quality of N-CQDs were investigated by Ultraviolet-visible absorption spectroscopy, infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential, high-resolution transmission electron microscopy and fluorescence spectroscopy. The fluorescence of the prepared N-CQDs can be quenched by Fe3+ through the synergistic effect of the formation of non-fluorescent complex and internal filtration effect (IFE) between Fe3+ and N-CQDs. And the quenched fluorescence can be "turned on" after adding ascorbic acid (AA) because Fe3+ can be released from the surface of N-CQDs through the redox reaction between AA and Fe3+. While the restored fluorescence can be "turned off" again by hydrogen peroxide (H2O2) due to the re-oxidation of Fe2+ to Fe3+. So, the three inputs "logic gate" is achieved and the "on-off-on-off" continuous response fluorescence sensor is formed, which can be applied for the continuous detection of Fe3+, AA and H2O2 with the linear range of 40-260 µM, 10-200 µM and 40-140 µM, respectively. Finally, the sensor was successfully applied to determine Fe3+, AA and H2O2 in real samples with the satisfactory recoveries (95.35%-104.10%) and repeatability (relative standard deviation (RSD) ≤ 1.68%). The continuous response fluorescence sensor prepared by simple green synthesis route has the characteristics of fast response, acceptable sensitivity and good selectivity.

Nitrogen-Doped Carbon Quantum Dots from Poly(ethyleneimine) for Optical Dual-Mode Determination of Cu2+ and l-Cysteine and Their Logic Gate Operation.

In this work, nitrogen-doped carbon quantum dots from poly(ethyleneimine) (PQDs) were synthesized by a low-cost and facile one-step hydrothermal method without other reagents. A quantum yield (QY) of up to 23.2% with maximum emission at 460 nm under an excitation wavelength of 340 nm was ascribed to the high nitrogen doping (20.59%). The PQDs selectively form a blue complex with Cu2+ accompanied by strong quenching of the fluorescence emission. Meanwhile, the PQD-Cu2+ complex exhibited selective fluorescence recovery and color disappearance on exposure to l-cysteine (Cys). The electron transfer from amino or oxygen groups on the PQDs to Cu2+ leads to fluorescence quenching, and a chromogenic reaction of the cuprammonium complex results in a color change. The strong affinity between Cys and Cu2+ causes the detachment of Cu2+ from the surface of PQDs, so the color of the solution disappears and the fluorescence of PQDs recovers. Under the optimized condition, the proposed sensor was applied to detect Cu2+ in the linear range of 0-280 µM. A detection limit of 4.75 µM is achieved using fluorescence spectroscopy and 4.74 µM by monitoring the absorbance variation at 272 nm. For Cys detection, the linear range of 0-800 µM with detection limits of 28.11 µM (fluorescence determination) and 19.74 µM (peak shift determination at 272 nm) was obtained. Meanwhile, the PQD-Cu2+ system exhibits distinguishable responses to other biothiols such as l-glutathione (GSH) and dl-homocysteine (Hcy). Based on the multimode signals, an "AND" logic gate was constructed successfully. Interestingly, besides Cu2+, Fe3+ can also quench the fluorescence of PQDs and the PQD-Fe3+ system exhibits superior selectivity for Cys detection. Most importantly, the proposed assay is not only simple, cheap, and stable but also suitable for detecting Cu2+ and Cys in some real samples.

Dietary supplement of Yunkang 10 green tea and treadmill exercise ameliorate high fat diet induced metabolic syndrome of C57BL/6 J mice.

BACKGROUND: Diet and exercise play important roles in ameliorating metabolic syndrome. Yunkang 10 (Camellia sinensis var. assamica) is a most cultivated tea variety for making tea in the Southwestern China. Currently, there is no report of healthy effects of Yunkang 10 green tea (YKGT) and treadmill exercise (Ex) on high fat diet induced metabolic syndrome (MetS). We aimed to investigate the beneficial effects and molecular mechanism of YKGT and Ex using high fat diet induced MetS of C57BL/6 mice. METHODS: Catechins and caffeine in water extract of YKGT were measured via high performance liquid chromatography (HPLC). 10-week old mice were fed with high fat diet (HFD) for 10 weeks to induce obese mice. Then the obese mice were fed with continuous high fat diet (HFD), HFD with YKGT, HFD with Ex, and HFD with both YKGT and Ex for 8 weeks, respectively. The another group of 10-week old mice fed with low fat diet (LFD) were used as control. RESULTS: HPLC data revealed that YKGT has abundantly high concentration of epigallocatechin gallate (EGCG) and caffeine compared to Longjing 43 (Camellia sinensis var. sinensis) green tea. YKGT and Ex significantly decreased the level of blood glucose, serum total cholesterol (TC), triglyceride (TG), insulin, and alanine aminotransferase activity (ALT) when compared to HFD group. The fatty liver and hepatic pro-inflammatory gene expression in the YKGT, Ex and YKGT+Ex groups was mitigated significantly compared with HFD group, respectively. The phosphorylation of inhibitor of nuclear factor kappa-B kinase α/ß (IKKα/ß) and inhibitor of nuclear factor kappa-B α (IkBα) protein in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway was also decreased in YKGT or YKGT+Ex groups. The combination of YKGT and Ex prevented gene expression for lipid synthesis in the liver tissue, and significantly upregulated mRNA level of glucose transport genes in the skeletal muscles, when compared to the HFD group. CONCLUSIONS: This study demonstrated that YKGT supplement or exercise appeared to reverse preexisting metabolic syndrome, and effectively relieved the fatty liver and hepatic inflammatory response induced by high fat diet. YKGT supplement and treadmill exercise together had better beneficial effects than only one intervention.

Medium-to-High Late-Life Physical Activity Is Associated with Lower Risk of Incident Dementia: The Shanghai Aging Study.

BACKGROUND: There is significant evidence that physical activity has profound effects on the neurochemistry and plasticity of the brain and may prevent cognitive decline. OBJECTIVE: This study aimed to determine the association between physical activity and incident dementia among older Chinese adults. METHODS: In the prospective phase of the Shanghai Aging Study, 1,648 community-dwellers aged 60 years or older were followed for an average of 5 years. Their physical activity was assessed based on questionnaires. The physical activities were further transformed into metabolic equivalent values. A consensus diagnosis of incident dementia was ascertained based on medical, neurological, and neuropsychological data and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: We identified 166 incident dementia cases; the incidence rate was 19.4 per 1000 person-years. A multivariate Cox regression model indicated that compared to low levels of physical activity, medium-to-high levels of physical activity were associated with a reduced risk of dementia (hazard ratio, 95% confidence interval = 0.62, 0.44-0.89) after adjusting for age, sex, years of education, apolipoprotein E ɛ4, and other confounders. CONCLUSION: Our findings demonstrate that medium-to-high level of physical activity is protective against dementia in older adults.

Effects and Mechanisms of Tea Regulating Blood Pressure: Evidences and Promises.

Cardiovascular diseases have overtaken cancers as the number one cause of death. Hypertension is the most dangerous factor linked to deaths caused by cardiovascular diseases. Many researchers have reported that tea has anti-hypertensive effects in animals and humans. The aim of this review is to update the information on the anti-hypertensive effects of tea in human interventions and animal studies, and to summarize the underlying mechanisms, based on ex-vivo tissue and cell culture data. During recent years, an increasing number of human population studies have confirmed the beneficial effects of tea on hypertension. However, the optimal dose has not yet been established owing to differences in the extent of hypertension, and complicated social and genetic backgrounds of populations. Therefore, further large-scale investigations with longer terms of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of hypertensive risk factors, and to determine differences in beneficial effects amongst diverse populations. Moreover, data from laboratory studies have shown that tea and its secondary metabolites have important roles in relaxing smooth muscle contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting rennin activity, and anti-vascular oxidative stress. However, the exact molecular mechanisms of these activities remain to be elucidated.

Using Caffeine and Free Amino Acids To Enhance the Transepithelial Transport of Catechins in Caco-2 Cells.

Catechins are well-known to possess health-promoting functions. The interaction of the catechins with other components in tea could alter their absorption and efflux. This study investigated whether the absorption of catechins is affected by caffeine and amino acids using the Caco-2 monolayer cell model. We found that (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) were all actively effluxed. Co-transportation of EGCG, ECG, or EC with caffeine, theanine, serine, or glycine increased their apparent permeability coefficient [ Papp(AP-BL)] value by 3.42-5.40- fold, 1.19-5.75-fold, and 1.55-8.01-fold, respectively. Meanwhile, their efflux ratio values were significantly decreased. Moreover, the expression of multi-drug resistance protein 2 (MRP2) after 3 h of incubation with either 50 µM EGCG or 50 µM EC was elevated by 1.58- and 2.98-fold, respectively, while 50 µM ECG had no significantly effects. In addition, the expression of P-glycoprotein (P-gp) after treatment with either 50 µM EGCG, 50 µM ECG, or 50 µM EC was enhanced by 1.53-, 1.63-, and 1.80-fold, respectively. The addition of either caffeine or any one of the three amino acids decreased the expression of both MRP2 and P-gp induced by EGCG, and the expression of P-gp induced by ECG or EC also decreased. In contrast, only glycine decreased the expression of MRP2 induced by EC. Taken together, our data indicated that caffeine and theanine, glycine, or serine in tea might increase the absorption of catechins by the selectively suppressed expression of the efflux transporters induced by catechins.

Synthesis, characterization, and reactivity of dinuclear organo-rare-earth-metal alkyl complexes supported by 2-amidate-functionalized indolyl ligands: substituent effects on coordination and reactivity.

Two series of new dinuclear organo-rare-earth-metal alkyl complexes supported by 2-amidate-functionalized indolyl ligands with different haptic modes were synthesized and characterized. The treatment of [RE(CH2SiMe3)3(THF)2] with 1 equiv. of 2-(2,6-iPr2C6H3NHC[double bond, length as m-dash]O)C8H5NH (H2L1) and 2-(2-tBuC6H4NHC[double bond, length as m-dash]O)C8H5NH (H2L2) in toluene yielded the dinuclear organo-rare-earth-metal alkyl complexes {[η1:(µ2-η1:η1)-L1]RE(CH2SiMe3)(THF)2}2 [RE = Gd (1a), Dy (1b), Y (1c), Er (1d), and Yb (1e)] and {[η1:(µ2-η1:η1):η1-L2]RE(CH2SiMe3)(THF)2}2 [RE = Gd (2a), Dy (2b), Y (2c), Er (2d), and Yb (2e)] in good yields. When [RE(CH2SiMe3)3(THF)2] were treated with 2 equiv. of H2L1 or H2L2 in THF, the dinuclear organo-rare-earth-metal complexes {(η1:η1-HL)[η1:(µ2-η1:η1):η1-L]RE(THF)}2 (1ca: RE = Y, L = L1; 2ea: RE = Yb, L = L2) were obtained. The complexes could react with small organic molecules such as N,N'-diisopropylcarbodiimide (DIC), phenyl isocyanate, N-methylallylamine, phenylacetylene, pyridine, N-phenylimidazole, or 4-dimethylaminopyridine (DMAP) to yield a series of new complexes with different reactivity patterns along with the reported rare-earth-metal alkyl complexes. In the presence of cocatalysts, these dinuclear organo-rare-earth-metal alkyl complexes could initiate isoprene polymerization with high activity (100% conversion of 2000 equiv. of isoprene in 12 h), yielding polymers with high regioselectivity (1,4 polymers up to 96.1%).

RNA-Sequencing Analysis Reveals l-Theanine Regulating Transcriptional Rhythm Alteration in Vascular Smooth Muscle Cells Induced by Dexamethasone.

l-Theanine, a unique amino acid in tea leaves, is known to have beneficial effects on stress relief, tumor suppression, and prevention of hypertension and cardiovascular diseases (CADs). The disruption of the circadian rhythm has been implied in the pathogenesis of CADs. However, it is unknown whether l-theanine has a modulatory effect on the vascular circadian rhythm. In this research, we have established a circadian gene expression model in rat vascular smooth muscle cells by dexamethasone induction. l-Theanine treatment enhanced the expression amplitude of clock genes, including Bmal1, Cry1, Rev-erbα, and Per2. Moreover, pairwise comparisons of the RNA-sequencing data showed that l-theanine is able to upregulate a ray of the rhythm genes and differentially expressed genes that are involved in vasoconstriction and actin cytoskeleton regulation pathways. Our data suggest that l-theanine changes the circadian gene rhythm involving in the process of vascular smooth muscle restructure.