Bitterness quantification and simulated taste mechanism of theasinensin A from tea.

Theasinensin A is an important quality chemical component in tea, but its taste characteristics and the related mechanism are still unclear. The bitterness quantification and simulated taste mechanism of theasinensin A were researched. The results showed that theasinensin A was significantly correlated with the bitterness of tea. The bitterness threshold of theasinensin A was identified as 65 µmol/L for the first time. The dose-over-threshold (DOT) value of theasinensin A was significantly higher than that of caffeine in black tea soup. The concentration-bitterness curve and time-intensity curve of theasinensin A were constructed. The bitterness contribution of theasinensin A in black tea was higher than in oolong and green tea. Theasinensin A had the highest affinity with bitterness receptor protein TAS2R16, which was compared to TAS2R13 and TAS2R14. Theasinensin A was mainly bound to a half-open cavity at the N-terminal of TAS2R13, TAS2R14, and TAS2R16. The different binding capacity, hydrogen bond, and hydrophobic accumulation effect of theasinensin A and bitterness receptor proteins might be the reason why theasinensin A presented different bitterness senses in human oral cavity.

Cu-MOFs based photocatalyst triggered antibacterial platform for wound healing: 2D/2D Schottky junction and DFT calculation.

Herein, we developed a multimodal antibacterial nanoplatform via synergism effect including knife-effect, photothermal, photocatalytic induced reactive oxygen species (ROS), and Cu2+ inherent attribute. Typically, 0.8-TC/Cu-NS possesses higher photothermal property with the higher photothermal conversion efficiency of 24% and the moderate temperature up to 97 °C. Meanwhile, 0.8-TC/Cu-NS exhibits the more active ROS, 1O2 and ·O2-. Hence, 0.8-TC/Cu-NS possesses best antibacterial properties against S. aureus and E. coli in vitro with efficiency of 99.94%/99.97% under near-infrared (NIR) light, respectively. In the therapeutic practical use for wound healing of Kunming mice, this system exhibits outstanding curing capacity and good biocompatibility. Based on the electron configuration measurement and density functional theory (DFT) simulation, it is confirmed that the electrons on CB of Cu-TCPP flow fleetingly to MXene trough the interface, with redistribution of charge and band upward bending over Cu-TCPP. As a result, the self-assembled 2D/2D interfacial Schottky junction have made great favor to accelerate photogenerated charges mobility, hamper charge recombination, and increases the photothermal/photocatalytic activity. This work gives us a hint to mostly design the multimodal synergistic nanoplatform under NIR light in biological applications without drug resistance.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).

Oxygen Vacancy Induced Boosted Visible-Light Driven Photocatalytic CO2 Reduction and Electrochemical Water Oxidation Over CuCo-ZIF@Fe2 O3 @CC Architecture.

Herein, the obtained Cu0.5 Co0.5 -ZIF@Fe2 O3 @CC-150 heterojunction (termed as Cu1- x Cox -ZFC-150) showed high hydrogen and oxygen evolution reaction (HER and OER) activities with low overpotential small Tafel slope. When employed to be the bifunctional anode and cathode, they only needed a cell voltage of 1.62 V. The composite also exhibited excellent photocatalytic performance on CO2 evolution into CO and CH4 . The enhanced OER kinetics and Z-scheme charge transfer model for photocatalytic property have been discussed based on the experiments and density functional theory (DFT) analysis. The optimized phase interfaces, abundant active sites, optional oxygen vacancy, and adjusted Gibbs free energy were beneficial for the fast electron/ion transport enhancing the water splitting performance.

Trilobatin rescues cognitive impairment of Alzheimer's disease by targeting HMGB1 through mediating SIRT3/SOD2 signaling pathway.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive impairment that currently is uncurable. Previous study shows that trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effect in experimental models of AD. In the present study we investigated the molecular mechanisms underlying the beneficial effect of TLB on experimental models of AD in vivo and in vitro. APP/PS1 transgenic mice were administered TLB (4, 8 mg· kg-1 ·d-1, i.g.) for 3 months; rats were subjected to ICV injection of Aß25-35, followed by administration of TLB (2.5, 5, 10 mg· kg-1 ·d-1, i.g.) for 14 days. We showed that TLB administration significantly and dose-dependently ameliorated the cognitive deficits in the two AD animal models, assessed in open field test, novel object recognition test, Y-maze test and Morris water maze test. Furthermore, TLB administration dose-dependently inhibited microglia and astrocyte activation in the hippocampus of APP/PS1 transgenic mice accompanied by decreased expression of high-mobility group box 1 (HMGB1), TLR4 and NF-κB. In Aß25-25-treated BV2 cells, TLB (12.5-50 µM) concentration-dependently increased the cell viability through inhibiting HMGB1/TLR4/NF-κB signaling pathway. HMGB1 overexpression abrogated the beneficial effects of TLB on BV2 cells after Aß25-35 insults. Molecular docking and surface plasmon resonance assay revealed that TLB directly bound to HMGB1 with a KD value of 8.541×10-4 M. Furthermore, we demonstrated that TLB inhibited Aß25-35-induced acetylation of HMGB1 through activating SIRT3/SOD2 signaling pathway, thereby restoring redox homeostasis and suppressing neuroinflammation. These results, for the first time, unravel a new property of TLB: rescuing cognitive impairment of AD via targeting HMGB1 and activating SIRT3/SOD2 signaling pathway.

The covalent Coordination-driven Bi2S3@NH2-MIL-125(Ti)-SH heterojunction with boosting photocatalytic CO2 reduction and dye degradation performance.

Herein, the optional and controllable growth of Bi2S3 onto NH2-MIL-125 via covalent conjunction strategy was reported. The experimental results demonstrate that the obtained heterojunction exhibits boosting photocatalytic reduction CO2 and organic dye degradation. The 18-Bi2S3@NH2-MIL-125-SH displays the highest yield of 12.46 µmol g-1h-1 of CO, >13 times that of pure NH2-MIL-125. Meanwhile, the reaction kinetic of 18-Bi2S3@NH2-MIL-125-SH in the degradation of methylene blue is uppermost, which is 160 times than that of the commercial P25. The enhancement of photocatalytic performance could be ascribed to the covalent coordination-driven intimate interfacial interaction in n-scheme heterojunction. Meanwhile, the plausible mechanism was also investigated by UV-vis diffuse reflectance (UV-vis), photoluminescence (PL), electrochemical photocurrent, electron spin resonance (ESR) and electrochemical impedance spectroscopy (EIS).

Visible-light driven boosting electron-hole separation in CsPbBr3 QDs@2D Cu-TCPP heterojunction and the efficient photoreduction of CO2.

CsPbBr3 quantum dots (CPB QDs) have great potential in photoreduction of CO2 to chemical fuels. However, the low charge transportation efficiency and chemical instability of CPB QDs presents a considerable challenge. Herein, we describe the electrostatic assemblies of negatively charged colloidal two dimensional (2D) Cu-Tetrakis(4-carboxyphenyl) porphyrins (Cu-TCPP) nanosheets and positively CPB QDs to construct the hydride heterojunction. The photogenerated electron migration from CPB QDs to Cu-TCPP nanosheets has been witnessed, providing the supply of long-lived electrons for the reduction of CO2 molecules adsorbed on Cu-TCPP matrix. As a direct result, The CPB@Cu-TCPP-x (x wt% of CPB QDs) photocatalysts exhibit significantly enhanced photocatalytic conversion of CO2, compared to the parent Cu-TCPP nanosheets or single CPB QDs. Especially, when with 20% CPB QDs, the heterostruture system achieves an evolution yield of 287.08 µmol g-1 in 4 h with highly CO selectivity (99%) under visible light irradiation, which is equivalent to a 3.87-fold improvement compared to the pristine CPB QDs. Meanwhile, the CH4 generation rate can be up to 3.25 µmol g-1. This optimized construction of heterostructure could provide a platform to funnel photoinduced electrons to the reaction center, which can both act as a crucial capture and the reaction actives of CO2.

Neuroprotective Effect of Ultrasound Triggered Astaxanthin Release Nanoparticles on Early Brain Injury After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a fatal disease. Within 72 h of SAH, the intracranial blood-brain barrier (BBB) is destroyed, and the nerve cells have responses such as autophagy, apoptosis, and oxidative stress. Antioxidation is an essential treatment of SAH. Astaxanthin (ATX) induces cells' antioxidant behaviors by regulating related signal pathways to reduce the damage of brain oxidative stress, inflammation, and apoptosis. Because of its easy degradability and low bioavailability, ATX is mainly encapsulated with stimulus-responsive nanocarriers to improve its stability, making it rapidly release in the brain and efficiently enter the lesion tissue. In this study, the ultrasonic cavitation agent perfluorocarbon (PFH), ATX, and fluorescent dye IR780 were loaded with polydopamine (PDA) to prepare a US triggered release nanoparticles (AUT NPs). The core-shell structure of AUT NPs formed a physical barrier to improve the bioavailability of ATX. AUT NPs have high ATX loading capacity and US responsiveness. The experimental results show that the AUT NPs have high stability in the physiological environment. Both US and pH stimuli can trigger the release. Under US, PFH breaks through the rigid shell. The structure of AUT NPs is destroyed in situ, releasing the loaded drugs into neuronal cells to realize the antioxidant and antiapoptotic effects. The in vivo experiment results show that the AUT NPs have good biosafety. They release the drugs in the brain under stimuli. The in vivo treatment results also show that AUT NPs have an excellent therapeutic effect. This approach presents an experimental basis for the establishment of Innovative SAH treatments.

Effective Material Basis and Mechanism Analysis of Compound Banmao Capsule against Tumors Using Integrative Network Pharmacology and Molecular Docking.

PURPOSE: Compound banmao capsule (CBC), a well-known traditional Chinese medical material, is known to inhibit various tumors. However, its material basis and pharmacological mechanisms remain to be elucidated. This study aimed to investigate the effective material basis and mechanisms of action of CBC against tumors. METHODS: Active compounds of CBC were identified using public database and reports to build a network. The corresponding targets of active compounds were retrieved from online databases, and the antitumor targets were identified by GeneCards database. The antitumor hub targets were generated via protein-protein interaction analysis using String, and key compounds and targets from the integrative network were detected by molecular docking and ADMET. Top targets in hepatocellular carcinoma were confirmed by quantitative real-time PCR (qPCR). Finally, the multivariate biological network was built to identify the integrating mechanisms of action of CBC against tumor cells. RESULTS: A total of 128 compounds and 436 targets of CBC were identified successfully. Based on the generated multivariate biological network analysis, 25 key compounds, nine hub targets, and two pathways were further explored. Effective material bases of cantharidin, baicalein, scutellarin, sesamin, and quercetin were verified by integrative network analysis. PTGS2, ESR1, and TP53 were identified as hub targets via multivariate biological network analysis and confirmed using qPCR. Furthermore, VEGF and estrogen signaling pathways seem to play a role in the antitumor activity of CBC. Thus, breast cancer may be a potential clinical indication of CBC. CONCLUSION: This study successfully identified the material basis of CBC and its synergistic mechanisms of action against tumor cells.

MOFs assembled from C3 symmetric ligands: structure, iodine capture and role as bifunctional catalysts towards the oxidation-Knoevenagel cascade reaction.

Three new NiII/CoII-metal organic frameworks were self-assembled by the reaction of C3 symmetric 1,3,5-tribenzoic acid (H3BTC) and 2,4,6-tris(4-pyridyl)-1,3,5-triazine (4-TPT) ligands and NiII/CoII salts under solvothermal conditions. Isomorphous MOF1 and MOF2 exhibit a 3D pillar-layer framework based on binuclear M2(OH)(COO)2 units connected by tritopic BTC3- and 4-TPT ligands with a novel (3,5)-connected topology net. MOF3 displays a 3-fold interpenetrated 3D network exhibiting a (3,4)-connected topology net. The porous MOF3 can reversibly take up I2. The activated MOFs contain both Lewis acid (NiII center) and basic (uncoordinated pyridyl or carboxylic groups) sites, and act as bifunctional acid-base catalysts. The catalytic measurements demonstrate that the activated MOF3 exhibits good activities for benzyl alcohol oxidation and the Knoevenagel reaction and can be recycled and reused for at least four cycles without losing its structural integrity and high catalytic activity. Thus, the catalytic properties for the oxidation-Knoevenagel cascade reaction have also been studied.

Analysis of the Volatile Components in Selaginella doederleinii by Headspace Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry.

Selaginella doederleinii (SD) is a perennial medicinal herb widely distributed in China. In this study, the volatile components of SD from two regions (24 batches), namely Zhejiang and Guizhou, were determined by combining headspace solid phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). After investigating different influence factors, the optimal conditions for extraction were as follows: The sample amount of 1 g, the polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber of 65 µm, the extraction time of 20 min, and the extraction temperature of 100 °C. Based on the above optimum conditions, 58 volatiles compounds, including 20 terpenes, 11 alkanes, 3 alcohols, 6 ketones, 3 esters, 11 aldehydes, 1 ether, 1 aromatic, 1 phenol, and 1 furan, were found and identified in SD. Furthermore, hierarchical cluster analysis and principal component analysis were successfully applied to distinguish the chemical constituents of SD from two regions. Additionally, anethol, zingerone, 2,4-di-tert-butylphenol, ledene, hexyl hexanoate, α-cadinol, phytone, hinesol, decanal, octadecene, cedren, 7-tetradecene, copaene, ß-humulene, 2-butyl-2-octenal, tetradecane, cedrol, calacorene, 6-dodecanone, ß-caryophyllene, 4-oxoisophorone, γ-nonanolactone, 2-pentylfuran, 1,2-epoxyhexadecane, carvacrol, n-pentadecane, diisobutyl phthalate, farnesene, n-heptadecane, linalool, 1-octen-3-ol, phytane, and ß-asarone were selected as the potential markers for discriminating SD from 24 habitats in Zhejiang and Guizhou by partial least squares discrimination analysis (PLS-DA). This study revealed the differences in the components of SD from different regions, which could provide a reference for the future quality evaluation.

Physicochemical Basis and Comparison of Two Type II Sex Pheromone Components Binding with Pheromone-Binding Protein 2 from Tea Geometrid, Ectropis obliqua.

Lepidopteran geometrid moth can produce complex Type II sex pheromone components to attract males and trigger mating behavior. Although several sex pheromone components have been identified, it remains unclear whether their physicochemical roles in sex pheromone sensing are the same. Therefore, we utilized tea geometrid ( Ectropis obliqua) as an example model to investigate and compare the physicochemical basis of two key Type II sex pheromone components, cis-6,7-epoxy-(3Z,9Z)-3,9-octadecadiene ( Z3 Z9-6,7-epo-18:Hy) and ( Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), interacting with pheromone-binding protein 2 ( EoblPBP2) from E. obliqua. Multispectral, thermodynamic, docking, and site-directed mutagenesis indicated that the major sex pheromone component Z3Z9-6,7-epo-18:Hy is more susceptible to pH-tuned than the minor component Z3Z6Z9-18:Hy, whereas Z3Z6Z9-18:Hy seems to be more susceptible to temperature and amino acid mutations than Z3Z9-6,7-epo-18:Hy. Our study suggests that different components of Type II sex pheromone play different binding characters under specific conditions in the physicochemical behavior. This deeply supplements the theoretical knowledge of Type II pheromones involved in the recognition and discrimination in the Lepidopteran sex pheromones family.

Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumatoid arthritis patients.

Biqi capsule is a Traditional Chinese Medicine preparation for treating rheumatoid arthritis (RA), and clinical studies have indicatedthat its effect may be more beneficial than that of Western medicine. The present study aimed to estimate the efficacy and safety of Biqi capsule alone or combined with methotrexate (MTX) compared with MTX alone for treating RA by performing a meta-analysis of randomized controlled trials and controlled clinical trials. A systematic literature search of studies published until March 2017 was performed. References from relevant studies were screened to obtain additional articles. The results were independently evaluated for relevance, and full-text studies were assessed for eligibility. The risk of bias was assessed using the Cochrane collaboration tool for assessing risk of bias. Out of 558 citations that were initially retrieved, a total of 5 studies comprising 522 patients met the inclusion criteria. The risk of bias of these trials was generally unclear or high. Meta-analysis indicated that Biqi capsule had better effects on C-reactive protein [standardized mean difference (SMD), -7.05; 95% CI -(10.77-3.33)] and tender joint count [SMD, -3.02; 95% CI, -(3.81-2.22)] and fewer adverse effects (AEs) than MTX [relative risk (RR), 0.19; 95% CI, 0.08-0.43]. Biqi capsule plus MTX was superior to MTX in terms of the total effect (RR, 1.17; 95% CI, 1.06-1.28), rheumatoid factor [SMD, -12.54; 95% CI, -(16.87-8.20)], swollen joint count [SMD, -1.50; 95% CI, -(1.99-1.01)], score of joint swelling [SMD -2.07; 95% CI, -(2.76-1.38)], tender joint count [SMD, -2.16; 95% CI, -(2.86-1.47)] and score of joint tenderness [SMD, -4.69; 95% CI, -(5.92-3.47)]. There was no difference in AEs between Biqi capsule plus MTX and MTX (RR, 0.71; 95% CI, 0.34-1.50). In conclusion, the present study indicated that compared with MTX, Biqi capsule plus MTX appeared to have more benefits but that Biqi capsule alone was not better for RA patients than MTX. In the other words, Biqi capsule plus MTX is more effective and has fewer AEs compared to MTX. However, the trials selected in the present meta-analysis have various limitations, including the lack of blinding and the short duration of the treatment; therefore, the conclusions are not sufficiently definitive. More randomized controlled trials are necessary to evaluate the use of Biqi capsule for managing RA.

The Effectiveness and Safety of Tripterygium wilfordii Hook. F Extracts in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Objective: To conduct a meta-analysis of the effectiveness and safety of Tripterygium wilfordii Hook. F (TwHF) extracts for the treatment of rheumatoid arthritis (RA). Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, Medline, CNKI, SinoMed and WanFang Library till 12 July 2017. All included studies were analyzed with the use of the Review Manager 5.2 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Results: Fourteen randomized controlled trials (RCTs) were identified. TwHF extracts provided a statistically significant improvement in grip strength (GS), swelling joint count (SJC) and morning stiffness (MS) compared with placebo (P < 0.001). The meta-analysis showed significant differences between TwHF extract-treated group and the DMARDs group in GS, MS, C-reactive protein (CRP), and tender joint count (TJC) (P < 0.05), aside from ESR and SJC (P > 0.05). The pooled results also displayed significant differences between the combination of TwHF extracts with DMARDs and the DMARDs alone group in ESR, CRP, SJC, and TJC (P ≤ 0.05). For the safety analysis, two trials favored TwHF extract-treatment and one trial favored non-TWHF extract-treatment in AEs (P < 0.05). Eleven trials showed no statistically significant differences between TwHF extract-treated group and the DMARDs group (P > 0.05). Conclusions: The findings of this systematic review with meta-analysis indicate that TwHF extracts provides statistically significant and clinically important improvement in RA symptoms and has an acceptable safety profile.