Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Steady and Robust CNTs-Based Electric Heating Membrane Fabricated by Addition of Nanocellulose and Hot-Press Encapsulation.

Herein, a type of biomass-based electric heating membrane (EHM) with excellent stability was fabricated; this was achieved by incorporating carbon nanotubes (CNTs) into the nanofibrillated cellulose (NFC) as a natural dispersant and a biological substrate, as well as via the control of ultrasonic dispersion, grammage, and encapsulation using poly(dimethylsiloxane) (PDMS) with hot pressing. NFC entangles with CNTs in the form of an intertwined network and non-covalent interactions to fabricate a flexible EHM with steady electric heating performance; this formation is attributed to not only their similar morphology and surface-active groups but also the use of NFC that avoids additional disturbances in the overlapped interface among CNTs as far as possible. The obtained steady resistance varies as low as 5.1% under energized operation. In the encapsulated EHM (EM), PDMS was anchored on its surface by using hot pressing and an intertwined structure to enhance flexibility and robustness. The encapsulated membrane can be used in low-voltage applications, which require flexibility, waterproofing, and insulation.

[Botanical origin identification of Rhei Radix et Rhizoma based on color digitalization].

The color characteristic information of Rhei Radix et Rhizoma powder was obtained by spectrophotometer, the feasibility of rapid identification of Rhei Radix et Rhizoma origin based on chromaticity value was studied by statistical analysis. The results of rank correlation analysis showed that a~*(P<0.01), b~*(P<0.01) had significantly correlation with the origin of medicinal herbs, which could be used as two important parameters to distinguish the origin of Rhei Radix et Rhizoma, the larger the a~* value, the more red the powder color,and the greater the b~* value, the more yellow the powder color. Meanwhile, through Fisher discriminant analysis, the linear discriminant functions of different genus Rhei Radix et Rhizoma were established, which was Rheum tanguticum=40.666a~*+0.019b~*-213.303, Rh. palmatum=34.121a~*+0.061b~*-151.770, Rh. officinale=28.071a~*+0.113b~*-104.604 3, the coincidence rate of cross-validation was over 95%, among them, the discriminant rate of Rh. tanguticum and Rh. officinale reached 100%;In addition, using the percentile method to analyze the 90% reference value range of three different origin of Rhei Radix et Rhizoma, as a result, Rh. tanguticum a~*(10.236 5-10.604 7), b~*(32.294 8-34.841 7); Rh. palmatum a~*(8.602 7-8.770 0), b~*(27.534 8-28.968 6), and Rh. officinale a~*(6.825 7-7.464 3),b~*(21.001 6-27.716 4). According to this study, rank correlation analysis and Fisher discriminant analysis are feasible to distinguish the base of Rhei Radix et Rhizoma in a certain range, and provide some theoretical basis for the identification of Rhei Radix et Rhizoma. It also provides a new method and idea for the identification of other multi-base Chinese medicine.

A Nanofibrillated Cellulose-Based Electrothermal Aerogel Constructed with Carbon Nanotubes and Graphene.

Nanofibrillated cellulose (NFC) as an environmentally friendly substrate material has superiority for flexible electrothermal composite, while there is currently no research on porous NFC based electrothermal aerogel. Therefore, this work used NFC as a skeleton, combined with multi-walled carbon nanotubes (MWCNTs) and graphene (GP), to prepare NFC/MWCNTs/GP aerogel (CCGA) via a simple and economic freeze-drying method. The electrothermal CCGA was finally assembled after connecting CCGA with electrodes. The results show that when the concentration of the NFC/MWCNTs/GP suspension was 5 mg mL-1 and NFC amount was 80 wt.%, the maximum steady-state temperature rise of electrothermal CCGA at 3000 W m-2 and 2000 W m-2 was of about 62.0 °C and 40.4 °C, respectively. The resistance change rate of the CCGA was nearly 15% at the concentration of 7 mg mL-1 under the power density of 2000 W m-2. The formed three-dimensional porous structure is conducive to the heat exchange. Consequently, the electrothermal CCGA can be used as a potential lightweight substrate for efficient electrothermal devices.

[Grey correlation analysis and path analysis between isoflavones content in Astragali Radix and climate factors].

In this study, HPLC was used to determine the content of the four isoflavones of Astragalus membranceus var. mongholicus from different regions(calycosin-7-glucoside, ononin, calycosin and formononetin), and gray correlation analysis and path analysis were used to explore the influence of climate factors on the content of isoflavone components in A. membranceus var. mongholicus. The results showed that there were significant differences in the content of the four isoflavones in different areas(P<0.05); grey correlation analysis showed that the highest temperature in July, the lowest temperature in January and the daily average temperature had a greater impact on the content of flavonoid glycosides, meanwhile precipitation and relative humidity were the more important factors for the accumulation of flavonoid aglycones. According to the general analysis, the direct positive effects of the lowest temperature in January and altitude on the contents of four isoflavones in A. membranceus var. mongholicus were significant. High altitude and extreme temperature conditions might be more adverse to the formation and accumulation of isoflavone components. Therefore, the religions of A. membranceus var. mongholicus with high contents of isoflavones should be chosen the low altitude region with higher minimum temperature in January. This study provides a reference basis for the quality evaluation of A. membranceus var. mongholicus, and basic data for the selection of suitable habitat, construction of planting standards and directional cultivation of medicinal materials in A. membranceus var. mongholicus.

[Analysis of flavonoids in Coreopsis tinctoria by integrating 2D-TLC and HPLC-IT-TOF-MS].

The qualitative analysis of flavonoids in Coreopsis tinctoria was carried out by a combination of 2 D-TLC and HPLC-IT-TOF-MS. The separation was conducted on 2 D-TLC and a Phenomenex Kinetex Evo C_(18) column(2.1 mm×100 mm, 2.6 µm) with methanol-0.05% aqueous formic acid by gradient elution. Electrospray ionization-(ESI) source was applied and operated in both positive and negative ionization modes. Eighteen flavonoids including three flavonoids, one flavonol, nine flavonones, one flavanonol and four chalcones, were putatively identified from the flavone-enriched fraction of C. tinctoria. 2 D-TLC could separate the flavonoids from C. tinctoria. HPLC-IT-TOF-MS was able to quickly and accurately analyze the flavonoids in C. tinctoria. The results would provide experimental information for the efficacy material basis clarification of C. tinctoria.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

Performance of the highly sensitive humidity sensor constructed with nanofibrillated cellulose/graphene oxide/polydimethylsiloxane aerogel via freeze drying.

A kind of capacitive humidity sensor with high sensitivity constructed with nanofibrillated cellulose (NFC), graphene oxide (GO) and polydimethylsiloxane (PDMS) is presented in this work, via a simple ultrasonic dispersion and freeze drying technology. The NFC and GO with a strong adsorption for water molecules were used as a substrate for the promotion of capacitive response of the humidity sensor. Moreover, anhydrous ethanol was added to inhibit the generation of big cracks in the humidity sensor in the freeze drying process, so as to obtain a regular network porous structure, then providing a great deal of conduction channels and active sites for molecular water. Also, the addition of PDMS can effectively enhance the flexibility and stability of its porous structure. The results confirmed that the humidity sensor with 30 wt% GO showed an excellent humidity sensitivity (6576.41 pF/% RH), remarkable reproducibility, low humidity hysteresis characteristic in 11-97% relative humidity (RH) at 25 °C, and short response/recovery times (57 s/2 s). In addition, the presented sensor exhibited small relative deviation of the measured relative humidity value compared with the commercial hygrometer. The realization of the high sensitivity can be attributed to the theories about interaction of the hydrophilic group, proton transfer of water molecules and the three-dimensional network transport structure model. Therefore, the NFC/GO/PDMS humidity sensor finally realizes stable, reproducible and fast humidity sensing via an eco-friendly process, exhibiting promising potential for wide practical application.

The use of nanofibrillated cellulose to fabricate a homogeneous and flexible graphene-based electric heating membrane.

Nanofibrillated cellulose (NFC) as a natural macromolecule, binder, dispersant, enhancer, was utilized to facilitate the assembly of graphene sheets, imparting a steady stacked structure by the sheets to the electric heating membrane with flexibility and uniform heating performance. Strong interface bonding formed in the membrane, which combined graphene sheets to be a steady conductive network structure for electric heating. The membrane attained an equilibrium temperature rise to 60°C in 3min under 2000Wm-2, which increased linearly with increasing power density and graphene content. Decreased resistance between two electrodes was caused by electric-heat coupling effect which led to a decrease in the membrane's oxygen-containing groups as conducting electrification. The temperature distributing on membrane surface, and that as bent and distorted to different angles even simultaneously at the electric heating status, were all characterized by infrared thermal imaging to indicate the uniform distribution and well bonding performance between NFC and graphene, as well as the great flexibility in the biomass membrane. This study would further broaden the utilization of the natural nanocellulose-graphene biomass composites.