Identification of key volatile and odor-active compounds in 10 main fragrance types of Fenghuang Dancong tea using HS-SPME/GC-MS combined with multivariate analysis.

Fenghuang Dancong tea (FHDC), a famous oolong tea originating from Guangdong Province in China, is known for its rich and unique fragrance. Nevertheless, the identification of the key aroma compounds with the difference fragrance types of FHDC remains uncertain. In order to characteristic the volatile components in different fragrance types of FHDC, 10 well-known fragrance types of FHDC and Tieguanyin (TGY) as a control were analyzed by headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography mass spectrometry (GC-MS). Results indicated that 172 volatile compounds were identified as common volatile compounds among all the tea samples. A total of 16 compounds were identified as key compounds that could be used to distinguish between FHDC and TGY. Among the 10 FHDC fragrance types, indole, hotrienol, benzyl nitrile, and jasmine lactone were found to be the most abundant compounds. Despite the presence of certain similarities in aroma components, each type exhibits unique fragrance characteristics as a result of variation in compound composition content and proportion. Furthermore, using statistical and odor activity value analysis, 20 aroma-active compounds were recognized as potential characteristic markers accountable for the diverse fragrance types of FHDC. This research enhances our comprehension of the various fragrance types of FHDC and provides reference values for their rapid identification in the market.

Mawangdui-Guidance Qigong Exercise for patients with chronic non-specific low back pain: Study protocol of a randomized controlled trial.

Introduction: Worldwide, there is a high frequency of chronic non-specific low back pain (CNLBP), which is a significant public health concern. The etiology is complicated and diverse, and it includes a number of risk factors such as diminished stability and weak core muscles. Mawangdui-Guidance Qigong has been employed extensively to bolster the body in China for countless years. However, the effectiveness of treating CNLBP has not been assessed by a randomized controlled trial (RCT). In order to verify the results of the Mawangdui-Guidance Qigong Exercise and examine its biomechanical mechanism, we intend to perform a randomized controlled trial. Methods and analysis: Over the course of 4 weeks, 84 individuals with CNLBP will be randomly assigned to receive either Mawangdui-Guidance Qigong Exercise, motor control exercise, or medication (celecoxib). Electromyographic data, including muscle activation time, iEMGs, root mean square value (RMS) and median frequency (MF), will be the main outcomes. The Japanese Orthopedic Association (JOA) Score, the Mcgill Pain Questionnaire (MPQ), beta-endorphin, and substance P are examples of secondary outcomes. At the start of treatment and 4 weeks later, all outcomes will be evaluated. SPSS version 20.0 (SPSS Inc., Chicago, IL, USA) will be used for all of the analysis. Discussion: The prospective findings are anticipated to offer an alternative treatment for CNLBP and provide a possible explanation of the mechanism of Mawangdui-Guidance Qigong Exercise on CNLBP. Ethics and dissemination: The Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine has given the study approval (Approval No. 2020KL-067). It has also registered at the website of China Clinical Trial Center Registration. The application adheres to the Declaration of Helsinki's tenets (Version Edinburgh 2000). Peer-reviewed papers will be used to publicize the trial's findings. Trial registration number: ClinicalTrials.gov, identifier ChiCTR2000041080.

The molecular mechanism on suppression of climacteric fruit ripening with postharvest wax coating treatment via transcriptome.

Wax coating is an important means to maintain fruit quality and extend fruit shelf life, especially for climacteric fruits, such as apples (Malus domestica). Here, we found that wax coating could inhibit ethylene production, chlorophyll degradation, and carotenoid synthesis, but the molecular mechanism remains unclear. The regulatory mechanism of wax coating on apple fruit ripening was determined by subjecting wax-treated apple fruits to transcriptome analysis. RNA-seq revealed that 1,137 and 1,398 genes were upregulated and downregulated, respectively. These differentially expressed genes (DEGs) were shown to be related to plant hormones, such as ethylene, auxin, abscisic acid, and gibberellin, as well as genes involved in chlorophyll degradation and carotenoid biosynthesis. Moreover, we found that some genes related to the wax synthesis process also showed differential expression after the wax coating treatment. Among the DEGs obtained from RNA-seq analysis, 15 were validated by quantitative RT-PCR, confirming the results from RNA-seq analysis. RNA-seq and qRT-PCR of pear (Pyrus ussuriensis) showed similar changes after wax treatment. Our data suggest that wax coating treatment inhibits fruit ripening through ethylene synthesis and signal transduction, chlorophyll metabolism, and carotenoid synthesis pathways and that waxing inhibits endogenous wax production. These results provide new insights into the inhibition of fruit ripening by wax coating.

Identification and characterization of the key volatile flavor compounds in black teas from distinct regions worldwide.

Volatile flavor compounds in 112 black teas from seven countries were analyzed by untargeted metabolomics using headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). Multivariate statistical analysis and odor activity values (OAVs) were used to classify these samples and identify key odorants. A total of 140 volatile flavor compounds (VFCs), including 12 different groups, were identified, and alcohols were prevalent in China and India samples, accounting for 40.83% and 34.96% of the total VFCs, respectively. Eight volatile compounds with OAVs > 1 were identified as key active differential odorants in Chinese, Indian, and Sri Lankan samples, including linalool, pentanoic acid, methyl salicylate, hexanoic acid, 1-methyl-naphthalene, phenylethyl alcohol, geraniol, and ß-ionone. Linalool, pentanoic acid, and hexanoic acid in Indian black teas, phenylethyl alcohol in Chinese black teas, and 1-methyl-naphthalene, ß-ionone in Sri Lankan black teas could be used to discriminate different black tea groups. A total of 12-14 VFCs with OAVs > 1 were identified as key active aromatics in Chinese black tea sample. Linalool and benzeneacetaldehyde in Yingde (Guangdong) black tea, methyl salicylate in Taiwanese samples, and benzeneacetic acid in Anhui black tea could be used as biomarkers to distinguish them from other Chinese samples. Sensory evaluation results showed that most black teas presented the common sweet, floral odors, which were consistent with GC-MS analysis. These results will contribute to characterize the odor metabolome of black teas and provide biochemical basis for identifying the authenticity of different black teas. PRACTICAL APPLICATION: Linalool, pentanoic acid, and hexanoic acid in Indian black teas, phenylethyl alcohol in Chinese black teas, 1-methyl-naphthalene, ß-ionone, and methyl salicylate in Sri Lankan black teas could be used to discriminate black teas from the three countries. Linalool and benzeneacetaldehyde in Yingde black teas, methyl salicylate in Taiwanese black teas, and benzeneacetic acid in Anhui black tea are the potential biomarkers to distinguish these teas from other Chinese black teas.

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy.

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo. Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity.

Hyperuricemia, a long-term purine metabolic disorder, is a well-known risk factor for gout, hypertension and diabetes. In maintaining normal whole-body purine levels, xanthine oxidase (XOD) is a key enzyme in the purine metabolic pathway, as it catalyzes the oxidation of hypoxanthine to xanthine and finally to uric acid. Here we used the protein-ligand docking software idock to virtually screen potential XOD inhibitors from 3167 approved small compounds/drugs. The inhibitory activities of the ten compounds with the highest scores were tested on XOD in vitro. Interestingly, all the ten compounds inhibited the activity of XOD at certain degrees. Particularly, the anti-ulcerative-colitis drug olsalazine sodium demonstrated a great inhibitory activity for XOD (IC50 = 3.4 mg/L). Enzymatic kinetic studies revealed that the drug was a hybrid-type inhibitor of xanthine oxidase. Furthermore, the drug strikingly decreased serum urate levels, serum/hepatic activities of XOD at a dose-dependent manner in vivo. Thus, we demonstrated a successful hunting process of compounds/drugs for hyperuricemia through virtual screening, supporting a potential usage of olsalazine sodium in the treatment of hyperuricemia.

USR-VS: a web server for large-scale prospective virtual screening using ultrafast shape recognition techniques.

Ligand-based Virtual Screening (VS) methods aim at identifying molecules with a similar activity profile across phenotypic and macromolecular targets to that of a query molecule used as search template. VS using 3D similarity methods have the advantage of biasing this search toward active molecules with innovative chemical scaffolds, which are highly sought after in drug design to provide novel leads with improved properties over the query molecule (e.g. patentable, of lower toxicity or increased potency). Ultrafast Shape Recognition (USR) has demonstrated excellent performance in the discovery of molecules with previously-unknown phenotypic or target activity, with retrospective studies suggesting that its pharmacophoric extension (USRCAT) should obtain even better hit rates once it is used prospectively. Here we present USR-VS (http://usr.marseille.inserm.fr/), the first web server using these two validated ligand-based 3D methods for large-scale prospective VS. In about 2 s, 93.9 million 3D conformers, expanded from 23.1 million purchasable molecules, are screened and the 100 most similar molecules among them in terms of 3D shape and pharmacophoric properties are shown. USR-VS functionality also provides interactive visualization of the similarity of the query molecule against the hit molecules as well as vendor information to purchase selected hits in order to be experimentally tested.