The Bmtret1 Gene Family and Its Potential Role in Response to BmNPV Stress in Bombyx mori.

Trehalose is a non-reducing disaccharide and participates in physiological activities such as organ formation, energy metabolism, and stress resistance in insects. The Bmtret1 gene family is mainly involved in in the sugar metabolism of silkworm. In the present study, phylogenetic analysis divided 21 Bmtret1 orthologs into three clades. These genes are equally distributed on the nine chromosomes. The cis-elements in the promoter regions of Bmtret1s indicated the possible function of Bmtret1s in response to hormones and environmental stimulus. The qPCR analysis showed the significantly different expression levels of Bmtret1s in different tissues and organs, indicating possible functional divergence. In addition, most Bmtret1s showed disturbed expression levels in response to silkworm nuclear polyhedrosis virus (BmNPV) stresses. Our results provide a clue for further functional dissection of the Tret1s in Bombyx mori and implicate them as potential regulators of antiviral responses.

Multifaceted Sulfone-Carbazole-Based D-A-D Materials: A Blue Fluorescent Emitter as a Host for Phosphorescent OLEDs and Triplet-Triplet Annihilation Up-Conversion Electroluminescence.

Electroluminescence (EL) from the singlet-excited (S1) state is the ideal choice for stable, high-performing deep-blue organic light-emitting diodes (OLEDs) owing to the advantages of an adequately short radiative lifetime, improved device durability, and low cost, which are the most important criteria for their commercialization. Herein, we present the design and synthesis of three donor-acceptor-donor (D-A-D)-configured deep-blue fluorescent materials (denoted as TC-1, TC-2, and TC-3) composed of a thioxanthone or diphenyl sulfonyl acceptor and phenyl carbazolyl donor. These systems exhibit strong deep-blue photoluminescence (422-432 nm) in solutions and redshifted emission (472-486 nm) in thin films. The solid-state photoluminescence quantum yield (PLQY) was estimated to be 78 and 94% for TC-2 and TC-3, respectively. TC-2 and TC-3 possess good molecular packing and large molecular cross-sectional areas, which not only improves the PLQY but enhances the triplet-triplet annihilation up-conversion (TTAUC) efficiency of fluorescent emitters. Furthermore, both compounds were applied as an acceptor for confirming their TTAUC property using bis(2-methyldibenzo[f,h]quinoxaline)(acetylacetonate)iridium(III) (Ir(MDQ)2acac) as the sensitizer. Non-doped OLEDs based on TC-2 and TC-3 exhibit blue EL in the 461-476 nm range. In particular, TC-3 exhibits a maximum external quantum efficiency (EQEmax) of 5.1%, and its EL maximum is 476 nm. In addition, the three emitters were employed as hosts in red OLEDs using bis(1-phenylisoquinoline)(acetylacetonate)iridium(III) (Ir(piq)2acac) as the phosphorescent dopant. The red phosphorescent OLEDs based on TC-1, TC-2, and TC-3 achieve excellent EQEmax values of 21.6, 22.9, and 21.9%, respectively, and peak luminance efficiencies of 12.0, 14.0, and 12.3 cd A-1. These results highlight these fluorophores' versatility and promising prospects in practical OLED applications.

Developing a Core Outcome Set for Clinical Trials of Chinese Medicine for Hyperlipidemia.

Background: Chinese medicine (CM) is widely used for treating hyperlipidemias, especially in China. However, the heterogeneity of outcomes measured and reported across trials exacerbates the obstacles of evidence synthesis and effectiveness comparison. In this study, we develop a core outcome set (COS) for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia) to tackle the outcome issues. Methods: We generated candidate outcomes through a systematic review of interventional and observational studies of Chinese medicine for hyperlipidemias. The comprehensive search strategy was employed. Study selection and data collection were independently done by two researchers. We searched clinical trial registry platform to supplement the outcomes list extracted by systematic review. Then, we conducted a three-round Delphi survey. The stakeholders were hyperlipidemia patients, clinicians or researchers, in either CM/integrated Chinese or Western medicine, clinical pharmacy, clinical epidemiology or statisticians, or editors of important relevant journals and an ethicist. They used a 9-point Likert scale to determine how important they felt each outcome was in determining treatment success. A consensus meeting was held to confirm the final COS, based on the Delphi survey results. Results: We identified a total of 433 outcomes from 3,547 articles, and 28 outcomes from 367 registered trials. After standardization, we selected 71 outcomes to develop a preliminary outcome list for further consensus. After three Delphi survey rounds and one consensus meeting, the most important outcomes were determined for COS-CM-Hyperlipidemia. It included cardiovascular events, low-density lipoprotein cholesterol, risk of cardiovascular disease, total cholesterol, carotid intima-media thickness, high-density lipoprotein cholesterol, triglycerides, cerebrovascular events, adverse drug reactions and patient-reported symptoms. Conclusion: COS-CM-Hyperlipidemia may improve outcome reporting consistency in clinical trials. Further work is needed to explore the optimal methods for measuring these outcomes. Registration: The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.cometinitiative.org/studies/details/983. Registered on 25 April 2017.

Screening and verification of CYP3A4 inhibitors from Bushen-Yizhi formula to enhance the bioavailability of osthole in rat plasma.

ETHNOPHARMACOLOGICAL RELEVANCE: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. AIM OF THE STUDY: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. MATERIALS AND METHODS: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance. RESULTS: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC50 = 0.339 µM), and even better than the clinically used drug (Ket) at the concentration of 5 µM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). CONCLUSIONS: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.

Chinese herbal formula siwutang for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Primary dysmenorrhea (PD) is a common gynecological disorder that usually begins in adolescence, and affects patients' daily activities and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDS) are considered the first-line treatment, and hormonal contraceptives are also recommended for PD, but both are prone to side-effects. The Chinese herbal formula Siwutang (SWT) and its derivative formulas are a common treatment for PD in China. This review assessed the efficacy and safety of SWT for the treatment of PD. METHODS: PubMed, EmBase, Cochrane CENTRAL, CNKI, Wanfang and CBM were searched. We included randomized controlled trials (RCTs) that investigated SWT for PD, compared with no intervention, placebo, or conventional Western medicine. The outcome measurements included pain intensity measured by visual analogue scale (VAS) or other validated scales, the Cox Menstrual Symptom Scale (CMSS), quality of life, response rate and adverse events. The Cochrane Collaboration's tool was used to assess the risk of bias. RevMan V.5.3 was used for data synthesis and meta-analysis. Risk ratio (RR) with 95 % confidence intervals (CIs) or mean difference (MD) with 95 % CIs was calculated for dichotomous data or continuous data, respectively. Heterogeneity among studies was evaluated using both a chi-square test and an I2 test. RESULTS: A total of 38 RCTs involving 3982 participants were identified. The methodological quality of the included trials was generally poor. Moreover, the results for SWT compared with placebo were unclear, as there was only 1 RCT. SWT improved pain intensity measured by VAS (3 RCTs, n = 220, MD:-2.61, 95 % CI:-3.72 to -1.51) when compared with conventional medicine, and these results were statistically significant. The meta-analysis showed the superior effect of SWT (including derivative formulas) on response rate (35 RCTs, n = 3,695, RR: 1.28, 95 % CI: 1.22-1.34) with medium heterogeneity (I2 = 48 %). Both original SWT and its derivative formula XFSWT had a higher response rate than conventional medicine (23 RCTs, n = 2,493, RR: 1.28, 95 % CI: 1.23-1.33) (11 RCTs, n = 1,076, RR: 1.36, 95 % CI: 1.20-1.53). These results were statistically significant. No trial reported on quality of life or CMSS. Adverse events were reported by 5 studies, and meta-analysis showed SWT may be safer than conventional medicine in terms of the incidence of adverse events (3 RCTs, n = 236, RR: 0.17, 95 % CI: 0.07-0.38, I2 = 0%). CONCLUSION: In conclusion, the included trials showed favorable effects of SWT for treating primary dysmenorrhea when compared with conventional medicine. SWT may be safer than conventional medicine, but insufficient data was reported. The level of evidence is low because of the high risk of bias. Thus, further well-designed clinical trials with large sample sizes are warranted. REGISTRATION NUMBER: CRD42019136230 in PROSPERO 2019.