Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na2SO3-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.

Gas barrier coating based on cellulose nanocrystals and its preservation effects on mango.

Mango is the "king of tropical fruits" because of its attractive appearance, delicious taste, rich aroma, and high nutritional value. However, mango keeps fast metabolizing after harvest, leading to water loss, starch conversion into sugar, texture softening, and decay. Here, a gas barrier coating based on cellulose nanocrystals (CNCs) is proposed to control the post-harvest metabolism of mango. The results of gas barrier permeability show that CNCs enhance the barrier ability of the chitosan (CS) membrane on mango by 202 % and 63 % for oxygen and water vapor, respectively. The gas-barrier coating reduces the climb in pH and the decrease in firmness by 84.9 % and 45.8 %, respectively, decelerating the conversion process from starch to sugar. Besides, introducing clove essential oil (CEO), the CEO mainly adsorbs and crystalizes on the hydrophobic facets of CNCs, presenting high compatibility, increases the antibacterial rate to nearly 100 %. As a consequence, the preservation period of the mango coated by the CNC-based membrane is at least 7-day longer than the control group. Such a gas-barrier coating based on eco-friendly composites must have excellent potential in the preservation of mango, and even for other tropical fruits.

Research Progress on Psychological Distress in Patients with Ectopic Pregnancy in China.

Ectopic pregnancy is a leading cause of death for child-bearing aged women. Most patients with ectopic pregnancy experience suffer psychological distress which seriously affects their physical and mental health. The psychological distress, influencing factors, measurement tools, and nursing interventions in patients with ectopic pregnancy in China are reviewed in this article. The results showed that the main psychological distress of patients with ectopic pregnancy is anxiety, depression, uncertainty sense of disease, and low self-esteem. The main factors affecting the psychological distress of ectopic pregnancy patients included life-threatening disease, different marital status, and reproductive needs. The main intervention methods for psychological distress in pregnant patients included: cognitive behavioral therapy, emotional therapy of traditional Chinese medicine, and family support. The majority of cross-sectional surveys in China focused on psychological conditions of the patients with ectopic pregnancy, and there are very few longitudinal studies. Large-sample, multi-center longitudinal studies should be conducted in the future to monitor the development of ectopic pregnancy. Qualitative research should be conducted on patient experience, to provide guidance and basis for the implementation of targeted nursing interventions and to further explore standardized, continuous, and generalizable psychological care protocols for distress interventions for patients with ectopic pregnancy, thereby minimizing psychological distress such as anxiety, depression, and uncertainty in patients with ectopic pregnancy.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study.

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION: Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapy on depression in poststroke patients-A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on depressive symptoms in people with stroke. METHODS: The PubMed, CINAL, Web of Science, Embase, The Cochrane Library, CNKI, and Wangfang databases were searched for relevant articles from inception to September 1st, 2022. Only randomized controlled trials (RCTs) examining the effect of MBSR and MBCT on depressive symptoms in poststroke patients were included. Data extraction and critical appraisal were conducted independently by two investigators. RESULTS: Seven trials with 502 participants were included. Using standardized mean differences, the meta-analysis showed evidence of a significant effect in depression (SMD = -0.93, 95% CI (-1.34 to -0.53), Z = 4.48, p < 0.001). MBSR and MBCT both affected depressive emotions in poststroke participants with depression (SMD = -1.27, 95% CI (-1.71 to -0.84), p < 0.001) and poststroke participants without clinically defined depression (SMD = -0.46, 95% CI (-0.75 to -0.17), p = 0.002). CONCLUSION: Although populations with stroke seem to potentially improve moods from MBSR/MBCT intervention, the impact on the physiological parameters of the disease has not been determined. Further studies with long-term follow-up and higher qualities are warranted for such interventions to determine the full effectiveness.

Remodeling and protecting the membrane system to resist phosphorus deficiency in wild soybean (Glycine soja) seedling leaves.

MAIN CONCLUSION: The poor-soil-tolerant wild soybean resist phosphorus deficiency by remodeling membrane lipids to reuse phosphorus. The plants synthesize phenolic acids and flavonoids to remove reactive oxygen species and protect membrane stability. Poor soil largely limits plant yields, and the development and utilization of high-quality wild plant resources is an effective approach to resolving this problem. Two ecotypes of wild soybean were used as experimental materials in this experiment. We integrated metabolomics and transcriptomics to determine whether wild soybean (Glycine soja) could resist phosphorus deficiency by remodeling and protecting its membrane system. Under phosphorus-deficient conditions, the plant height and aboveground fresh and dry weight of poor-soil-tolerant wild soybean seedlings were less inhibited than those in common wild soybean. In poor-soil-tolerant wild soybean seedling leaves, the glycerol-3-phosphate content decreased significantly, while caffeic acid, ferulic acid, shikimic acid, phenylalanine, tyrosine, and tryptophan increased significantly. ß-Glucosidase and chalcone synthase genes and those that encode SQD2, a crucial enzyme in thiolipid biosynthesis, were specifically up-regulated, whereas the glucosyltransferase UGT74B1 gene was down-regulated. The poor-soil-tolerant wild soybean enhanced glycerolipid metabolism to decompose phospholipids and release phosphorus for reuse to improve resistance to phosphorus deficiency. The plants synthesized thiolipids to replace phospholipids and maintain membrane structure integrity and inhibited glucosinolate biosynthesis to promote phenylpropanoid biosynthesis, leading to the production of phenolic acids and flavonoids that removed reactive oxygen species and protected membrane system stability. The experiments evaluated and provided insight into the innovative utilization of wild soybean germplasm resources.

Ginsenoside Rb1 Alleviates Lipopolysaccharide-Induced Inflammatory Injury by Downregulating miR-222 in WI-38 Cells.

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

A Model for Predicting Significant Hyperbilirubinemia in Neonates From China.

OBJECTIVES: To develop and validate a predischarge risk stratification model by using transcutaneous bilirubin (TcB) values and clinical factors to predict significant postdischarge hyperbilirubinemia in healthy term and late preterm Chinese neonates. METHODS: In a prospective cohort study, 8215 healthy term and late preterm neonates in 8 hospitals in China underwent TcB measurement at <168 hours of age. TcB percentiles were calculated and used to develop an hour-specific nomogram, and 9 empirically weighted items were used to derive a prediction model. A risk stratification model was developed by combining the TcB nomogram with clinical risk scores to predict significant hyperbilirubinemia, defined as a postdischarge bilirubin level that exceeded the hour-specific recommended threshold value for phototherapy. Data from another 13,157 neonates were used to validate the model. RESULTS: A TcB nomogram for every 12 hours of the studied interval was constructed from the development set. Gestational age, male gender, history of previous neonate who received phototherapy, bruising, feeding mode, weight loss, and early discharge were predictors of postdischarge significant hyperbilirubinemia. The combination of the TcB nomogram and clinical risk score provided the best prediction of significant hyperbilirubinemia with an area under the curve of 0.95 (95% confidence interval: 0.94-0.95) in the development data set and 0.94 (95% confidence interval: 0.93-0.94) in the validation data set. A risk stratification model with 6 distinct risk levels was developed and validated. CONCLUSIONS: A risk classification model, combining discharge transcutaneous bilirubin values and clinical risk factors, separated term and late preterm Chinese neonates into 6 risk classes for the timely follow-up of postdischarge hyperbilirubinemia detection.

Screening of mammalian target of rapamycin inhibitors in natural product extracts by capillary electrophoresis in combination with high performance liquid chromatography-tandem mass spectrometry.

In this study, capillary electrophoresis (CE) combined with HPLC-MS/MS were used as a powerful platform for screening of inhibitors of mammalian target of rapamycin (mTOR) in natural product extracts. The screening system has been established by using 5-carboxyfluorescein labeled substrate peptide F-4EBP1, a known mTOR inhibitor AZD8055, and a small chemical library consisted of 18 natural product extracts. Biochemical screening of natural product extracts was performed by CE with laser induced fluorescence detection. The CE separation allowed a quantitative measurement of the phosphorylated product, hence the quantitation of enzymatic inhibition as well as inhibition kinetics. The hits are readily identified as long as the peak area of the phosphorylated product is reduced in comparison with the negative control. Subsequent assay-guided isolation of the active natural product extract was performed with HPLC-MS/MS to track the particular active components. The structures of the identified active components were elucidated by the molecular ions and fragmentation information provided by MS/MS analysis. The CE-based assay method only requires minute pure compounds, which can be readily purified by HPLC. Therefore, the combination of CE and HPLC-MS/MS provides a high-throughput platform for screening bioactive compounds from the crude nature extracts. By taking the advantage of the screening system, salvianolic acid A and C in extract of Salvia miltiorrhiza were discovered as the new mTOR inhibitors.

Triadic motifs in the dependence networks of virtual societies.

In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

Extract of okra lowers blood glucose and serum lipids in high-fat diet-induced obese C57BL/6 mice.

Okra is an important tropical vegetable and source of dietary medicine. Here, we assayed the effects of an ethanol extract of okra (EO) and its major flavonoids isoquercitrin and quercetin 3-O-gentiobioside on metabolic disorders in high-fat diet-induced obese mouse. We found that treatment with EO, isoquercitrin and quercetin 3-O-gentiobioside reduced blood glucose and serum insulin levels and improved glucose tolerance in obese mice. Meanwhile, serum triglyceride levels and liver morphology in the mice were significantly ameliorated by EO and isoquercitrin treatment. Total cholesterol levels in isoquercitrin and quercetin 3-O-gentiobioside treated mice were also reduced. We also found that EO inhibited the expression of nuclear receptor transcription factor PPARγ, which is an important regulator of lipid and glucose homeostasis. Furthermore, we determined that EO and quercetin 3-O-gentiobioside have antioxidant activity in vitro. Our results indicate that okra may serve as a dietary therapy for hyperglycemia and hypertriglyceridemia.

Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

INTRODUCTION: Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. METHODS: The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. RESULTS: In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. CONCLUSION: Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

Relationship of cell-wall bound fatty acids and the demulsification efficiency of demulsifying bacteria Alcaligenes sp. S-XJ-1 cultured with vegetable oils.

Considering that the surface properties of demulsifying cells correlate with their demulsification efficiency, the demulsifying bacteria Alcaligenes sp. S-XJ-1 with various surface properties were obtained using different vegetable oils as carbon sources. The results show that better performance was achieved with demulsifying bacteria S-XJ-1 possessing a relatively high cell surface hydrophobicity (CSH) and total unsaturated degree for the cell-wall bound fatty acids. There also appeared to be a correlation between the specific cell-wall bound fatty acid components of the bacteria, in terms of carbon chain length or degree of unsaturation, and either CSH or demulsification efficiency. The fatty acids attached to the cell wall were mainly composed of palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2) and linolenic acid (C18:3). C18:1 and C18:2 had a positive effect on the formation of CSH, while C18:0 and C18:3 had the opposite effect.

[Bioactivity and action modes of bisdemethoxycurcumin against Tetranychus cinnabarinus Bois. (Acari:Tetranychidae)].

This paper determined the contact-killing and fumigant activities of natural plant product bisdemethoxycurcumin (BDMC) on the important phytophagous mite Tetranychus cinnabarinus (Acari:Tetranychidae) at its different life stages, and studied the repellency effects of BDMC on the mite larvae, nymphs, and adults, and the inhibition efficiency of BDMC on the female mite oviposition under the conditions of 26 degrees C +/- 1 degree C, 60%-80% RH, and light cycle 14L : 10D h. The median lethal concentration (LC50) of BDMC at 48 h against female adults determined by slide-dip method was 0.433 mg x mL(-1). At concentration 0.883 mg x mL(-1) (LC70), the contact-killing activity of BDMC against different life stage T. cinnabarinus was in the order of larva > nymph > adult > egg, and the corrected mortality of larvae at 24 h and 48 h was 60.0% and 83.3%, respectively. BDMC had no obvious fumigant activity against different life stage T. cinnabarinus, and the corrected mortality was all less than 3% after treatment 24 h and 48 h. BDMC had stronger repellency activity against the mite, with the repellency rate against larvae at different treatment times all above 85%, followed by against nymphs, and that against adults after 72 h being only 47.8%. BDMC had obvious oviposition inhibition activity against female adults, with the inhibition rate after 120 h reached 89.3%. All the results suggested that the main action modes of BDMC against T. cinnabarinus were contact-killing, repellency, and oviposition inhibition.