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This study aims to extract phenolic-enriched compounds, specifically oleuropein, luteoloside, and hydroxytyrosol, from olive leaves using ball milling-assisted extraction (BMAE). Response surface methodology (RSM) and the Box–Behnken design (BBD) were used to evaluate the effects of the temperature, solvent-to-solid ratio, and milling speed on extraction recovery. The contents of the extract were determined by ultra-high-performance liquid chromatography–mass spectrometry (UPLC-MS) and converted to recoveries to evaluate the extraction efficiency. The optimal extraction conditions for oleuropein, luteoloside, and hydroxytyrosol were identified. Oleuropein had a recovery of 79.0% ± 0.9% at a temperature of 56.4 °C, a solvent-to-solid ratio of 39.1 mL/g, and a milling speed of 429 rpm. Luteoloside’s recovery was 74.6% ± 1.2% at 58.4 °C, 31.3 mL/g, and 328 rpm. Hydroxytyrosol achieved 43.1% ± 1.3% recovery at 51.5 °C, 32.7 mL/g, and 317 rpm. The reason for the high recoveries might be that high energy ball milling could reduce the sample size further, breaking down the cell walls of olive leaves, to enhance the mass transfer of these components from the cell to solvent. BMAE is displayed to be an efficient approach to extracting oleuropein, luteoloside, and hydroxytyrosol from olive leaves, which is easy to extend to industrial production.

Abstract. Objective:. To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta (PA). Methods:. This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. According to the intraoperative findings after delivery, the study population was divided into PA and non-PA groups. We compared the pregnancy outcomes between the two groups, used multivariate logistic regression to analyze the risk factors for placental accreta. Results:. For this study we included 11,074 pregnant women with a history of cesarean section; and of these, 869 cases were in the PA group and 10,205 cases were in the non-PA group. Compared with the non-PA group, the probability of postpartum hemorrhage (236/10,205, 2.31% vs. 283/869, 32.57%), severe postpartum hemorrhage (89/10,205, 0.87% vs. 186/869, 21.75%), diffuse intravascular coagulation (3/10,205, 0.03% vs. 4/869, 0.46%), puerperal infection (33/10,205, 0.32% vs. 12/869, 1.38%), intraoperative bladder injury (1/10,205, 0.01% vs. 16/869, 1.84%), hysterectomy (130/10,205, 1.27% vs. 59/869, 6.79%), and blood transfusion (328/10,205,3.21% vs. 231/869,26.58%) was significantly increased in the PA group (P

Mn3O4-Fe2O3 composite catalysts are in-situ synthesized via advanced oxidation followed by modifying with hydrochloric acid to improve the catalytic toluene oxidation performance. Mn3O4-Fe2O3 modified with 1.0 M HCl (A-1.0) exhibited best activity of toluene oxidation. The temperature of 50% toluene conversion is 245 °C and the temperature of 90% conversion is 279 °C. There are much more abundant surface lattice oxygen species and higher amount of high valence manganese and iron ions on A-1.0 catalyst, which are beneficial for improving catalytic activity. In-situ DRIFTs indicated that benzaldehyde and benzoic acid are main intermediate products on A-1.0 catalyst during toluene oxidation.

In this paper, a distributed energy grid control method based on collaborative consensus algorithm is proposed. Faced with the problem of insufficient control ability of independent power grid, multiple system control objectives are optimized. Moreover, according to the research goal of the consistency algorithm, the Pareto solution of the micro-grid control system is obtained. In addition, the optimized topology includes many categories, corresponding to different optimization goals respectively. Meanwhile, according to the micro-grid power control and voltage recovery studied in this paper, the ring network topology has obvious advantages. Through the simulation results, compared with other topologies, the ring topology has obvious advantages in both convergence and delay robustness, which proves its effectiveness.

The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (RBD) and found that peptide 391–465 aa is the major hACE2-interacting sites in SARS-CoV-2 spike RBD. We then identified essential amino acid residues (403R, 449Y, 454R) of peptide 391–465 aa that were critical for the interaction between the RBD and hACE2. Additionally, a pseudotyped virus containing SARS-CoV-2 spike with individual mutation (R454G, Y449F, R403G, N439I, or N440I) was determined to have very low infectivity compared with the pseudotyped virus containing the wildtype (WT) spike from reference strain Wuhan 1, respectively. Furthermore, we showed the key amino acids had the potential to drug screening. For example, molecular docking (Docking) and infection assay showed that Cephalosporin derivatives can bind with the key amino acids to efficiently block infection of the pseudoviruses with wild type spike or new variants. Moreover, Cefixime inhibited live SARS-CoV-2 infection. These results also provide a novel model for drug screening and support further clinical evaluation and development of Cephalosporin derivatives as novel, safe, and cost-effective drugs for prevention/treatment of SARS-CoV-2.

Black walnut (Juglans nigra) is considered one of the most valuable plants, with a global production of 3.5 million tons of dried fruit yearly. Throughout the past two millennia, its allelopathic effects have been widely recognized. Black walnuts produce a natural naphthoquinone called juglone, which occurs naturally in all parts of the tree, particularly the green husk, and contributes significantly to the allelopathic effects of black walnut. Except for the fruit’s edible nature, the walnut green husk (Pericarpium Juglandis) has been used for centuries to make wine, natural dyes, and traditional medicines to cure certain diseases. Within the extracts of walnut green husk, 1,4-naphthoquinones, gallic acid, caffeic acid, and quercitrin were separated and characterized. Among these compounds, the major active ingredient with a good application prospect is juglone, which has proven to be a natural chemical compound with anticancer, antitumor, antibacterial, and antiviral activities, especially the strong anticancer activity. Juglone is also an environmentally friendly biological pesticide and herbicide. Certainly, the environmental impact of juglone also needs to be considered. Significant quantities of walnut green husk are currently produced as a byproduct of walnut production; however, its value has not been fully utilized and explored, which raises environmental concerns. This review attempts to: 1) summarize the origin and historical use of walnut and walnut green husk; 2) introduce the structure, biosynthesis pathway, extraction method, biological activity, and potential applications of juglone, as well as its environmental impact assessment.

Abstract To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

The paper proposes a low-pass filter adaptive iterative learning control (LPF-AILC) strategy for unmatched, uncertain, time-varying, non-parameterized nonlinear systems (NPNL systems). To address the difficulty of nonlinear parameterization terms in system models, a new function approximator (FSE-RBFNN), which combines the radial basis function neural network (RBFNN) and Fourier series expansion (FSE), is introduced to model each time-varying nonlinear parameterized function. The adaptive backstepping method is used to design control laws and parameter adaptive laws. In the process of controller design, we may encounter the problem of too many derivatives, which can cause parameter explosions after derivatives. Therefore, we introduce a first-order low-pass filter to solve this problem and simplify the structure of the controller. As the number of iterations increases, the maximum tracking error gradually decreases until it converges to the nearby region, approaching zero within the entire given interval [0, T], according to the Lyapunov-like synthesis. To mitigate the impact of initial state errors, a dynamically changing boundary layer is introduced, along with a series to deal with the unknown error upper bounds. Finally, two simulation examples prove the correctness of the proposed control method. [ABSTRACT FROM AUTHOR]

Abstract Background To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. Methods This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. Results The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25–29, 30–34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12–2.01), placenta previa (aOR, 1.349; 95% CI, 1.07–1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24–3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05–2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21–1.91) in the second cesarean compared with the reference group (aged 25–29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08–2.24), placental abruption (aOR, 6.464, 95% CI, 1.33–31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43–44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95–24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53–12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54–220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54–5.17) compared with the reference group (aged 25–29 years). Conclusions Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Depression, one of the most prevalent psychiatric diseases, affects the quality of life of millions of people. Studies have shown that the lower polar fraction of Bupleuri Radix (PBR) elicited therapeutic effects in chronic unpredictable mild stress (CUMS) rats. In contrast, comparatively mild liver injury was observed in normal rats administered a high PBR dose. It is essential to clarify the effective and safe dose of PBR and its dose-effect/toxicity relationship. In this study, we used the CUMS model to evaluate the effects and toxicities of PBR and to decipher the dose-effect/toxicity relationship and mechanism using the liver metabonomics combined with multivariate statistical analysis. In CUMS rats, PBR improved the depression-like behaviors including reduced body growth rate, anhedonia, and locomotor activities, and markedly reduced the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In control rats, PBR treatment altered ALT and AST from typical levels. Moreover, the effective dose range for CUMS rats was 12.6–163 g (herb)/kg, the median toxicity dose for CUMS and normal rats were 388 and 207 g (herb)/kg. The toxicological results showed that the cytokeratin-18 fragment level was increased significantly in CUMS rats given with 100 g (herb)/kg PBR. After a comprehensive analysis, the use of PBR dose was determined to be 12.6–50 g (herb)/kg. In CUMS rats, PBR could reverse amino acid metabolism, energy metabolism, sphingolipid metabolism, and β-oxidation of fatty acids to produce an anti-depressant effect in a dose-dependent manner. In control rats, two additional metabolic pathways were significantly perturbed by PBR, including glycerophospholipid metabolism and bile acid metabolism. Moreover, the comprehensive metabolic index including dose-effect index (DEI) and dose toxicity index (DTI) had a remarkable ability (ROC = 0.912, ROC = 0.878) to predict effect and toxicity. The DEI and DTI were used to determine the dose range of effect and toxicity which was shown high concordance with previous results. Furthermore, the CUMS rats possessed a higher toxicity tolerance dose of PBR which was consistent with the theory of “You Gu Wu Yun” in traditional Chinese medicine. The metabonomics techniques combined with correlation analysis could be used to discover indicators for comprehensive evaluations of efficacy and toxicity.

The bromodomain-containing protein BRD4 has been thought to transmit epigenetic information across cell divisions by binding to both mitotic chromosomes and interphase chromatin. UV-released BRD4 mediates the recruitment of active P-TEFb to the promoter, which enhances transcriptional elongation. However, the dynamic associations between BRD4 and P-TEFb and BRD4-mediated gene regulation after UV stress are largely unknown. In this study, we found that BRD4 dissociates from chromatin within 30 min after UV treatment and thereafter recruits chromatin. However, P-TEFb binds tightly to chromatin right after UV treatment, suggesting that no interactions occur between BRD4 and P-TEFb within 30 min after UV stress. BRD4 knockdown changes the distribution of P-TEFb among nuclear soluble and chromatin and downregulates the elongation activity of RNA polymerase II. Inhibition of JNK kinase but not other MAP kinases impedes the interactions between BRD4 and P-TEFb. RNA-seq and ChIP assays indicate that BRD4 both positively and negatively regulates gene transcription in cells treated with UV stress. These results reveal previously unrecognized dynamics of BRD4 and P-TEFb after UV stress and regulation of gene transcription by BRD4 acting as either activator or repressor in a context-dependent manner.

Abstract Background Microbial fermentation has been widely applied in traditional Chinese medicine (TCM) for thousands of years in China. Various beneficial effects of fermentation for applications in TCM or herbals have been reported, such as enhanced anti-ovarian cancer, antioxidative activity, and neuroprotective effects. Ge-Gen-Qin-Lian decoction (GQD), a classic TCM formula, has been used to treat type 2 diabetes mellitus in China. In this study, GQD was fermented with Saccharomyces cerevisiae, and the antidiabetic activities and overall chemical profiles of raw and fermented GQD (FGQD) were systematically compared. Methods First, the antidiabetic effects of GQD and FGQD on high-fat diet and streptozotocin (STZ)-induced diabetic rats were compared. Then, high-performance liquid chromatography Q Exactive MS was applied for rapid characterization of the chemical components of GQD. Additionally, we proposed an integrated chromatographic technique based untargeted metabolomics identifying differential chemical markers between GQD and FGQD and targeted analysis determining the fermenting-induced quantitative variation tendencies of chemical marker strategy for overall chemical profiling of raw and fermented GQD. Results Both GQD and FGQD displayed effects against HFD and STZ-induced diabetes, and FGQD showed a better recovery trend associated with profound changes in the serum lipoprotein profile and body weight gain. In addition, 133 compounds were characterized from GQD. It was demonstrated that the integrated strategy holistically illuminated 30 chemical markers contributed to the separation of GQD and FGQD, and further elucidated the fermenting-induced chemical transformation mechanisms and inherent chemical connections of secondary metabolites. Although there were no new secondary metabolites in FGQD compared with GQD, the amounts of secondary metabolites, which were mostly deglycosylated, were redistributed in FGQD. Conclusion The anti-diabetic activities of GQD could be improved by applying fermentation technology. Moreover, the proposed strategy could serve as a powerful tool for systematically exploring the chemical profiles of raw and fermented formulas.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.