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Electrocatalytic C-N coupling reaction by co-activation of both N 2 and CO 2 molecules under ambient conditions to synthesize valuable urea opens a new avenue for sustainable development, while the actual catalytic activity is limited by poor adsorption and coupling capability of gas molecules on the catalyst surface. Herein, theoretical calculation predicts that the well-developed built-in electric field in perovskite hetero-structured BiFeO 3 /BiVO 4 hybrids can accelerate the local charge redistribution and thus promote the targeted adsorption and activation of inert N 2 and CO 2 molecules on the generated local electrophilic and nucleophilic regions. Thus, a BiFeO 3 /BiVO 4 heterojunction is designed and synthesized, which delivers a urea yield rate of 4.94 mmol h -1 g -1 with a faradaic efficiency of 17.18% at -0.4 V vs. RHE in 0.1 M KHCO 3 , outperforming the highest values reported as far. The comprehensive analysis further confirms that the local charge redistribution in the heterojunction effectively suppresses CO poisoning and the formation of the endothermic *NNH intermediate, which thus guarantees the exothermic coupling of *N[double bond, length as m-dash]N* intermediates with the generated CO via C-N coupling reactions to form the urea precursor *NCON* intermediate. This work opens a new avenue for effective electrocatalytic C-N coupling under ambient conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hepatic fibrosis is an inflammatory response that leads to liver cirrhosis in the most advanced condition. Liver cirrhosis is a leading cause of deaths associated with liver diseases; hence, understanding the underlying mechanisms of hepatic fibrosis is critical to develop effective therapies. Tripartite motif (TRIM) family proteins have been shown to be involved in liver fibrosis; however, the exact role of several TRIM proteins in this process remained unexplored. In this study, we investigated the role of TRIM37 in hepatitis B virus (HBV)-associated hepatic fibrosis. We analyzed TRIM37 expression in hepatic fibrosis patients and performed functional and mechanistic studies in tissue culture and mouse models to identify the role of TRIM37 in hepatic fibrosis. We found an increased expression of TRIM37 in hepatic fibrosis patients. Mechanistically, we showed that TRIM37 physically interacts with SMAD7 and promotes ubiquitination-mediated degradation of SMAD7, and that SMAD7 is a key mediator of TRM37-induced hepatic fibrosis. Furthermore, we showed nuclear factor κB (NF-κB) activation mediated by reactive oxygen species (ROS) is necessary for the transcriptional induction of TRIM37 during HBV infection. Our study shows TRIM37 as an important promoter of HBV-associated hepatic fibrosis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Home-based cardiac rehabilitation is considered as an alternative strategy of cardiac rehabilitation, aims to enhance patients participation rate. Since it emphasizes patients subjective initiative, patients require a better understanding of their illness and manage their conditions. We perform this systematic review and meta-analysis to identify the role and effectiveness of the self-management program in home-based cardiac rehabilitation., Method: We conduct the search strategy from an online database: PubMed, web of science, CINAL, EMBASE, OVID/Medline, and google scholar. Studies meet the inclusion criterion and published in the English language in recent 10 years will be screened by 2 independent reviewers. Then they extract data and assess the risk of bias. The disagreement between them will be resolved by the third reviewer. Data analysis is performed by Review Manager (Version 5.3)., Result: This is systematic review and meta-analysis will identify the role of self-management in home-based cardiac rehabilitation program and evaluate its effectiveness., Conclusion: The findings of this study will be published in a related peer-reviewed journal.Protocol registration number: INPLASY202050093.

Background: The benefits of high-intensity interval training (HIIT) are well-known, there is insufficient evidence about the effects of HIIT on heart failure with preserved ejection fraction (HFpEF)., Method: Multiple databases include MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, PEDro, Cochrane Library, and Google Scholar are used to search for randomized controlled trials investigating the effects of HIIT on HFpEF. All related articles published with the English language with no time limitation will be included. Two reviews independently conducted the selection, data extraction, and quality assessment. The primary outcome is exercise capacity. The secondary outcomes include quality of life (QoL), blood pressure (BP), ventricular function, and left ventricular diastolic function, symptom improvement, endothelial function, and arterial stiffness. Data analysis is performed with Review Manager Software (Version 5.3)., Result: This systematic review and meta-analysis aim to evaluate the efficacy of HIIT on HFpEF, its outcome will provide reliable evidence for future studies., Conclusion: The findings of this study will be published in a related peer-reviewed journal., Registration Number: INPLASY202050097.

In this study, a cetylpyridinium bromide (CPB)/montmorillonite-graphene oxide (GM) composite (GM-CPB) was prepared by loading CPB in a carrier of GM. The chemical structure, elemental composition, morphology, thermogravimetric analysis, antibacterial activity, sustained release property and cytotoxicity were analyzed. The loading rate of CPB in a GM carrier was higher than that of the graphene oxide (GO) carrier under the same loading condition. The antibacterial activity and sustained release performance of GM-CPB were also better than that of GO-CPB; furthermore, GM-CPB showed lower cytotoxicity than CPB.

Objective: To understand the epidemiological characteristics and risk factors of dyslipidemia in adult residents of Jiangsu Province in 2014., Methods: A total of 8677 permanent residents over 18 years old were selected from 12 monitoring sites in Jiangsu Province in 2014 by multi-stage stratified cluster random sampling and were enrolled for questionnaire survey, physic examination and biochemical tests., Results: Totally, 8299 cases were analyzed including 3732 males(45. 0%) and 4567 females(55. 0%). The rate of dyslipidemia was 38. 2%(standardized prevalence rate was38. 5%). Among the 8299 cases, 25. 8% had high TG(standardized rate was 25. 9%), 13. 2% had low HDL-C(standardized rate was 13. 4%), 6. 0% had high TC(standardized rate was 5. 9%). With the increase of age, the prevalence of dyslipidemia in males showed a downward trend(P<0. 05), and the dyslipidemia in females showed an increasing trend(P<0. 05). The prevalence of dyslipidemia in urban and rural adults was42. 9% and 36. 9%. The Logistic multivariate analysis showed that heavy physical and other types of labor were protective factors for dyslipidemia(OR = 0. 422 and 0. 749). Primary school education or above, occupational labor of medium type, overweight and obesity, central obesity were risk factors for dyslipidemia. Hypertension, diabetes, stroke were positively correlated with dyslipidemia(OR = 1. 045, 1. 927, 1. 927 and 1. 501)., Conclusion: The prevalence of dyslipidemia in adults in Jiangsu Province is on the rise. Hyperlipidemia and low HDL-C are the main forms of dyslipidemia in Jiangsu Province.

In this work, we proposed a feasible approach to prepare multifunctional composite films by introducing a nanoscaled filler into a polymer matrix. Specifically, thanks to isophorone diisocyanate (IPDI) acting as a coupling agent, the hydroxyl groups and carboxyl groups on the surface of graphene oxide (GO) and the hydroxyl groups on the surface of silver-coated zinc oxide nanoparticles (Ag/ZnO) are covalently grafted, forming GO-IPDI-Ag/ZnO (AGO). The prepared AGO was then introduced into the hydroxypropyl cellulose (HPC) matrix to form AGO@HPC nanocomposite films by solution blending. AGO@HPC nanocomposite films exhibited improved mechanical, anti-ultraviolet, and antibacterial properties. Specifically, a tensile test showed that the tensile strength of the prepared AGO@HPC nanocomposite film with the addition of as low as 0.5 wt % AGO was increased by about 16.2% compared with that of the pure HPC film. In addition, AGO@HPC nanocomposite films showed a strong ultraviolet resistance and could effectively inactivate both Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria at a low loading of AGO, and rapid sterilization plays a crucial role in wound-healing. In vivo results show that the AGO@HPC release of Ag + and Zn 2+ stimulates the immune function to produce a large number of white blood cells and neutrophils, thereby producing the synergistic antibacterial effects and accelerated wound-healing. Therefore, our results suggest that these novel AGO@HPC nanocomposite films with improved mechanical, anti-ultraviolet, and antibacterial properties could be promising candidates for antibacterial packaging, biological wound-dressing, etc. The abuse of antibiotics has brought about serious drug-resistant bacteria, and our nanofilm antibacterial does not entail such problems. In addition, local administration reduces the possibility of changing the body's immune system and organ toxicity, which greatly increases the safety., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

A novel and selective cascade reaction of primary amines and alkynes for the synthesis of the corresponding secondary propargylamines is described. This protocol proceeds with a CuBr 2 /TBHP system through a process of oxidative deamination of primary amines to imine and alkynylation, featuring a wide scope of substrates with good functional-group tolerance and operational simplicity. Additionally, the use of two different primary amines could also work smoothly using this protocol.

Due to secondary pollution from bactericidal substances, the importance of eliminating microbial contamination has become a controversial topic. Three antibacterial nanorod materials of carbon quantum dots-zinc oxide (1/3CQDs-ZnO, CQDs-ZnO, and 2CQDs-ZnO), in which ZnO nanorods are surrounded by carbon quantum dots (CQDs), were successful prepared via in-situ sol-gel chemistry. Antibacterial nanorods of CQDs-ZnO had strong antibacterial activity under visible light irradiation, and a concentration of 0.1 mg/L was able to kill more than 96% of bacteria. The photocatalytic antibacterial mechanism was also studied. CQDs-ZnO produced more than three times the free radicals than pure ZnO under visible light irradiation. These free radicals destroyed the bacterial matrix of the cell wall and released cell proteins and nucleic acids. Moreover, CQDs-ZnO showed low cytotoxicity and can be used in medical applications.

To increase antibacterial activity and reduce the cytotoxicity of copper nanoparticles (CuNPs), we used reduced graphene oxide with montmorillonite to support CuNPs and fixed CuNPs on reduced graphene oxide to synthesize the hybrid montmorillonite-reduced graphene oxide copper nanoparticles (MMT-rGO-CuNPs). The synthesized MMT-rGO-CuNPs complex showed a stronger antibacterial activity against Gram-positive bacteria S. aureus than Gram-negative E. coli . This may be due to the protective effect of the outer membrane of E. coli , as well as the fact that the MMT-rGO-CuNPs complex adsorbs S. aureus more strongly than E. coli . The hybrid molecule's antibacterial efficacy is the combined result of the synergistic effects of electrostatic adsorption and copper ion sterilization ability. At the same time, the MMT-rGO-CuNPs complex exhibits a lower cytotoxicity than PVP-CuNPs and provides a biocompatible composite material with a reduced cytotoxicity.

The applications of graphene-based adsorbents were limited because of their complicated manufacturing technology and hi cost, thus it is very important to prepare new inexpensive and easily manufactured graphene-based adsorbents. Herein, novel GCP hydrogels with different graphene oxide (GO), chitosan (CS), and poly(vinyl alcohol) (PVA) ratios were facilely prepared through a method of freeze-thaw physical cross-linking, which was green and low-cost, and the structural characterization and adsorptive property of the optimum GCP 1:2:4 hydrogel toward Cd 2+ and Ni 2+ in wastewater was evaluated. It was found that the GCP 1:2:4 hydrogel had good mechanical strength and a special 3D interconnection porous structure. The isotherms of adsorption used the Langmuir model, and the kinetics of adsorption following the pseudo-second-order model were confirmed. Moreover, the adsorption property with respect to Cd 2+ and Ni 2+ in wastewater has been largely effected by the pH and was less influenced by the ionic strength and humic acid, and the GCP 1:2:4 hydrogel possessed excellent adsorptive and recyclable properties. These results demonstrated that the GCP 1:2:4 hydrogel could serve as a desirable adsorbent to get rid of heavy metal ions in sewage.

The presence of illegally adulterated sildenafil and related compounds in dietary supplements was qualitatively analyzed by employing ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Samples were extracted by ultrasonic method using methanol. The analysis was performed on an Agilent Poroshell 120 SB-C18 column (75 mm×3.0 mm, 2.7 μm) using gradient elution with a mixture of aqueous formic acid solution (0.1%, v/v) and acetonitrile as the mobile phase at a flow rate of 0.4 mL/min. Q-TOF-MS equipped with ESI ion source was operated in a positive ionization mode. Qualitative analysis was based on the retention time and the accurate relative molecular mass of elemental compositions of the precursor ion and product ions. The limits of detection (LODs) of sildenafil and other 99 compounds were found to be 0.1-50 mg/kg or 0.1~50 mg/L in 10 different matrices. In this manuscript, the fragmentation behavior of 98 phosphodiesterase-5 inhibitors are categorically summarized, which can provide information for referencing and identification of suspicious compounds. The method was successfully applied to the analysis of actual samples, of which 19 compounds combated the illegal adulteration behavior effectively.

Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of histone acetyltransferases. Data obtained using purified histones further validate the results obtained in mice and in cultured oligodendrocyte progenitors. Together, these results identify PRMT5 as critical for oligodendrocyte differentiation and developmental myelination by modulating the cross-talk between histone arginine methylation and lysine acetylation.

Breast cancer progression, treatment resistance, and relapse are thought to originate from a small population of tumor cells, breast cancer stem cells (BCSCs). Identification of factors critical for BCSC function is therefore vital for the development of therapies. Here, we identify the arginine methyltransferase PRMT5 as a key in vitro and in vivo regulator of BCSC proliferation and self-renewal and establish FOXP1, a winged helix/forkhead transcription factor, as a critical effector of PRMT5-induced BCSC function. Mechanistically, PRMT5 recruitment to the FOXP1 promoter facilitates H3R2me2s, SET1 recruitment, H3K4me3, and gene expression. Our findings are clinically significant, as PRMT5 depletion within established tumor xenografts or treatment of patient-derived BCSCs with a pre-clinical PRMT5 inhibitor substantially reduces BCSC numbers. Together, our findings highlight the importance of PRMT5 in BCSC maintenance and suggest that small-molecule inhibitors of PRMT5 or downstream targets could be an effective strategy eliminating this cancer-causing population., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The transcriptional network acting downstream of LIF, WNT and MAPK-ERK to stabilize mouse embryonic stem cells (ESCs) in their naive state has been extensively characterized. However, the upstream factors regulating these three signaling pathways remain largely uncharted. PR-domain-containing proteins (PRDMs) are zinc-finger sequence-specific chromatin factors that have essential roles in embryonic development and cell fate decisions. Here we characterize the transcriptional regulator PRDM15, which acts independently of PRDM14 to regulate the naive state of mouse ESCs. Mechanistically, PRDM15 modulates WNT and MAPK-ERK signaling by directly promoting the expression of Rspo1 (R-spondin1) and Spry1 (Sprouty1). Consistent with these findings, CRISPR-Cas9-mediated disruption of PRDM15-binding sites in the Rspo1 and Spry1 promoters recapitulates PRDM15 depletion, both in terms of local chromatin organization and the transcriptional modulation of these genes. Collectively, our findings uncover an essential role for PRDM15 as a chromatin factor that modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency.

Key Message: A Salvia miltiorrhiza R2R3-MYB gene, SmMYB9b , has been cloned and characterized. Overexpression of SmMYB9b resulted in a significant improvement of tanshinones, the lipophilic active ingredients in danshen hairy roots. Plant R2R3-MYB transcription factors play important roles in various physiological and biochemical processes. Danshen (Salvia miltiorrhiza bunge) is a valuable medicinal herb with tanshinones and salvianolic acids as the principal bioactive ingredients. A number of putative R2R3-MYB transcription factors have been identified in the plant, but their function remains to be studied. Here, we report the cloning of SmMYB9b, an S20 R2R3-MYB member and its regulatory properties. SmMYB9b contains an open reading frame of 792 bp in length and encodes a 264-amino acid protein. Its transcripts were most abundant in blooming flowers (except for calyces) and increased with flower development. Exogenous abscisic acid strongly activated its transcription. Gibberellins and methyl jasmonate also showed a time-dependent activation effect on its transcription, but to a weaker degree. Overexpression of SmMYB9b in danshen hairy roots enhanced tanshinone concentration to 2.16 ± 0.39 mg/g DW, a 2.2-fold improvement over the control. In addition to increased tanshinone concentration, the hairy root growth and lateral hairy root formation were also suppressed. KEGG pathway enrichment analysis with de novo RNAseq data indicated that stress-response-related metabolic pathways, such as the terpenoid and plant hormone signal transduction pathways, were significantly enriched, implying possible implication of SmMYB9b in such processes. Quantitative RT-PCR analysis showed that the transcription of terpenoid biosynthetic genes SmDXS2, SmDXR, SmGGPPS, and SmKSL1 was significantly up-regulated in danshen hairy roots over expressing SmMYB9b. These data suggest that overexpression of SmMYB9b results in enhanced tanshinone concentration through stimulation of the MEP pathway. The present findings shed new light on elucidating the roles of R2R3-MYB in the biosynthesis of diterpenoids in S. miltiorrhiza.

An analytical method was developed for the determination of 34 illegally adulterated weight loss compounds in foods and dietary supplements by ultra high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). A Waters CORTECS T3 column (100 mm×2.1 mm, 2.7 μm) was used with 0.1% (v/v) formic acid aqueous solution-acetonitrile containing 0.1% (v/v) formic acid as mobile phases by gradient elution. The compounds were detected by electrospray ion source in positive or negative mode with multiple reaction monitoring (MRM) mode. The calibration curves showed good linearity in the range of 0.5-10 μg/L for 29 compounds such as sibutramine, and in the range of 2.5-50 μg/L for five compounds such as chlorothiazide. The correlation coefficients ( r ) of the standard calibration curves for the 34 analytes were all greater than 0.99. The recoveries of the 29 compounds at spiked levels of 5, 10 and 20 μg/kg were in the range of 49.2%-136.2%, and the RSDs were 0.7%-15.0% ( n =6). The recoveries of the five compounds at spiked levels of 25, 50 and 100 μg/kg were in the range of 51.5%-130.9%, and the RSDs were 0.8%-14.0% ( n =6). The limits of detection (LODs) and limits of quantification (LOQs) were 5 μg/kg and 10 μg/kg for the 29 compounds, 25 μg/kg and 50 μg/kg for the five compounds, respectively. The method was successfully applied to the analysis of actual samples, and 12 compounds were checked out, which combated the illegal adulteration behavior effectively.

Animal-derived medicines have been a vital component for traditional Chinese medicine. However, their quality control remains challenging due to the large polarity of the contained endogenous small molecules (ESMs) that are difficult to separate by reversed-phase HPLC. Herein, an intelligentized strategy by ultra-high performance hydrophilic interaction chromatography/quadrupole time-of-flight mass spectrometry (HILIC/QTOF-MS(E)) is presented, and used for the ESMs characterization and differentiation of two geographic origins of earthworm (Guang Di-long, GD; Hu Di-long, HD) as a case study. Chromatographic separation was performed on a BEH Amide column (2.1 × 100 mm, 1.7 μm). The MS(E) data in both negative and positive ion modes were acquired to record the high-accuracy MS and MS/MS data of all precursor ions. Automatic data processing was enabled by use of Progenesis QI software. As a consequence, 926 metabolites among 4705 features and 761 among 3418 features were characterized in the negative and positive modes, respectively, by searching the human metabolome database (HMDB). To reduce the false positive identifications, structural confirmation was conducted by comparison with the reference standards (tR and MS, MS/MS data) or matching with theoretical data or commercial library. Principal component analysis (PCA) of the GD and HD samples showed distinct classifications. Further orthogonal partial least squares discriminant analysis (OPLS-DA) and variable importance in projection (VIP) plot revealed the potential discriminatory markers between GD and HD. The present study provides a powerful and practical strategy that facilitates the primary metabolites characterization and quality evaluation of animal-derived medicines more efficiently. Graphical Abstract A general flowchart illustrating the application of ultra-high performance HILIC/QTOFMS(E) coupled with data processing by Progenesis QI to characterization of the endogenous small molecules and discriminatory analysis of animal-derived traditional medicine: earthworm as a case study.

Background: Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates., Results: We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors., Conclusions: SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

The three wavelength fusion high performance liquid chromatographic fingerprin (TWFFP) of Longdanxiegan pill (LDXGP) was established to identify the quality of LDXGP by the systematic quantified fingerprint method. The chromatographic fingerprints (CFPs) of the 12 batches of LDXGP were determined by reversed-phase high performance liquid chromatography. The technique of multi-wavelength fusion fingerprint was applied during processing the fingerprints. The TWFFPs containing 63 co-possessing peaks were obtained when choosing baicalin peak as the referential peak. The 12 batches of LDXGP were identified with hierarchical clustering analysis by using macro qualitative similarity (S(m)) as the variable. According to the results of classification, the referential fingerprint (RFP) was synthesized from 10 batches of LDXGP. Taking the RFP for the qualified model, all the 12 batches of LDXGP were evaluated by the systematic quantified fingerprint method. Among the 12 batches of LDXGP, 9 batches were completely qualified, the contents of 1 batch were obviously higher while the chemical constituents quantity and distributed proportion in 2 batches were not qualified. The systematic quantified fingerprint method based on the technique of multi-wavelength fusion fingerprint ca effectively identify the authentic quality of traditional Chinese medicine.