Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

[Mechanism of Huangqi Simiao Decoction in treatment of type 2 diabetes mellitus based on network pharmacology and metabonomics].

This article analyzed the mechanism of Huangqi Simiao Decoction(HSD) for the treatment of type 2 diabetes mellitus(T2DM). The component targets of HSD and the related disease targets of T2DM were screened through network pharmacology. The protein-protein interaction(PPI) network of intersecting targets and the drug-component-intersecting target network were constructed to screen the potential active ingredients and targets. Molecular docking was performed using AutoDock Vina software to verify the interaction between potential components and core targets. The serum was tested by ultra performance liquid chromatography-tandem mass spectrometry, and multivariate statistical analyses, such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), were used to search for the differential metabolites and related metabolic pathways of each group by combining with the MetaboAnalyst database. The same metabolic pathways were analyzed by combining the screened differential metabolites with the intersecting targets screened by network pharmacology. Network pharmacology showed that the nine core components of HSD for the treatment of T2DM were quercetin, kaempferol, stigmasterol, baicalein, ß-sitosterol, flavodoxin, canthaxanthin, canthaxanthin, berberine, and berberine, and the five core targets included AKT1, TP53, TNF, IL6, and VEGFA. Molecular docking showed that the core components bound well to the target genes. Metabolomics showed that a total of 112 common differential metabolites were identified, of which 88 metabolites exhibited increased concentration and 24 metabolites decreased concentration after treatment with HSD. Enrichment analysis showed that HSD regulated the body metabolism of patients with T2DM, mainly related to seven metabolic pathways, such as amino acid metabolism and tricarboxylic acid cycle. The joint analysis of metabolomics and network pharmacology showed that both involved histidine metabolism, arginine and proline metabolic pathways. This study suggests that HSD has a good efficacy for T2DM. Based on the combined analysis of metabolomics and network pharmacology, it was found that the mechanism may be that the pharmacodynamic bases of quercetin, kaempferol, and stigmasterol in HSD enhance the effects on histidine metabolism, arginine and proline metabolic pathways by modulating a variety of metabolites, which provides the basis for further prevention and treatment of T2DM.

Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an important target in the development of anti-influenza virus drugs. Compounds containing 1,3, 4-oxadiazole heterocycles have good biological activity and have been proved to have wide applications in antibacterial and antiviral drugs. In this paper, a series of novel 1, 3, 4-oxadiazole neuraminidase inhibitors (6a-6l) were designed and synthesized and their inhibitory activities of NA was tested in vitro. The results displayed that compound 6d exerts the best inhibitory activity (IC50 = 0.027 µM), which was obviously lower than that of oseltamivir carboxylate (OSC) (IC50 = 0.082 µM). Molecular docking analysis showed that the 1, 3, 4-oxadiazole heterocycle plays crucial part in compound 6d, and it can interact with the key arginine triad (Arg118, Arg292 and Arg 371) at the NA S1 site. The good efficacy of 6d may also be attributed to the extension of the substituted aniline ring to the 150-cavitiy. The theoretical and experimental results may provide reference for development of new anti-influenza drugs.

Circular RNA PVT1 silencing prevents ischemia-reperfusion injury in rat by targeting microRNA-125b and microRNA-200a.

Circular RNAs (circRNAs) are essential regulators associated with many cardiac conditions, including myocardial infarction (MI). This study aimed to explore circRNA expression during MI development in an animal model and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Microarray and real-time quantitative PCR showed that the circRNA PVT1 (circPVT1) was expressed at high levels in MI tissues and H/R-triggered cardiomyocytes. Loss-of-function assays were utilized for examining the influence of circPVT1 on cardiac function and cardiomyocyte properties. Cardiac function was measured by echocardiography at 7 d after MI. Reduced circPVT1 expression significantly decreased MI-triggered myocardial infarct size by 60% and prevented MI-triggered reductions in fractional shortening (%FS) and ejection fraction (EF%). Results of LDH, CCK-8, EdU staining, colony formation assays, and flow cytometry showed that circPVT1 silencing restored cell viability and proliferation while decreased apoptosis. Mechanistic experiments indicated that microRNAs (miR)-125b and miR-200a associated with circPVT1. We demonstrated that circPVT1 functioned as a competitive endogenous RNA (ceRNA) to sponge both miR-125b and miR-200a. Gain-of-function assays showed that miR-125b and miR-200a upregulation partially eliminated the effects of circPVT1 on cardiomyocyte properties. In addition, we found that the previously reported p53/TRAF6, SIRT7, Keap1/Nrf2, and PDCD4 pathways were regulated by the circPVT1/miR-125b/miR-200a axis. In conclusion, our study suggests that circPVT1 protects the myocardium from MI and H/R injury by preventing miR-125b- and miR-200a-mediated apoptotic signaling.

Additive-free coupling of bromoalkynes with secondary phosphine oxides to generate alkynylphosphine oxides in acetic anhydride.

A coupling of bromoalkynes with secondary phosphine oxides was developed for the synthesis of alkynylphosphine oxides. This transformation was accomplished under additive-free conditions in acetic anhydride (Ac2O). The reaction could be carried out under mild conditions, and a wide range of secondary phosphine oxides were obtained in good yields.

Glycyrrhiza glabra suppresses nasopharyngeal carcinoma cell proliferation through inhibiting the expression of lncRNA, AK027294.

Glycyrrhiza glabra is considered as potential drug for nasopharyngeal carcinoma (NPC). However, whether the long noncoding RNAs' (lncRNAs) contributes to the anti-cancer function of this herb is unknown. In present study, we analyzed the differential expression of lncRNA between G. glabra-treated and untreated C666-1 cells. Out of those tumor-related lncRNAs, AK027294 had a strongest down-regulation upon G. glabra treatment. Knockdown of AK027294 suppresses the proliferation of C666-1 cells by inducing the apoptosis. Moreover, either G. glabra treatment or knockdown of AK027294 significantly increases the production of EZH1 (Enhancer of zeste 1 polycomb repressive complex 2 subunit). Collectively, we have identified a potential mechanism that the down-regulation of AK027294 contributes to the anti-cancer function of G. glabra and also provide the potential inter-relationship between AK027294 and EZH1.

Impact of an intelligent chronic disease management system on patients with type 2 diabetes mellitus in a Beijing community.

BACKGROUND: Rapid demographic and economic changes have made chronic disease the number one health issue in China, contributing to more than 80% of the country's 10.3 million annual deaths and nearly 70% of its total disease burden (Wang et al., Toward a Healthy and Harmonious Life in China: Stemming the Rising Tide of Non-Communicable Diseases, 2011; Yip and Hsiao, Lancet 384: 805-18, 2014). Diabetes is a major contributor to the chronic disease burden and is experienced by nearly 11% of the adult population of China (Yang et al., N Engl J Med 362:1090-101, 2010). In response to the challenges of chronic disease, the Chinese government initiated comprehensive health care reforms nationwide in 2009. A key measure was a hierarchical diagnosis and treatment system for monitoring and reducing chronic diseases and improving the community health service system (Barber et al., Health Policy Plan 29:367-78, 2014). Primary hospitals, such as community health service centers, are the main gatekeepers for management of diabetes and other chronic diseasesin China. In recognition of the need for a more patient-centered approach, the Chinese government has piloted a program incorporating methods of diabetes self-management for chronic care: the Happy Life Club (Browning et al., Front in Public Health 2:181, 2015). This program is modeled on a similar program developed in Australia (Kelly et al., Aust J Prim Health 9:186-9, 2003). The ICDMS is an important tool in the implementation of patient-centered programs targeting chronic health issues, and its success is determined by factors, such as frequent contact between patients and doctors and effective website training for patients. This retrospective study used de-identified data from the Fangzhuang (Beijing) intelligent chronic disease management system (ICDMS) database to evaluate the effect of an intelligent chronic disease management system on selected Beijing community patients who have type 2 diabetes mellitus (T2DM). METHODS: A comparative study before and after ICDMS implementation was performed to evaluate the effect of ICDMS on the rates of follow-up and laboratory examinations, measurement rates of blood glucose and lipids, glycosylated hemoglobin (HbA1c) and blood lipid levels, as well as the corresponding health parameters. Continuous variables and categorical variables were analyzed using paired t-test and McNemar's tests, respectively. RESULTS: A total of 2451 T2DM patients met inclusion/exclusion criteria. Compared with the pre-index period, the laboratory examination, rates of blood glucose and blood lipids increased significantly in the post-index period (p < 0.001). Triglyceride (TC) levels decreased significantly from 5.22 mmol/L to 5.11 mmol/L (p < 0.05), and high density lipoprotein-cholesterol (HDL-C) levels increased significantly from 1.35 mmol/L to 1.48 mmol/L (p < 0.05). The control rate of TC increased from 24.86 to 29.76% (p = 0.079). The control rate of low density lipoprotein-cholesterol (LDL-C) increased from 12.16 to 13.97% (p = 0.421), while the control rate of HDL-C increased significantly from 68.60 to 78.77%. Importantly, Compared with the patients with HbA1C above 7% in the pre-index period, the mean HbA1c decreased significantly from 7.84 to 6.94%((p < 0.001) in the post-index period, and the control rate of HbA1c was 57.43%. CONCLUSIONS: The intelligent chronic disease management system is an effective tool in the management of T2DM and should be promoted by the Community Health Service Center in China as well as in other developing countries.

Visible-Light-Initiated Na2-Eosin Y Catalyzed Highly Regio- and Stereoselective Difunctionalization of Alkynes with Alkyl Bromides.

A highly regioselective and stereoselective addition of alkyl bromides (amino-brominated aromatic ß,ß-dicyanoalkenes) to arylacetylenes by photoredox catalysis was developed. This difunctionalization of arylacetylenes was accomplished under ambient and metal-free conditions to produce alkenyl bromides in high efficiency with a wide range of group tolerance.

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism.

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30-120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8-20 µM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta.

Photochemical Mn-Mediated Generation of Azide Radicals for Improvement of Alkene Hydroxyazidation.

State-of-the-art strategies for alkene-hydroxyazidation, which yield a mixture of ß-azido alcohol and ß-azido peroxide, must rely on phosphine reagents to improve the chemoselectivity. To overcome the above problems, we present a photochemical hydroxyazidation of alkenes via Mn-mediated ligand-to-metal charge transfer (LMCT) in O2, which activates N3- to •N3 and incorporates O2 to be used as an oxygen source in the hydroxyazidation products. Broad alkene range and step-economy chemistry for the hydroxyazidation transformation were also demonstrated.

Super-Stretchable and High-Energy Micro-Pseudocapacitors Based on MXene Embedded Ag Nanoparticles.

The advancement of aqueous micro-supercapacitors offers an enticing prospect for a broad spectrum of applications, spanning from wearable electronics to micro-robotics and sensors. Unfortunately, conventional micro-supercapacitors are characterized by low capacity and slopy voltage profiles, limiting their energy density capabilities. To enhance the performance of these devices, the use of 2D MXene-based compounds has recently been proposed. Apart from their capacitive contributions, these structures can be loaded with redox-active nanowires which increase their energy density and stabilize their operation voltage. However, introducing rigid nanowires into MXene films typically leads to a significant decline in their mechanical properties, particularly in terms of flexibility. To overcome this issue, super stretchable micro-pseudocapacitor electrodes composed of MXene nanosheets and in situ reconstructed Ag nanoparticles (Ag-NP-MXene) are herein demonstrated, delivering high energy density, stable operation voltage of ≈1 V, and fast charging capabilities. Careful experimental analysis and theoretical simulations of the charging mechanism of the Ag-NP-MXene electrodes reveal a dual nature charge storage mechanism involving ad(de)sorption of ions and conversion reaction of Ag nanoparticles. The superior mechanical properties of synthesized films obtained through in situ construction of Ag-NP-MXene structure show an ultra stretchability, allowing the devices to provide stable voltage and energy output even at 100% elongation.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

An efficient tandem elimination-cyclization-desulfitative arylation of 2-(gem-dibromovinyl)phenols(thiophenols) with sodium arylsulfinates.

An efficient tandem elimination-cyclization-desulfitative arylation of 2-(gem-dibromovinyl)phenols(thiophenols) with sodium arylsulfinates has been developed. In the presence of TBAF-PdCl(2)-Cu(OAc)(2)-NEt(3), the reactions generated 2-arylbenzofurans(thiophenes) with good yields in one-pot under ligand-free conditions.

Research on the treatment of phosphoric wastewater by ultrasound-assisted microelectrolysis method.

In this research work, ultrasound was introduced to the microelectrolysis (ME) method to improve the treatment efficiency for phosphoric wastewater. The effects of treatment time, Fe/C ratio (v/v) and iron filings dosage on the efficiency of phosphorus removal from wastewater with different initial pH values were investigated. The results showed that the phosphorus removal efficiency by the ME method was significantly enhanced in the presence of ultrasound. The maximum removal rate of phosphorus (RRP) for the wastewater with an initial pH value of 4.0 was 92.4% after 60 min of treatment when the Fe/C and Fe/H2O volume ratio were 2/1 and 1/10, respectively. The reaction kinetics analysis indicated that the phosphorus degradation processes for the ultrasonic and ME methods as well as the ultrasonically assisted ME method (UME) were in accordance with the pseudo-first-order kinetic model. The synergetic effect of the combined ultrasound and ME method for phosphorus removal was also studied by reaction kinetics analysis.

Combinatorial constraint coding based on the EORS algorithm in DNA storage.

The development of information technology has produced massive amounts of data, which has brought severe challenges to information storage. Traditional electronic storage media cannot keep up with the ever-increasing demand for data storage, but in its place DNA has emerged as a feasible storage medium with high density, large storage capacity and strong durability. In DNA data storage, many different approaches can be used to encode data into codewords. DNA coding is a key step in DNA storage and can directly affect storage performance and data integrity. However, since errors are prone to occur in DNA synthesis and sequencing, and non-specific hybridization is prone to occur in the solution, how to effectively encode DNA has become an urgent problem to be solved. In this article, we propose a DNA storage coding method based on the equilibrium optimization random search (EORS) algorithm, which meets the Hamming distance, GC content and no-runlength constraints and can reduce the error rate in storage. Simulation experiments have shown that the size of the DNA storage code set constructed by the EORS algorithm that meets the combination constraints has increased by an average of 11% compared with previous work. The increase in the code set means that shorter DNA chains can be used to store more data.

Discovery of the EL-0052 as a potential anesthetic drug.

As a γ-aminobutyric acid A receptor (GABAAR) inhibitor, etomidate fulfills several characteristics of an ideal anesthetic agent, such as rapid onset with rapid clearance and high potency, along with cardiovascular stability. Unfortunately, etomidate has been reported to inhibit CYP11B1 at hypnotic doses, which is associated with a marked increase in patient deaths due to this unexpected off-target effect. In this study, molecular docking was used to simulate the binding mode of etomidate with GABAAR and CYP11B1. Based on the in-depth analysis of the binding mode, strong electron-withdrawing group on the C4 position of the imidazole ring was introduced to reduce the charge density of the nitrogen, which is beneficial in reducing the coordination bond between the imidazole nitrogen and heme iron in CYP11B1, as well as in reducing the adrenocortical suppression. Based on the results of ADMET property prediction, MEP analysis, and molecular docking simulation, 4-fluoroetomidate (EL-0052) was designed and synthesized. In vivo studies in rats and mice confirmed that EL-0052 had the efficacy similar to etomidate, but without adrenocortical suppression. These findings suggested that EL-0052 was superior to etomidate and support the continued development of EL-0052 as a preclinical candidate as an anesthetic.

Ultrathin carbon nanotube-DNA hybrid membrane formation by simple physical adsorption onto a thin alumina substrate.

Ultrathin carbon nanotube membranes can be prepared on alumina substrates by a facile immersion-adsorption approach, which involves two steps, the first step DNA wrapping and the second step uniform adsorption of the DNA-wrapped nanotubes onto porous alumina. In this approach, DNA wrapping imparts a hydrophilic nature to the carbon nanotubes, which enhances the interaction between the nanotubes and hydrophilic porous alumina and results in the self-assembly formation of ultrathin nanotube membranes with well-controlled thickness, biocompatibility, conductivity and optical properties.

Guide wire electrode versus liquid electrode for intravascular electrocardiography-guided central venous catheterization in adults: A systematic review and meta-analysis.

AIM: To assess the effectiveness and safety of guide wire electrode versus liquid electrode for intravascular electrocardiography-guided central venous catheter placement in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched the main electronic databases (Cochrane Library, the Joanna Briggs Institute Library, Embase, PubMed, CINAHL, China National Knowledge Infrastructure, and Wanfang) with articles published from inception up to March 2018. References of important articles were also screened for relevant studies. We used a structured search strategy and did not apply any search limitations. REVIEW METHODS: Randomized, controlled trials, quasi-experimental studies or studies using a within-subject design, evaluating guide wire electrode versus liquid electrode for intravascular electrocardiography-guided central venous catheter placement in adults, were eligible for inclusion. Risk of bias assessment was performed using the Cochrane Collaboration's tool and meta-analysis was performed using RevMan 5.3. RESULTS: In total, six studies with a total of 2176 participants were included. Meta-analysis showed that there was no statistically significant difference in accuracy of tip location placement between guide wire and liquid electrodes. Use of guide wire electrode had a higher risk of complications which were transient and there were an insufficient number of studies using the same parameters to evaluate intravascular electrocardiography signal quality. CONCLUSION: Due to the small number and low quality of identified studies, it is difficult to draw definitive conclusions on the relative effectiveness and safety of guide wire versus liquid electrodes for the placement of central venous catheters in adults. More well-designed studies are needed in the future.

Room-temperature reduction of NO2 in a Li-NO2 battery: a proof of concept.

Although considerable effort has been devoted to purifying nitrogen oxides (NOx), it is still challenging to effectively reduce NOx at room temperature and ambient pressure without catalysts. In this study, as a proof-of-concept, we have for the first time demonstrated the room-temperature reduction of nitrogen dioxide (NO2) using a rechargeable lithium-nitrogen dioxide (Li-NO2) battery. The battery shows a capacity of 884 mAh g-1 at 50 mA g-1 (an actual energy density of 666 Wh kg-1) and a promising electrochemical Faraday efficiency (FE) of 67%. The unique properties of Li-NO2 rechargeable batteries not only provide a way to reduce and recycle NO2 but also highlight the potential of oxidative air pollutants as energy sources for next-generation electrochemical energy storage (EES) systems.