Hypertension in China: burdens, guidelines and policy responses: a state-of-the-art review.

Hypertension is a leading risk factor of cardiovascular disease and it is becoming increasingly prevalent globally. Correspondingly, the Chinese government and public health institutions have issued a series of policy documents and guidelines for hypertension. However, no comprehensive review of such documents has been conducted. Hence, this review aims to provide an up-to-date and comprehensive assessment of not only the disease burden, but also hypertension management policies and guidelines in China. A total of 15 epidemiological studies based on national population surveys, 15 Chinese Hypertension Guidelines, and seven policy documents were identified. We found a larger burden of hypertension in men, while the awareness, treatment, and control rates have remained low in both sexes. The ranges of hypertension prevalence, awareness, treatment, and control rate among hypertensive patients were 18.0-44.7%, 23.6-56.2%, 14.2-48.5%, and 4.2-30.1% respectively. Chinese hypertension guidelines provide evidence-based instructions to healthcare practitioners over hypertension management in which primary healthcare is increasingly emphasized. Finally, the policy documents set national goals for hypertension management and standardized the services provided in primary healthcare. The findings highlight the importance of integrating new guidelines into hypertension management provided by primary healthcare practitioners and the need to evaluate the implementation of guidelines and policies

Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections

How country image affects tourists’ destination evaluations: A moderated mediation approach

Limited tourism research has as yet drawn attention to the differences and interactions between country image and destination image. Therefore, this research explored the relationships among country image, destination image, familiarity, and destination evaluation. Based on an empirical study of international tourists in Beijing, China, a model was proposed covering these four variables. Country image mainly affected international tourists’ evaluations of China as a destination in a conditional indirect way, mediated by destination image and especially by psychological image, and moderated by familiarity. Moreover, familiarity directly and positively influenced functional destination image and negatively moderated the relationship between country and psychological destination images

Dynamic modeling of construction and demolition waste management processes : an empirical study in Shenzhen, China

Purpose – The aim of this paper is to develop a model based on system dynamics (SD) approach, which integrates three subsystems for simulating construction and demolition (C&D) waste management in Shenzhen, Mainland China. Design/methodology/approach – SD approach was first used to construct the model for C&D waste management in Shenzhen. The model was then converted for running on computer through the software package “iThink”, which was specifically designed for SD modeling. The data required for model simulation was derived through various ways, including literature review, examination of official reports and yearbooks, and questionnaires. After all the parameters in the model were determined, simulation was carried out. Findings – The model proposed in this research can provide an experimental simulation platform to investigate the complexity and interdependencies of factors in managing C&D waste in Shenzhen, Mainland China. The simulation results show that the pressing situation of C&D waste management in Shenzhen would aggravate if no effective measures were taken to address it during the simulation period. Participants’ active participation and cost consideration are the two major factors affecting C&D waste reduction. Furthermore, new landfills should be planned to properly handle the C&D waste accumulated in Shenzhen over the past few years. Originality/value – Although some studies have been conducted under the topic of C&D waste management during the past few years in Shenzhen – how to effectively and efficiently handle the waste is still unsolved. Factors affecting the effectiveness of C&D waste management have separately been examined in the previous studies, without considering their interrelations. The SD-based model is developed in this research to investigate the complex and interdependent relationships among these factors. The model can deepen participants’ understandings about C&D waste management and help explore the major factors affecting the effectiveness of management activities. The measures, which are proposed based on the simulation results, can serve as a valuable reference for planning C&D waste management in Shenzhen

Aqueous humor protein dysregulation in primary angle-closure glaucoma

Purpose: Primary angle-closure glaucoma (PACG) is associated with increased intraocular pressure, optic nerve damage, and progressive vision loss, but the molecular mechanism that underpins retinal ganglion neuropathy in PACG remains poorly understood. To better understand the pathogenesis of human PACG, we performed the first comprehensive proteomic analysis of aqueous humor (AH) samples from PACG patients and matched control donors to study pathogenic alteration in AH composition in disease. Methods: High-resolution, label-free, liquid chromatography–tandem mass spectrometry-based quantitative proteomic analyses were performed in AH samples collected from PACG patients and a matched control cohort of patients with cataracts. Results: The AH proteome comprised of 1363 distinct proteins, of which more than 50% were differentially expressed in PACG (773 total; 501 up-regulated, 272 down-regulated). AH from PACG patients was enriched in atypical collagens and fibronectins, suggesting that the composition of the trabecular matrix is significantly altered in disease. Pathway and cluster analyses revealed that AH protein modulation in PACG is closely associated with biological processes including platelet degranulation, cellular import/export mechanisms, and control of protease activity. In addition, critical mediators of oxygen homeostasis and neuronal function in AH were significantly dysregulated in disease, strongly implicating oxidative stress responses in PACG-associated nerve damage. Conclusions: Altered AH proteome in human PACG indicated oxidative stress in the neuronal damage that preceded vision loss. Identifying key mediators of PACG pathology will yield new prognostic biomarkers and novel targets for future therapeutic interventions.Ministry of Education (MOE)National Medical Research Council (NMRC)This work is in part supported by grants from the Singapore Ministry of Education (MOE2014-T2-2-043 and MOE2016-T2-2-018), the National Medical Research Council of Singapore (NMRC-OF-IRG-0003-2016), and National Healthcare Group Small Innovative Grant (Grant # 13018)

The SaeRS two-component system is a direct and dominant transcriptional activator of toxic shock syndrome toxin 1 in Staphylococcus aureus

Toxic shock syndrome toxin 1 (TSST-1) is a Staphylococcus aureus superantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. The S. aureus exotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins in S. aureus, although regulation of TSST-1 by the Sae system has not been investigated. We generated a defined deletion mutant of the Sae histidine kinase sensor (saeS) in the prototypic menstrual TSS strain S. aureus MN8. Mutation of saeS resulted in a complete loss of TSST-1 expression. Using both luciferase reporter experiments and quantitative real-time PCR, we demonstrate that the Sae system is an important transcriptional activator of TSST-1 expression. Recombinant SaeR was able to bind directly to the tst promoter to a region containing two SaeR consensus binding sites. Although the stand-alone SarA transcriptional regulator has been shown to be both a positive and a negative regulator of TSST-1, deletion of sarA in S. aureus MN8 resulted in a dramatic overexpression of TSST-1. As expected, mutation of agr also reduced TSST-1 expression, but this phenotype appeared to be independent of Sae. A double mutation of saeS and sarA resulted in the loss of TSST-1 expression. This work indicates that the Sae system is a dominant and direct transcriptional activator that is required for expression of TSST-1

Assembling well-arranged covalent organic frameworks on MOF-derived graphitic carbon for remarkable formaldehyde sensing

Constructing heterostructures with advanced architectures is an effective strategy for enhancing the crystallinity and functional performance of covalent organic frameworks (COFs). Herein, a novel core–shell heterostructure integrating a metal–organic framework (MOF)-derived graphitic carbon core (GC) and a well-arranged COF shell, termed MOF-GC@COF, is reported. ZIF-67 dodecahedra are first chemically etched with a weak organic acid and further converted to MOF-GC via thermal pyrolysis. In the subsequent step, β-ketoenamine-linked COF nanofibers are vertically assembled on the surface of the MOF-GC cores to generate the MOF-GC@COF heterostructure. As a proof-of-concept application, the as-prepared MOF-GC@COF heterostructure is used as an effective quartz crystal microbalance (QCM) sensor for the adsorption of formaldehyde. Benefiting from the synergistic effect of the hybrid composition and the advantages of the core–shell heterostructure, the newly prepared MOF-GC@COF heterostructure exhibits excellent sensing performance toward formaldehyde with rapid adsorption kinetics, high sensitivity, and superior selectivity