Cyclic Amine Synthesis via Catalytic Radical-Polar Crossover Cycloadditions.

The rapid assembly of valuable cyclic amine architectures in a single step from simple precursors has been recognized as an ideal platform in term of efficiency and sustainability. Although a vast number of studies regarding cyclic amine synthesis has been reported, new synthetic disconnection approaches are still high in demand. Herein, we report a catalytic radical-polar crossover cycloaddition to cyclic amine synthesis triggered from primary sulfonamide under photoredox condition. This newly developed disconnection, comparable to established synthetic approaches, will allow to construct ß, ß-disubstituted cyclic amine and ß-monosubstituted cyclic amine derivatives efficiently. This study highlights the unique utility of primary sulfonamide as a bifunctional reagent, which acts as a radical precursor and a nucleophile. The open-shell methodology demonstrates broad tolerance to various functional groups, drug derivatives and natural products in an economically and sustainable fashion.

Autonomous Visualization of Damage in Polymers by Metal-Free Polymerizations of Microencapsulated Activated Alkynes.

The development of autonomous materials with desired performance and built-in visualizable sensing units is of great academic and industrial significance. Although a wide range of damage indication methods have been reported, the "turn-on" sensing mechanism by damaging events based on microcapsule systems, especially those relying on chemical reactions to elicit a chromogenic response, are still very limited. Herein, a facile and metal-free polymerization route with an interesting reaction-induced coloration effect is demonstrated. Under the catalysis of 1,4-diazabicyclo[2.2.2]octane (DABCO), the polymerizations of difunctional or trifunctional activated alkynes proceed very quickly at 0 °C in air. A series of polymers composed of stereoregular enyne structure (major unit) and divinyl ether structure (minor unit) are obtained. Both the catalyst and monomers are colorless while the polymerized products are deep-colored. This process can be applied for the damage visualization of polymers using the microencapsulation technique. Microcapsules containing the reactive alkyne monomer are prepared and mixed in a DABCO-dispersed polymer film. Both the external and internal damage regions of this composite film can be readily visualized once the reaction is initiated from the ruptured microcapsules. Moreover, the newly formed polymer automatically seals the cracks with an additional protection function.

Robust Microcapsules with Durable Superhydrophobicity and Superoleophilicity for Efficient Oil-Water Separation.

The poor ultraviolet (UV) resistance and insufficient solvent compatibility are challenges for long-term storage and service of oil-water separation materials in practical applications. Herein, a superhydrophobic/superoleophilic surface with nano- to microscale hierarchical structures was formed spontaneously on robust microcapsules (MCs) via in situ polymerization and a sol-gel surface treatment. The resultant MCs possessed superior UV-resistant and solvent-proof superhydrophobicity. The water contact angles (WCAs) of the MC coating remained above 160° and the sliding angles (SAs) were below 3° after 9 days of UV aging test or 20 days of nonpolar and polar aprotic solvent immersion tests. More interestingly, these MCs can be used to separate the oil phase from its aqueous emulsion effectively, achieving a high and reusable separation efficiency with over 90% oil purity after 10 cycles of filtrations even after 13 days of UV aging. Therefore, these novel MCs will exhibit effective oil-water separation performance, superior chemical stability, outstanding reusability, and long-term storage stability for promising practical applications.

Anal human papillomavirus and its associations with abnormal anal cytology among men who have sex with men.

Human papillomavirus (HPV) infection contributes to most anal cancers and premalignant intraepithelial lesions. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM). Sociodemographic characteristics and sexual behaviors were collected by using a structured questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV Genotyping test. Logistic regression was used to estimate risk factors and their associations with high-risk HPV infection and cytological abnormalities. Among 163 MSM, 101 were seropositive for human immunodeficiency virus (HIV) and 62 were seronegative for HIV. The overall prevalence of HPV was 66.2%. A total of 61.9% and 48.2% of participants had never acquired any of either the quadrivalent or nonavalent vaccine HPV types, respectively. Cytological findings showed 15.3% atypical squamous cells of undetermined significance, 16.6% low-grade squamous intraepithelial lesion, 4.9% atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion and 17% high-grade squamous intraepithelial lesion. The number of high-risk HPV types was the predominant risk factor for abnormal anal cytology (OR 2.02, 95% CI 1.27-3.24). Infection with high-risk HPV was a significant predictor for cytological abnormality. MSM should be encouraged to obtain the HPV vaccine.

Shall I trust the report? Variable performance of Sanger sequencing revealed by deep sequencing on HIV drug resistance mutation detection.

BACKGROUND: The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. OBJECTIVES: To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. METHODS: We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. RESULTS: At 15-25% minority detection thresholds, 9-15% cases had underestimated DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68-82% in protease-reverse transcriptase region and 88-97% in integrase region at 5-25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. CONCLUSIONS: Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10-15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection.

Taiwan guideline on oral pre-exposure prophylaxis for HIV prevention - 2018 update.

Pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus infection is proved to be effective and has been implemented worldwide. This article introduces the guideline development and revised recommendations and guidance on PrEP provision in the updated Taiwan PrEP guideline. The Taiwan PrEP guideline writing group searched randomized controlled trials and guidelines published before October 2017 through Medline/PubMed, Cochrane Database, Embase and ClinicalTrials.gov database. Keywords included pre(-)exposure prophylaxis, PrEP, Truvada, tenofovir, HIV, and AIDS. Each selected article was assessed by two authors using the Grading of Recommendations Assessment, Development and Evaluation. External reviewers were invited to independently evaluate the revised manuscript per the Appraisal of Guidelines for Research and Evaluation II. Before publication, a public consultation was held to reach consensus on the updated guideline among providers, civil society, and Taiwan Centers for Disease Control. Four systematic reviews and 28 original articles were reviewed by Taiwan PrEP writing group. The second version of the Taiwan PrEP guideline was released in March 2018. We recommended daily PrEP use for the following populations: strong recommendation and high quality of evidence for men who have sex with men (MSM) and transgender women (TGW), as well as heterosexual serodiscordant couples; weak recommendation and high quality of evidence for people who inject drugs, while weak recommendation and moderate quality of evidence for at-risk heterosexual men and women. There is high-quality evidence for event-driven PrEP in MSM and likely TGW, and we additionally recognized these key populations could benefit from such dosing regimen.

A Facile Strategy To Prepare Smart Coatings with Autonomous Self-Healing and Self-Reporting Functions.

Herein, we report a smart coating with autonomous self-healing and self-reporting functions by simple integration of one-component microcapsules into the matrix without external intervention. The microcapsules containing hexamethylene diisocyanate (HDI) solution of aggregation-induced emission luminogens (AIEgens) were synthesized, and their properties, such as their composition, thermal stability, morphology, and damage-indicating ability, were investigated systematically. The AIEgen/HDI microcapsule-embedded coatings display adaptive self-repair of scratches and simultaneous high-contrast indication of the healed damage. Two commercialized AIEgens, tetraphenylethylene (TPE) and its derivative with dimethoxyl and benzylidene-methyloxazolone moieties (DM-TPE-BMO), were utilized as examples to demonstrate the feasibility of this concept in diverse polymer matrixes (including blue autofluorescent matrixes). It was found that the content of AIEgens can even be lowered to 0.05 wt %. This facile, economical, and feasible strategy toward the dual functions of self-repairing and self-sensing provides a new route for enhancing the longevity and reliability of polymer coatings, which is appealing and of great importance in practical applications.

Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action of Huo-Xiang-Zheng-Qi Formula for the Treatment of Gastrointestinal Diseases.

Multi-components Traditional Chinese Medicine (TCM) treats various complex diseases (multi-etiologies and multi-symptoms) via herbs interactions to exert curative efficacy with less adverse effects. However, the ancient Chinese compatibility theory of herbs formula still remains ambiguous. Presently, this combination principle is dissected through a systems pharmacology study on the mechanism of action of a representative TCM formula, Huo-xiang-zheng-qi (HXZQ) prescription, on the treatment of functional dyspepsia (FD), a chronic or recurrent clinical disorder of digestive system, as typical gastrointestinal (GI) diseases which burden human physical and mental health heavily and widely. In approach, a systems pharmacology platform which incorporates the pharmacokinetic and pharmaco-dynamics evaluation, target fishing and network pharmacological analyses is employed. As a result, 132 chemicals and 48 proteins are identified as active compounds and FD-related targets, and the mechanism of HXZQ formula for the treatment of GI diseases is based on its three function modules of anti-inflammation, immune protection and gastrointestinal motility regulation mainly through four, i.e., PIK-AKT, JAK-STAT, Toll-like as well as Calcium signaling pathways. In addition, HXZQ formula conforms to the ancient compatibility rule of "Jun-Chen-Zuo-Shi" due to the different, while cooperative roles that herbs possess, specifically, the direct FD curative effects of GHX (serving as Jun drug), the anti-bacterial efficacy and major accompanying symptoms-reliving bioactivities of ZS and BZ (as Chen), the detoxication and ADME regulation capacities of GC (as Shi), as well as the minor symptoms-treating efficacy of the rest 7 herbs (as Zuo). This work not only provides an insight of the therapeutic mechanism of TCMs on treating GI diseases from a multi-scale perspective, but also may offer an efficient way for drug discovery and development from herbal medicine as complementary drugs.

Overproduction of active efflux pump and variations of OprD dominate in imipenem-resistant Pseudomonas aeruginosa isolated from patients with bloodstream infections in Taiwan.

BACKGROUND: The emergence of imipenem-resistant Pseudomonas aeruginosa (IRPA) has become a great concern worldwide. The aim of this study was to investigate resistance mechanisms associated with bloodstream isolated IRPA strains in Taiwan. RESULTS: A total of 78 non-duplicated IRPA isolates were isolated from patients with bloodstream infection. The average prevalence of imipenem-resistance in those isolates was 5.9 % during a 10-year longitudinal surveillance in Taiwan. PFGE results showed high clonal diversity among the 78 isolates. VIM-2, VIM-3, OXA-10, and OXA-17 ß-lactamases were identified in 2 (2.6 %), 3 (3.8 %), 2 (2.6 %), and 1 (1.3 %) isolates, respectively. Active efflux pumps, AmpC ß-lactamase overproduction, and extended-spectrum AmpC cephalosporinases (ESACs) were found in 58 (74.4 %), 25 (32.1 %) and 15 (19.2 %) of IRPA isolates, respectively. oprD mutations with amino acid substitution, shortened putative loop L7, premature stop codon caused by point mutation, frameshift by nucleotide insertion or deletion, and interruption by insertion sequence were found in 19 (24.4 %), 18 (23.1 %), 15 (19.2 %), 14 (17.9 %), and 10 (12.8 %) of isolates, respectively. CONCLUSIONS: This study suggests that alterations in the OprD protein and having an active efflux pump are the main mechanisms associated with bloodstream isolated IRPA. Overproduction of AmpC, ESACs, and the presence of VIM- and OXA-type ß-lactamases play additional roles in reduced susceptibility to imipenem in P. aeruginosa isolates in Taiwan.

Polydopamine as an efficient and robust platform to functionalize carbon fiber for high-performance polymer composites.

Carbon fibers (CFs), which exhibit excellent physical performances and low density, suffer from their low surface activity in some application. Herein, based on dopamine chemistry, we proposed an efficient method to functionalize them: through a simple dip-coating procedure, the CFs were inverted from amphiphobic to hydrophilic with deposition of polydopamine film. Furthermore, using polydopamine as a bridge, the hydrophilic functionalized CFs were transformed to be oleophilic after following octadecylamine grafting. To illustrate applications of this functionalization strategy, we added 15 wt % functionalized CFs into polar epoxy and nonpolar poly(ethylene-co-octene), and as a consequence, their tensile strength respectively increase by 70 and 60%, which show greater reinforcing effect than the unmodified ones (35 and 35%). The results of dynamic mechanical analysis and scanning electron microscope observations indicate that this polydopamine-based functionalization route brought about satisfactory improvements in interfacial adhesion between fillers and matrix. Considering that this simple approach is facile and robust enough to allow further specific functionalization to adjust surface properties, these findings may lead to the development of new efficient strategies for surface functionalization of CFs that are of great interest to the industrial field.

Establishing indices for groundwater contamination risk assessment in the vicinity of hazardous waste landfills in China.

Groundwater contamination by leachate is the most damaging environmental impact over the entire life of a hazardous waste landfill (HWL). With the number of HWL facilities in China rapidly increasing, and considering the poor status of environmental risk management, it is imperative that effective environmental risk management methods be implemented. A risk assessment indices system for HWL groundwater contamination is here proposed, which can simplify the risk assessment procedure and make it more user-friendly. The assessment framework and indices were drawn from five aspects: source term, underground media, leachate properties, risk receptors and landfill management quality, and a risk assessment indices system consisting of 38 cardinal indicators was established. Comparison with multimedia models revealed that the proposed indices system was integrated and quantitative, that input data for it could be easily collected, and that it could be widely used for environmental risk assessment (ERA) in China.