Efficient identification of trait-associated loss-of-function variants in the UK Biobank cohort by exome-sequencing based genotype imputation.

The large-scale open access whole-exome sequencing (WES) data of the UK Biobank ~200,000 participants is accelerating a new wave of genetic association studies aiming to identify rare and functional loss-of-function (LoF) variants associated with complex traits and diseases. We proposed to merge the WES genotypes and the genome-wide genotyping (GWAS) genotypes of 167,000 UKB homogeneous European participants into a combined reference panel, and then to impute 241,911 UKB homogeneous European participants who had the GWAS genotypes only. We then used the imputed data to replicate association identified in the discovery WES sample. The average imputation accuracy measure r2 is modest to high for LoF variants at all minor allele frequency intervals: 0.942 at MAF interval (0.01, 0.5), 0.807 at (1.0 × 10-3 , 0.01), 0.805 at (1.0 × 10-4 , 1.0 × 10-3 ), 0.664 at (1.0 × 10-5 , 1.0 × 10-4 ) and 0.410 at (0, 1.0 × 10-5 ). As applications, we studied associations of LoF variants with estimated heel BMD and four lipid traits. In addition to replicating dozens of previously reported genes, we also identified three novel associations, two genes PLIN1 and ANGPTL3 for high-density-lipoprotein cholesterol and one gene PDE3B for triglycerides. Our results highlighted the strength of WES based genotype imputation as well as provided useful imputed data within the UKB cohort.

New strategy of using double-network hydrogel extravascular stent for preventing venous graft restenosis after coronary artery bypass grafting.

OBJECTIVE: Effective therapies for the prevention of vein graft failure, which frequently occurs in coronary artery bypass grafting (CABG) due to intimal hyperplasia (IH), are still lacking. Here, we investigated the effects of the perivenous application of double-network hydrogel on vein grafts in carotid artery bypass grafting in a rabbit model. METHODS: Healthy New Zealand white rabbits were randomized into the following groups: no graft, graft, or graft + Double-network hydrogel external stent (DNHES). The rabbits' carotid artery was bypassed via the jugular vein. Double-network hydrogel external stent was wrapped around the jugular graft after the anastomoses were completed. Blood flow parameters and tissue histology of the vein grafts were evaluated. RESULTS: Compared with the untreated vein grafts at 12 weeks after the surgery, the DNHES significantly improved graft flow, attenuated intimal and medial thickening, reduced the anti-proliferating cell nuclear antigen proliferation index of the vein grafts, decreased the mRNA and protein expression of Mitogen-Activated Protein Kinase (MAPK) and Transforming Growth Factor-ß (TGF-ß), and increased the mRNA and protein expression of endothelial Nitric Oxide Synthase (eNOS). CONCLUSION: The perivenous application of DNHES exerts beneficial effects on vein grafts, reduces the inflammatory response in carotid artery bypass grafting in a rabbit model, and appears to be a safe and promising strategy to prevent vein graft failure.

Administration of a new nano delivery system coated with Tirofiban to prevent early thrombosis of vein graft.

OBJECTIVE: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. METHODS: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. RESULTS: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. CONCLUSION: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function.

TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF-κB signalling.

TNF-stimulated gene (TSG-6) was reported to suppress hypertrophic scar (HS) formation in a rabbit ear model, and the overexpression of TSG-6 in human HS fibroblasts (HSFs) was found to induce their apoptotic death. The molecular basis for these findings, however, remains to be clarified. HSFs were subjected to TSG-6 treatment. Treatment with TSG-6 significantly suppressed HSF proliferation and induced them to undergo apoptosis. Moreover, TSG-6 exposure led to reductions in collagen I, collagen III, and α-SMA mRNA and protein levels, with a corresponding drop in proliferating cell nuclear antigen (PCNA) expression indicative of impaired proliferative activity. Endoplasmic reticulum (ER) stress was also suppressed in these HSFs as demonstrated by decreases in Bip and p-IRE1α expression, downstream inositol requiring enzyme 1 alpha (IRE1α) -Tumor necrosis factor receptor associated factor 2 (TRAF2) pathway signalling was inhibited and treated cells failed to induce NF-κB, TNF-α, IL-1ß, and IL-6 expression. Overall, ER stress was found to trigger inflammatory activity in HSFs via the IRE1α-TRAF2 axis, as confirmed with the specific inhibitor of IRE1α STF083010. Additionally, the effects of TSG-6 on apoptosis, collagen I, collagen III, α-SMA, and PCNA of HSFs were reversed by the IRE1α activator thapsigargin (TG). These data suggest that TSG-6 administration can effectively suppress the proliferation of HSFs in part via the inhibition of IRE1α-mediated ER stress-induced inflammation (IRE1α/TRAF2/NF-κB signalling).

Asymmetrical cross-modal influence on neural encoding of auditory and visual features in natural scenes.

Natural scenes contain multi-modal information, which is integrated to form a coherent perception. Previous studies have demonstrated that cross-modal information can modulate neural encoding of low-level sensory features. These studies, however, mostly focus on the processing of single sensory events or rhythmic sensory sequences. Here, we investigate how the neural encoding of basic auditory and visual features is modulated by cross-modal information when the participants watch movie clips primarily composed of non-rhythmic events. We presented audiovisual congruent and audiovisual incongruent movie clips, and since attention can modulate cross-modal interactions, we separately analyzed high- and low-arousal movie clips. We recorded neural responses using electroencephalography (EEG), and employed the temporal response function (TRF) to quantify the neural encoding of auditory and visual features. The neural encoding of sound envelope is enhanced in the audiovisual congruent condition than the incongruent condition, but this effect is only significant for high-arousal movie clips. In contrast, audiovisual congruency does not significantly modulate the neural encoding of visual features, e.g., luminance or visual motion. In summary, our findings demonstrate asymmetrical cross-modal interactions during the processing of natural scenes that lack rhythmicity: Congruent visual information enhances low-level auditory processing, while congruent auditory information does not significantly modulate low-level visual processing.

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease.

BACKGROUND: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). METHODS: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. RESULTS: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. CONCLUSIONS: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

Effects of obstructive sleep apnea hypopnea syndrome on postoperative complications in patients who undergo off-pump coronary artery bypass grafting.

PURPOSE: To investigate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) and analyze the effects of OSAHS on the incidence of post-OPCABG complications, length of stay in intensive care unit (ICU) and hospitalization, and hospital expense. MATERIALS AND METHODS: This prospective study included patients undergoing OPCABG at Beijing An Zhen hospital from January 2018 to December 2018. OSAHS was diagnosed by using a portable sleep monitor before surgery. RESULTS: Among 74 patients, the prevalence of OSAHS and moderate to severe OSAHS (apnea hypopnea index (AHI) ≥ 15) was 70% and 53%, respectively. Compared with the no to mild OSAHS group (AHI < 15), the moderate to severe OSAHS group presented a lower ejection fraction (P = 0.013). Between these two groups, the incidence of post-OPCABG complications; the duration of intubation, ICU stay, and hospitalization; and the hospital expense did not differ. Notably, the ejection fraction was significantly negatively correlated with the duration of ICU stay and hospital expense. CONCLUSIONS: Patients undergoing OPCABG with severe OSAHS are likely to exhibit a low ejection fraction and poor heart function, which may require a longer ICU stay and incur higher hospital expenses.

LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p.

Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

Adventitial Collagen Crosslink Reduces Intimal Hyperplasia in a Rabbit Arteriovenous Graft Model.

BACKGROUND: Intimal hyperplasia (IH) is the initial lesion of vein graft failure after coronary artery bypass grafting. The weak venous wall is likely one of the primary reasons for IH after exposure to the arterial environment. We investigate whether adventitial collagen cross-link by glutaraldehyde (GA) reinforces the venous wall and then reduces IH. MATERIALS AND METHODS: Adventitial collagen cross-link by 0.3% GA was performed on the rabbit jugular veins. The degree of cross-link was accessed by tensile test. The jugular vein with or without cross-link was implanted into the carotid artery of rabbit. Vein dilatation at the immediate anastomosis and pathological remodeling of vein graft after 4 wk was assessed. RESULTS: Tensile test indicated that the mechanical property of 3-min cross-linked veins more closely resembled that of the carotid artery. In rabbit arteriovenous graft models, 3-min adventitial collagen cross-link limited overdistension (diameter: 3.24 mm versus 4.65 mm, P < 0.01) at the immediate anastomosis and reduced IH (intima thickness: 78.83 µm versus 140.19 µm, P < 0.01) of vein grafts 4 wk after implantation in the cross-link group as compared with the graft group (without cross-link). Compared with the cross-link group, the expression of proliferating cell nuclear antigen and vascular cell adhesion molecule-1 increased significantly at both the mRNA and protein levels within the graft group (P < 0.01), but the expression of smooth muscle-22α decreased significantly (P < 0.01). CONCLUSIONS: Adventitial collagen cross-link by GA increased the vessel stiffness and remarkably reduced IH in a rabbit arteriovenous graft model.

Highly efficient utilization of light and charge separation over a hematite photoanode achieved through a noncontact photonic crystal film for photoelectrochemical water splitting.

The trade-off problem between light absorption and charge collection under lower band-bending (bias) is extremely difficult to resolve in water splitting on photoelectrodes. Although the use of metallic back-reflectors, antireflection coatings, and textured substrates and light absorbers enable the improvement of light utilization efficiency, these methods still suffer from high cost and complex fabrication process, especially, incompetent separation of photogenerated carriers. Here taking the hematite (α-Fe2O3) photoanode as a model, we report that a noncontact photonic crystal (PC) film composed of silica nanoparticles and ethoxylated trimethylolpropane triacrylate (ETPTA) resin can significantly enhance the photoelectrochemical (PEC) activity of the photoelectrode. Specifically, more than 250 mV cathodic shift in the onset potential and 4 times larger photocurrent at 1.0 V versus a reversible hydrogen electrode (RHE) were achieved over the α-Fe2O3-PC photoanode hybrid system, compared with the pristine α-Fe2O3 photoanode. Our work showed that a PC film not only boosted light absorption of the α-Fe2O3 layer but also improved its charge transfer efficiency under light illumination. These new findings of the synergistic effect will open a new avenue to design high-performance solar energy conversion devices.

The dominant role of functional action representation in object recognition.

Action representation of manipulable objects has been found to be involved in object recognition. Recently, studies have indicated the existence of two distinct action systems: functional action specifying how to use an object and structural action concerning how to grasp an object. Despite evidence revealing the systems' anatomical and functional differences, few preceding studies have dissociated their respective roles in object recognition. The present study aimed to tease apart their roles in the recognition of manipulable objects with a priming paradigm. Specifically, we used static stimuli (photos, Experiments 1 and 2) and dynamic stimuli (video clips, Experiments 3 and 4) depicting functional and structural action hand gestures as primes and measured the magnitude of functional and structural action priming effect in object recognition. We found that static and dynamic priming stimuli induced a robust action priming effect only for functional action prime-target pairs. Naming latencies of the target objects were shorter when functional action representations of the prime and target were congruent than when they were incongruent. Moreover, as compared to static priming photos, dynamic priming stimuli induced a larger functional action priming effect. By contrast, neither static nor dynamic priming stimuli elicited a structural action priming effect. Behavioral data from our four experiments provide consistent evidence of the dominant role of functional action representation in the recognition of manipulable objects, suggesting that action knowledge regarding how to use rather than grasp an object is more likely an intrinsic component of objects' conceptual representation.

Mortality Trends in Colorectal Cancer in China During 2000-2015: A Joinpoint Regression and Age-Period-Cohort Analysis.

INTRODUCTION: As lifestyles have increasingly become westernized in China, public health strategies have increasingly focused on cancer prevention. The objective of this study was to describe trends in colorectal cancer (CRC) mortality and the age, period, and cohort effects of CRC mortality in urban and rural China from 2000 to 2015. METHODS: We collected CRC mortality data from the China Health Statistics Yearbook. We used joinpoint regression analysis to estimate the slope of mortality trends. We then used the age-period-cohort (APC) model with intrinsic estimator to estimate the age, period, and cohort effects of CRC mortality. RESULTS: CRC mortality was higher in urban areas than in rural areas, and the average annual percentage change was also larger in urban areas (4.1%) than in rural areas (3.7%). CRC mortality risk was higher among older adults than among adults aged 20 to 24: the relative risk among adults aged 60 to 64 was 31.09 times higher in urban China and 11.46 times higher in rural China. CRC mortality risk increased with period: compared with period 2000, the relative risk was 1.01 in period 2005, 1.36 in period 2010, and 1.42 in period 2015 in urban China and 1.12 in period 2005, 1.24 in period 2010, and 1.69 in period 2015 in rural China. More recent cohorts had lower CRC mortality risk: compared with the cohort born during 1920-1924, the relative risk of cohort 1950-1954 was 0.70 in urban China and 0.69 in rural China. CONCLUSION: More interventions to reduce the burden of CRC should be conducted, and it is more necessary for older people and urban residents to adopt a healthy lifestyle in China.

Evaluation of a consulting training course for international development assistance for health.

BACKGROUND: Development assistance for health (DAH) is an important component of foreign assistance. International health consultants usually play a key role in the international DAH field. However, there is still a shortage of consulting training in China. To address this issue and develop new backup force of DAH for China, the Global Health Institute of Wuhan University (GHIWHU) launched a training program called the "Consulting Training Course for International Development Assistance for Health". The purpose of this article is to evaluate the impact of the training on participants. METHODS: We conducted the analysis using Kirkpatrick's model. An evaluation survey examining participants' reaction (level 1) and learning (level 2) was carried out among trainees following the training, and a follow-up telephone interview of application (level 3) was made in three months after the training. RESULTS: A total of 25 participants from Chinese Consortium of Universities for Global Health (CCUGH) attended the training program. Results of satisfaction evaluation indicated that the training program was well received, with more than 85% of participants felt satisfied or relatively satisfied with the training. Trainees' self-ratings of the consulting knowledge and skills showed a significant increase (p < 0.001) from pre- to post-training. The follow-up interview revealed that the majority of participants applied the acquired knowledge and skills under various circumstances such as consulting program, teaching processes, writing reports, and et al. Meanwhile, participants considered that the lack of opportunities was one of the major application barriers. In addition, they expressed the willingness to participate in more relevant training and the need for more practice opportunities. CONCLUSIONS: This is the first study evaluating a consulting training program in China. The results show that the training course has been successfully implemented and participants have been given consulting knowledge and skills. Future research should use better-designed training methods based on demand surveys and consider providing participants with practice or practicum opportunities. Also, it is necessary to conduct both primary and advanced training courses and evaluate participants' long-term behavior changes resulting from the training.

Total Synthesis Confirms the Molecular Structure Proposed for Oxidized Levuglandin D2.

Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aß1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins. In view of this high proclivity for covalent adduction, it is understandable that free LGs have never been detected in vivo. Recently a catabolite, believed to be an oxidized derivative of LGD2 (ox-LGD2), a levulinic acid hydroxylactone with prostanoid side chains, was isolated from the red alga Gracilaria edulis and detected in mouse tissues and in the lysate of phorbol-12-myristate-13-acetate-treated THP-1 cells incubated with arachidonic acid. Such oxidative catabolism of LGD2 is remarkable because it must be outstandingly efficient to prevail over adduction with proteins and because it requires a unique dehydrogenation. We now report a concise total synthesis that confirms the molecular structure proposed for ox-LGD2. The synthesis also produces ox-LGE2, which readily undergoes allylic rearrangement to Δ6-ox-LGE2.

In-Hospital and Long-Term Mortality in 35,173 Chinese Patients Undergoing Coronary Artery Bypass Grafting in Beijing: Impact of Sex, Age, Myocardial Infarction, and Cardiopulmonary Bypass.

OBJECTIVE: The purpose of this study was to investigate the independent risk factors for mortality, the correlation between female sex and mortality, and the effects of cardiopulmonary bypass on prognosis in Chinese patients undergoing coronary artery bypass grafting (CABG). SETTING: A retrospective, observational study. PARTICIPANTS: The study included 26,926 (76.6%) men and 8,247 (23.4%) women. INTERVENTIONS: Patients undergoing isolated CABG were included in this study. MEASUREMENTS AND MAIN RESULTS: The medical records of patients undergoing CABG between January 1, 2006, and December 31, 2011, in Beijing were reviewed. Multivariate logistic regression and propensity score-matched analyses were performed to analyze the independent risk factors for in-hospital and long-term mortality. A total of 35,173 patients (76.6% men) were included in this study. Women were significantly older than men, and the proportions of women presenting with hypertension and unstable angina at hospital admission were significantly higher than those of men (all p<0.05). Women showed significantly higher in-hospital mortality (1.62% v 1.30%, p = 0.0248) and long-term mortality (3-year mortality, 10.2% v 7.3%, p<0.0001) than did men. Multivariate logistic regression analyses on the total patients and the propensity score-matched group revealed that female sex was not an independent risk factor for in-hospital mortality, whereas age and off-pump CABG were associated significantly with mortality (all p<0.0001). Age, a history of myocardial infarction before CABG, and on-pump CABG were independent risk factors for long-term mortality (all p<0.0001), but female sex was not. CONCLUSIONS: These findings suggested that advancing age but not female sex, appeared to be an independent risk factor for post-CABG in-hospital and long-term mortality, and off-pump CABG may be associated with worse in-hospital mortality and better long-term survival compared with on-pump CABG.

Independent Risk Factors Contributing to Acute Kidney Injury According to Updated Valve Academic Research Consortium-2 Criteria After Transcatheter Aortic Valve Implantation: A Meta-analysis and Meta-regression of 13 Studies.

OBJECTIVES: This study aimed to examine the risk factors for transcatheter aortic valve implantation (TAVI)-associated acute kidney injury (AKI) according to the AKI definition from the Valve Academic Research Consortium-2 (VARC-2). SETTING: A meta-analysis. PARTICIPANTS: A total of 661 patients with post-TAVI AKI according to the VARC-2 definition and 2,012 controls were included in the meta-analysis. INTERVENTIONS: Patients undergoing TAVI were included in this meta-analysis. MEASUREMENTS AND MAIN RESULTS: Multiple electronic databases were searched using predefined criteria. The diagnosis of AKI was based on the VARC-2 classification. The authors found that preoperative New York Heart Association class IV (odds ratio [OR], 7.77; 95% confidence interval [CI], 3.81-15.85), previous chronic renal disease (CKD) (OR, 2.81; 95% CI, 1.96-4.03), and requirement for transfusion (OR, 2.03; 95% CI, 1.59-2.59) were associated significantly with an increased risk for post-TAVI AKI. Furthermore, previous peripheral vascular disease (PVD), hypertension, atrial fibrillation, congestive heart failure, diabetes mellitus, and stroke were also risk factors for TAVI-associated AKI. Additionally, transfemoral access significantly correlated with a reduced risk for post-TAVI AKI (OR, 0.43; 95% CI, 0.33-0.57). The potential confounders, including Society of Thoracic Surgeons Score, the logistic European System for Cardiac Operative Risk Evaluation, aortic valve area, mean pressure gradient, left ventricular ejection fraction, age, body mass index, contrast volume, and valve type, had no impact on the association between the risk factors and post-TAVI AKI. Subgroup analysis of the eligible studies presenting multivariate logistic regression analysis on the independent risk factors for post-TAVI AKI revealed that previous CKD, previous PVD, and transapical access were independent risk factors for TAVI-associated AKI. CONCLUSIONS: The current meta-analysis suggested that previous CKD, previous PVD, and transapical access may be independent risk factors for TAVI-associated AKI.

The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands.

The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ∼6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques.

Electrically triggered photonic crystal anti-counterfeiting tags with multi-level response fabricated by regioselective modification of ITO electrode surface.

Anticounterfeiting materials based on the photonic crystal (PC) have attracted great interest due to their unique visual effects originating from the changeable structural colors under various external stimuli. However, there still are challenges to improving the anticounterfeiting performance by enhancing the complexity and diversity of the color changes. Here, we fabricated an electrically triggered anticounterfeiting tag by encapsulating the responsive PC with the surface-modified and patterned ITO electrode. The degree of Au deposition or chemical etching in different regions of the ITO was precisely controlled to achieve multi-level differentiated electrical responses, which made the invisible pattern of the tag at 0 V be "revealed in multicolor form" or "gradually revealed" under increasing voltages. The tag possessed two working modes, more diversified visual effects, good usability, and reversibility, which let it become a potentially useful material for anti-counterfeiting applications in the future.

Association between long-term exposure to PM2.5 chemical components and metabolic syndrome in middle-aged and older adults.

Background: Previous studies indicated that exposure to ambient fine particulate matter (PM2.5) could increase the risk of metabolic syndrome (MetS). However, the specific impact of PM2.5 chemical components remains uncertain. Methods: A national cross-sectional study of 12,846 Chinese middle-aged and older adults was conducted. Satellite-based spatiotemporal models were employed to determine the 3-year average PM2.5 components exposure, including sulfates (SO4 2-), nitrates (NO3 -), ammonia (NH4 +), black carbon (BC), and organic matter (OM). Generalized linear models were used to investigate the associations of PM2.5 components with MetS and the components of MetS, and restricted cubic splines curves were used to establish the exposure-response relationships between PM2.5 components with MetS, as well as the components of MetS. Results: MetS risk increased by 35.1, 33.5, 33.6, 31.2, 32.4, and 31.4% for every inter-quartile range rise in PM2.5, SO4 2-, NO3 -, NH4 +, OM and BC, respectively. For MetS components, PM2.5 chemical components were associated with evaluated risks of central obesity, high blood pressure (high-BP), high fasting glucose (high-FBG), and low high-density lipoprotein cholesterol (low-HDL). Conclusion: This study indicated that exposure to PM2.5 components is related to increased risk of MetS and its components, including central obesity, high-BP, high-FBG, and low-HDL. Moreover, we found that the adverse effect of PM2.5 chemical components on MetS was more sensitive to people who were single, divorced, or widowed than married people.