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OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.
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Angioplastia Coronária com Balão , Reestenose Coronária , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Reestenose Coronária/etiologia , Reestenose Coronária/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Angioplastia Coronária com Balão/métodos , Angioplastia Coronária com Balão/efeitos adversos , Stents Farmacológicos , Seguimentos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Vasos Coronários/cirurgiaRESUMO
Very late antigen-4 (VLA-4) is a transmembrane integrin protein that is highly expressed in aggressive forms of metastatic melanoma. A small-molecule peptidomimetic, LLP2A, was found to have a low pM affinity binding to VLA-4. Because LLP2A itself does not inhibit cancer cell proliferation and survival, it is an ideal candidate for the imaging and delivery of therapeutic payloads. An analog of [177Lu]Lu-labeled-LLP2A was previously investigated as a therapeutic agent in melanoma tumor-bearing mice, resulting in only a modest improvement in tumor growth inhibition, likely due to rapid clearance of the agent from the tumor. To improve the pharmacokinetic profile, DOTAGA-PEG4-LLP2A with a 4-(p-iodophenyl)butyric acid (pIBA) albumin binding moiety was synthesized. We demonstrate the feasibility of this albumin binding strategy by comparing in vitro cell binding assays and in vivo biodistribution performance of [177Lu]Lu-DOTAGA-PEG4-LLP2A ([177Lu]Lu-1) to the albumin binding [177Lu]Lu-DOTAGA-pIBA-PEG4-LLP2A ([177Lu]Lu-2). In vitro cell binding assay results for [177Lu]Lu-1 and [177Lu]Lu-2 showed Kd values of 0.40 ± 0.07 and 1.75 ± 0.40 nM, with similar Bmax values of 200 ± 6 and 315 ± 15 fmol/mg, respectively. In vivo biodistribution data for both tracers exhibited specific uptake in the tumor, spleen, thymus, and bone due to endogenous expression of VLA-4. Compound [177Lu]Lu-2 exhibited a much longer blood circulation time compared to [177Lu]Lu-1. The tumor uptake for [177Lu]Lu-1 was highest at 1 h (â¼15%ID/g) and that for [177Lu]Lu-2 was highest at 4 h (â¼23%ID/g). Significant clearance of [177Lu]Lu-1 from the tumor occurs at 24 h (<5%ID/g) while[177Lu]Lu-2 is retained for greater than 96 h (â¼10%ID/g). An efficacy study showed that melanoma tumor-bearing mice receiving compound [177Lu]Lu-2 given in two fractions (2 × 14.8 MBq, 14 days apart) had a greater median survival time than mice administered a single 29.6 MBq dose of compound [177Lu]Lu-1, while a single 29.6 MBq dose of [177Lu]Lu-2 imparted hematopoietic toxicity. The in vitro and in vivo data show addition of pIBA to [177Lu]Lu-DOTAGA-PEG4-LLP2A slows blood clearance for a higher tumor uptake, and there is potential of [177Lu]Lu-2 as a theranostic in fractionated administered doses.
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Lutécio , Radioisótopos , Animais , Camundongos , Distribuição Tecidual , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Humanos , Compostos Radiofarmacêuticos/farmacocinética , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Feminino , Integrina alfa4beta1/metabolismo , Integrina alfa4beta1/antagonistas & inibidores , Albuminas , Peptídeos/química , Peptídeos/farmacocinética , Nanomedicina Teranóstica/métodos , Camundongos Endogâmicos C57BL , Dipeptídeos , Compostos de FenilureiaRESUMO
Particulate materials arising from road-deposited sediments (RDS) are an essential target for the control and management of surface runoff pollution. However, the heterogeneity of urban spaces hinders the identification and quantification of particulate pollution, which is challenging when formulating precise control measures. To elucidate the factors that drive particulate pollution in heterogeneous urban spaces, the accumulation of RDS on dry days and the total suspended solids during six natural rainfall events were investigated across three urban-rural spatial units (central urban, central suburban, and remote suburban). The underlying surface type (asphalt or cement roads) and particle size composition jointly determined the spatial heterogeneity in the static accumulation and dynamic output loads of RDS during rainfall. These two factors explained 59.6% and 18.9% of the spatial heterogeneity, respectively, according to principal component analysis. A novel CPSI exponential wash-off equation that incorporates particle size composition and underlying surface type was applied. It precisely described the spatial heterogeneity of RDS wash-off loads, the estimated values exhibiting event mean concentration errors of 10.8-18.2%. When coupled with the M(V) curve, this CPSI exponential wash-off equation more precisely split the initial volume of runoff: a lower total volume (17.6-38.0%) was shown to carry a higher proportion of the load (70.0-93.7%) compared to the traditional coupled exponential wash-off equation (volume: 31.6-49.0%, load: 37-90%). This study provides a new approach to characterizing RDS wash-off processes and splitting initial runoff in heterogeneous spaces.
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Chuva , Poluentes Químicos da Água , Movimentos da Água , Monitoramento Ambiental , Poluição Ambiental/análise , Tamanho da Partícula , Poeira/análise , Poluentes Químicos da Água/análiseRESUMO
Azaspiro[3.3]heptanes are valuable synthetic targets for drug discovery programs. The challenges associated with the preparation and diversification of this moiety as compared to other small, saturated rings have led to limited applications of compounds containing this spirocycle. In this regard, important advances in the field of synthetic photochemistry have exploited the biradical nature of the triplet excited state of 2-isoxazoline-3-carboxylates, engaging these species in intermolecular coupling reactions under visible light irradiation. As a continuation of our program preparing F(sp3)-rich, structurally complex molecules for DNA-encoded library technology (DELT) applications via photocatalysis, we disclose herein the incorporation of unique and densely functionalized 2-oxa-1-azabicyclo[3.2.0]heptanes via [2+2] cycloaddition energy transfer sensitization, providing access to an unexplored library of azaspiro compounds, many of which include additional synthetic handles important for further functionalization of the DNA-conjugated products and for library production.
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Heptanos , Luz , Transferência de Energia , Catálise , DNARESUMO
DNA-encoded library (DEL) screens have significantly impacted new lead compound identification efforts within drug discovery. An advantage of DELs compared to traditional screening methods is that an exponentially broader chemical space can be effectively screened using only nmol quantities of billions of DNA-tagged, drug-like molecules. The synthesis of DELs containing diverse, sp3-rich spirocycles, an important class of molecules in drug discovery, has not been previously reported. Herein, we demonstrate the synthesis of complex and novel spirocyclic cores via an on-DNA, visible light-mediated intermolecular [2 + 2] cycloaddition of olefins with heterocycles, including indoles, azaindoles, benzofurans, and coumarins. The DNA-tagged exo-methylenecyclobutane substrates were prepared from easily accessible alkyl iodides and styrene derivatives. Broad reactivity with many other DNA-conjugated alkene substrates was observed, including unactivated and activated alkenes, and the process is tolerant of various heterocycles. The cycloaddition was successfully scaled from 10 to 100 nmol without diminished yield, indicative of this reaction's suitability for DNA-encoded library production. Evaluation of DNA compatibility with the developed reaction in a mock-library format showed that the DNA barcode was maintained with high fidelity, with <1% mutated sequences and >99% amplifiable DNA from quantitative polymerase chain reaction (PCR) and next generation sequencing (NGS).
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In the coal-burning fluorosis areas of China, over 10 million people suffer from dental fluorosis caused by multiple pathways of fluoride intake. However, the link between dental fluorosis prevalence, the geochemical distribution of fluoride, and contributions of different exposure pathways remain unclear. Here, we aimed to quantify the various fluoride exposure pathways and establish the association between dental fluorosis and fluoride intake in Southwest China. Epidemiological data on the peak time of fluorosis prevalence were combined with geochemical analyses of the fluoride content in coal and clay over a large scale, the amounts and ratios of fluoride intake through different exposure pathways were calculated, and the association between the total daily fluoride intake (TDFI) and dental fluorosis severity was analyzed. The prevalence of dental fluorosis was not significantly correlated with the fluoride geo-background of coal and clay on a large scale (P > 0.05). The co-combustion of coal and clay contained in hand-made briquettes is the main pathway of fluoride contamination, which occurs through the inhalation of polluted air and consumption of contaminated roasted products. Furthermore, the TDFI per person ranged from 2.78 to 17.32 mg, and it was significantly positively correlated with the prevalence of dental fluorosis (P < 0.05). The TDFI from breathing and eating was 1.1-3.2 mg and 1.1-15.1 mg, which accounted for 9%-54% and 40%-90% of the total TDFI, respectively. The combination of living habits and soil geochemical fluoride anomalies resulted in the higher prevalence of fluorosis in rural areas of Southwest China.
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The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals and bioactive compounds. To construct such prevalent bonds, most alkene difunctionalization methods demand the use of precious metals or activated alkenes. We report a metal-free, photochemically mediated imino-alkylation of electronically diverse alkenes to install both alkyl and iminyl groups in a highly efficient manner. The exceptionally mild reaction conditions, broad substrate scope, excellent functional group tolerance, and facile one-pot reaction protocol highlight the utility of this method to prepare privileged motifs from readily available alkene and acid feedstocks. One key and striking feature of this transformation is that an electrophilic trifluoromethyl radical is equally efficient with both electron-deficient and electron-rich alkenes. Additionally, dispersion-corrected density functional theory (DFT) and empirical investigations provide detailed mechanistic insight into this reaction.
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Alcenos , Ésteres , Alcenos/química , Alquilação , Catálise , OximasRESUMO
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Recent studies have shown that n6-methyladenosine (m6A) plays a major role in cardiovascular homeostasis and pathophysiology. These studies have confirmed that m6A methylation affects the pathophysiology of cardiovascular diseases by regulating cellular processes such as differentiation, proliferation, inflammation, autophagy, and apoptosis. Moreover, plenty of research has confirmed that m6A modification can delay the progression of CVD via the post-transcriptional regulation of RNA. However, there are few available summaries of m6A modification regarding CVD. In this review, we highlight advances in CVD-specific research concerning m6A modification, summarize the mechanisms underlying the involvement of m6A modification during the development of CVD, and discuss the potential of m6A modification as a therapeutic target of CVD.
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Strained bicyclic substructures are increasingly relevant in medicinal chemistry discovery research because of their role as bioisosteres. Over the last decade, the successful use of bicyclo[1.1.1]pentane (BCP) as a para-disubstituted benzene replacement has made it a highly valuable pharmacophore. However, various challenges, including limited and lengthy access to useful BCP building blocks, are hampering early discovery research. Here we report a single-step transition-metal-free multi-component approach to synthetically versatile BCP boronates. Radicals derived from commonly available carboxylic acids and organohalides perform additions onto [1.1.1]propellane to afford BCP radicals, which then engage in polarity-matched borylation. A wide array of alkyl-, aryl- and alkenyl-functionalized BCP boronates were easily prepared. Late-stage functionalization performed on natural products and approved drugs proceeded with good efficiency to generate the corresponding BCP conjugates. Various photoredox transformations forging C-C and C-N bonds were demonstrated by taking advantage of BCP trifluoroborate salts derived from the BCP boronates.
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Produtos Biológicos , Elementos de Transição , MetaisRESUMO
DNA-encoded libraries have proven their tremendous value in the identification of new lead compounds for drug discovery. To access libraries in new chemical space, many methods have emerged to transpose traditional mol-scale reactivity to nmol-scale, on-DNA chemistry. However, procedures to access libraries with a greater fraction of C(sp3) content are still limited, and the need to "escape from flatland" more readily on-DNA remains. Herein, we report a Giese addition to install highly functionalized bicyclo[1.1.1]pentanes (BCPs) using tricyclo[1.1.1.01,3]pentane (TCP) as a radical linchpin, as well as other diverse alkyl groups, on-DNA from the corresponding organohalides as non-stabilized radical precursors. Telescoped procedures allow extension of the substrate pool by at least an order of magnitude to ubiquitous alcohols and carboxylic acids, allowing us to "upcycle" these abundant feedstocks to afford non-traditional libraries with different physicochemical properties for the small-molecule products (i.e., non-peptide libraries with acids). This approach is amenable to library production, as a DNA damage assessment revealed good PCR amplifiability and only 6% mutated sequences for a full-length DNA tag.
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Pentanos , Bibliotecas de Moléculas Pequenas , DNA/química , Biblioteca Gênica , Halogênios , Bibliotecas de Moléculas Pequenas/químicaRESUMO
Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide with regulated cell death playing an important role in cardiac pathophysiology. However, the classical mode of cell death cannot fully explain the occurrence and development of heart disease. In recent years, much research has been performed on ferroptosis, a new type of cell death that causes cell damage and contributes to the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In this review, we discuss the role of different organelles in ferroptosis and also focus on the relationship between autophagy and ferroptosis. Additionally, we describe the specific mechanism by which ferroptosis contributes to the development of CVD. Finally, we summarize the current research on ferroptosis-related pathway inhibitors and the applications of clinically beneficial cardiovascular drugs.
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PURPOSE: The combined use of drug coated balloon (DCB) and optical coherence tomography (OCT) for the treatment of non-small coronary de novo lesion remains to be evaluated. We investigated the safety and efficacy of OCT-guided DCB in non-small coronary de novo lesion patients with predilation of cutting balloon. METHODS: https://clinicaltrials.gov/, ClinicalTrials.gov Identifier: NCT04795144. This study was a prospective, and open-label study. We enrolled patients with non-small de novo lesions treated with OCT-guided DCB. The non-small de novo lesions indicated vessel lesions with a diameter ≥ 2.5 mm. The primary endpoints were the success rate of the procedure and the occurrence of target lesion revascularization. The secondary endpoints were myocardial infarction, cardiac death, and major adverse cardiac events (MACE) within 3 months after the procedure. RESULTS: At the Second Hospital of Jilin University, we enrolled 54 patients (54 lesions) with non-small de novo lesions who were treated with OCT-guided DCB from October 2018 to June 2019. A total of 52 patients were successfully treated with DCB-only strategy, while 2 patients turned to bailout stenting. A total of 21 patients had undergone angiography 3 months after the procedure with the late lumen loss of 0.24±0.57 mm. There was no statistically significant difference in minimal lumen diameter (MLD) between post-DCB and at 3-month angiographic follow-up (2.25±0.40 mm vs 2.04±0.54 mm; P = 0.110). Only 1 patient developed restenosis with the incidence of MACE rate of only 1.92% (n = 1). There was no significant difference in the stenosis of the lumen diameter of the target lesion vessel between 3 months after operation and immediately after operation. CONCLUSIONS: Our study showed that OCT-guided DCB with cutting balloon under guidance may be a novel approach in non-small de novo coronary artery disease.
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BACKGROUND: Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. METHODS: The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DSâ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287âdays in group A and 227âdays in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DSâ≥50%) at mid-term follow-up using the area under the curve (AUC). RESULTS: A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; Pâ<â0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; Pâ<â0.001). CONCLUSIONS: The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.
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Doença da Artéria Coronariana , Reestenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Preparações Farmacêuticas , Constrição Patológica , Angiografia Coronária , Doença da Artéria Coronariana/terapia , Seguimentos , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Atherosclerosis (AS) is a major cause of CVD. Oxidative stress, endothelial dysfunction, and inflammation are key factors involved in the development and progression of AS. Exosomes are nano-sized vesicles secreted into the extracellular space by most types of cells, and are ideal substances for the transmission and integration of signals between cells. Cells can selectively encapsulate biologically active substances, such as lipids, proteins and RNA in exosomes and act through paracrine mechanisms. Non-coding RNAs (ncRNAs) are important for communication between cells. They can reach the recipient cells through exosomes, causing phenotypic changes and playing a molecular regulatory role in cell function. Elucidating their molecular mechanisms can help identify therapeutic targets or strategies for CVD. Coronary artery disease (CAD) is the most important disease in CVD. Here, we review the role and the regulatory mechanism of exosomal ncRNAs in the pathophysiology of CAD, as well as the potential contribution of exosomal ncRNA to diagnosis and treatment of CAD.
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INTRODUCTION: Kawasaki disease (KD) is an acute vasculitis syndrome that mainly affects children and is the first cause of acquired heart disease. Coronary artery lesion is the most serious complication of KD. Only two previous studies have reported similar cases, but we reported patient was younger and had a longer follow-up. PATIENT CONCERNS: We reported a case of coronary sequelae of KD treated with rotational atherectomy and drug coated balloon (DCB). During the week after surgery, the patient complained of a slight chest pain intermittently, but no longer appeared after that. DIAGNOSIS: We diagnosed by electrocardiogram and angiography. Angiography showed that the anterior descending branch (LAD) proximal stenosis was 95%, the right coronary artery (RCA) middle stenosis was 99%, and the calcification was severe. INTERVENTIONS: We treat the patient with rotational atherectomy using a 1.25âmm burr, pre-dilatation of the stenosis lesion with a 3.5âmmâ×â15âmm non-compliant balloon was achieved. Then 3.5âmmâ×â15âmm drug eluting balloon was inflated at 10âatm for 60âseconds. OUTCOMES: After the 6-month follow-up (from October 2018 to March 2019), the symptom of angina disappeared. Coronary angiography 6 months later showed no apparent progression of vessel narrowing. CONCLUSION: The present case suggests that rotational atherectomy followed by DCB dilation could be an alternative revascularization therapy of choice in coronary KD sequelae complicated with atherosclerosis.
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Aterectomia Coronária/métodos , Aneurisma Coronário/cirurgia , Síndrome de Linfonodos Mucocutâneos/complicações , Adulto , Angioplastia Coronária com Balão/métodos , Calcinose/patologia , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Vasos Coronários/patologia , Eletrocardiografia , Humanos , MasculinoRESUMO
Timely awareness of hypertension is among the most crucial components in reducing the burden of hypertension. However, there is limited information about the awareness of hypertension in northern China. Therefore, in this cross-sectional study, we aimed to investigate the awareness of hypertension and its associated factors in the Jilin province in China; the study was conducted between July 2014 and December 2015 in four cities and four rural counties in the Jilin province as part of a national study. A stratified multistage random-sampling method was used to select a representative sample: a total of 15,206 participants aged ≥15 years were initially recruited, among which 14,956 were finally included in the survey. The awareness of hypertension in the Jilin province was found to be 42.3%. Moreover, the awareness of hypertension was associated with age, sex, region, marital status, body mass index, and family history of hypertension or coronary artery disease. Employment was associated with a lower awareness in rural areas, whereas high education was associated with a higher awareness in urban areas. Policies targeting specific subgroups may be helpful in increasing the awareness of hypertension in the Jilin province.
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Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde , Hipertensão , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Atitude Frente a Saúde , China/epidemiologia , Informação de Saúde ao Consumidor , Estudos Transversais , Feminino , Letramento em Saúde/normas , Letramento em Saúde/estatística & dados numéricos , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Prevalência , Fatores SocioeconômicosRESUMO
The thermal (3 + 2) dipolar azide-alkyne cycloaddition, proceeding without copper or strained alkynes, is an underutilized ligation with potential applications in materials, bioorganic, and synthetic chemistry. Herein, we investigate the effects of alkyne substitution on the rate of this reaction, both experimentally and computationally. Electron-withdrawing groups accelerate the reaction, providing a range of relative rates from 1.0 to 2100 between the slowest and fastest alkynes studied. Unexpectedly, aryl groups conjugated to the alkyne significantly retard the reaction rate. In contrast, a sulfonyl, ester-substituted alkyne is reactive enough that it couples with an azide at room temperature in a few hours. This reactivity scale should provide a guide to those who wish to use this ligation under mild conditions.
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BACKGROUND: Hypertension is a significant global public health problem and recognized as an important risk factor for cardiovascular diseases. This study was designed to assess the current prevalence of hypertension and to explore risk factors associated with hypertension by urban and rural status to guide the prevention and control of hypertension in Jilin province. METHODS: A multi-stage stratified random cluster sampling method was used to obtain data on hypertension, which was investigated by physical examination and face-to-face questionnaire in July 2014-December 2015. Sample data were analyzed by complex weighted statistical analysis to estimate blood pressure levels and prevalence of hypertension in the province. Multivariable logistic regression analysis was used to identify factors influencing hypertension rates. RESULTS: The prevalence of hypertension was significantly higher in rural areas than urban areas (25.93% versus 22.73%, respectively). The rates of hypertension known (46.7% versus 38.1%, respectively), control (13.7% versus 5.0%, respectively), and controlled among treated subjects (38.3% versus 17.5%, respectively) were higher in urban areas than in rural areas (all p < 0.001), while the treatment rate was not statistically significantly different between urban and rural areas (35.9% versus 28.4%, respectively). After adjusting for demographic covariates, hypertension prevalence in rural areas was still significantly greater than in urban areas (adjusted OR = 1.22; 95%CI: 1.10, 1.36; p < 0.001). Common risk factors for hypertension among urban and rural residents included older age; male; married; employed; less education; overweight/obese; greater abdominal waist circumference; family history of hypertension, stroke, or coronary heart disease; current smoker; alcohol consumption; higher visceral adiposity index; and higher body fat percentage. CONCLUSIONS: This study identified an increased risk for hypertension in rural regions of Jilin province, suggesting that rural hypertension screening and treatment guidelines should receive greater attention.
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Hipertensão/etnologia , Hipertensão/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Pressão Sanguínea , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade Abdominal , Sobrepeso , Prevalência , Fatores de Risco , População Rural , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários , População Urbana , Circunferência da CinturaRESUMO
OBJECTIVE: This study aimed to investigate the prevalence and distribution of hypertension and its related factors in Jilin province, China. DESIGN: A cross-sectional study in four cities and four rural counties in Jilin as part of a national Chinese study. PARTICIPANTS AND SETTING: A total of 15 206 participants who were ≥15 years old and were selected using a stratified multistage random sampling method. MAIN OUTCOME MEASURES: The prevalence of hypertension. RESULTS: The prevalence of hypertension in Jilin province was 24.7%. Moreover, the prevalence of hypertension increased with age in both sexes, and was higher in men than in women. The modifiable factors that were associated with hypertension were body mass index, smoking and alcohol drinking. The risk factors identified are similar to those in southern China, except smoking, which has no association with hypertension prevalence in the South. CONCLUSIONS: Age, sex, body mass index, smoking and alcohol drinking were risk factors of hypertension. Control of these related risk factors, especially smoking, may be helpful in the treatment and management of hypertension in Jilin province.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Hipertensão/epidemiologia , Hipertensão/etiologia , Obesidade/complicações , Fumar/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND/AIMS: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. METHODS: Cell survival was analyzed via CCK assay. The energy metabolism shift was detected by lactate assay, ATP assay and RT2 profiler glucose metabolism PCR array. Protein and mRNA expression levels were determined by western blot and qPCR. We also used kits to detect the activity of Complex I, Sirt3 and the NAD+/NADH ratio. RESULTS: We determined that miR-210 promoted the energy metabolism shift. The iron-sulfur cluster assembly protein (ISCU) was a target of miR-210. Additionally, we detected the activity of complex I and found that miR-210 inhibits mitochondrial respiration. Interestingly, miR-210 may also indirectly regulate SIRT3 by regulating ISCU. CONCLUSION: Our results confirm that miR-210 is essential and sufficient for modulating the cellular energy metabolism shift during H2O2-induced oxidative stress in H9c2 cardiomyocytes by targeting ISCU.