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Drought stress poses a substantial challenge to plant growth and agricultural productivity worldwide. Upon water depletion, plants activate an abscisic acid (ABA) signaling pathway, leading to stomatal closure to reduce water loss. The MYB family of transcription factors plays diverse roles in growth, development, stress responses and biosynthesis, yet their involvement in stomatal regulation remains unclear. Here, we demonstrate that ABA significantly upregulates the expression of MYB41, MYB74, and MYB102, with MYB41 serving as a key regulator that induces the expression of both MYB74 and MYB102. Through luciferase assays, chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSA), we reveal that MYB41 engages in positive feedback regulation by binding to its own promoter, thus amplifying its transcription in Arabidopsis (Arabidopsis thaliana). Furthermore, our investigation showed that MYB41 recruits BRAHMA (BRM), the core ATPase subunit of the SWI/SNF complex, to the MYB41 promoter, facilitating the binding of HISTONE DEACETYLASE 6 (HDA6). This recruitment triggers epigenetic modifications, resulting in reduced MYB41 expression characterized by elevated H3K27me3 levels and concurrent decreases in H3ac, H3K27ac, and H3K14ac levels in wild-type plants compared to brm knockout mutant plants. Our genetic and molecular analyses show that ABA mediates autoregulation of the MYB41-BRM module, which intricately modulates stomatal movement in A. thaliana. This discovery sheds light on a drought response mechanism with the potential to greatly enhance agricultural productivity.
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Plants have an incredible ability to sustain root and vascular growth after initiation of the embryonic root and the specification of vascular tissue in early embryos. Microarray assays have revealed that a group of transcription factors, TARGET OF MONOPTEROS (TMO), are important for embryonic root initiation in Arabidopsis. Despite the discovery of their auxin responsiveness early on, their function and mode of action remained unknown for many years. The advent of genome editing has accelerated the study of TMO transcription factors, revealing novel functions for biological processes such as vascular development, root system architecture, and response to environmental cues. This review covers recent achievements in understanding the developmental function and the genetic mode of action of TMO transcription factors in Arabidopsis and other plant species. We highlight the transcriptional and post-transcriptional regulation of TMO transcription factors in relation to their function, mainly in Arabidopsis. Finally, we provide suggestions for further research and potential applications in plant genetic engineering.
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Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Desenvolvimento Vegetal , Raízes de Plantas/metabolismoRESUMO
Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.
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Clorofilídeos , Fotoquimioterapia , Porfirinas , Neoplasias da Bexiga Urinária , Animais , Camundongos , Catalase/uso terapêutico , Linhagem Celular Tumoral , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , HumanosRESUMO
Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.
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Carcinógenos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/induzido quimicamente , Carcinógenos/toxicidade , Carcinógenos/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Povo Asiático/genética , China/epidemiologia , Nicotiana , Idoso , População Branca/genética , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Nitrosaminas/toxicidade , Hidroxiesteroide DesidrogenasesRESUMO
The artificial potential field method has efficient obstacle avoidance ability, but this traditional method suffers from local minima, unreasonable paths, and sudden changes in heading angles during obstacle avoidance, leading to rough paths and increased energy consumption. To enable autonomous mobile robots (AMR) to escape from local minimum traps and move along reasonable, smooth paths while reducing travel time and energy consumption, in this paper, an artificial potential field method based on subareas is proposed. First, the optimal virtual subgoal was obtained around the obstacles based on the relationship between the AMR, obstacles, and goal points in the local environment. This was done according to the virtual subgoal benefit function to solve the local minima problem and select a reasonable path. Secondly, when AMR encountered an obstacle, the subarea-potential field model was utilized to solve problems such as path zigzagging and increased energy consumption due to excessive changes in the turning angle; this helped to smooth its planning path. Through simulations and actual testing, the algorithm in this paper demonstrated smoother heading angle changes, reduced energy consumption, and a 10.95% average reduction in movement time when facing a complex environment. This proves the feasibility of the algorithm.
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The use of tunable metasurface technology to realize the underwater tracking function of submarines, which is one of the hotspots and difficulties in submarine design. The structure-to-sound-field metasurface design approach is a highly iterative process based on trial and error. The process is cumbersome and inefficient. Therefore, an inverse design method was proposed based on parallel deep neural networks. The method took the global and local target sound field feature information as input and the metasurface physical structure parameters as output. The deep neural network was trained using a kernel loss function based on a radial basis kernel function, which established an inverse mapping relationship between the desired sound field to the metasurface physical structure parameters. Finally, the sound field intensity modulation at a localized target range was achieved. The results indicated that within the regulated target range, this method achieved an average prediction error of less than 5 dB for 92.9% of the sample data.
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Algoritmos , Redes Neurais de ComputaçãoRESUMO
Existing research in metasurface design was based on trial-and-error high-intensity iterations and requires deep acoustic expertise from the researcher, which severely hampered the development of the metasurface field. Using deep learning enabled the fast and accurate design of hypersurfaces. Based on this, in this paper, an integrated learning approach was first utilized to construct a model of the forward mapping relationship between the hypersurface physical structure parameters and the acoustic field, which was intended to be used for data enhancement. Then a dual-feature fusion model (DFCNN) based on a convolutional neural network was proposed, in which the first feature was the high-dimensional nonlinear features extracted using a data-driven approach, and the second feature was the physical feature information of the acoustic field mined using the model. A convolutional neural network was used for feature fusion. A genetic algorithm was used for network parameter optimization. Finally, generalization ability verification was performed to prove the validity of the network model. The results showed that 90% of the integrated learning models had an error of less than 3 dB between the real and predicted sound field data, and 93% of the DFCNN models could achieve an error of less than 5 dB in the local sound field intensity.
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BACKGROUND AND OBJECTIVE: The pathogenesis of coronal suture craniosynostosis is often attributed to the dysregulated cellular dynamics, particularly the excessive proliferation and abnormal osteogenic differentiation of suture cells. Despite its clinical significance, the molecular mechanims of this condition remain inadequately understood. This study is dedicated to exploring the influence of the Periostin/Bone Morphogenetic Protein 1 (BMP1) axis on the growth and osteogenic maturation of Suture Mesenchymal Stem Cells (SMSCs), which are pivotal in suture homeostasis. METHODS: Neonatal TWIST Basic Helix-Loop-Helix Transcription Factor 1 heterozygous (TWIST1+/-) mice, aged one day, were subjected to adenoviral vector-mediated Periostin upregulation. To modulate Periostin/BMP1 levels in SMSCs, we employed siRNA and pcDNA 3.1 vectors. Histological and molecular characterizations, including hematoxylin and eosin staining, Western blot, and immunohistochemistry were employed to study suture closure phenotypes and protein expression patterns. Cellular assays, encompassing colony formation, 5-ethynyl-2'deoxyuridine, and wound healing tests were conducted to analyze SMSC proliferation and migration. Osteogenic differentiation was quantified using Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) staining, while protein markers of proliferation and differentiation were evaluated by Western blotting. The direct interaction between Periostin and BMP1 was validated through co-immunoprecipitation assays. RESULTS: In the TWIST1+/- model, an upregulation of Periostin coupled with a downregulation of BMP1 was observed. Augmenting Periostin expression mitigated craniosynostosis. In vitro, overexpression of Periostin or BMP1 knockdown suppressed SMSC proliferation, migration, and osteogenic differentiation. Periostin knockdown manifested an inverse biological impact. Notably, the suppressive influence of Periostin overexpression on SMSCs was effectively counteracted by upregulating BMP1. There was a direct interaction between Periostin and BMP1. CONCLUSION: These findings underscore the significance of the Periostin/BMP1 axis in regulating craniosynostosis and SMSC functions, providing new insights into the molecular mechanisms of craniosynostosis and potential targets for therapeutic intervention.
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Craniossinostoses , Células-Tronco Mesenquimais , Camundongos , Animais , Osteogênese/genética , Periostina , Proteína Morfogenética Óssea 1/metabolismo , Craniossinostoses/genética , Craniossinostoses/metabolismo , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Modelos Animais de Doenças , Proliferação de Células/genética , Células CultivadasRESUMO
AIMS: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. METHODS AND RESULTS: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. CONCLUSIONS: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.
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Fragilidade , Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Índice de Massa Corporal , Fragilidade/complicações , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/uso terapêuticoRESUMO
Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.
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BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear. OBJECTIVE: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF. METHODS: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required.
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AIMS: Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. METHODS: A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. RESULTS: The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (pï¼0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. CONCLUSIONS: In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.
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Colon adenocarcinoma (COAD) is the most common malignancy of the digestive tract, which is characterized by a dismal prognosis. No effective treatment has been established presently, thus there is an urgent need to understand the mechanisms driving COAD progression in order to develop effective therapeutic approaches and enhance clinical outcomes. In this study, we found that KLF7 is overexpressed in COAD tissues and correlated with clinicopathological features of COAD. Both gain-of-function and loss-of-function experiments have unequivocally demonstrated that overexpression of KLF7 promotes the growth and metastasis of COAD in vitro and in vivo, while KLF7 knockdown attenuated these effects. Mechanistically, our findings reveal that KLF7 can specifically bind to the promoter region of PDGFB (TGGGTGGAG), thus promoting the transcription of PDGFB and increasing its secretion. Subsequently, secreted PDGFB facilitates the progression of COAD by activating MAPK/ERK, PI3K/AKT, and JAK/STAT3 signaling pathways through PDGFRß. Additionally, we found that sunitinib can block PDGFB signaling and inhibit COAD progression, offering a promising therapeutic strategy for COAD treatment.
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Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Adenocarcinoma/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Becaplermina , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismoRESUMO
BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. METHODS: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. RESULTS: A total of 5700 patients were included, with a mean age of 66.4âyears old. During a median of 3.29âyears follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P â>â0.05). CONCLUSION: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. REGISTRATION: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.
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Pressão Sanguínea , Hipertensão , Insuficiência Renal Crônica , Humanos , Hipertensão/fisiopatologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Feminino , Idoso , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Pessoa de Meia-Idade , Fatores de Risco , Albuminúria/fisiopatologia , Rim/fisiopatologia , Anti-Hipertensivos/uso terapêutico , Taxa de Filtração Glomerular , IncidênciaRESUMO
BACKGROUND: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. METHODS: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. RESULTS: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). CONCLUSIONS: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.
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Sobreviventes de Câncer , Hipertensão , Infarto do Miocárdio , Neoplasias , Humanos , Pessoa de Meia-Idade , Idoso , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Resultado do Tratamento , Fatores de Risco , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológicoRESUMO
Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).
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Anti-Hipertensivos , Pressão Sanguínea , Hipertensão Essencial , Renina , Humanos , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão Essencial/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Renina/sangue , Resultado do Tratamento , Adulto , ComprimidosRESUMO
Solid polymer electrolytes (SPEs) represent a pivotal advance toward high-energy solid-state lithium metal batteries. However, inadequate interfacial contact remains a significant bottleneck, impeding scalability and application. Inadequate interfacial contact remains a significant bottleneck, impeding scalability and application. Recent efforts have focused on transforming liquid/solid interfaces into solid/solid ones through in situ polymerization, which shows potential especially in reducing interface impedance. Here, we designed high-voltage SSLMBs with dual-reinforced stable interfaces by combining interface modification with an in situ polymerization technology inspired by targeted effects in medicine. Theoretical calculations and time-of-flight secondary ion mass spectrometry (TOF-SIMS) analysis demonstrate that tetramethylene sulfone (TMS) and bis(2,2,2-trifluoromethyl) carbonate (TFEC) exhibit selective adsorption at the interface of the LiNi0.8Co0.1Mn0.1O2 (NCM) cathode and Li anode, respectively. These compounds further decompose to form a stable cathode-electrolyte interface (CEI) film and a solid electrolyte interface (SEI) film, thereby simultaneously achieving a superior interface between the SPE and both the Li anode and NCM cathode. The developed Li||SPE||Li cell sustained cycling for more than 1000 h at 0.3 mA cm-2, and the NCM||SPE||Li cell also demonstrated an excellent capacity retention of 86.8% after 1000 cycles at 1 °C. This work will provide valuable insights for the rational design of high-voltage SSLMBs with stable interfaces, leveraging in situ polymerization as a cornerstone technology.