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1.
Heart Rhythm ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38848863

ABSTRACT

BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack conduction system. However, it is unclear whether autoantibodies are associated with conduction disturbances in patients with HF. OBJECTIVE: Assess whether anti-SSA, anti-Ro/Sjögren's syndrome-related antigen A antibodies known for congenital atrioventricular block, is associated with conduction disturbances in patients with HF METHODS: This retrospective observational study used data from patients with HF who admitted to Beijing Anzhen Hospital between January 2018 and June 2022. We included patients who had anti-SSA tested and had electrocardiogram (ECG) examination during hospitalization. Conduction disturbances, including atrioventricular block (AVB), bundle branch block (BBB), and intraventricular conduction delay were confirmed by a cardiologist blinded to the anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: 766 patients were included in this study, 70(9.1%) of whom 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 bundle branch block (LBBB) and right bundle branch block (RBBB) (all P<0.05). After adjusting for known risk factors, anti-SSA were independently associated with AVB (OR 2.42 (1.18-5.43), P = 0.03) and BBB (OR 3.15(1.68-5.89), P<0.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. We need to study the role of autoantibodies in the development of conduction abnormalities in patient with HF to generate possible targeted treatments.

2.
Sensors (Basel) ; 24(11)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38894395

ABSTRACT

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.

3.
J Hypertens ; 42(7): 1203-1211, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38690929

ABSTRACT

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 66.4 years old. During a median of 3.29 years 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  > 0.05). 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.


Subject(s)
Blood Pressure , Hypertension , Renal Insufficiency, Chronic , Humans , Hypertension/physiopathology , Hypertension/complications , Hypertension/drug therapy , Male , Female , Aged , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Middle Aged , Risk Factors , Albuminuria/physiopathology , Kidney/physiopathology , Antihypertensive Agents/therapeutic use , Glomerular Filtration Rate , Incidence
4.
Materials (Basel) ; 17(9)2024 May 06.
Article in English | MEDLINE | ID: mdl-38730972

ABSTRACT

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.

5.
Arch Toxicol ; 98(7): 2269-2279, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38662237

ABSTRACT

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.


Subject(s)
Carcinogens , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/chemically induced , Carcinogens/toxicity , Carcinogens/metabolism , Male , Female , Middle Aged , Case-Control Studies , Asian People/genetics , China/epidemiology , Nicotiana , Aged , White People/genetics , Cigarette Smoking/adverse effects , Cigarette Smoking/genetics , Nitrosamines/toxicity , Hydroxysteroid Dehydrogenases
6.
Heliyon ; 10(8): e29198, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644863

ABSTRACT

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.

7.
Hypertens Res ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632457

ABSTRACT

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).

8.
Mol Pharm ; 21(4): 1705-1718, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38466144

ABSTRACT

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.


Subject(s)
Chlorophyllides , Photochemotherapy , Porphyrins , Urinary Bladder Neoplasms , Animals , Mice , Catalase/therapeutic use , Cell Line, Tumor , Oxygen , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Humans
9.
PLoS One ; 19(3): e0301211, 2024.
Article in English | MEDLINE | ID: mdl-38547089

ABSTRACT

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.


Subject(s)
Algorithms , Neural Networks, Computer
10.
J Orthop Surg Res ; 19(1): 146, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38369459

ABSTRACT

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.


Subject(s)
Craniosynostoses , Mesenchymal Stem Cells , Mice , Animals , Osteogenesis/genetics , Periostin , Bone Morphogenetic Protein 1/metabolism , Craniosynostoses/genetics , Craniosynostoses/metabolism , Cell Differentiation/genetics , Mesenchymal Stem Cells/metabolism , Disease Models, Animal , Cell Proliferation/genetics , Cells, Cultured
11.
Hypertension ; 81(3): 620-628, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38164752

ABSTRACT

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.


Subject(s)
Cancer Survivors , Hypertension , Myocardial Infarction , Neoplasms , Humans , Middle Aged , Aged , Blood Pressure/physiology , Antihypertensive Agents/pharmacology , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/chemically induced , Myocardial Infarction/drug therapy , Treatment Outcome , Risk Factors , Neoplasms/epidemiology , Neoplasms/drug therapy
12.
J Exp Bot ; 75(8): 2214-2234, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38195092

ABSTRACT

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.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Transcription Factors/metabolism , Arabidopsis/metabolism , DNA-Binding Proteins/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Indoleacetic Acids , Plant Development , Plant Roots/metabolism
13.
Int J Biol Sci ; 20(1): 387-402, 2024.
Article in English | MEDLINE | ID: mdl-38164176

ABSTRACT

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.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Colonic Neoplasms/metabolism , Proto-Oncogene Proteins c-sis/metabolism , Adenocarcinoma/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/genetics , Becaplermin , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism
14.
Luminescence ; 39(1): e4585, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37635303

ABSTRACT

In past decades, organic crystals have presented considerable potential in the field of optoelectronics due to their rich tunable physical and chemical properties and excellent optoelectronic characteristics. White-light emission, as a special application, has received widespread attention and has been applied in various fields, generating significant interest in the scientific community. By preparing white light-emitting organic crystals, a series of applications for future white-light sources can be realized. This article reviews the research progress on the molecular design and synthesis, preparation, and application of white light-emitting organic crystals in recent years. We hope that this review will help to understand and facilitate the development of white light-emitting organic crystals.


Subject(s)
Light
15.
Nat Chem ; 16(2): 201-209, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38036642

ABSTRACT

Two-dimensional organic lateral heterostructures (2D OLHs) are attractive for the fabrication of functional materials. However, it is difficult to control the nucleation, growth and orientation of two distinct components. Here we report the combination of two methods-liquid-phase growth and vapour-phase growth-to synthesize 2D OLHs from perylene and a perylenecarboxaldehyde derivative, with a lateral size of ~20 µm and a tunable thickness ranging from 20 to 400 nm. The screw dislocation growth behaviour of the 2D crystals shows the spiral arrangement of atoms within the crystal lattice, which avoids volume expansion and contraction of OLH, thereby minimizing lateral connection defects. Selective control of the nucleation and sequential growth of 2D crystals leads to structural inversion of the 2D OLHs by the vapour-phase growth method. The resulting OLHs show good light-transport capabilities and tunable spatial exciton conversion, useful for photonic applications. This synthetic strategy can be extended to other families of organic polycyclic aromatic hydrocarbons, as demonstrated with other pyrene and perylene derivatives.

16.
ESC Heart Fail ; 11(2): 709-718, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38131256

ABSTRACT

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.


Subject(s)
Frailty , Heart Failure , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Body Mass Index , Frailty/complications , Stroke Volume , Mineralocorticoid Receptor Antagonists/therapeutic use
17.
J Biomed Res ; 37(6): 405-417, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37936490

ABSTRACT

Aberrant alternative polyadenylation (APA) events play an important role in cancers, but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer. Previous genome-wide association study performed APA quantitative trait loci (apaQTL) analyses in bladder cancer, and identified 17 955 single nucleotide polymorphisms (SNPs). We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways, high mutational burden, and immune infiltration. Association analysis showed that apaQTL-associated SNPs rs34402449 C>A, rs2683524 C>T, and rs11540872 C>G were significantly associated with susceptibility to bladder cancer (rs34402449: OR = 1.355, 95% confidence interval [CI]: 1.159-1.583, P = 1.33 × 10 -4; rs2683524: OR = 1.378, 95% CI: 1.164-1.632, P = 2.03 × 10 -4; rs11540872: OR = 1.472, 95% CI: 1.193-1.815, P = 3.06 × 10 -4). Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer ( P trend = 2.87 × 10 -12). We found that PRR13, being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines, was more highly expressed in bladder cancer tissues than in adjacent normal tissues. Moreover, the rs2683524 T allele was correlated with shorter 3' untranslated regions of PRR13 and increased PRR13 expression levels. Collectively, our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

18.
Amino Acids ; 55(12): 1819-1827, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37819474

ABSTRACT

An important subtype of the innate-like T lymphocytes is mucosal-associated invariant T (MAIT) cells expressing a semi-invariant T cell receptor α (TCR-α) chain. MAIT cells could be activated mainly by TCR engagement or cytokines. They have been found to have essential roles in various immune mediated. There have been growing preclinical and clinical findings that show an association between MAIT cells and the physiopathology of inflammatory bowel diseases (IBD). Of note, published reports demonstrate contradictory findings regarding the role of MAIT cells in IBD patients. A number of reports suggests a protective effect, whereas others show a pathogenic impact. The present review article aimed to explore and discuss the findings of experimental and clinical investigations evaluating the effects of MAIT cells in IBD subjects and animal models. Findings indicate that MAIT cells could exert opposite effects in the course of IBD, including an anti-inflammatory protective effect of blood circulating MAIT cells and an effector pathogenic effect of colonic MAIT cells. Another important finding is that blood levels of MAIT cells can be considered as a potential biomarker in IBD patients.


Subject(s)
Inflammatory Bowel Diseases , Mucosal-Associated Invariant T Cells , Animals , Humans , Mucosal-Associated Invariant T Cells/pathology , Inflammatory Bowel Diseases/pathology , Cytokines , Biomarkers , Receptors, Antigen, T-Cell, alpha-beta
19.
Adv Sci (Weinh) ; 10(30): e2303473, 2023 10.
Article in English | MEDLINE | ID: mdl-37705121

ABSTRACT

Identification of cancer-associated variants, especially those in functional regions of long noncoding RNAs (lncRNAs), has become an essential task in tumor etiology. However, the genetic function of lncRNA variants involved in bladder cancer susceptibility remains poorly understood. Herein, it is identified that the rs62483508 G > A variant in microRNA response elements (MREs) of lncRNA Bladder cancer Cell Cytoplasm-Enriched abundant transcript 4 (BCCE4) is significantly associated with decreased bladder cancer risk (odds ratio = 0.84, P = 7.33 × 10-8 ) in the Chinese population (3603 cases and 4986 controls) but not in the European population. The protective genetic effect of the rs62483508 A allele is found in smokers or cigarette smoke-related carcinogen 4-aminobiphenyl (4-ABP) exposure. Subsequent biological experiments reveal that the A allele of rs62483508 disrupts the binding affinity of miR-328-3p to facilitate USP18 from miRNA-mediated degradation and thus specifically attenuates the downstream PD-L1/PD-1 interaction. LncRNA BCCE4 is also enriched in exosomes from bladder cancer plasma, tissues, and cells. This comprehensive study clarifies the genetic mechanism of lncRNA BCCE4 in bladder cancer susceptibility and its role in the regulation of the immune response in tumorigenesis. The findings provide a valuable predictor of bladder cancer risk that can facilitate diagnosis and prevention.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Urinary Bladder Neoplasms , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Programmed Cell Death 1 Receptor , B7-H1 Antigen/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Smoking/adverse effects , Smoking/genetics , Ubiquitin Thiolesterase
20.
Front Plant Sci ; 14: 1254548, 2023.
Article in English | MEDLINE | ID: mdl-37746016

ABSTRACT

Introduction: As the third largest food crop in the world, maize has wide varieties with similar appearances, which makes identification difficult. To solve the problem of identification of hybrid maize varieties, a method based on hyperspectral image technology combined with a convolutional neural network (CNN) is proposed to identify maize varieties. Methods: In this study, 735 maize seeds from seven half-parent hybrid maize varieties were regarded as the research object. The maize seed images in the range of 900 ~ 1700nm were obtained by hyperspectral image acquisition system. The region of interest (ROI) of the embryo surface was selected, and the spectral reflectance of maize seeds was extracted. After Savitzky-Golay (SG) Smoothing pretreatment, Maximum Normalization (MN) pretreatment was performed. The 56 feature wavelengths were selected by Competitive Adaptive Reweighting Algorithm (CARS) and Successive Projection Algorithm (SPA). And the 56 wavelengths were mapped to high-dimensional space by high-dimensional feature mapping and then reconstructed into three-dimensional image features. A five-layer convolution neural network was used to identify three-dimensional image features, and nine (SG+MN)-(CARS+SPA)-CNN maize variety identification models were established by changing the input feature dimension and the depth factor size of the model layer. Results and Discussion: The results show that the maize variety classification model works best, when the input feature dimension is 768 and the layer depth factor d is 1.0. At this point, the model accuracy of the test set is 96.65% and the detection frame rate is1000 Fps/s in GPU environment, which can realize the rapid and effective non-destructive detection of maize varieties. This study provides a new idea for the rapid and accurate identification of maize seeds and seeds of other crops.

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