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BACKGROUND: Prostate cancer is one of the most common cancers in men with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles in tumor progression and can potentially serve as prognostic and therapeutic biomarkers in PCa. This study aimed to develop a prognostic signature for BCR in PCa using PCD-related genes. MATERIALS AND METHODS: We conducted an analysis of 19 different modes of PCD to develop a comprehensive model. Bulk transcriptomic, single-cell transcriptomic, genomic, and clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, and GSE193337. We analyzed the expression and mutations of the 19 PCD modes and constructed, evaluated, and validated the model. RESULTS: Ten PCD modes were found to be associated with BCR in PCa, with specific PCD patterns exhibited by various cell components within the tumor microenvironment. Through Lasso Cox regression analysis, we established a Programmed Cell Death Index (PCDI) utilizing an 11-gene signature. High PCDI values were validated in five independent datasets and were found to be associated with an increased risk of BCR in PCa patients. Notably, older age and advanced T and N staging were associated with higher PCDI values. By combining PCDI with T staging, we constructed a nomogram with enhanced predictive performance. Additionally, high PCDI values were significantly correlated with decreased drug sensitivity, including drugs such as Docetaxel and Methotrexate. Patients with lower PCDI values demonstrated higher immunophenoscores (IPS), suggesting a potentially higher response rate to immune therapy. Furthermore, PCDI was associated with immune checkpoint genes and key components of the tumor microenvironment, including macrophages, T cells, and NK cells. Finally, clinical specimens validated the differential expression of PCDI-related PCDRGs at both the gene and protein levels. CONCLUSION: In conclusion, we developed a novel PCD-based prognostic feature that successfully predicted BCR in PCa patients and provided insights into drug sensitivity and potential response to immune therapy. These findings have significant clinical implications for the treatment of PCa.
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BACKGROUND: Although retinitis pigmentosa (RP) is the most common type of hereditary retinal dystrophy, approximately 25%-45% of cases remain without a molecular diagnosis. von Willebrand factor A domain containing 8 (VWA8) encodes a mitochondrial matrix-targeted protein; its molecular function and pathogenic mechanism in RP remain unexplained. METHODS: Family members of patients with RP underwent ophthalmic examinations, and peripheral blood samples were collected for exome sequencing, ophthalmic targeted sequencing panel and Sanger sequencing. The importance of VWA8 in retinal development was demonstrated by a zebrafish knockdown model and cellular and molecular analysis. RESULTS: This study recruited a Chinese family of 24 individuals with autosomal-dominant RP and conducted detailed ophthalmic examinations. Exome sequencing analysis of six patients revealed heterozygous variants in VWA8, namely, the missense variant c.3070G>A (p.Gly1024Arg) and nonsense c.4558C>T (p.Arg1520Ter). Furthermore, VWA8 expression was significantly decreased both at the mRNA and protein levels. The phenotypes of zebrafish with VWA8 knockdown are similar to those of clinical individuals harbouring VWA8 variants. Moreover, VWA8 defects led to severe mitochondrial damage, resulting in excessive mitophagy and the activation of apoptosis. CONCLUSIONS: VWA8 plays a significant role in retinal development and visual function. This finding may provide new insights into RP pathogenesis and potential genes for molecular diagnosis and targeted therapy.
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Retinose Pigmentar , Peixe-Zebra , Animais , Humanos , Mitofagia/genética , Mutação/genética , Linhagem , Retinose Pigmentar/diagnóstico , Peixe-Zebra/genéticaRESUMO
Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100â¯nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.
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Disfunção Erétil , Estresse Oxidativo , Pênis , Poliestirenos , Ratos Sprague-Dawley , Animais , Disfunção Erétil/induzido quimicamente , Masculino , Poliestirenos/toxicidade , Ratos , Estresse Oxidativo/efeitos dos fármacos , Pênis/efeitos dos fármacos , Testosterona/sangue , Nanopartículas/toxicidade , Apoptose/efeitos dos fármacos , Poluentes Ambientais/toxicidadeRESUMO
One of the main quests in quantum metrology is to attain the ultimate precision limit with given resources, where the resources are not only of the number of queries, but more importantly of the allowed strategies. With the same number of queries, the restrictions on the strategies constrain the achievable precision. In this Letter, we establish a systematic framework to identify the ultimate precision limit of different families of strategies, including the parallel, the sequential, and the indefinite-causal-order strategies, and provide an efficient algorithm that determines an optimal strategy within the family of strategies under consideration. With our framework, we show there exists a strict hierarchy of the precision limits for different families of strategies.
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BACKGROUND: This study aimed to investigate the value of the neutrophil-to-lymphocyte ratio (NLR), B-type natriuretic peptide (BNP), and D-dimer (D-D) in predicting pneumonia severity in older adults with community-acquired pneumonia (CAP). METHODS: The retrospective study included older adults with CAP at the General Hospital of Northern Theater Command from January 2017 to December 2019. Patient demographic information and clinical characteristics were collected. Logistic multivariable analysis was used to analyze the factors associated with CAP severity. Receiver operating curve (ROC) analysis was used to evaluate the value of each biomarker in severity prediction. RESULTS: A total of 158 patients were included: 85 with mild-moderate CAP and 73 with severe CAP. The multivariable logistic analysis showed that CRP (OR = 1.011; 95% CI: 1.011 - 1.022; p = 0.039), BNP (OR = 1.003; 95% CI: 1.001 - 1.004; p = 0.001), D-D (OR = 1.289; 95% CI: 1.031 - 1.611; p = 0.026), and NLR (OR = 1.111; 95% CI: 1.011 - 1.222; p = 0.030) were independent factors associated with pneumonia severity. ROC analysis demonstrated the value of each biomarker in pneumonia severity prediction: CRP (AUC = 0.791, 95% CI: 0.720 - 0.861), BNP (AUC = 0.803, 95% CI: 0.649 - 0.806), D-D (AUC = 0.727, 95% CI: 0.734 - 0.872), and NLR (AUC = 0.817, 95% CI: 0.751 - 0.883). The positive and negative predictive values were 0.68 and 0.81 for CRP, 0.79 and 0.75 for BNP, 0.62 and 0.80 for D-D, and 0.80 and 0.76 for NLR. CONCLUSIONS: CRP, BNP, D-D, and NLR might be helpful independent factors in predicting pneumonia severity in older adults with CAP.
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Neutrófilos , Pneumonia , Humanos , Idoso , Peptídeo Natriurético Encefálico , Estudos Retrospectivos , Pneumonia/diagnóstico , Linfócitos , Biomarcadores , Prognóstico , Curva ROC , Proteína C-Reativa/análiseRESUMO
In Trypanosoma brucei, mitochondrial pre-mRNAs undergo 3'-5' exonucleolytic processing, 3' adenylation and uridylation, 5' pyrophosphate removal, and, often, U-insertion/deletion editing. The 3' modifications are modulated by pentatricopeptide repeat (PPR) Kinetoplast Polyadenylation Factors (KPAFs). We have shown that KPAF3 binding to the 3' region stabilizes properly trimmed transcripts and stimulates their A-tailing by KPAP1 poly(A) polymerase. Conversely, poly(A) binding KPAF4 shields the nascent A-tail from uridylation and decay thereby protecting pre-mRNA upon KPAF3 displacement by editing. While editing concludes in the 5' region, KPAF1/2 dimer induces A/U-tailing to activate translation. Remarkably, 5' end recognition and pyrophosphate hydrolysis by the PPsome complex also contribute to mRNA stabilization. Here, we demonstrate that KPAF4 functions as a heterodimer with KPAF5, a protein lacking discernable motifs. We show that KPAF5 stabilizes KPAF4 to enable poly(A) tail recognition, which likely leads to mRNA stabilization during the editing process and impedes spontaneous translational activation of partially-edited transcripts. Thus, KPAF4/5 represents a poly(A) binding element of the mitochondrial polyadenylation complex. We present evidence that RNA editing substrate binding complex bridges the 5' end-bound PPsome and 3' end-bound polyadenylation complexes. This interaction may enable mRNA circularization, an apparently critical element of mitochondrial mRNA stability and quality control.
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Polinucleotídeo Adenililtransferase/genética , Proteínas de Protozoários/genética , RNA de Protozoário/genética , Trypanosoma brucei brucei/genética , Mitocôndrias/genética , Poliadenilação/genética , Proteínas de Protozoários/química , Edição de RNA/genética , Precursores de RNA/genética , Estabilidade de RNA , RNA Mensageiro/química , RNA Mensageiro/genética , RNA de Protozoário/química , Fatores de Poliadenilação e Clivagem de mRNA/genéticaRESUMO
The primary goal of this systematic review and meta-analysis was to compare the efficacy and safety of fluoxetine with other oral pharmaceuticals in the treatment of premature ejaculation (PE). We searched through databases including CNKI, PubMed, EMBASE and Cochrane to find research published up to 31 March 2022. PROSPERO was used to pre-register this meta-analysis (registration number CRD42022315459). Two separate writers extracted relevant details from all of the papers included in the study. To analyse the quality of literature publishing, we used the Cochrane risk of bias tool. The severity of premature ejaculation was determined using intravaginal ejaculatory latency time (IELT), and the effectiveness and safety of pharmacological interventions were determined using standardized mean difference (SMD) and risk ratio (RR) values with matching 95% confidence level intervals (95% CIs). Our meta-analysis includes a total of ten trials to investigate into the differences in treatment efficacy and safety between fluoxetine and other medicines. The findings revealed that fluoxetine was more effective than placebo in treating PE, whereas sertraline and paroxetine were more effective than fluoxetine (p < 0.05). The side effects of the medications were not significantly different, and they were all acceptable. The results of the sensitivity analysis were unaffected by the removal of any of the articles. There was no evidence of bias in the media. This meta-analysis examined the differences in efficacy and safety between fluoxetine and other oral medications and can be used by clinicians in the treatment of PE.
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Ejaculação Precoce , Ejaculação , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Humanos , Masculino , Paroxetina/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina , Resultado do TratamentoRESUMO
The tip-enhanced Raman spectroscopy (TERS) imaging technique is designed to provide correlated morphological and chemical information with a nanoscale spatial resolution by utilizing the plasmonic resonance supported by metallic nanostructures at the tip apex of a scanning probe. However, limited by the scattering cross sections of these nanostructures, only a small fraction of the incident light can be coupled to the plasmonic resonance to generate Raman signals. The uncoupled light then directly excites background spectra with a diffraction-limited resolution, which becomes the background noise that often blurs the TERS image. Here, we demonstrate how this problem can be solved by physically separating the light excitation region from the Raman signal generation region on the scanning probe. The remote-excitation TERS (RE-TERS) probe, which can be fabricated with a facile, robust and reproducible method, utilizes silver nanoparticles as nanoantennas to mediate the coupling of free-space excitation light to propagating surface plasmon polaritons (SPPs) in a sharp-tip silver nanowire to excite Raman signals remotely. With this RE-TERS probe, a 10 nm spatial resolution was demonstrated on a single-walled carbon nanotube sample, and the strain distribution in a monolayer molybdenum disulfide (MoS2) was mapped.
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A simple and clean method of transferring two-dimensional (2D) materials plays a critical role in the fabrication of 2D electronics, particularly the heterostructure devices based on the artificial vertical stacking of various 2D crystals. Currently, clean transfer techniques rely on sacrificial layers or bulky crystal flakes (e.g., hexagonal boron nitride) to pick up the 2D materials. Here, we develop a capillary-force-assisted clean-stamp technique that uses a thin layer of evaporative liquid (e.g., water) as an instant glue to increase the adhesion energy between 2D crystals and polydimethylsiloxane (PDMS) for the pick-up step. After the liquid evaporates, the adhesion energy decreases, and the 2D crystal can be released. The thin liquid layer is condensed to the PDMS surface from its vapor phase, which ensures the low contamination level on the 2D materials and largely remains their chemical and electrical properties. Using this method, we prepared graphene-based transistors with low charge-neutral concentration (3 × 1010 cm-2) and high carrier mobility (up to 48â¯820 cm2 V-1 s-1 at room temperature) and heterostructure optoelectronics with high operation speed. Finally, a capillary-force model is developed to explain the experiment.
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Hepatitis B virus (HBV) envelope particles have been synthesized in eukaryotic cells (e.g., mammalian cells, insect cells, and yeast cells) as an HB vaccine immunogen and drug delivery system (DDS) nanocarrier. Many researchers had made attempts to synthesize the particles in Escherichia coli for minimize the cost and time for producing HBV envelope particles, but the protein was too deleterious to be synthesized in E. coli. In this study, we generated deletion mutants of HBV envelope L protein (389 amino acid residues (aa)) containing three transmembrane domains (TM1, TM2, TM3). The ΔNC mutant spanning from TM2 to N-terminal half of TM3 (from 237 aa to 335 aa) was found as a shortest form showing spontaneous particle formation. After the N-terminal end of ΔNC mutant was optimized by the N-end rule for E. coli expression, the modified ΔNC mutant (mΔNC) was efficiently expressed as particles in E. coli. The molecular mass of mΔNC particle was approx. 670 kDa, and the diameter was 28.5 ± 6.2 nm (mean ± SD, N = 61). The particle could react with anti-HBV envelope S protein antibody, indicating the particles exhibited S antigenic domain outside as well as HBV envelope particles. Taken together, the E. coli-derived mΔNC particles could be used as a substitute of eukaryotic cell-derived HBV envelope particles for versatile applications.
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Escherichia coli/metabolismo , Proteínas do Envelope Viral/biossíntese , Animais , Células COS , Chlorocebus aethiops , Mutação , Tamanho da Partícula , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismoRESUMO
Despite many efforts to fabricate high-aspect-ratio atomic force microscopy (HAR-AFM) probes for high-fidelity, high-resolution topographical imaging of three-dimensional (3D) nanostructured surfaces, current HAR probes still suffer from unsatisfactory performance, low wear-resistivity, and extravagant prices. The primary objective of this work is to demonstrate a novel design of a high-resolution (HR) HAR AFM probe, which is fabricated through a reliable, cost-efficient benchtop process to precisely implant a single ultrasharp metallic nanowire on a standard AFM cantilever probe. The force-displacement curve indicated that the HAR-HR probe is robust against buckling and bending up to 150 nN. The probes were tested on polymer trenches, showing a much better image fidelity when compared with standard silicon tips. The lateral resolution, when scanning a rough metal thin film and single-walled carbon nanotubes (SW-CNTs), was found to be better than 8 nm. Finally, stable imaging quality in tapping mode was demonstrated for at least 15 continuous scans indicating high resistance to wear. These results demonstrate a reliable benchtop fabrication technique toward metallic HAR-HR AFM probes with performance parallel or exceeding that of commercial HAR probes, yet at a fraction of their cost.
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A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i.e., membrane fusion, membrane disruption, and payload release) upon interaction with target LPs. In this study, instead of BNC and HBV, we generated LPs displaying a mutated form of the pre-S1 (9-24) peptide, and performed a membrane disruption assay using target LPs containing pyranine (fluorophore) and p-xylene-bis (N-pyridinium bromide) (DPX) as a quencher. The membrane disruption activity was found to correlate with the hydrophobicity of the whole structure, while the peptide retained a random-coil structure even under low pH condition. One large hydrophobic cluster (I) and one small hydrophobic cluster (II) residing in the peptide would be connected by the protonation of residues D16 and D20, and thereby exhibit strong membrane disruption activity in a low pH-dependent manner. Furthermore, the introduction of a positively charged residue enhanced the activity significantly, suggesting that a sole positively charged residue (H17) may be important for the interaction with target LPs by electrostatic interaction. Collectively, these results suggest that the pre-S1 (9-24) peptide may be involved in the endosomal escape of the BNC's payloads, as well as in the HBV uncoating process.
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Membrana Celular/química , Análise Mutacional de DNA/métodos , Antígenos de Superfície da Hepatite B/química , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Mutação/genética , Precursores de Proteínas/química , Precursores de Proteínas/genética , Sequência de Bases , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Domínios Proteicos/genéticaRESUMO
BACKGROUND: Aging populations require higher quality care. However, few undergraduate nursing students choose careers in aged care. Negative death attitudes and loss of meaning in life may reduce motivation to choose geriatric nursing (GN) as a career. The relationships among these variables have yet to be clarified in the literature. PURPOSE: The purpose of this study was to investigate the relationships among death attitude, meaning in life, and motivation to choose a career in GN among undergraduate nursing students in China. METHODS: This cross-sectional study was conducted using an online survey. Five hundred ninety-five final-year undergraduate nursing students in four nursing schools completed the Career Choice Motivation Questionnaire for Geriatric Nursing, Death Attitude Profile-Revised, and Meaning in Life Questionnaire. A t test, analysis of variance, Pearson's correlation, and multiple linear regression model were used to analyze the data using SPSS Version 22.0. RESULTS: The mean Career Choice Motivation Questionnaire for Geriatric Nursing item score was 3.15 ( SD = 0.49; 1-5 points), indicating the participants were moderately motivated to choose GN as a career. The multiple linear regression revealed statistically significant associations among death attitude, meaning in life, and motivation to care for older adults, explaining 14.5% of the total variance ( R2 = .15, F = 9.01, p < .001). Perceiving meaning in life, having escape acceptance, and having approach acceptance were each shown to be positively associated with choosing a career in GN. Conversely, fear of death and death avoidance were found to be negatively associated with choosing this career path. CONCLUSIONS: Death attitude and perceptions regarding the meaning of life are associated with the motivation of nursing students to care for older adults.
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Bacharelado em Enfermagem , Enfermagem Geriátrica , Estudantes de Enfermagem , Idoso , Humanos , Escolha da Profissão , Motivação , Estudos Transversais , Inquéritos e Questionários , Atitude do Pessoal de SaúdeRESUMO
The characteristics of patients with endophthalmitis due to penetrating ocular trauma are still limited. The aim of the study was to fill these gaps among Chinese population. This retrospective study included patients diagnosed as penetrating ocular traumatic endophthalmitis between January 2016 to December 2018. During the past 3-year period, a total of 201 patients with antecedent penetrating eye injuries were evaluated. Of which, 42 (20.9%) patients presented a clinical course compatible with acute infectious endophthalmitis. 39 (92.86%) patients were males, and 15 (35.71%) patients had mechanical injuries from intraocular foreign body (IOFB), the rate of endophthalmitis due to IOFB was 13.43%, higher to the rate among patients without IOFB (7.46%). The duration between injury occurrence and endophthalmitis onset was 1 day in 10 (23,80%) patients; 2 to 7 days in 31 (73.80%) patients, and 7 to 14 days in 1 (2.38%) patient. After 1 year follow-up, best corrected visual acuity (BCVA) better than 20/400 was observed in 15 (35.71%) patients, counting fingers and hand move in 17 (40.48%) patients, light perception in 5 (11.9%) patients and no light perception in 5 (11.9%) patients, respectively. Patients with promising outcomes had better initial BCVA at baseline (Pâ <â .001). Endophthalmitis is a severe ocular infectious condition that may lead to irreversible vision loss. A greater attention must be paid to penetrating eye injuries within males, who had poor BCVA at baseline, particularly with obvious IOFB.
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Endoftalmite , Corpos Estranhos no Olho , Ferimentos Oculares Penetrantes , Acuidade Visual , Humanos , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Masculino , Ferimentos Oculares Penetrantes/epidemiologia , Ferimentos Oculares Penetrantes/complicações , Feminino , Estudos Retrospectivos , Adulto , Corpos Estranhos no Olho/epidemiologia , Pessoa de Meia-Idade , China/epidemiologia , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Recent years revealed key molecules in lung cancer research, yet their exact roles in disease onset and progression remain uncertain. Lung cancer's heterogeneity complicates prognosis prediction. This study integrates pivotal molecules to evaluate patient prognosis and immunotherapy efficacy. METHODS: The WGCNA algorithm identified module genes linked to immunity. The Lasso-Cox method built a prognostic model for outcome prediction. GO and KEGG analyses explored gene pathways. ssGSEA quantified immune cell types and functions. The riskScore predicts the effectiveness of immunotherapy based on its correlation with DNA repair and immune checkpoint genes. Single-cell sequencing examined key gene expression across cell types. RESULTS: Using WGCNA, we identified the MEbrown module related to immunity. Lasso-Cox selected "BLK," "ITGB4," "PRKCH," and "SNAI1" for the prognostic model. MF analysis revealed enriched functions including antigen binding, GTPase regulator activity. In terms of BP, processes like immune signaling and mitotic division were enriched. CC enrichment included immunoglobulin complexes and chromosomal regions. Enriched pathways encompassed Cell cycle, Focal adhesion, Cellular senescence, and p53 signaling. ssGSEA evaluated immune cell abundance. RiskScore correlated with CTLA4 and PD1 through MMR and immune checkpoint analysis. Single-cell analysis indicated gene expression across cell types for BLK, ITGB4, PRKCH, and SNAI1. CONCLUSION: In summary, our developed prognostic model utilizing age-related genes effectively predicts lung cancer prognosis and the efficacy of immune therapy.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico , Multiômica , Envelhecimento , Imunoterapia , Aprendizado de Máquina , Microambiente TumoralRESUMO
AIMS: To examine any potential links between remnant cholesterol (RC) and comorbid chronic kidney disease (CKD) in individuals with prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We used data from 2709 American people aged > 20 years from the National Health and Nutrition Examination Survey (NHANES) during 2011-2018. Subjects were categorized according to whether they had comorbid CKD. Logistic regression models and smoothed curve fitting methods were employed to assess the association of RC with comorbid CKD in patients with prediabetes and T2DM. RESULTS: The 2709 participants included 1473 patients with T2DM and 1236 with prediabetes [impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)], of whom 744 (27.46%) had comorbid CKD. In multivariate-adjusted analysis, both RC and triglycerides (TG) were significantly associated with an increased risk of comorbid CKD, and a 1 mmol/L elevation of RC increased the risk by 38.1% [OR (95% CI) 1.636 (1.242, 2.156)], which was higher than the risk associated with a 1 mmol/L increase in TG [1.255 (1.106, 1.424)]. Additionally, those in the highest quartile of RC had a 43.6% higher risk of concomitant renal damage than those in the lowest quartile. RC was linearly and positively associated with the incidence of comorbid CKD in this population. CONCLUSIONS: RC is an independent risk factor for comorbid CKD in patients with prediabetes and T2DM. This finding provides a novel insight into the management and early detection of renal disease in patients with impaired glucose metabolism.
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Colesterol , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Estado Pré-Diabético/epidemiologia , Masculino , Feminino , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Pessoa de Meia-Idade , Estudos Transversais , Fatores de Risco , Adulto , Estados Unidos/epidemiologia , Colesterol/sangue , Idoso , Inquéritos Nutricionais , Triglicerídeos/sangueRESUMO
BACKGROUND: Premature ejaculation (PE) is the most prevalent sexual dysfunction among men. Eejaculation involves a complex nervous mechanism in which the ejaculatory centers play a key role in modulating sperm emission. Although treatment possibilities span from psychotherapy to pharmacological approaches, results show inconsistent efficacy. In this context, the emergence of repetitive transcranial magnetic stimulation (rTMS) as a non-invasive neuromodulatory approach represents a compelling avenue for potential therapeutic exploration. OBJECTIVE: To investigate whether high-frequency transcranial magnetic stimulation can modulate the ejaculatory behavior of rats with rapid ejaculation by altering neurotransmitter levels and neuroplasticity in the hippocampus. METHODS: Rats have been screened for rapid ejaculation by observing behavioral indices of mating, and subsequently divided into two groups. The intervention group was administered with a 10 Hz rTMS stimulation, whereas the control group received a sham procedure. Upon the delivery of rTMS, we investigated ejaculation latency (EL), the hippocampal 5-hydroxytryptamine (5-HT) concentration, brain-derived neurotrophic factor (BDNF), synaptophysin (SYN), and postsynaptic density protein 95 (PSD95) expressions, as well as BDNF-receptor tyrosine kinase receptor B (TrkB) pathway upregulation. RESULTS: After 14 days, EL was increased in the intervention group compared with the control group. 5-HT concentration in the hippocampal region was increased, and high-frequency rTMS activated the BDNF and TrkB pathways, including phosphorylation of cAMP response element-binding protein (CREB), and upregulated the transcription and protein expression of SYN, and PSD95. CONCLUSION: RTMS upregulates BDNF, SYN, and PSD95 expression through activation of the BDNF-TrkB pathway and increases brain 5-hydroxytryptamine thereby regulating neuroplasticity and improving ejaculation.
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Fator Neurotrófico Derivado do Encéfalo , Ejaculação , Hipocampo , Plasticidade Neuronal , Receptor trkB , Comportamento Sexual Animal , Estimulação Magnética Transcraniana , Animais , Estimulação Magnética Transcraniana/métodos , Plasticidade Neuronal/fisiologia , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Ratos , Ejaculação/fisiologia , Receptor trkB/metabolismo , Comportamento Sexual Animal/fisiologia , Serotonina/metabolismo , Sinaptofisina/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Ejaculação Precoce/metabolismo , Ejaculação Precoce/fisiopatologiaRESUMO
The stability classification of loess deposits around tunnels is a vital prerequisite for safe construction in underground environment. Due to the fuzziness and randomness of loess physical and mechanical parameters, the stability prediction of loess deposits shows uncertainty. Existing loess deposit stability classification models rarely consider the uncertainty of influencing factors. A novel classification probability model of loess deposits is proposed for the above problems based on Monte Carlo simulation and multi-dimensional normal cloud (MCS-Cloud). Specifically, five loess parameters, including water content, cohesion, internal friction angle, elastic modulus, and Poisson ratio, were selected as predictors for the stability level of loess deposits. The weights of the predictors were obtained through 50 test samples. After acquiring the numerical characteristics of the normal cloud, the stability level can be comprehensively evaluated with the weighted multi-dimensional normal cloud model. The classification model was applied to the loess tunnel in Yan'an, China. The prediction results are in good agreement with practical engineering, denoting the rationality of the weighted multi-dimensional normal cloud. Finally, the stability classification of loess deposits was discussed from the perspective of uncertainty analysis with the application of MCS. Results proved that the MCS-Cloud model is feasible for classifying the stability of loess deposits surrounding tunnels. The obtained classification probability can be used for quantitative risk assessment of loess tunnels.
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Simulação por Computador , Incerteza , China , Método de Monte Carlo , Medição de RiscoRESUMO
Rockburst is one of the major engineering geological disasters of underground engineering. Accurate rockburst intensity level prediction is vital for disaster control during underground tunnel construction. In this work, a hybrid model integrating the back propagation neural network (BPNN) with beetle antennae search algorithm (BAS) has been developed for rockburst prediction. Before model building, 173 groups of rockburst dataset were collected. Six geological parameters are selected as predictors for rockburst, including the maximum tangential stress of the surrounding rock σθ, the uniaxial compressive strength of rock σc, the tensile strength of rock σt, the stress ratio σθ/σc, the rock brittleness ratio σc/σt, and the elastic energy index Wet. After preprocessed by outlier detection and synthetic minority oversampling technique (SMOTE), the new dataset was divided into training and test parts. BAS could optimize the weights and biases of BPNN from the training process. Then the established hybrid model was applied to the test samples with predicted accuracy of 94.3%, proving that the hybrid model has practical value in researching rockburst prediction.
Assuntos
Desastres , Redes Neurais de Computação , Algoritmos , Engenharia , Força CompressivaRESUMO
PURPOSE: Testosterone deficiency and changes in testosterone levels are important in men's health and may be associated with fat accumulation. In order to investigate the connection between testosterone and fat accumulation in adult males, we employed lipid accumulation product and compared it to triglyceride-glucose and Homeostasis Model Assessment of Insulin Resistance. MATERIALS AND METHODS: An intersecting surface research of participators from 2013 to 2014 was carried out using National Health and Nutrition Examination Survey, in addition, participants from 2015 to 2016 were selected. Using multivariate adjusted logistic regression, the connection between lipid accumulation product, testosterone levels, and testosterone insufficiency was investigated, smoothed curve fitting was calculated to integrate non-linear relationships, and subgroup analysis was performed to identify sensitive populations. RESULTS: After removing all potential confounders, testosterone levels in 1651 subjects tended to decrease with increasing continuous variable lipid accumulation product (ß = -0.49, 95% confidence interval [-0.77, -0.22], p = 0.0005) and adding the chance of testosterone deficiency (odds ratio = 1.01, 95% confidence interval [1.01, 1.01], p < 0.0001). In the lipid accumulation product quartile, testosterone levels decreased the most (ß = -77.65, 95% confidence interval [-110.99, -44.31], p < 0.0001) and the risk of testosterone deficiency was highest (odds ratio = 2.76, 95% confidence interval [1.47, 5.20], p = 0.0016). The area under the curve values were 0.718 (95% confidence interval: 0.688-0.750) for lipid accumulation product, 0.723 (95% confidence interval: 0.689-0.756) for Homeostasis Model Assessment of Insulin Resistance, and 0.673 (95% confidence interval: 0.640-0.708) for triglyceride-glucose, with no statistical difference between lipid accumulation product and Homeostasis Model Assessment of Insulin Resistance comparisons. The cut-off value of lipid accumulation product ≥52.408 predicted testosterone deficiency with good sensitivity and specificity. CONCLUSION: Higher lipid accumulation product was linked to a higher incidence of testosterone loss and inadequate, especially in hypertensive and non-smoker. Lipid accumulation product is a better predictor of testosterone deficiency than triglyceride-glucose and does not differ significantly from the Homeostasis Model Assessment of Insulin Resistance phase.