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Glycolysis is a major determinant of pulmonary artery smooth muscle cell (PASMC) proliferation in pulmonary hypertension (PH). Circular RNAs (circRNAs) are powerful regulators of glycolysis in multiple diseases; however, the role of circRNAs in glycolysis in PH has been poorly characterized. The aim of this study was to uncover the regulatory mechanism of a new circRNA, circNAP1L4, in human pulmonary artery smooth muscle cell (HPASMC) proliferation through the host protein NAP1L4 to regulate the super-enhancer-driven glycolysis gene hexokinase II (HK II). CircNAP1L4 was downregulated in hypoxic HPASMCs and plasma of PH patients. Functionally, circNAP1L4 overexpression inhibited glycolysis and proliferation in hypoxic HPASMCs. Mechanistically, circNAP1L4 directly bound to its host protein NAP1L4 and affected the ability of NAP1L4 to move into the nucleus to regulate the epigenomic signals of the super-enhancer of HK II. Intriguingly, circNAP1L4 overexpression inhibited the proliferation but not the migration of human pulmonary arterial endothelial cells (HPAECs) cocultured with HPASMCs. Furthermore, pre-mRNA-processing-splicing Factor 8 (PRP8) was found to regulate the production ratio of circNAP1L4 and linear NAP1L4. In vivo, targeting circNAP1L4 alleviates SU5416 combined with hypoxia (SuHx)-induced PH. Overall, these findings reveal a new circRNA that inhibits PASMC proliferation and serves as a therapeutic target for PH.
Subject(s)
Cell Proliferation , Glycolysis , Hexokinase , Hypertension, Pulmonary , Myocytes, Smooth Muscle , Pulmonary Artery , RNA, Circular , Humans , Hexokinase/metabolism , Hexokinase/genetics , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/genetics , Myocytes, Smooth Muscle/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Animals , Mice , Male , Cells, Cultured , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/cytologyABSTRACT
OBJECTIVE: Depression is a global health challenge, but only a few studies have fully assessed and predicted the disease burden. This study described the trend of global depression burden from 1990 to 2019 through age-standardized incidence rate (ASIR), age-standardized disability-adjusted life rate (ASDR), and predicted the number of cases of depression during 2020-2030. METHODS: Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. The trends of global depression burden from 1990 to 2019 were analyzed by age, sex, and socio-demographic index (SDI) across various regions. Finally, we used the Bayesian age-period-cohort (BAPC) model to predict the disease burden in the coming 10 years. RESULTS: Globally, the ASIR of depression decreased from 3681.24 per 100,000 population in 1990 to 3588.25 per 100,000 population in 2019 and the EAPC was -0.29%. ASDR also decreased, following a similar trend as the ASIR. The highest ASDR was observed in adults aged 60-64 years. The burden of depressive illness was higher in women, with the greatest increase in incidence in low SDI areas. BAPC predicted that the worldwide ASIR and ASDR of depression would stabilize from 2020 to 2030, with an increasing number of cases. By 2030, the ASIR was estimated to be 2519.88 per 100,000 men and 3835.11 per 100,000 women. CONCLUSION: From 1990 to 2019, the global burden of depression remained significant, especially among women. It is important to address depression in older people, and it is therefore necessary to develop measures for prevention.
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BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. METHODS: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. RESULTS: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58). CONCLUSIONS: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.
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BACKGROUND: Klebsiella pneumoniae is a zoonotic opportunistic pathogen, and also one of the common pathogenic bacteria causing mink pneumonia. The aim of this study was to get a better understanding of the whole-genome of multi-drug resistant Klebsiella pneumoniae with K2 serotype in China. This study for the first time to analyze Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, resistance and virulence genes of Klebsiella pneumoniae in mink. RESULTS: The isolate was Klebsiella pneumoniae with serotype K2 and ST6189 by PCR method. The string test was positive and showed high mucus phenotype. There was one plasmid with IncFIB replicons in the genome. The virulence factors including capsule, lipopolysaccharide, adhesin, iron uptake system, urease, secretory system, regulatory gene (rcsA, rcsB), determinants of pili adhesion, enolase and magnesium ion absorption related genes. The strain was multi-drug resistant. A total of 26 resistance genes, including beta-lactam, aminoglycosides, tetracycline, fluoroquinolones, sulfonamides, amide alcohols, macrolides, rifampicin, fosfomycin, vancomycin, diaminopyrimidines and polymyxin. Multidrug-resistant efflux protein AcrA, AcrB, TolC, were predicted in the strain. CONCLUSION: It was the first to identify that serotype K2 K. pneumonia with ST6189 isolated from mink in China. The finding indicated that hypervirulent and multi-drug resistant K. pneumoniae was exist in Chinese mink. The whole-genome of K. pneumoniae isolates have importance in mink farming practice.
Subject(s)
Drug Resistance, Multiple, Bacterial , Klebsiella pneumoniae , Mink , Serogroup , Whole Genome Sequencing , Animals , Drug Resistance, Multiple, Bacterial/genetics , Mink/microbiology , China , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Genome, Bacterial , Klebsiella Infections/veterinary , Klebsiella Infections/microbiology , Anti-Bacterial Agents/pharmacology , Virulence Factors/geneticsABSTRACT
Allergic rhinitis ï¼ARï¼ is a nasal hypersensitivity disease that is influenced by environmental factors, genetic factors, and various inflammatory factors. The role and mechanisms of ozone, as a component of air pollution, in the pathogenesis of AR are not yet fully understood. This article provides a review of the impact of ozone on the epidemiology and pathology of AR, as well as its possible mechanisms, to provide new insights into the prevention and treatment of AR.
Subject(s)
Ozone , Rhinitis, Allergic , Humans , Ozone/adverse effects , Rhinitis, Allergic/etiology , Rhinitis, Allergic/epidemiology , Air Pollution/adverse effects , Air Pollutants/adverse effectsABSTRACT
Rapidly obtaining the chlorophyll content of crop leaves is of great significance for timely diagnosis of crop health and effective field management. Multispectral imagery obtained from unmanned aerial vehicles (UAV) is being used to remotely sense the SPAD (Soil and Plant Analyzer Development) values of wheat crops. However, existing research has not yet fully considered the impact of different growth stages and crop populations on the accuracy of SPAD estimation. In this study, 300 materials from winter wheat natural populations in Xinjiang, collected between 2020 to 2022, were analyzed. UAV multispectral images were obtained in the experimental area, and vegetation indices were extracted to analyze the correlation between the selected vegetation indices and SPAD values. The input variables for the model were screened, and a support vector machine (SVM) model was constructed to estimate SPAD values during the heading, flowering, and filling stages under different water stresses. The aim was to provide a method for the rapid acquisition of winter wheat SPAD values. The results showed that the SPAD values under normal irrigation were higher than those under water restriction. Multiple vegetation indices were significantly correlated with SPAD values. In the prediction model construction of SPAD, the different models had high estimation accuracy under both normal irrigation and water limitation treatments, with correlation coefficients of predicted and measured values under normal irrigation in different environments the value of r from 0.59 to 0.81 and RMSE from 2.15 to 11.64, compared to RE from 0.10% to 1.00%; and under drought stress in different environments, correlation coefficients of predicted and measured values of r was 0.69-0.79, RMSE was 2.30-12.94, and RE was 0.10%-1.30%. This study demonstrated that the optimal combination of feature selection methods and machine learning algorithms can lead to a more accurate estimation of winter wheat SPAD values. In summary, the SVM model based on UAV multispectral images can rapidly and accurately estimate winter wheat SPAD value.
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In this study, the "milky disease" model of Eriocheir sinhensis was constructed via intramuscular injection with the pathogenic yeast Metschnikowia bicuspidata. The dynamic pathological changes of E. sinensis after injection were elucidated with two staining methods (haemotoxylin-eosin and alcian blue periodic acid-Schiff) and fluorescence in situ hybridization technology. Anatomical observation revealed three stages of the "milky disease": no clinical signs (1-4 days after infection), the appearance of signs of disease (5-7 days), and significant liquefaction (10 days). Histological observation also revealed three stages of the disease: yeast diffusion (1-2 days after infection), yeast slow development (3-4 days), and yeast rapid proliferation (5 days). And FISH technique was suitable for the early detection of infection with M. bicuspidata in E. sinensis. We found that M. bicuspidata spread to the whole body of the crab through the haemolymph and developed into fungal septicaemia. These results elucidate the systemic pathological characteristics of "milky disease" in E. sinensis and suggest the pathogenic mechanism of M. bicuspidata.
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SRY-box transcription factor 30 (SOX30) participates in tumor cell apoptosis in lung cancer. The occurrence of somatic SOX30 mutations, the expression signature of SOX30 in normal and cancer tissues, the correlation of SOX30 with immune cells and immune-related genes, and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer biomarker. SOX30 influences drug sensitivity and tumor immunity in specific cancer types. In this review, we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature review. We summarize recent research on SOX30 in cancer regarding somatic mutations, trials, transcriptome analysis, clinical information, and SOX30-mediated regulation of malignant phenotypes. Additionally, we report on the diagnostic value of SOX30 mRNA expression levels across different cancer types. This review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies.
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Tomatoes are prone to mechanical damage due to improper gripping forces during automated harvest and postharvest processes. To reduce this damage, a dynamic viscoelastic model based on long short-term memory (LSTM) is proposed to fit the dynamic compression stress relaxation characteristics of the individual fruit. Furthermore, the classical stress relaxation models involved, the triple-element Maxwell and Caputo fractional derivative models, are compared with the LSTM model to validate its performance. Meanwhile, the LSTM and classical stress relaxation models are used to predict the stress relaxation characteristics of tomato fruit with different fruit sizes and compression positions. The results for the whole test dataset show that the LSTM model achieves a RMSE of 2.829×10-5 Mpa and a MAPE of 0.228%. It significantly outperforms the Caputo fractional derivative model by demonstrating a substantial enhancement with a 37% decrease in RMSE and a 36% reduction in MAPE. Further analysis of individual tomato fruit reveals the LSTM model's performance, with the minimum RMSE recorded at the septum position being 3.438×10-5 Mpa, 31% higher than the maximum RMSE at the locule position. Similarly, the lowest MAPE at the septum stands at 0.375%, outperforming the highest MAPE at the locule position by a significant margin of 90%. Moreover, the LSTM model consistently reports the smallest discrepancies between the predicted and observed values compared to classical stress relaxation models. This accuracy suggests that the LSTM model could effectively supplant classical stress relaxation models for predicting stress relaxation changes in individual tomato fruit.
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Diabetic peripheral neuropathy (DPN) and diabetic osteoporosis (DOP) are conditions that significantly impact the quality of life of patients worldwide. Rehmanniae Radix Preparata, a component of traditional Chinese medicine with a history spanning thousands of years, has been utilized in the treatment of osteoporosis and diabetes. Specifically, Rehmannia glutinosa Libosch polysaccharide (RGP), a key bioactive compound of Rehmanniae Radix Preparata, has demonstrated immune-modulating properties and beneficial effects on hyperglycemia, hyperlipidemia, and vascular inflammation in diabetic mice. Despite these known actions, the precise mechanisms of RGP in addressing DOP and DPN remain unclear. Our study aimed to explore the impact of RGP on osteoporosis and peripheral neuropathic pain in diabetic mice induced by streptozotocin (STZ). The findings revealed that RGP not only improved hyperglycemia and osteoporosis in STZ-induced diabetic mice but also enhanced osteogenesis, insulin production, and nerve health. Specifically, RGP alleviated distal pain, improved nerve conduction velocity, nerve fiber integrity, and immune cell balance in the spleen. Mechanistically, RGP was found to upregulate HDAC6 mRNA expression in regulatory T cells, potentially shedding light on novel pathways for preventing DOP and DPN. These results offer promising insights for the development of new therapeutic approaches for diabetic complications.
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Phytohormones possess unique chemical structures, and their physiological effects are regulated through intricate interactions or crosstalk among multiple phytohormones. MALDI-MSI enables the simultaneous detection and imaging of multiple hormones. However, its application for tracing phytohormones is currently restricted by low abundance of hormone in plant and suboptimal matrix selection. 2,4-Dihydroxy-5-nitrobenzoic acid (DHNBA) was reported as a new MALDI matrix for the enhanced detection and imaging of multiple phytohormones in plant tissues. DHNBA demonstrates remarkable sensitivity improvement when compared to the commonly used matrix, 2,5-dihydroxybenzoic acid (DHB), in the detection of isoprenoid cytokinins (trans-zeatin (tZ), dihy-drozeatin (DHZ), meta-topolin (mT), and N6-(Δ2-isopentenyl) adenine (iP)), jasmonic acid (JA), abscisic acid (ABA), and 1-aminocyclo-propane-1-carboxylic acid (ACC) standards. The distinctive properties of DHNBA (i.e. robust UV absorption, uniform matrix deposition, negligible background interference, and high ionization efficiency of phytohormones) make it as an ideal matrix for enhanced detection and imaging of phytohormones, including tZ, DHZ, ABA, indole-3-acetic acid (IAA), and ACC, by MALDI-MSI in various plant tissues, for example germinating seeds, primary/lateral roots, and nodules. Employing DHNBA significantly enhances our capability to concurrently track complex phytohormone biosynthesis pathways while providing precise differentiation of the specific roles played by individual phytohormones within the same category. This will propel forward the comprehensive exploration of phytohormonal functions in plant science.
Subject(s)
Plant Growth Regulators , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Plant Growth Regulators/metabolism , Plant Growth Regulators/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Gentisates/metabolism , Gentisates/chemistryABSTRACT
Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
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This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.
Subject(s)
Biomarkers , Deoxycholic Acid , Hemodynamics , Pulmonary Embolism , Humans , Pulmonary Embolism/blood , Pulmonary Embolism/physiopathology , Pulmonary Embolism/diagnosis , Male , Female , Middle Aged , Aged , Prospective Studies , Biomarkers/blood , Risk Factors , Deoxycholic Acid/blood , Acute Disease , Prognosis , Risk Assessment , Predictive Value of Tests , Natriuretic Peptide, Brain/blood , Adult , Peptide Fragments/bloodABSTRACT
Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.
Subject(s)
Neoplasm Staging , Stomach Neoplasms , Tomography, X-Ray Computed , Humans , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Male , Female , Middle Aged , Prospective Studies , Aged , Tomography, X-Ray Computed/methods , Gastrectomy/methods , Adult , Magnetic Resonance Imaging/methods , Multiparametric Magnetic Resonance Imaging/methodsABSTRACT
Ionic strength plays a significant role in the aggregation behavior of myofibrillar proteins. The study investigated the effects of KCl or CaCl2 as substitutes for NaCl on the gel properties and taste of shrimp surimi at a constant ionic strength (IS = 0.51). Increased KCl substitution ratio resulted in a reduction in α-helix content and an increase in ß-sheet content of myofibrillar proteins, thereby enhancing water holding capacity. Optimal KCl substitutions (1.5% NaCl +1.94% KCl) contributed to maintaining the desired taste and improving gel properties. CaCl2 facilitates the extraction and dissolution of myofibrillar proteins, resulting in an organized and dense gel network with significant water-holding capacity. However, excessive additions (>1.27%) resulted in a notable decrease in taste and gel strength due to excessive aggregation and precipitation of myofibrillar proteins. These findings provide a solid theoretical foundation for production of high-quality, low-salt shrimp surimi.
Subject(s)
Calcium Chloride , Penaeidae , Potassium Chloride , Sodium Chloride , Taste , Animals , Sodium Chloride/chemistry , Sodium Chloride/analysis , Penaeidae/chemistry , Calcium Chloride/chemistry , Potassium Chloride/chemistry , Humans , Shellfish/analysis , Osmolar Concentration , Food HandlingABSTRACT
In addition to considering the main effects, understanding gene-environment (G × E) interactions is imperative for determining the etiology of diseases and the factors that affect their prognosis. In the existing statistical framework for censored survival outcomes, there are several challenges in detecting G × E interactions, such as handling high-dimensional omics data, diverse environmental factors, and algorithmic complications in survival analysis. The effect heredity principle has widely been used in studies involving interaction identification because it incorporates the dependence of the main and interaction effects. However, Bayesian survival models that incorporate the assumption of this principle have not been developed. Therefore, we propose Bayesian heredity-constrained accelerated failure time (BHAFT) models for identifying main and interaction (M-I) effects with novel spike-and-slab or regularized horseshoe priors to incorporate the assumption of effect heredity principle. The R package rstan was used to fit the proposed models. Extensive simulations demonstrated that BHAFT models had outperformed other existing models in terms of signal identification, coefficient estimation, and prognosis prediction. Biologically plausible G × E interactions associated with the prognosis of lung adenocarcinoma were identified using our proposed model. Notably, BHAFT models incorporating the effect heredity principle could identify both main and interaction effects, which are highly useful in exploring G × E interactions in high-dimensional survival analysis. The code and data used in our paper are available at https://github.com/SunNa-bayesian/BHAFT.
Subject(s)
Bayes Theorem , Computer Simulation , Gene-Environment Interaction , Lung Neoplasms , Humans , Survival Analysis , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Models, Statistical , Prognosis , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , AlgorithmsABSTRACT
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
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Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We describe a new biological fingerprint of 49 protein-cSVD associations, predominantly in the CSF. We implemented a multipronged follow-up, across fluids, platforms, and ancestries (Europeans and East-Asian), including testing associations of direct plasma protein measurements with MRI-cSVD. We highlight 16 proteins robustly associated in both CSF and plasma, with 24/4 proteins identified in CSF/plasma only. cSVD-proteins were enriched in extracellular matrix and immune response pathways, and in genes enriched in microglia and specific microglial states (integration with single-nucleus RNA sequencing). Immune-related proteins were associated with MRI-cSVD already at age twenty. Half of cSVD-proteins were associated with stroke, dementia, or both, and seven cSVD-proteins are targets for known drugs (used for other indications in directions compatible with beneficial therapeutic effects. This first cSVD proteogenomic signature opens new avenues for biomarker and therapeutic developments.
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Objective: This study aimed to explore the experiences and challenges of prostate cancer patients suffering from urinary incontinence following radical prostatectomy. Methods: A descriptive qualitative research design was employed. Purposeful sampling was used to select 22 prostate cancer patients who underwent radical prostatectomy and experienced urinary incontinence after surgery. These patients were interviewed between August to October 2023 at a tertiary B-grade hospital's pelvic floor center in Shanghai. The data were collected through semi-structured in-depth interviews and analyzed using content analysis to identify and refine themes. Results: The experiences of urinary incontinence in patients can be categorized into four main themes: (1) Daily life disturbances (including 4 sub-themes: sleep disorders, fluid intake restriction, travel inconvenience, loss of sexual life); (2) Negative emotional experiences (including 4 sub-themes: perceived discrimination, concerns about recovery, loss of confidence in life, doubts about the surgical decision); (3) Social withdrawal (including 2 sub-themes: reduced desire for social interaction, decreased ability to socialize); (4) Limited support obtained (including 4 sub-themes: reliance on personal experience, seeking help from relatives and friends, difficulty discerning online information, lack of professional guidance). Conclusion: Postoperative urinary incontinence in prostate cancer patients presents a multidimensional experience. Healthcare professionals need to pay attention to these patients' daily life, psychological state, and social interactions. Integrating various resources to provide professional support and rehabilitation guidance is crucial.