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In this work, we focus on solving the problem of timbre transfer in audio samples. The goal is to transfer the source audio's timbre from one instrument to another while retaining as much of the other musical elements as possible, including loudness, pitch, and melody. While image-to-image style transfer has been used for timbre and style transfer in music recording, the current state of the findings is unsatisfactory. Current timbre transfer models frequently contain samples with unrelated waveforms that affect the quality of the generated audio. The diffusion model has excellent performance in the field of image generation and can generate high-quality images. Inspired by it, we propose a kind of timbre transfer technology based on the diffusion model. To be specific, we first convert the original audio waveform into the constant-Q transform (CQT) spectrogram and adopt image-to-image conversion technology to achieve timbre transfer. Lastly, we reconstruct the produced CQT spectrogram into an audio waveform using the DiffWave model. In both many-to-many and one-to-one timbre transfer tasks, we assessed our model. The experimental results show that compared with the baseline model, the proposed model has good performance in one-to-one and many-to-many timbre transfer tasks, which is an interesting technical progress.
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Arsenic is a widespread carcinogen and an important etiological factor for lung cancer. Dysregulated miRNAs have been implicated in arsenic carcinogenesis and the mechanisms of arsenic-induced dysregulated miRNAs have not been fully elucidated. N6-methyladenosine (m6A) modification is known to modulate pri-miRNA processing. However, whether m6A-mediated pri-miRNA processing is involved in arsenic carcinogenesis is poorly understood. Here, we found that m6A modification was significantly increased in arsenite-transformed human bronchial epithelial BEAS-2B cells (0.5⯵M arsenite, 16 weeks). Meanwhile, METTL3 was significantly upregulated at week 12 and 16 during cell transformation. The proliferation, migration, invasion, and anchorage-independent growth of arsenite-transformed cells were inhibited by the reduction of m6A levels through METTL3 knockdown. Further experiments suggest that the oncogene miR-106b-5p is a potentially essential m6A target mediating arsenic-induced lung cancer. miR-106b-5p was observed to be upregulated after exposure to arsenite for 12 and 16 weeks, and the reduction of m6A levels caused by METTL3 knockdown inhibited miR-106b-5p maturation in arsenite-transformed cells. What's more, miR-106b-5p overexpression successfully rescued METTL3 knockdown-induced inhibition of the neoplastic phenotypes of transformed cells. Additionally, Basonuclin 2 (BNC2) was uncovered as a potential target of miR-106b-5p and downregulated by METTL3 via enhancing miR-106b-5p maturation. Additionally, the METTL3 inhibitor STM2457 suppressed neoplastic phenotypes of arsenite-transformed BEAS-2B cells by blocking pri-miR-106b methylation. These results demonstrate that m6A modification promotes the neoplastic phenotypes of arsenite-transformed BEAS-2B cells through METTL3/miR-106b-5p/BNC2 pathway, providing a new prospective for understanding arsenic carcinogenesis.
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In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2â µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of â¼18â mW around 1962â nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2â µm solid-state laser.
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During remediation of black-odorous sediment, the pathways of phosphorus immobilization require clarification alongside the oxidation of sulfide and ferrous. This study separated the oxidation stages of sulfide and ferrous through controlled sodium nitrate dosing ratios and methods, and analyzed the changes in phosphorus species and immobilization effects throughout these processes. Results showed that iron-bound phosphorus was the primary contributor to the phosphorus immobilization in the oxidation process, with increased 19% in ferrous oxidation stage and affected the transformation between phosphorus sources or sinks in the adsorption experiment. Additionally, the increase in abundance of phosphorus uptake and transport genes, and denitrifying phosphorus accumulation genes in sediment after ferrous oxidation (1 %-18 % and 87 %-164 %, respectively) indicated the potential for biological phosphorus immobilization. These results demonstrated that higher degrees of sediment oxidation correlate with stronger phosphorus immobilization capacities, providing theoretical bases for phosphorus immobilization during the restoration of black-odorous water bodies.
Subject(s)
Geologic Sediments , Nitrates , Oxidation-Reduction , Phosphorus , Sulfides , Phosphorus/chemistry , Geologic Sediments/chemistry , Sulfides/chemistry , Ferrous Compounds/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Environmental Restoration and Remediation/methods , Biodegradation, EnvironmentalABSTRACT
OBJECTIVE: This study aimed to evaluate the effectiveness and safety of coils plus glue (CPG) in slope embankment technology vs coils plus sclerosant (CPS) in treating reflux-type pelvic venous disorders. METHODS: The analysis included patients diagnosed with reflux-type pelvic venous disorders who were treated with CPG or CPS from 2019 to 2021. The inclusion criteria were noncyclic pain lasting more than 6 months, atypical varicose, and transvaginal Doppler ultrasound (TVDUS) and computed tomographic venography confirming the diagnosis and excluding compression factors and other diseases. Propensity score matching was performed at a 1:1.1 ratio based on the following covariates: age, pregnancy, body mass index, pretreatment visual analog scale (VAS), dysmenorrhea, dyspareunia, urinary urgency, tenesmus, low back pain, vulvar varicosities, vaginal varicosities, and lower limb varices. The pain was relieved by embolizing the target lesions with different embolic materials. The efficacy and safety of the different embolization materials were compared by VAS and TVDUS examinations at 1, 3, 6, 12, 24, and 36 months. RESULTS: From a total of 495 patients, 88 patients were selected from the CPG group and 77 patients from the CPS group by propensity score matching. The patients were followed up for 36 months. The preoperative VAS score of the CPG group was 8 (range, 6-8), and the CPS score was 8 (range, 7-8; P = .64). The postembolization VAS score of the CPG group was 2.05 ± 0.37, and the CPS score was 2.14 ± 0.35 (P = .55). A total of 28 cases (16.9%) showed complications, most of which were transient pain after embolization. No serious complications such as coil embolization to the lungs occurred. In addition, the CPG group used fewer coils than the CPS group by using the slope embankment technique. The mean coil length of the CPG group was 77.18 ± 33.82 cm, and the CPS group was 105.29 ± 71 cm (P = .001). The CPG group had an average operative time of 44.49 ± 5.72 minutes, whereas the CPS group took 43.45 ± 4.18 minutes on average (P = .19). The radiation dose in the CPG group was 398.40 ± 76.16 mGy, and the radiation dose in the CPS group was 388 ± 44.23 mGy (P = .30). The median recurrence-free survival in the CPG group was 34.23 months (95% confidence interval, 33.2-35.2), and the median recurrence-free survival in the CPS group was 30.39 months (95% confidence interval, 28.2-32.6; log rank P = .018). CONCLUSIONS: Embolization therapy for refluxing PeVD was safe and effective, and proficient use of slope embankment technique with CPG increased efficacy and reduced complications.
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BACKGROUND: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC). METHOD: A total of 181 Chinese pregnant women (Mage = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed. RESULTS: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (ß = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms. CONCLUSIONS: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic.
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ETHNOPHARMACOLOGICAL RELEVANCE: Lindera aggregata (Sims) Kosterm is a common traditional herb that has multiple bioactivities. Radix Linderae (LR), the dry roots of Lindera aggregata (Sims) Kosterm, is a traditional Chinese herbal medicine with antioxidant, anti-inflammatory and immunomodulatory properties, first found in Kaibao Era. Norboldine (Nor) is an alkaloid extracted from LR and is one of the primary active ingredients of LR. However, the pharmacological functions and mechanism of Nor in Alzheimer's disease (AD) are still unknown. AIM OF THE STUDY: This study aims to investigate the effect and mechanism of Nor therapy in improving the cognitive impairment and pathological features of 3 × Tg mice. MATERIALS AND METHODS: 3 × Tg mice were treated with two concentrations of Nor for one month and then the memory and cognitive abilities of mice were assessed by novel object recognition experiment and Morris water maze. The impact of Nor on the pathology of ADwere examined in PC12 cells and animal tissues using western blotting and immunofluorescence. Finally, western blotting was used to verify the anti-apoptotic effect of Nor by activating AMPK/GSK3ß/Nrf2 signaling pathway at animal and cellular levels. RESULTS: In this study, we showed that Nor treatment improved the capacity of the learning and memory of 3 × Tg mice and alleviated AD pathology such as Aß deposition. In addition, Nor restored the abnormalities of mitochondrial membrane potential, significantly reduced the production of intracellular ROS and neuronal cell apoptosis. Mechanistically, we combined network pharmacology and experimental verification to show that Nor may exert antioxidant stress and anti-apoptotic through the AMPK/GSK3ß/Nrf2 signaling pathway. CONCLUSION: Our data provide some evidence that Nor exerts a neuroprotective effect through the AMPK/GSK3ß/Nrf2 pathway, thereby improving cognitive impairment in AD model mice. Natural products derived from traditional Chinese medicines are becoming increasingly popular in the process of new drug development and discovery, and our findings provide new perspectives for the discovery of improved treatment strategies for AD.
Subject(s)
Alkaloids , Alzheimer Disease , Cognitive Dysfunction , Lindera , Plant Extracts , Signal Transduction , Animals , Male , Mice , Rats , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , AMP-Activated Protein Kinases/metabolism , Apoptosis/drug effects , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Disease Models, Animal , Glycogen Synthase Kinase 3 beta/metabolism , Mice, Transgenic , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , NF-E2-Related Factor 2/metabolism , PC12 Cells , Signal Transduction/drug effects , Lindera/chemistry , Plant Extracts/administration & dosage , Alkaloids/administration & dosageABSTRACT
UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Agaricus blazei Murill (ABM) is an edible medicinal and nutritional fungus. One of its constituents, Agaricus blazei Murill polysaccharide (ABP), has been reported to exhibit antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, which suggests potential effects that protect against photodamage. In this study, a UVB-induced photodamage HaCaT model was established to investigate the potential reparative effects of ABP and its two constituents (A1 and A2). Firstly, two purified polysaccharides, A1 and A2, were obtained by DEAE-52 cellulose column chromatography, and their physical properties and chemical structures were studied. A1 and A2 exhibited a network-like microstructure, with molecular weights of 1.5 × 104 Da and 6.5 × 104 Da, respectively. The effects of A1 and A2 on cell proliferation, the mitochondrial membrane potential, and inflammatory factors were also explored. The results show that A1 and A2 significantly promoted cell proliferation, enhanced the mitochondrial membrane potential, suppressed the expression of inflammatory factors interleukin-1ß (IL-1ß), interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and increased the relative content of filaggrin (FLG) and aquaporin-3 (AQP3). The down-regulated JAK-STAT signaling pathway was found to play a role in the response to photodamage. These findings underscore the potential of ABP to ameliorate UVB-induced skin damage.
Subject(s)
Agaricus , Cell Proliferation , Filaggrin Proteins , HaCaT Cells , Ultraviolet Rays , Agaricus/chemistry , Humans , Ultraviolet Rays/adverse effects , Cell Proliferation/drug effects , Membrane Potential, Mitochondrial/drug effects , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/radiation effects , Cytokines/metabolismABSTRACT
OBJECTIVE: The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC). METHODS: The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method. RESULTS: Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen densityâ¦37.00HU). Kaplan-Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method. CONCLUSION: Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator.
Subject(s)
Colorectal Neoplasms , Spleen , Humans , Prognosis , Neoplasm Staging , Spleen/diagnostic imaging , Spleen/surgery , Spleen/pathology , Retrospective Studies , Colorectal Neoplasms/pathology , Nomograms , Biomarkers, TumorABSTRACT
Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.
Subject(s)
Pregnancy, Twin , Premature Birth , Infant, Newborn , Pregnancy , Humans , Female , Adult , Cervical Length Measurement , Cohort Studies , Premature Birth/epidemiology , China/epidemiologyABSTRACT
Acne is a chronic inflammatory skin disease with a recurring nature that seriously impacts patients' quality of life. Currently, antibiotic resistance has made it less effective in treating acne. However, Paris polyphylla (P. polyphylla) is a valuable medicinal plant with a wide range of chemical components. Of these, P. polyphylla saponins modulate the effects in vivo and in vitro through antibacterial, anti-inflammatory, immunomodulatory, and antioxidant effects. Acne is primarily associated with inflammatory reactions, abnormal sebum function, micro-ecological disorders, hair follicle hyperkeratosis, and, in some patients, immune function. Therefore, the role of P. polyphylla saponins and their values in treating acne is worthy of investigation. Overall, this review first describes the distribution and characteristics of P. polyphylla and the pathogenesis of acne. Then, the potential mechanisms of P. polyphylla saponins in treating acne are listed in detail (reduction in the inflammatory response, antibacterial action, modulation of immune response and antioxidant effects, etc.). In addition, a brief description of the chemical composition of P. polyphylla saponins and its available extraction methods are described. We hope this review can serve as a quick and detailed reference for future studies on their potential acne treatment.
Subject(s)
Acne Vulgaris , Anti-Bacterial Agents , Anti-Inflammatory Agents , Antioxidants , Saponins , Humans , Acne Vulgaris/drug therapy , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/chemistry , Saponins/pharmacology , Saponins/chemistry , Saponins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/chemistry , Animals , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Immunologic Factors/chemistry , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/isolation & purification , Melanthiaceae/chemistry , Liliaceae/chemistryABSTRACT
Recent evidence suggests that ferroptosis, an iron-facilitated cell death with excessive lipid peroxidation, is a critical mechanism underlying doxorubicin (DOX)-induced cardiotoxicity (DIC). Although dioscin has been reported to improve acute DIC, direct evidence is lacking to clarify the role of dioscin in chronic DIC and its potential mechanism in cardiac ferroptosis. In this study, we used chronic DIC rat models and H9c2 cells to investigate the potential of dioscin to mitigate DIC by inhibiting ferroptosis. Our results suggest that dioscin significantly improves chronic DIC-induced cardiac dysfunction. Meanwhile, it significantly inhibited DOX-induced ferroptosis by reducing Fe2+ and lipid peroxidation accumulation, maintaining mitochondrial integrity, increasing glutathione peroxidase 4 (GPX4) expression, and decreasing acyl-CoA synthetase long-chain family 4 (ACSL4) expression. Through transcriptomic analysis and subsequent validation, we found that the anti-ferroptotic effects of dioscin are achieved by regulating the nuclear factor-erythroid 2-related factor 2 (Nrf2)/GPX4 axis and Nrf2 downstream iron metabolism genes. Dioscin further downregulates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and upregulates expression of frataxin (FXN) and ATP-binding cassette B8 (ABCB8) to limit mitochondrial Fe2+ and lipid peroxide accumulation. However, Nrf2 inhibition diminishes the anti-ferroptotic effects of dioscin, leading to decreased GPX4 expression and increased lipid peroxidation. This study is a compelling demonstration that dioscin can effectively reduce DIC by inhibiting ferroptosis, which is dependent on the Nrf2/GPX4 pathway modulation.
Subject(s)
Cardiotoxicity , Diosgenin , Ferroptosis , NF-E2-Related Factor 2 , Phospholipid Hydroperoxide Glutathione Peroxidase , Animals , Rats , Cardiotoxicity/metabolism , Cardiotoxicity/drug therapy , Cardiotoxicity/prevention & control , Cardiotoxicity/etiology , Cell Line , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/genetics , Diosgenin/analogs & derivatives , Diosgenin/pharmacology , Doxorubicin/adverse effects , Doxorubicin/pharmacology , Ferroptosis/drug effects , Iron/metabolism , Lipid Peroxidation/drug effects , NF-E2-Related Factor 2/drug effects , NF-E2-Related Factor 2/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Rats, Sprague-DawleyABSTRACT
The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.
Subject(s)
Head and Neck Neoplasms , Tumor Microenvironment , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Tumor Microenvironment/genetics , Prognosis , Circadian Rhythm/genetics , Head and Neck Neoplasms/geneticsABSTRACT
Aberrant autophagy could promote cancer cells to survive and proliferate in prostate cancer (PCa). LncRNAs play key roles in autophagy regulatory network. We established a prognostic model, which autophagy-related lncRNAs (au-lncRNAs) were used as biomarkers to predict prognosis of individuals with PCa. Depending on au-lncRNAs from the Cancer Genome Atlas and the Human Autophagy Database, a risk score model was created. To evaluate the prediction accuracy, the calibration, Kaplan-Meier, and receiver operating characteristic curves were used. To clarify the biological function, gene set enrichment analyses (GSEA) were performed. Quantitative real-time PCR (qRT-PCR) was employed to determine the au-lncRNAs expression in PCa cell lines and healthy prostate cells for further confirmation. We identified five au-lncRNAs with prognostic significance (AC068580.6, AF131215.2, LINC00996, LINC01125 and LINC01547). The development of a risk scoring model required the utilization of multivariate Cox analysis. According to the model, we categorized PCa individuals into low- and high-risk cohorts. PCa subjects in the high-risk group had a worse disease-free survival rate than those in the low-risk group. The 1-, 3-, and 5-year periods had corresponding areas under curves (AUC) of 0.788, 0.794, and 0.818. The prognosis of individuals with PCa could be predicted by the model with accuracy. Further analysis with GSEA showed that the prognostic model was associated with the tumor microenvironment, including immunotherapy, cancer-related inflammation, and metabolic reprogramming. Four lncRNAs expression in PCa cell lines was greater than that in healthy prostate cells. The au-lncRNA prognostic model has significant clinical implications in prognosis of PCa patient.
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Introduction: The incidence of chronic kidney disease (CKD) has been increasing in recent years, gradually becoming a global health crisis. Due to limited treatment options, novel molecular pathways are urgently required to advance the treatment and diagnosis of CKD. Materials and methods: The characteristics of differentially expressed genes (DEGs) in CKD patients were analyzed using Gene Expression Omnibus (GEO) database, and genes related to oxidative stress were retrieved from the Genecard database. Subsequently, a comprehensive approach was applied, including immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis, to identify hub genes among differentially expressed immune-related oxidative stress genes (DEIOSGs). Validation of hub genes was performed using an external data set, and diagnostic potential capability was evaluated through receiver operating curve (ROC) analysis. In animal experiments, the expression of hub genes in CKD was confirmed by inducing a CKD model through a 5/6 nephrectomy procedure. Finally, the relationship between these hub genes and clinical characteristics were assessed using the Nephroseq v5 database. Results: 29 DEIOSGs were identified by comprehensive bioinformatics analysis. PPI analysis screened the hub genes NCF2, S100A9, and SELL. ROC analysis demonstrated excellent diagnostic efficacy. Further validation from other databases and animal experiments confirmed a substantial upregulation in the expression of hub genes in CKD. Additionally, clinical correlation analysis established a clear link between hub gene expression and renal function deterioration. Conclusions: Our study confirms NCF2, S100A9, and SELL as diagnostic biomarkers associated with immune response and oxidative stress in CKD, suggesting their potential as novel targets for CKD diagnosis and treatment.
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Excessive use of tetracycline antibiotics in poultry farming results in significant concentrations of these drugs and tetracycline resistance genes (TRGs) in chicken manure, impacting both environmental and human health. Our research represents the first investigation into the removal dynamics of chlortetracycline (CTC) and TRGs in different layers of an ex situ fermentation system (EFS) for chicken waste treatment. By pinpointing and analyzing dominant TRGs-harboring bacteria and their interactions with environmental variables, we've closed an existing knowledge gap. Findings revealed that CTC's degradation half-lives spanned 3.3-5.8 days across different EFS layers, and TRG removal efficiency ranged between 86.82% and 99.52%. Network analysis highlighted Proteobacteria and Actinobacteria's essential roles in TRGs elimination, whereas Chloroflexi broadened the potential TRG hosts in the lower layer. Physical and chemical conditions within the EFS influenced microbial community diversity, subsequently impacting TRGs and integrons. Importantly, our study reports that the middle EFS layer exhibited superior performance in eliminating CTC and key TRGs (tetW, tetG, and tetX) as well as intI2. Our work transcends immediate health and environmental remediation by offering insights that encourage sustainable agriculture practices.
Subject(s)
Chlortetracycline , Manure , Animals , Humans , Manure/analysis , Chickens , Fermentation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/analysis , Tetracycline , Genes, BacterialABSTRACT
OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66â¯%) type I cases were stable, whereas 25/100 (25â¯%) cases changed to type II and 9/100 (9â¯%) changed to sFGR complicated twin-twin transfusion syndrome (TTTS). A total of 48.9â¯% (22/45) sFGR cases were complicated with polyhydramnios and 30.4â¯% (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3â¯%, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.
Subject(s)
Fetal Growth Retardation , Ultrasonography, Doppler , Ultrasonography, Prenatal , Humans , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/physiopathology , Female , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal/methods , Infant, Newborn , Ultrasonography, Doppler/methods , Umbilical Arteries/diagnostic imaging , Fetofetal Transfusion/diagnostic imaging , Fetofetal Transfusion/diagnosis , Fetofetal Transfusion/physiopathology , Twins, Monozygotic , Adult , Pregnancy, Twin , Pregnancy Outcome/epidemiology , Gestational AgeABSTRACT
Introduction: This study aimed to analyze how authoritative parenting affects behavioral problems among primary, junior high, and secondary high school students. Today, parental educational anxiety and parent-child relationship conflicts are common in China and are resulting in a high incidence of child behavioral problems. High-quality family education is becoming increasingly important in China. This study sought to provide a reference for developing responsive family education services. Methods: A total of 10,441 parents in Hubei Province, including urban and rural areas, were evaluated using the Parents' Education Anxiety Questionnaire, Parental Authority Parenting Questionnaire, Parent-Child Relationship Scale, and Self-Made Behavior Problem Scale to determine the internal mechanisms of child behavioral problems in the family system. To make the sample more representative, this study collected data from primary and secondary schools representative of the southeast, northwest, and center of Hubei Province; further, the number of parents involved in each school was controlled at approximately 300 to ensure that the final sample had analytical value. Results: Educational anxiety directly affected children's behavioral problems and indirectly affected them through the conflicts between parent and child. This conflict partially mediated educational anxiety and child behavioral problems, and authoritative parenting played a significant regulatory role in this relationship. Discussion: Higher levels of educational anxiety among parents increased the likelihood of a depressed family environment. This can lead to deteriorating parent-child relationships, which can result in children's problem behaviors. Parents can address these problems by changing their approach to education and adjusting their emotions accordingly.
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Background: IκB kinase ß (IKKß) plays a pivotal role in the NF-κB signaling pathway and is considered a promising therapeutic target for various diseases. Materials & methods: The authors developed and validated a 3D pharmacophore model of IKKß inhibitors via the HypoGen algorithm in Discovery Studio 2019, then performed virtual screening, molecular docking and kinase assays to identify hit compounds from the ChemDiv database. The compound with the highest inhibitory activity was further evaluated in adjuvant-induced arthritis rat models. Results: Among the four hit compounds, Hit 4 had the highest IKKß inhibitory activity (IC50 = 30.4 ± 3.8), and it could significantly ameliorate joint inflammation and damage in vivo. Conclusion: The identified compound, Hit 4, can be optimized as a therapeutic agent for inflammatory diseases.
This research paper focuses on the development and validation of IκB kinase ß (IKKß) inhibitors. IKKß is a crucial enzyme that plays an important role in the NF-κB signaling pathway, which is involved in many diseases such as inflammatory diseases and cancers. The researchers used computer-aided drug design strategies to identify potential IKKß inhibitors. First, they used a model to screen a large database of chemical compounds. Then, they conducted further tests to pinpoint the ones that could effectively inhibit IKKß. Out of all the tested compounds, one referred to as 'Hit 4' showed the highest inhibitory activity. It was even able to significantly reduce joint inflammation and damage in rat models. Although many drugs targeting IKKß have been developed, none are commercially available yet due to issues with efficacy or safety. Therefore, the findings of this study are significant and could lead to the development of new effective therapeutic agents for inflammatory diseases.
Subject(s)
I-kappa B Kinase , Pharmacophore , Animals , Rats , I-kappa B Kinase/antagonists & inhibitors , Molecular Docking Simulation , NF-kappa B , Signal TransductionABSTRACT
Light-driven microrobots capable of moving rapidly on water surfaces in response to external stimuli are widely used in a variety of fields, such as drug delivery, remote sampling, and biosensors. However, most light-driven microrobots use graphene and carbon nanotubes as photothermal materials, resulting in poor biocompatibility and degradability, which greatly limits their practical bioapplications. To address this challenge, a composition and microstructure design strategy with excellent photothermal properties suitable for the fabrication of light-driven microrobots was proposed in this work. The Mg-based metallic glass nanowires (Mg-MGNWs) were embedded with polyhydroxyalkanoates (PHA) to fabricate biocompatible and degradable microrobots with excellent photothermal effect and complex shapes. Consequently, the microrobot can be precisely driven by a near-infrared laser to achieve high efficiency and remote manipulation on the water surface for a long period of time, with a velocity of 9.91 mm/s at a power density of 2.0 W/cm2. Due to the Marangoni effect, programmable and complex motions of the microrobot such as linear, clockwise, counterclockwise, and obstacle avoidance motions can be achieved. The biocompatible and degradable microrobot fabrication strategy could have great potential in the fields of environmental detection, targeted drug delivery, disease diagnosis, and detection.