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Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.
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PURPOSE: This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. METHODS: This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. RESULTS: The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p < 0.05). Harris and VAS scores were higher in the FNS group than in the CCS group (p < 0.05). Postoperative changes in the neck shaft angle and femoral neck shortening were significantly lower in the FNS group than in the CCS group (p < 0.05). The results of the finite element analysis indicated that the maximum stress on the femoral head and varus angle were generally lower in the FNS group than in the CCS group and that the maximum displacement of the femoral head and FNS was generally lower in the FNS group than in the CCS group. However, the superiority of FNS over CCS decreased with increasing Pauwels angle. Additionally, the effectiveness of FNS in limiting displacement of the femoral neck upper wall was not as favourable as that of CCS. CONCLUSIONS: The treatment of femoral neck fractures with FNS is superior and contributes to improved hip joint function. Biomechanical research has confirmed its structural stability and advantages in resisting femoral head varus. However, challenges to its fixation efficacy persist, particularly at higher Pauwels angles.
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Tornillos Óseos , Fracturas del Cuello Femoral , Fijación Interna de Fracturas , Humanos , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/fisiopatología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Fenómenos Biomecánicos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Curación de Fractura , Cuello Femoral/cirugía , Cuello Femoral/diagnóstico por imagen , Tiempo de Internación , Anciano de 80 o más AñosRESUMEN
The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.
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Lithium-sulfur (Li-S) batteries have attracted much attention due to their high specific capacity. However, at high loads and rates, the polysulfides conversion rate and ion transport of batteries are slow, limiting their commercialization. This work reports zero-dimensional (0D) bimetallic MOF derivatives grown in situ on two-dimensional (2D) MXene by electrostatic adsorption (FeCo@Ti3C2). The 0D bimetallic structure effectively avoids the stacking of MXene while providing a dual catalytic site for polysulfides. The 2D structure of MXene also provides a large number of pathways for the rapid diffusion of lithium ions. This 0D-2D heterostructured heterogeneous catalyst with bimetallic synergistic active sites efficiently immobilizes and catalyzes polysulfides, providing a fast charge transfer pathway for the electrochemical reaction of lithium polysulfides. The Li-S battery with this multifunctional 0D-2D heterojunction structure catalyst has outstanding high rate capacity (703 mAh g-1 at 4 C at room temperature and 555 mAh g-1 at 2 C at 0 °C), fascinating capacity at high load (5.5 mAh cm-2 after 100 cycles at a high sulfur content of 8.2 mg cm-2). The study provides new ideas for the commercialization of high-efficiency Li-S batteries.
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Apoptotic proteins play a crucial role in the apoptosis process, ensuring a balance between cell proliferation and death. Thus, further elucidating the regulatory mechanisms of apoptosis will enhance our understanding of their functions. However, the development of computational methods to accurately identify positive and negative regulation of apoptosis remains a significant challenge. This work proposes a machine learning model based on multi-feature fusion to effectively identify the roles of positive and negative regulation of apoptosis. Initially, we constructed a reliable benchmark dataset containing 200 positive regulation of apoptosis and 241 negative regulation of apoptosis proteins. Subsequently, we developed a classifier that combines the support vector machine (SVM) with pseudo composition of k-spaced amino acid pairs (PseCKSAAP), composition transition distribution (CTD), dipeptide deviation from expected mean (DDE), and PSSM-composition to identify these proteins. Analysis of variance (ANOVA) was employed to select optimized features that could yield the maximum prediction performance. Evaluating the proposed model on independent data revealed and achieved an accuracy of 0.781 with an AUROC of 0.837, demonstrating our model's potent capabilities.
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BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.
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Introduction: The liver is the only organ capable of full regeneration in mammals. However, the exact mechanism of gut microbiota and metabolites derived from them relating to liver regeneration has not been fully elucidated. Methods: To demonstrate how the gut-liver axis contributes to liver regeneration, using an LC-QTOF/MS-based metabolomics technique, we examine the gut microbiota-derived metabolites in the gut content of C57BL/6J mice at various points after 2/3 partial hepatectomy (PHx). Compound identification, multivariate/univariate data analysis and pathway analysis were performed subsequently. The diversity of the bacterial communities in the gastrointestinal content was measured using 16S rRNA gene sequencing. Then, the integration analysis of gut microbiota and metabolome was performed. Results: After 2/3 PHx, the residual liver proliferated quickly in the first 3 days and had about 90% of its initial weight by the seventh day. The results of PLS-DA showed that a significant metabolic shift occurred at 6 h and 36 h after 2/3 PHx that was reversed at the late phase of liver regeneration. The α and ß-diversity of the gut microbiota significantly changed at the early stage of liver regeneration. Specifically, Escherichia Shigella, Lactobacillus, Akkermansia, and Muribaculaceae were the bacteria that changed the most considerably during liver regeneration. Further pathway analysis found the most influenced co-metabolized pathways between the host and gut bacteria including glycolysis, the TCA cycle, arginine metabolism, glutathione metabolism, tryptophan metabolism, and purine and pyrimidine metabolism. Specifically, steroid hormone biosynthesis is the most significant pathway of the host during liver regeneration. Discussion: These findings revealed that during liver regeneration, there was a broad modification of gut microbiota and systemic metabolism and they were strongly correlated. Targeting specific gut bacterial strains, especially increasing the abundance of Akkermansia and decreasing the abundance of Enterobacteriaceae, may be a promising beneficial strategy to modulate systemic metabolism such as amino acid and nucleotide metabolism and promote liver regeneration.
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Single-atom nanozymes have garnered significant attention due to their exceptional atom utilization and ability to establish well-defined structure-activity relationships. However, conventional pyrolytic synthesis methods pose challenges such as high energy consumption and random local environments at the active sites, while achieving non-pyrolytic synthesis of single-atom nanozymes remains a formidable technical hurdle. The present study focuses on the synthesis of laccase-like iron-based single-atom nanozymes (Fe-SAzymes) using a non-pyrolysis method facilitated by microwave irradiation. Under low iron loading conditions, Fe-SAzymes exhibited significantly enhanced laccase activity (12.1 U/mg), surpassing that of laccase by 24-fold. Moreover, Fe-SAzymes demonstrated efficient catalytic oxidation of epinephrine (EP), enabling its colorimetric detection. Owing to the remarkable laccase activity of Fe-SAzymes, the conventional nanozymes EP detection time was reduced from 60 min to 20 min, with an impressive low detection limit as low as 2.95 µM. In addition, an ultra-sensitive fluorescence method for EP detection was developed using the internal filter effect of EP oxidation products and CDs combined with carbon dots probe. The detection limit of fluorescence method was only 0.39 µM. Therefore, an visual, fast, and highly sensitive dual-mode EP detection strategy has great potential in the clinical diagnostic industry.
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Colorimetría , Epinefrina , Hierro , Lacasa , Lacasa/química , Lacasa/metabolismo , Colorimetría/métodos , Epinefrina/análisis , Hierro/química , Espectrometría de Fluorescencia , Límite de Detección , Nanoestructuras/química , Oxidación-Reducción , Fluorescencia , MicroondasRESUMEN
Objective: By utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets. Methods: To begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment. Results: First, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway. Conclusion: CDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.
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Background: Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation. Methods: A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses. Results: The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91-3.83)] and day 14 (SMD 2.89, 95%CI 1.47-4.30). Day 14 (SMD 3.43, 95%CI 1.28-5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos. Conclusions: A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.
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AIMS: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects. MAIN METHODS: 6-Hydroxydopamine was used to establish in vivo and in vitro PD models. Western blotting, flow cytometry, and immunofluorescence were used to detect the effects of BDNF-EXO on apoptosis and ferroptosis in SH-SY5Y cells. The in vivo biological distribution of BDNF-EXO was detected using a small animal imaging system, and dopaminergic neuron improvements in brain tissue were detected using western blotting, immunofluorescence, immunohistochemistry, and Nissl and Prussian blue staining. KEY FINDINGS: BDNF-EXO effectively suppressed 6-hydroxydopamine-induced apoptosis and ferroptosis in SH-SY5Y cells. Following intravenous administration, BDNF-EXO crossed the blood-brain barrier to reach afflicted brain regions in mice, leading to a notable enhancement in neuronal survival. Furthermore, BDNF-EXO modulated microtubule-associated protein 2 and phosphorylated tau expression, thereby promoting neuronal cytoskeletal stability. Additionally, BDNF-EXO bolstered cellular antioxidant defense mechanisms through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway, thereby conferring neuroprotection against damage. SIGNIFICANCE: The novel drug delivery system, BDNF-EXO, had substantial therapeutic effects in both in vivo and in vitro PD models, and may represent a new treatment strategy for PD.
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Factor Neurotrófico Derivado del Encéfalo , Exosomas , Células Madre Mesenquimatosas , Enfermedad de Parkinson , Cordón Umbilical , Exosomas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Humanos , Animales , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Ratones , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacos , Oxidopamina , Masculino , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Ferroptosis/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos C57BLRESUMEN
Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of Magnolia officinalis which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of Magnolia officinalis were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from Magnolia officinalis. Multidimensional chemical-biological analysis (MCBA) of Magnolia officinalis was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of Magnolia officinalis. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants.
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Magnolia , Espectrometría de Masas , Magnolia/química , Espectrometría de Masas/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Simulación del Acoplamiento Molecular , Plantas Medicinales/química , Inhibidores de Glicósido Hidrolasas/análisis , Inhibidores de Glicósido Hidrolasas/químicaRESUMEN
Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.
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Atrazina , Fibrosis , Herbicidas , Inflamación , Ovario , Animales , Atrazina/toxicidad , Femenino , Ratones , Ovario/efectos de los fármacos , Ovario/metabolismo , Herbicidas/toxicidad , Inflamación/inducido químicamenteRESUMEN
Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.
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Agaricales , Alcaloides , Amidas , Antioxidantes , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Piper nigrum , Extractos Vegetales , Raíces de Plantas , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Antioxidantes/química , Antioxidantes/farmacología , Raíces de Plantas/química , Alcaloides/química , Alcaloides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Piper nigrum/química , Agaricales/química , Agaricales/enzimología , Amidas/química , Amidas/farmacología , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Estructura MolecularRESUMEN
Major depression is a complex psychiatric disorder that includes genetic, neurological, and cognitive factors. Early detection and intervention can prevent progression, and help select the best treatment. Traditional clinical diagnosis tends to be subjective and misdiagnosed. Based on this, this study leverages clinical scale assessments and sequencing data to construct disease prediction models. Firstly, data undergoes preprocessing involving normalization and other requisite procedures. Feature engineering is then applied to curate subsets of features, culminating in the construction of a model through the implementation of machine learning and deep learning algorithms. In this study, 18 features with significant differences between patients and healthy controls were selected. The depression recognition model was constructed by deep learning with an accuracy of 87.26 % and an AUC of 91.56 %, which can effectively distinguish patients with depression from healthy controls. In addition, 33 features selected by recursive feature elimination method were used to construct a prognostic effect model of patients after 2 weeks of treatment, with an accuracy of 75.94 % and an AUC of 83.33 %. The results show that the deep learning algorithm based on clinical and sequencing data has good accuracy and provides an objective and accurate method for the diagnosis and pharmacodynamic prediction of depression. Furthermore, the selected differential features can serve as candidate biomarkers to provide valuable clues for diagnosis and efficacy prediction.
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BACKGROUND: To examine the safety and effectiveness of proactive tracheoplasty for pediatric ring-sling complexes. METHODS: We retrospectively collected the data from 304 children who were diagnosed with a ring-sling complex and underwent surgery at three cardiac centers in China between January 2010 and June 2023. Children were categorized into three surgical groups: concurrent sling and tracheal surgery (Group A, n=258), staged sling and tracheal surgery (Group B, n=25), and sling-only surgery (Group C, n=21). We compared perioperative clinical characteristics, tracheal morphology changes, and outcomes across the groups. RESULTS: The median age of the children was 1.2 (IQR: 0.7-1.9) years. The anomalous tracheobronchial arborization rates were higher in Groups A (52.5%) and B (60.0%) than in Group C (15.0%). The preoperative narrow-wide ratio (NWR) was lower in Groups A and B than in Group C, with values of 0.44 (IQR: 0.35-0.52), 0.44 (0.33-0.59), and 0.68 (0.54-0.72), respectively (P<0.001). Preoperative subcarina angles were similar among the groups (P=0.54). After specific surgeries, the NWR and subcarina angle significantly improved in Groups A and B but not in Group C. There were seven in-hospital deaths and two post-discharge deaths. Respiratory symptoms improved in Groups A and B but seven children in Group C remained respiratory dysfunction. Six children presented with residual stenosis of the left pulmonary artery. CONCLUSION: Concurrent sling and tracheal surgeries for children with the ring-sling complex are safe and effective and are especially preferable for those with NWR ≤0.6, long-segment or diffuse tracheal stenosis, anomalous tracheobronchial arborization, and pronounced respiratory symptoms.
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Wave-particle resonance, a ubiquitous process in the plasma universe, occurs when resonant particles observe a constant wave phase to enable sustained energy transfer. Here, we present spacecraft observations of simultaneous Landau and anomalous resonances between oblique whistler waves and the same group of protons, which are evidenced, respectively, by phase-space rings in parallel-velocity spectra and phase-bunched distributions in gyrophase spectra. Our results indicate the coupling between Landau and anomalous resonances via the overlapping of the resonance islands.
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Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.
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Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.
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2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.