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Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.
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Degradable phosphate glasses have shown favorable properties for tissue engineering. By changing the composition of the glasses, the degradation rate, and ion release are controllable. Zinc oxide can function as a glass network modifier and has been shown to play a positive role in bone formation. Also, phosphate glasses can easily be processed into microspheres, which can be used as microcarriers. This study aims to develop zinc phosphate glasses microspheres and explore the optimized size and composition for applications in bone tissue engineering. Zinc-titanium-calcium-sodium phosphate glasses with 0, 1, 3, 5, or 10 mol % zinc oxide were prepared and processed into microspheres. The smaller microspheres ranged in size from 50 to 106 µm, while the larger ones ranged from 106 to 150 µm. The characteristics of glasses were examined. The osteoblastic cell line MC3T3-E1 was cultured on the surface of microspheres and the cell viability was examined. To evaluate osteogenic differentiation, Alizarin Red S staining, quantitative reverse transcription polymerase chain reaction, and western blot analysis were performed after 14 days. Different sizes of zinc phosphate glass microspheres were successfully made. The glass microspheres with <10 mol % zinc oxide were able to support the adhesion and proliferation of MC3T3-E1 cell lines. The relative gene expression of BMP2 was significantly upregulated in the smaller glass microspheres containing 3 mol % zinc oxide (26-fold, p < .001) and both sizes of microspheres containing 5 mol % zinc oxide (smaller: 27-fold, p < .001; larger: 35-fold, p < .001). Additionally, cluster formation was observed in glass microspheres after 14 days, and the mineralization of MC3T3-E1 cell lines was promoted. Based on these findings, the glass microspheres containing 3-5 mol % of zinc oxide can promote osteogenic differentiation for MC3T3-E1 cells.
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The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) patients that have undergone percutaneous coronary intervention (PCI). Further, the study aims to construct a ratio nomogram for prediction with this ratio. The training cohort comprised of 511 STEMI patients who underwent emergency PCI at the Huaibei Miners' General Hospital between January 2019 and May 2023. Simultaneously, 384 patients treated with the same strategy in First People's Hospital of Hefei formed the validation cohort during the study period. LASSO regression was used to screen predictors of nonzero coefficients, multivariate logistic regression was used to analyze the independent factors of in-hospital MACE in STEMI patients after PCI, and nomogram models and validation were established. The LASSO regression analysis demonstrated that systolic blood pressure, diastolic blood pressure, D-dimer, urea, and glycosylated hemoglobin A1c (HbA1c)/apolipoprotein A1 (ApoA1) were significant predictors with nonzero coefficients. Multivariate logistic regression analysis was further conducted to identify systolic blood pressure, D-dimer, urea, and HbA1c/ApoA1 as independent factors associated with in-hospital MACE after PCI in STEMI patients. Based on these findings, a nomogram model was developed and validated, with the C-index in the training set at 0.77 (95% CI: 0.723-0.817), and the C-index in the validation set at 0.788 (95% CI: 0.734-0.841), indicating excellent discrimination accuracy. The calibration curves and clinical decision curves also demonstrated the good performance of the nomogram models. In patients with STEMI who underwent PCI, it was noted that a higher HbA1c of the ApoA1 ratio is significantly associated with in-hospital MACE. In addition, a nomogram is constructed having considered the above-mentioned risk factors to provide predictive information on in-hospital MACE occurrence in these patients. In particular, this tool is of great value to the clinical practitioners in determination of patients with a high risk.
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Apolipoproteína A-I , Hemoglobina Glucada , Nomogramas , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/cirugía , Masculino , Femenino , Apolipoproteína A-I/sangre , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Anciano , Medición de Riesgo/métodos , Modelos Logísticos , Factores de RiesgoRESUMEN
INTRODUCTION: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. METHODS: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-ß1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay. RESULTS: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-ß1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-ß1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-ß1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression. CONCLUSION: MiR-150-5p suppresses TGF-ß1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.
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To study the long-term variation in ozone (O3) pollution in Sichuan Basin,the spatiaotemporal distribution of O3 concentrations during 2017 to 2020 was analyzed using ground-level O3 concentration data and meteorological observation data from 18 cities in the basin. The dominant meteorological factors affecting the variation in O3 concentration were screened out,and a prediction model between meteorological factors and O3 concentration was constructed based on a random forest model. Finally,a prediction analysis of O3 pollution in the Sichuan Basin urban agglomeration during 2020 was carried out. The results showed that:â O3 concentrations displayed a fluctuating trend during the period from 2017 to 2020,with a downward trend in 2019 and a rebound in 2020. â¡ The fluctuating trend of O3 concentration was significantly influenced by relative humidity,daily maximum temperature,and sunshine hours,whereas wind speed,air pressure,and precipitation had less impact. The linear relationships between meteorological factors were different. Air pressure was negatively correlated with other meteorological factors,whereas the remaining meteorological factors had a positive correlation. ⢠The goodness of fit statistics (R2) between the predicted and actual values of the O3 prediction model constructed based on random forest demonstrated a strong predictive performance and ability to accurately forecast the long-term daily variations in O3 concentration. The random forest O3 prediction model exhibited excellent stability and generalization capability. ⣠The prediction analysis of O3 concentrations in 18 cities in the basin showed that the explanation rate of variables in the prediction model reached over 80% in all cities (except Ya'an),indicating that the random forest model predicted the trend of O3 concentration accurately.
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NKX2-5 is a member of the homeobox-containing transcription factors critical in regulating tissue differentiation in development. Here, we report a role for NKX2-5 in vascular smooth muscle cell phenotypic modulation in vitro and in vascular remodeling in vivo. NKX2-5 is upregulated in scleroderma patients with pulmonary arterial hypertension. Suppression of NKX2-5 expression in smooth muscle cells halted vascular smooth muscle proliferation and migration, enhanced contractility, and blocked the expression of extracellular matrix genes. Conversely, overexpression of NKX2-5 suppressed the expression of contractile genes (ACTA2, TAGLN, CNN1) and enhanced the expression of matrix genes (COL1) in vascular smooth muscle cells. In vivo, conditional deletion of NKX2-5 attenuated blood vessel remodeling and halted the progression to hypertension in a mouse chronic hypoxia model. This study revealed that signals related to injury such as serum and low confluence, which induce NKX2-5 expression in cultured cells, is potentiated by TGF-ß and further enhanced by hypoxia. The effect of TGF-ß was sensitive to ERK5 and PI3K inhibition. Our data suggest a pivotal role for NKX2-5 in the phenotypic modulation of smooth muscle cells during pathological vascular remodeling and provide proof of concept for therapeutic targeting of NKX2-5 in vasculopathies.
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Proteína Homeótica Nkx-2.5 , Músculo Liso Vascular , Remodelación Vascular , Animales , Ratones , Proteína Homeótica Nkx-2.5/genética , Proteína Homeótica Nkx-2.5/metabolismo , Humanos , Remodelación Vascular/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Masculino , Esclerodermia Sistémica/patología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/genética , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/patología , Hipertensión Arterial Pulmonar/etiología , Femenino , Factor de Crecimiento Transformador beta/metabolismo , Modelos Animales de Enfermedad , Proliferación Celular/genética , Persona de Mediana Edad , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patologíaRESUMEN
Nighttime object detection is challenging due to dim, uneven lighting. The IIHS research conducted in 2022 shows that pedestrian anti-collision systems are less effective at night. Common solutions utilize costly sensors, such as thermal imaging and LiDAR, aiming for highly accurate detection. Conversely, this study employs a low-cost 2D image approach to address the problem by drawing inspiration from biological dark adaptation mechanisms, simulating functions like pupils and photoreceptor cells. Instead of relying on extensive machine learning with day-to-night image conversions, it focuses on image fusion and gamma correction to train deep neural networks for dark adaptation. This research also involves creating a simulated environment ranging from 0 lux to high brightness, testing the limits of object detection, and offering a high dynamic range testing method. Results indicate that the dark adaptation model developed in this study improves the mean average precision (mAP) by 1.5-6% compared to traditional models. Our model is capable of functioning in both twilight and night, showcasing academic novelty. Future developments could include using virtual light in specific image areas or integrating with smart car lighting to enhance detection accuracy, thereby improving safety for pedestrians and drivers.
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Pine wood nematode (PWN) disease is one of the major disasters in forests of southern China, causing substantial forest resources and ecological and economic losses. Based on field surveys and WFV image data from the GF-1 satellite, we constructed a spatial identification model of PWN disease with the random forest model to explore the relative influences of topography, human activities and stand factors on the occurrence of diseases and predict their spatial distribution. We then used the spatial autocorrelation analysis to assess the distribution characteristics of PWN disease at the regional scale. The results showed that the random forest model constructed in this study was effective in identifying pine nematode diseases (AUC value=0.99, overall accuracy=0.96). The norma-lized difference greenness index (NDGI), the distance to the highway, and normalized vegetation index (NDVI) were important factors in explaining the spatial variations of PWN disease occurrence. There was a positive spatial correlation in the occurrence of PWN disease (not randomly distributed but with obvious spatial aggregation characteristics). The high occurrence areas of pine wood nematode disease concentrated in Chitu Township, Zhufang Township and Shibatang Township, low occurrence areas concentrated in the vicinity of Rongjiang Street. The areas far away from the highway, low in elevation, and close to county roads were suffered to PWN disease. The results could serve the regional monitoring of pine nematode disease occurrence and provide practical guidance for PWN disease management.
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Nematodos , Pinus , Tylenchida , Animales , Humanos , Enfermedades de las Plantas , ChinaRESUMEN
Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.
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Técnicas Biosensibles , Polímeros Impresos Molecularmente , Colorimetría/métodos , Peroxidasa/química , PeroxidasasRESUMEN
INTRODUCTION: Colonocyte oxidation of bacterial-derived butyrate has been reported to maintain synergistic obligate anaerobe populations by reducing colonocyte oxygen levels; however, it is not known whether this process is disrupted during the progression of type 2 diabetes. Our aim was to determine whether diabetes influences colonocyte oxygen levels in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model. RESEARCH DESIGN AND METHODS: Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry. RESULTS: HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia-Shigella, and Streptococcus (false discovery rate <0.05) genera in colon contents. The intensity of pimonidazole staining of colonic epithelia did not differ across groups (p=0.37). Colon content concentrations of acetate and propionate also did not differ across UCD-T2DM groups; however, colonic butyric acid levels were higher in D3M rats relative to PD rats (p<0.01). CONCLUSIONS: The advancement of diabetes in UCD-T2DM rats was associated with an increase in facultative anaerobes; however, this was not explained by changes in colonocyte oxygen levels. The mechanisms underlying shifts in gut microbe populations associated with the progression of diabetes in the UCD-T2DM rat model remain to be identified.
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Diabetes Mellitus Tipo 2 , Nitroimidazoles , Humanos , Ratas , Masculino , Animales , Recién Nacido , Hipoxia , OxígenoRESUMEN
Nuclear magnetic resonance (NMR) chemical shift calculations are powerful tools for structure elucidation and have been extensively employed in both natural product and synthetic chemistry. However, density functional theory (DFT) NMR chemical shift calculations are usually time-consuming, while fast data-driven methods often lack reliability, making it challenging to apply them to computationally intensive tasks with a high requirement on quality. Herein, we have constructed a 54-layer-deep graph convolutional network for 13C NMR chemical shift calculations, which achieved high accuracy with low time-cost and performed competitively with DFT NMR chemical shift calculations on structure assignment benchmarks. Our model utilizes a semiempirical method, GFN2-xTB, and is compatible with a broad variety of organic systems, including those composed of hundreds of atoms or elements ranging from H to Rn. We used this model to resolve the controversial J/K ring junction problem of maitotoxin, which is the largest whole molecule assigned by NMR calculations to date. This model has been developed into user-friendly software, providing a useful tool for routine rapid structure validation and assignation as well as a new approach to elucidate the large structures that were previously unsuitable for NMR calculations.
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Teoría Funcional de la Densidad , Estructura Molecular , Espectroscopía de Resonancia Magnética con Carbono-13/métodos , Oxocinas/química , Programas InformáticosRESUMEN
Upcycling nickel (Ni) to useful catalyst is an appealing route to realize low-carbon treatment of electroplating wastewater and simultaneously recovering Ni resource, but has been restricted by the needs for costly membranes or consumption of large amount of chemicals in the existing upcycling processes. Herein, a biological upcycling route for synchronous recovery of Ni and sulfate as electrocatalysts, with certain amount of ferric salt (Fe3+) added to tune the product composition, is proposed. Efficient biosynthesis of bio-NiFeS nanoparticles from electroplating wastewater was achieved by harnessing the sulfate reduction and metal detoxification ability of Desulfovibrio vulgaris. The optimal bio-NiFeS, after further annealing at 300 °C, served as an efficient oxygen evolution electrocatalyst, achieving a current density of 10 mA·cm-1 at an overpotential of 247 mV and a Tafel slope of 60.2 mV·dec-1. It exhibited comparable electrocatalytic activity with the chemically-synthesized counterparts and outperformed the commercial RuO2. The feasibility of the biological upcycling approach for treating real Ni-containing electroplating wastewater was also demonstrated, achieving 99.5 % Ni2+removal and 41.0 % SO42- removal and enabling low-cost fabrication of electrocatalyst. Our work paves a new path for sustainable treatment of Ni-containing wastewater and may inspire technology innovations in recycling/ removal of various metal ions.
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Níquel , Aguas Residuales , Níquel/química , Galvanoplastia , Sulfatos , Compuestos Férricos/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mushrooms in the genus Hericium are used as functional food and traditional medicines for a long history in East Asian countries such as China, India, Japan, and Korea. Some species of Hericium are called as monkey head mushroom (Houtougu) in China and Yamabushitake in Japan, which are traditionally considered as rare and precious health promoting food and medicinal materials for the treatment of dyspepsia, insomnia, chronic gastritis, and digestive tract tumors. THE AIM OF THE REVIEW: This review aims to summarize the ethnopharmacology and structural diversity of secondary metabolites from Hericium species, as well as the pharmacological activities of the crude extracts and pure compounds from Hericium species in recent years. MATERIALS AND METHODS: All the information was gathered by searching Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar databases and other published materials (books and Ph.D. and M. Sc. Dissertations) using the keywords "Hericium", "Traditional uses", "Chemical composition", "Quality control" and "Pharmacological activity" (1971-May 2023). The species name was checked with https://www.mycobank.org/. RESULTS: The traditional uses of Hericium species were summarized, and 230 secondary metabolites from Hericium species were summarized and classified into six classes, mainly focusing on their chemical diversity, biosynthesis, biological activities. The modern pharmacological experiments in vivo or in vitro on their crude and fractionated extracts showed that the chemical components from Hericium species have a broad range of bioactivities, including neuroprotective, antimicrobial, anticancer, α-glucosidase inhibitory, antioxidant, and anti-inflammatory activities. CONCLUSIONS: The secondary metabolites discovered from Hericium species are highly structurally diverse, and they have the potential to be rich resources of bioactive fungal natural products. Moreover, the unveiled bioactivities of their crude extracts and pure compounds are closely related to critical human health concerns, and in-depth studies on the potential lead compounds, mechanism of pharmacological effects and pharmaceutical properties are clearly warranted.
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Hericium , Fitoterapia , Humanos , Etnofarmacología , Medicina Tradicional , Extractos Vegetales/uso terapéutico , Fitoquímicos/uso terapéuticoRESUMEN
Sulfamethoxazole (SMX) is a widely used antibiotic to treat bacterial infections prevalent among humans and animals. SMX undergoes several transformation pathways in living organisms and external environments. Therefore, the development of efficient remediation methods for treating SMX and its metabolites is needed. We fabricated a photo-Fenton catalyst using an UIO-66 (Zr) metal-organic framework (MOF) dispersed in diatomite by a single-step solvothermal method for hydroxylation (HO-UIO-66). The HO-UIO-66-0/DE-assisted Fenton-like process degraded SMX with 94.7% efficiency; however, HO-UIO-66 (Zr) is not stable. We improved the stability of the catalyst by introducing a calcination step. The calcination temperature is critical to improving the catalytic efficiency of the composite (for example, designated as HO-UIO-66/DE-300 to denote hydroxylated UIO-66 dispersed in diatomite calcined at 300 °C). The degradation of SMX by HO-UIO-66/DE-300 was 93.8% in 120 min with 4 mmol/L H2O2 at pH 3 under visible light radiation. The O1s XPS signatures signify the stability of the catalyst after repeated use for SMX degradation. The electron spin resonance spectral data suggest the role of h+, â¢OH, â¢O2-, and 1O2 in SMX degradation routes. The HO-UIO-66/DE-300-assisted Fenton-like process shows potential in degrading pharmaceutical products present in water and wastewater.
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While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero. Six-week-old female C57BL/6 mice were divided into two groups: with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24 h access to wheels for 10 weeks prior to conception until late pregnancy (18.5 days post coitum). Sex-stratified placentas and fetal livers were collected. Microarray analysis of SED and EX placentas revealed that EX affected gene transcript expression of 283 and 661 transcripts in male and female placentas, respectively (±1.4-fold, p < 0.05). Gene Set Enrichment and Ingenuity Pathway Analyses of male placentas showed that EX led to inhibition of signaling pathways, biological functions, and down-regulation of transcripts related to lipid and steroid metabolism, while EX in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that the effects of maternal EX on the placenta and presumably on the offspring are sexually dimorphic.
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Ejercicio Físico , Madres , Placenta , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Placenta/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To verify whether miR-150-5p modulates the development of renal fibrosis and its mechanism. METHODS: Transforming growth factor (TGF)-ß1 was implemented on HK-2 cells to construct a renal fibrosis in vitro model. Inhibition of autophagy was performed on HK-2 cells by treating with 3-methyladenine (3-MA, an inhibitor of autophagy). HK-2 cells experienced transfection by miR-150-5p mimics/inhibitor and pcDNA-ß-catenin plasmids, and the negative controls. Dual luciferase reporter gene assay was applied to validate the relationship between miR-150-5p and ß-catenin. Cell apoptosis exploration was implemented by flow cytometry assay. The level detection of CoII, α-SMA, miR-150-5p and ß-catenin was executed by real-time quantitative reverse transcription-polymerase chain reaction. The expression of CoII, α-SMA, LC3I, LC3II, Bax, Cleaved Caspase 3, Beclin 1, Bcl-2 and ß-catenin proteins was monitored by western blot. RESULTS: Autophagy was inhibited in TGF-ß1-induced HK-2 cells. MiR-150-5p alleviated fibrosis, enhanced autophagy, and inhibited apoptosis in TGF-ß1-induced HK-2 cells. ß-catenin was a target of miR-150-5p. Autophagy inhibition or ß-catenin partially counteracted miR-150-5p effect on TGF-ß1-induced fibrosis in HK-2 cells. CONCLUSIONS: MiR-150-5p alleviates renal tubular epithelial cell fibrosis by activating autophagy via ß-catenin signaling.
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Enfermedades Renales , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , beta Catenina/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Fibrosis , Enfermedades Renales/metabolismo , Células Epiteliales/metabolismo , Autofagia/genéticaRESUMEN
BACKGROUND: The progression of colorectal cancer (CRC) has been linked to metabolism alteration. Because insulin resistance (IR) is the basic mechanism of metabolism alteration, IR related indicators are considered to be associated with prognostic of CRC. In this study, we compared the prognostic values of common IR related indicators for CRC and selected the best one. Moreover, we explored the association between that indicator and CRC prognosis and possible interactive covariates. METHODS: Medical records of patients with CRC (n = 1765) were retrieved from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. We compared the prognostic values of IR related indicators and select the best one using concordance index (C-index) and area under curve (AUC). Using Cox proportional hazard regression models, we evaluated the association between that indicator and CRC prognosis. Interaction tests were performed to evaluate possible interactions among covariates and the IR related indicator. RESULTS: Results of C-index and AUC indicated that the ratio of low-density lipoprotein-to-high-density lipoprotein (LHR) showed the highest ability to predict the prognosis of patients with CRC. LHR independently predicted CRC prognosis [hazard ratio (HR) = 1.14; 95 % confidence interval (CI) = 1.05-1.22; P = 0.001]. The interactions between LHR, and age (<65 vs. ≥65; P for interaction = 0.001) or neutrocyte-to-lymphocyte ratio (NLR) (<3 vs. ≥3; P for interaction = 0.055) were also observed. CONCLUSION: LHR was found to be the best IR related indicators to predict prognosis of CRC, and it was negatively correlated with the prognosis of patients with CRC. NLR and aging might interact with LHR.
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Neoplasias Colorrectales , Resistencia a la Insulina , Humanos , Pronóstico , Modelos de Riesgos Proporcionales , Linfocitos/metabolismo , Neoplasias Colorrectales/complicacionesRESUMEN
The prothoracicotropic hormone (Ptth) is well-known for its important role in controlling insect developmental timing and body size by promoting the biosynthesis and release of ecdysone. However, the role of Ptth in adult physiology is largely unexplored. Here we show that Ptth null mutants (both males and females) show extended lifespan and healthspan, and exhibit increased resistance to oxidative stress. Transcriptomic analysis reveals that age-dependent upregulation of innate immunity pathway is attenuated by Ptth mutants. Intriguingly, we find that Ptth regulates the innate immunity pathway, specifically in fly oenocytes, the homology of mammalian hepatocytes. We further show that oenocyte-specific overexpression of Relish shortens the lifespan, while oenocyte-specific downregulation of ecdysone signaling extends lifespan. Consistently, knocking down torso, the receptor of Ptth in the prothoracic gland also promotes longevity of the flies. Thus, our data reveal a novel function of the insect hormone Ptth in longevity regulation and innate immunity in adult Drosophila.
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Exploring the vegetation carbon cycle and the factors influencing vegetation carbon sequestration in areas with complex plateau-basin topography and fragile ecosystems is crucial. In this study, spatial and temporal characteristics of carbon sequestration by vegetation in Sichuan and Chongqing from 2010 to 2020 and the influencing factors were investigated through simulations of net primary productivity (NPP) using the modified Carnegie-Ames-Stanford approach (CASA) and the Thornthwaite Memorial (TM) model and using chemical equations of photochemical reactions. The results indicated that: The spatial distribution of carbon sequestration capacity (CSC) trends showed an increase in the east (the most prominent increased trend along the mountainous areas of the basin) and a decrease in the west (western Sichuan plateau). Differences exist in the impact factors of CSC in different regions. In the basin margins and mountainous areas, where the proportion of forests was high, a combination of climate change and human activities contributed to the increase in CSC. The relatively warm and humid meteorological conditions in the hinterland of the basin were more conducive to the increase in CSC, and climate change also affected the region more significantly. In contrast, in the relatively high altitude of western Sichuan, controlled human activities were the key to improving CSC. The results of the study contribute to the understanding of the basic theory of vegetation carbon cycle in areas with complex plateau-basin topography and fragile ecosystems, as well as to provide suggestions for ecological shelter construction and ecological restoration in the upper Yangtze River.
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Secuestro de Carbono , Ecosistema , Humanos , Cambio Climático , Bosques , Actividades Humanas , China , CarbonoRESUMEN
BACKGROUND: Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. METHODS: A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa. The Student's t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. RESULTS: ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients' prognosis (HR = 0.60, 95% CI 0.40-0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. CONCLUSION: Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.