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BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. OBJECTIVE: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes. METHODS: Chondrocytes were treated with interleukin (IL)-1ß to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay. RESULTS: CircTRIM25 was upregulated in OA tissues and IL-1ß-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1ß-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo. CONCLUSION: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.
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Condrocitos , Condrogénesis , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , MicroARNs , Osteoartritis , ARN Circular , Animales , Femenino , Humanos , Masculino , Ratones , Condrocitos/metabolismo , Condrocitos/patología , Condrogénesis/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Regulación de la Expresión Génica , Silenciador del Gen , Interleucina-1beta/metabolismo , MicroARNs/genética , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , ARN Circular/genética , Transducción de Señal , Persona de Mediana Edad , AncianoRESUMEN
Indoor UV damage is a serious problem that is often ignored. Common glasses cannot filter UV rays well and have fragility and environmental issues. UV-shielding transparent wood (TW) holds promise, yet striking the right balance between blocking UV rays and allowing sufficient visible-light transmission poses a challenge. The pronounced capillary force, fueled by persistent moisture and extractives in wood, alongside the existence of multiphase interfaces, collectively hinder the uniform penetration of polymers and the effective dispersion of nanomaterials within the wood skeleton. Here, we incorporate high-pressure supercritical CO2 fluid-assisted impregnation (HSCFI) into fabricating UV-shielding TW. The supercritical CO2 pretreatment efficiently eliminates moisture and refines wood structure by extracting polar substances, resulting in a prominent 52.4% increase in average water permeability. Subsequently, this HSCFI method facilitates the infiltration of methyl methacrylate (MMA) monomer and Ce-ZnO nanorods (NRDs) into the refined anhydrous wood, leveraging the excellent solvency of supercritical CO2 for MMA. The impregnation rate of PMMA undergoes a substantial increase from 34.5 to 59.1%. With the robust UV-blocking capability of Ce-ZnO NRDs, thanks to dual-valence Ce doping widening the ZnO energy gap via the Burstein-Moss effect and their unique photoactive microstructure featuring a solid prism with a sharp hexahedral pyramidal tip, along with intrinsic physical scattering/reflection actions, Ce-ZnO NRDs@TW achieves an impressive 99.6% UVA radiation blockage (the highest for TW) and maintains high visible-light transmission (83.2%). Furthermore, Ce-ZnO NRDs@TW presents favorable energy-saving, sound absorption, and antifungal abilities, making it a promising candidate for future green buildings.
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Rice (Oryza sativa L.) feeds more than half of the global population and faces the critical issues related to food security and environmental sustainability. This study analyzed double rice production data from 2010 to 2020 to assess its spatiotemporal dynamic in food production and carbon (C) footprint in Hainan province, China. The results revealed a 29.5% reduction in rice planting area, leading to a significantly decreased rice self-sufficiency rate from 38% to 33% from 2010 to 2020. During this period, the carbon footprint per unit area (CFa) for early, late, and double rice showed a fluctuating upward trend ranging from 8.1 to 8.4, 8.9 to 9.2, and 17.0 to 17.4 t CO2-eq ha-1, respectively. The total greenhouse gas (GHG) emissions of rice production decreased to around 2 million t CO2-eq, primarily due to reduced planting area. The C sequestration initially increased before decreasing to 1.2 million t C in 2020 at a temporal scale. Spatially, the northeast and southwest regions exhibited â¼70% of the total GHG emissions and â¼80% of C sequestration. The regional C footprint per unit yield displayed less favorable outcomes, with some areas (e.g., Wenchang and Haikou) experiencing emission hotspots in recent years. Higher yield and smaller CFa for Lingao and Tunchang were observed compared to the average between 2010 and 2020. This study provides insights into the spatiotemporal dynamics of double rice production and GHG emissions in Hainan, offering a scientific reference for regional food security and environmental sustainability.
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Agricultura , Huella de Carbono , Seguridad Alimentaria , Oryza , China , Agricultura/métodos , Gases de Efecto Invernadero/análisis , Conservación de los Recursos Naturales/métodos , Monitoreo del AmbienteRESUMEN
Introduction: The composition and structure of natural soil are very complex, leading to the difficult contact between hydrophobic organic compounds and degrading-bacteria in contaminated soil, making pollutants hard to be removed from the soil. Several researches have reported the bacterial migration in unsaturated soil mediated by fungal hyphae, but bacterial movement in soil of different particle sizes or in heterogeneous soil was unclear. The remediation of contaminated soil enhanced by hyphae still needs further research. Methods: In this case, the migration and biodegradation of Diaphorobacter sp. LW2 in soil was investigated in presence of Pythium ultimum. Results: Hyphae could promote the growth and migration of LW2 in culture medium. It was also confirmed that LW2 was able to migrate in the growth direction and against the growth direction along hyphae. Mediated by hyphae, motile strain LW2 translocated over 3 cm in soil with different particle size (CS1, 1.0-2.0 mm; CS2, 0.5-1.0mm; MS, 0.25-0.5 mm and FS, <0.25 mm), and it need shorter time in bigger particle soils. In inhomogeneous soil, hyphae participated in the distribution of introduced bacteria, and the total number of bacteria increased. Pythium ultimum enhanced the migration and survival of LW2 in soil, improving the bioremediation of polluted soil. Discussion: The results of this study indicate that the mobilization of degrading bacteria mediated by Pythium ultimum in soil has great potential for application in bioremediation of contaminated soil.
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BACKGROUND: Cardiac arrest (CA) induced by electric shock is a rare occurrence, particularly in cases of prolonged CA. Currently, there is limited literature on similar incidents, and we present a relevant case report. CASE SUMMARY: A 27-year-old Asian male man, experiencing respiratory CA due to electric shock, was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions. In the subsequent stages, the patient received multiple organ function protection measures, leading to a successful recovery and eventual discharge from the hospital. CONCLUSION: Prolonging resuscitation time can enhance the chances of survival for patients, this study provide valuable insights into the management of electric shock-induced CA.
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Osteoarthritis (OA) is a disease of the joints, characterized by chronic inflammation, cartilage destruction and extracellular matrix (ECM) remodeling. Aberrant chondrocyte hypertrophy promotes cartilage destruction and OA development. Collagen X, the biomarker of chondrocyte hypertrophy, is upregulated by runt-related transcription factor 2 (Runx2), which is mediated by the bone morphogenetic protein 4 (BMP4)/Smad1 signaling pathway. BMP binding endothelial regulator (BMPER), a secreted glycoprotein, acts as an agonist of BMP4. 5,7,3',4'-tetramethoxyflavone (TMF) is a natural flavonoid derived from Murraya exotica L. Results of our previous study demonstrated that TMF exhibits chondroprotective effects against OA development through the activation of Forkhead box protein O3a (FOXO3a) expression. However, whether TMF suppresses chondrocyte hypertrophy through activation of FOXO3a expression and inhibition of BMPER/BMP4/Smad1 signaling remains unknown. Results of the present study revealed that TMF inhibited collagen X and Runx2 expression, inhibited BMPER/BMP4/Smad1 signaling, and activated FOXO3a expression; thus, protecting against chondrocyte hypertrophy and OA development. However, BMPER overexpression and FOXO3a knockdown impacted the protective effects of TMF. Thus, TMF inhibited chondrocyte hypertrophy in OA cartilage through mediating the FOXO3a/BMPER signaling pathway.
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Dyes contaminating the sewages have seriously threatened the living beings and their separation from wastewater in terms of potential resource recovery is of high value. Herein, both of metal node doping and ligand group grafting were taken into account to enhance the adsorption selectivity of Fe-MOFs towards cationic dyes. The positive correlation between copper doping amount and selective coefficient (∂MOMB) for methylene blue (MB) over methyl orange (MO) within a certain range was mainly attributed to the increased surface negative charges via partial replacement of Fe(III) with Cu(II). Moreover, the amount of surface negative charges was further increased after amino functionalization and there was a synergism between Cu(II) and -NH2 in selectivity enhancement. As a result, Fe0.6Cu0.4-BDC-NH2 exhibited a 22.5-times increase in ∂MOMB and other cationic dyes including malachite green (MG) and rhodamine B (Rh. B) could also be selectively separated from binary and quaternary mixed dye systems. Moreover, Fe0.6Cu0.4-BDC-NH2 showed many superiorities like a wide pH range of 4.0-8.0, strong anti-interference ability over various inorganic ions, good recyclability, and stability. The adsorption kinetics and isotherm suggested that the MB adsorption process was a homogeneous single-layer chemisorption. Additionally, the thermodynamics manifested that the overall process was exothermic and spontaneous. According to the FT-IR and XPS spectra analysis, the electrostatic interaction and hydrogen bonding were determined as the main driving forces, and π-π interaction also contributed to the adsorption process.
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BACKGROUNDS: The role of O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) has been reported in multiple human diseases. However, its specific functions in osteoarthritis (OA) progression remain undetermined. OBJECTIVE: This study focused on the target proteins of OGT-induced O-GlcNAcylation in OA and the specific functional mechanism. METHODS: The levels of total O-GlcNAc and OGT were measured in both in vitro and in vivo OA models using western blot. The effects of OGT knockout on OA progression were detected through Safranin O staining, immunohistochemical staining and OARSI score evaluation. The effects of OGT silencing on LPS-induced chondrocyte injury were assessed by performing loss-of function assays. Co-immunoprecipitation (co-IP) was conducted to verify the effect of OGT-induced O-GlcNAcylation on the interaction between NEK7 and NLRP3. The role of OGT in modulating the O-GlcNAcylation and phosphorylation levels of NEK7 was analysed using western blot. RESULTS: The OGT-indued O-GlcNAcylation level was increased in both in vitro and in vivo OA models. Knockout of OGT mitigated OA progression in model mice. Additionally, silencing of OGT suppressed LPS-induced chondrocyte pyroptosis. Moreover, silencing of OGT inhibited the O-GlcNAcylation and enhanced the phosphorylation of NEK7 at S260 site, thereby blocking the binding of NEK7 with NLRP3. CONCLUSION: OGT-induced NEK7 O-GlcNAcylation promotes OA progression by promoting chondrocyte pyroptosis via the suppressing interaction between NEK7 and NLRP3.
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N-Acetilglucosaminiltransferasas , Proteína con Dominio Pirina 3 de la Familia NLR , Osteoartritis , Humanos , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Lipopolisacáridos , Ratones Noqueados , Quinasas Relacionadas con NIMA/genéticaRESUMEN
Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/fisiología , Infecciones por Pseudomonas/microbiología , Inmunidad Innata , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , Interacciones Huésped-Patógeno , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Legume-based cropping increased the diversity of residues and rhizodeposition input into the soil, thus affecting soil organic matter (SOM) stabilization. Despite this, a comprehensive understanding of the mechanisms governing SOM mineralization and its temperature sensitivity across bulk soil and aggregate scales concerning legume inclusion remains incomplete. Here, a 6-year field experiment was conducted to investigate the effects of three cropping systems (i.e., winter wheat/summer maize, winter wheat/summer maize-soybean, and nature fallow) on SOM mineralization, its temperature sensitivity, and the main drivers in both topsoil (0-20 cm) and subsoil (20-40 cm). Soybean inclusion decreased the SOM mineralization by 17%-24%, while concurrently increasing the majority of soil biochemical properties, such as carbon (C) acquisition enzyme activities (5%-22%) and microbial biomass C (5%-9%), within the topsoil regardless of temperature. This is attributed to the increased substrate availability (e.g., dissolved organic C) facilitating microbial utilization, thus devoting less energy to mining nutrients under diversified cropping. In addition, SOM mineralization was lower within macroaggregates (â¼12%), largely driven by substrate availability irrespective of aggregate sizes. In contrast, diversified cropping amplified the Q10 of SOM mineralization in mesoaggregates (+6%) and microaggregates (+5%) rather than in macroaggregates. This underscores the pivotal role of mesoaggregates and microaggregates in dominating the Q10 of SOM mineralization under soybean-based cropping. In conclusion, legume-based cropping diminishes soil organic matter mineralization despite increasing its temperature sensitivity, which proposes a potential strategy for C-neutral agriculture and climate warming mitigation.
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Fabaceae , Suelo , Suelo/química , Glycine max , Temperatura , Agricultura , Verduras , Carbono , Microbiología del SueloRESUMEN
Silica glass, known for its brittleness, weight, and non-biodegradable nature, faces challenges in finding suitable alternatives. Transparent wood, made by infusing polymers into wood, shows promise but is hindered by limited availability of wood in China and fire risks associated with its use. This study explores the potential of utilizing bamboo, which has a shorter growth cycle, as a valuable resource for developing flame-retardant, smoke-suppressing, and superhydrophobic transparent bamboo. A 3-layered flame-retardant barrier, composed of a top silane layer, an intermediate layer of SiO2 formed through hydrolysis-condensation of Na2SiO3 on the surface, and an inner layer of Na2SiO3, has been confirmed to be effective in reducing heat release, slowing flame spread, and inhibiting the release of combustible volatiles, toxic smoke, and CO. Compared to natural bamboo and other congeneric transparent products, the transparent bamboo displays remarkable superiority, with the majority of parameters being notably lower by an entire order of magnitude. It achieves a long ignition time of 116 s, low total heat release (0.7 MJ/m2), low total smoke production (0.063 m2), and low peak CO concentration (0.008 kg/kg). Moreover, when used as a substrate for perovskite solar cells, the transparent bamboo displays the potential to act as a light management layer, leading to a marked efficiency enhancement of 15.29%. The excellent features of transparent bamboo make it an enticing choice for future advancements in flame-retardant glasses and optical devices.
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Objective: To explore and construct a 3D bone remodeling research model displaying stability, repeatability, and precise simulation of the physiological and biochemical environment in vivo. Methods: In this study, 3D bioprinting was used to construct a bone reconstruction model. Sodium alginate (SA), hydroxyapatite (HA) and gelatin (Gel) were mixed into hydrogel as scaffold material. The osteoblast precursor cells MC3T3-E1 and osteoclast precursor cells RAW264.7 were used as seed cells, which may or may not be separated by polycarbonate membrane. The cytokines osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were used to induce cell differentiation. The function of scaffolds in the process of bone remodeling was analyzed by detecting the related markers of osteoblasts (alkaline phosphatase, ALP) and osteoclasts (tartrate resistant acid phosphatase, TRAP). Results: The scaffold showed good biocompatibility and low toxicity. The surface morphology aided cell adhesion and growth. The scaffold had optimum degradability, water absorption capacity and porosity, which are in line with the conditions of biological experiments. The effect of induced differentiation of cells was the best when cultured alone. After direct contact between the two types of cells at 2D or 3D level, the induced differentiation of cells was inhibited to varying degrees, although they still showed osteogenesis and osteoclast. After the cells were induced by indirect contact culture, the effect of induced differentiation improved when compared with direct contact culture, although it was still not as good as that of single culture. On the whole, the effect of inducing differentiation at 3D level was the same as that at 2D level, and its relative gene expression and enzyme activity were higher than that in the control group. Hence the scaffold used in this study could induce osteogenesis as well as osteoclast, thereby rendering it more effective in inducing new bone formation. Conclusion: This method can be used to construct the model of 3D bone remodeling mechanism.
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Continuous monocropping can lead to soil sickness and increase of soil-borne disease, which finally reduces crop yield. Microorganisms benefit plants by increasing nutrient availability, participating in auxin synthesis, and defending against pathogens. However, little is known about the influence of short-term successive peanuts cropping on soil properties, enzyme activities, its yield, plant-associated microbes, and their potential correlations in peanut production. Here, we examined the community structure, composition, network structure and function of microbes in the rhizosphere and bulk soils under different monocropping years. Moreover, we assessed the impact of changes in the soil micro-environment and associated soil microbes on peanut yield. Our results showed that increase of monocropping year significantly decreased most soil properties, enzyme activities and peanut yield (p < 0.05). Principal co-ordinates analysis (PCoA) and analysis of similarities (ANOSIM) indicated that monocropping year significantly influenced the fungal community structure in the rhizosphere and bulk soils (p < 0.01), while had no effect on the bacterial community. With the increase of continuous monocropping year, peanut selectively decreased (e.g., Candidatus_Entotheonella, Bacillus and Bryobacter) or increased (e.g., Nitrospira, Nocardioides, Ensifer, Gaiella, and Novosphingobium) the abundance of some beneficial bacterial genera in the rhizosphere. Continuous monocropping significantly increased the abundance of plant pathogens (e.g., Plectosphaerella, Colletotrichum, Lectera, Gibberella, Metarhizium, and Microdochium) in the rhizosphere and negatively affected the balance of fungal community. Besides, these species were correlated negatively with L-leucine aminopeptidase (LAP) activity. Network co-occurrence analysis showed that continuous monocropping simplified the interaction network of bacteria and fungi. Random forest and partial least squares path modeling (PLS-PM) analysis further showed that fungal community, pathogen abundance, soil pH, and LAP activity negatively affected peanut yield. In conclusion, short-term continuous monocropping decreased LAP activity and increased potential fungal pathogens abundance, leading to reduction of peanut yield.
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Micobioma , Suelo , Suelo/química , Arachis/microbiología , Microbiología del Suelo , BacteriasRESUMEN
China has implemented policies like Leading areas for Agricultural Green Development (LAGD) to mitigate livestock and poultry farming pollution while promoting industry growth. However, it remains uncertain whether LAGDs have successfully balanced emission reduction with stable development. This study examines 165 LAGDs to analyze changes in emissions, assess the decoupling of emission reduction from output value, and identify influencing factors. Findings reveal that emissions from livestock and poultry in LAGDs initially increased and then decreased between 2010 and 2019. Cattle were responsible for over 40% of fecal emissions, and pigs for more than 20%. Additionally, pigs contributed to over 61% of urine emissions. From 2010 to 2014, increases in chemical oxygen demand were mainly due to pigs and cattle. Total nitrogen levels were significantly impacted by cattle, while pigs were affected by total phosphorus. From 2014 to 2019, reductions in emissions were largely attributed to a decrease in pig-related pollutants. The decoupling status shifted from strong to weak and then back to strong between 2014 and 2019. Production efficiency played a crucial role in reducing emissions, while changes in industrial structure moved from supporting to hindering this reduction. Economic development was a primary factor in driving these changes. Standard emissions in Chinese regions showed a rising and then declining trend from 2010 to 2019. The Northeast and Northwest regions of China demonstrated emission trends that were in sync with the growth in rural income. This study offers insights into the successes and challenges of LAGDs in achieving a balance between reduced emissions and development, using quantitative analysis. The findings are instrumental in informing policies for a sustainable livestock and poultry industry. Recommendations include evaluating coordinated approaches to pollution reduction and industrial growth, setting decoupling goals, designing policies based on influential factors, conducting regional assessments of livestock and poultry demand, and implementing region-specific strategies.
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Ganado , Aves de Corral , Animales , Bovinos , Agricultura , China , Análisis de la Demanda Biológica de Oxígeno , Desarrollo Económico , Dióxido de CarbonoRESUMEN
OBJECTIVE: To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. METHODS: A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. RESULTS: A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). CONCLUSIONS: The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
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Puntuaciones en la Disfunción de Órganos , Sepsis , Humanos , Estudios Retrospectivos , Proteína C-Reactiva , Curva ROC , Sepsis/metabolismo , Pronóstico , Anticoagulantes , Antitrombina III , Unidades de Cuidados IntensivosRESUMEN
Signal transducer and activator of transcription 3 (STAT3) is an attractive target for cancer therapy. However, identifying potent and selective STAT3 small-molecule inhibitors with drug-like properties remains challenging. Based on a scaffold combination strategy, compounds with a novel N-(benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine scaffold were designed and their inhibition of the interleukin-6 (IL-6)/JAK/STAT3 pathway was tested in HEK-Blue IL-6 reporter cells. After optimization of lead compound 12, compound 40 was identified as a selective STAT3 inhibitor that directly binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. Compound 40 exhibited antiproliferative activities against STAT3-overactivated DU145 (IC50 value = 2.97 µM) and MDA-MB-231 (IC50 value = 3.26 µM) cancer cells and induced cell cycle arrest and apoptosis. In the DU145 xenograft model, compound 40 showed in vivo antitumor efficacy following intraperitoneal administration, with a tumor growth inhibition rate of 65.3% at 50 mg/kg, indicating promise for further development.
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Neoplasias , Factor de Transcripción STAT3 , Humanos , Aminas , Interleucina-6 , Dominios Homologos src , ApoptosisRESUMEN
Prunella vulgaris L. (P. vulgaris) has long been considered to have antipyretic, analgesic and anti-inflammatory effects, lowering blood lipids and pressure. Many studies show that in addition to the traditional telomere attrition, DNA damage and epigenetic changes, immunosenescence is also a new possibility to explore the mechanism of ageing. Therefore, this herb may have potential anti-ageing effects. Typically, there are a series of markers that identify senescent cells, such as superoxide dismutase (SOD)2, an inhibitor of CDK4 (p16INK4A), tumor necrosis factor (TNF)-α, immune cells number, proliferation, and nuclear abnormalities. These changes rarely present in young tissues, while greatly increasing in response to ageing. Firstly, the ageing model of the Institute of Cancer Research (ICR) mouse was established by D-galactose subcutaneous injection. Then, SOD2, p16INK4A and TNF-α were detected by quantitative Real-time PCR (qPCR), Western Blot (WB) and Enzyme-Linked Immunosorbent Assay (ELISA). Simultaneously, senescent cells in livers were stained by hematoxylin and eosin (HE). The viability of splenocytes was detected by Cell Counting Kit-8(CCK-8). The difference in specific immune cells (NK cells, B lymphocytes and T lymphocytes) was detected by flow cytometry. Both low (100 mg/kg) and high (300 mg/kg) concentrations of P. vulgaris treated ageing ICR mice show anti-ageing alterations, such as p16INK4A decreased approximately 1/2 and SOD2 tripled in livers, TNF-α decreased from 1 to 0.6 in plasma, and T cells increased from 0.09 to 0.19%. Compared with the ageing group, the spleen cells in the Prunella-treated group had stronger proliferation ability. Thus, P. vulgaris could have an anti-ageing effect. This is the first study to demonstrate the anti-ageing effect of P. vulgaris. It may also be capable of preventing a variety of age-related diseases.
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Prunella , Ratones , Animales , Factor de Necrosis Tumoral alfa , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Extractos Vegetales/farmacología , EnvejecimientoRESUMEN
BACKGROUND: In large-scale high-throughput sequencing projects and biobank construction, sample tagging is essential to prevent sample mix-ups. Despite the availability of fingerprint panels for DNA data, little research has been conducted on sample tagging of whole genome bisulfite sequencing (WGBS) data. This study aims to construct a pipeline and identify applicable fingerprint panels to address this problem. RESULTS: Using autosome-wide A/T polymorphic single nucleotide variants (SNVs) obtained from whole genome sequencing (WGS) and WGBS of individuals from the Third China National Stroke Registry, we designed a fingerprint panel and constructed an optimized pipeline for tagging WGBS data. This pipeline used Bis-SNP to call genotypes from the WGBS data, and optimized genotype comparison by eliminating wildtype homozygous and missing genotypes, and retaining variants with identical genomic coordinates and reference/alternative alleles. WGS-based and WGBS-based genotypes called from identical or different samples were extensively compared using hap.py. In the first batch of 94 samples, the genotype consistency rates were between 71.01%-84.23% and 51.43%-60.50% for the matched and mismatched WGS and WGBS data using the autosome-wide A/T polymorphic SNV panel. This capability to tag WGBS data was validated among the second batch of 240 samples, with genotype consistency rates ranging from 70.61%-84.65% to 49.58%-61.42% for the matched and mismatched data, respectively. We also determined that the number of genetic variants required to correctly tag WGBS data was on the order of thousands through testing six fingerprint panels with different orders for the number of variants. Additionally, we affirmed this result with two self-designed panels of 1351 and 1278 SNVs, respectively. Furthermore, this study confirmed that using the number of genetic variants with identical coordinates and ref/alt alleles, or identical genotypes could not correctly tag WGBS data. CONCLUSION: This study proposed an optimized pipeline, applicable fingerprint panels, and a lower boundary for the number of fingerprint genetic variants needed for correct sample tagging of WGBS data, which are valuable for tagging WGBS data and integrating multi-omics data for biobanks.
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Genoma , Sulfitos , Humanos , Secuenciación Completa del Genoma , Genotipo , Metilación de ADN , ADN , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The introduction of legumes into rotations can improve nitrogen use efficiency and crop yield; however, its microbial mechanism involved remains unclear. This study aimed to explore the temporal impact of peanut introduction on microorganisms related to nitrogen metabolism in rotation systems. In this study, the dynamics of diazotrophic communities in two crop seasons and wheat yields of two rotation systems: winter wheat - summer maize (WM) and spring peanut â winter wheat - summer maize (PWM) in the North China Plain were investigated. Our results showed that peanut introduction increased wheat yield and biomass by 11.6% (p < 0.05) and 8.9%, respectively. Lower Chao1 and Shannon indexes of the diazotrophic communities were detected in soils that sampling in June compared with those sampling in September, although no difference was found between WM and PWM. Principal co-ordinates analysis (PCoA) showed that rotation system significantly changed the diazotrophic community structures (PERMANOVA; p < 0.05). Compared with WM, the genera of Azotobacter, Skermanella, Azohydromonas, Rhodomicrobium, Azospirillum, Unclassified_f_Opitutaceae, and Unclassified_f_Rhodospirillaceae were significantly enriched (p < 0.05) in PWM. Furthermore, rotation system and sampling time significantly influenced soil properties, which significantly correlated with the top 15 genera in relative abundance. Partial least squares path modeling (PLS-PM) analysis further showed that the diazotrophic community diversity (alpha- and beta-diversity) and soil properties (pH, SOC and TN) significantly affected wheat yield. In conclusion, legume inclusion has the potential to stabilize diazotrophic community structure at the temporal scales and increase subsequent crop yield.