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Introduction: Osteosarcoma is a bone-derived malignancy that often leads to lung metastasis and death. Material and methods: The RNA-seq data of TARGET-osteosarcoma were collected from TARGET database. GSE16088 and GSE12865 datasets of osteosarcoma x from Gene Expression Database (GEO) were donwloaded. ConsensusClusterPlus was used for molecular subtype classification. Univariate Cox and Lasso regression was employed to develop a risk model. To analyze the regulatory effects of model feature genes on the malignant phenotype of osteosarcoma cell lines, qRT-PCR, Transwell and wound healing assays were performed. The abundance of immune cell infiltration was assessed using MCP-Counter, Gene Set Enrichment Analysis (GSEA), and ESTIMATE. The Tumor Immune Dysfunction and Exclusion (TIDE) software was employed to evaluate immunotherapy and response to conventional chemotherapy drugs. Results: Three clusters (C1, C2 and C3) were classified using 39 necroptosis score-associated genes. In general, C1 and C2 showed better prognosis outcome and lower death rate than C3. Specifically, C2 could benefit more from immunotherapy, while C3 was more sensitive to traditional medicines, and C1 had higher immune cell infiltration. Next, an 8-gene signature and a risk score model were developed, with a low risk score indicating better survival and immune cell infiltration. ROC analysis showed that 1-, 3-, and 5-year overall survival of osteosarcoma could be correctly predicted by the risk score model. Cellular experiments revealed that the model feature gene IFITM3 promoted the osteosarcoma cell migration and invasion. Furthermore, the overall survival of osteosarcoma patients from TARGET and validation datasets can be accurately evaluated using the nomogram model. Conclusions: Our prognostic model developed using necroptosis genes could facilitate the prognostic prediction for patients suffering from osteosarcoma, offering potential osteosarcoma targets.

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Despite advances in treatment, the prognosis of patients with osteosarcoma remains unsatisfactory, and searching for potential targets is imperative. Here, we identify N4-acetylcytidine (ac4C) acetyltransferase 10 (NAT10) as a candidate therapeutic target in osteosarcoma through functional screening. NAT10 overexpression is correlated with a poor prognosis, and NAT10 knockout inhibits osteosarcoma progression. Mechanistically, NAT10 enhances mRNA stability of activating transcription factor 4 (ATF4) through ac4C modification. ATF4 induces the transcription of asparagine synthetase (ASNS), which catalyzes asparagine (Asn) biosynthesis, facilitating osteosarcoma progression. Utilizing virtual screening, we identify paliperidone and AG-401 as potential NAT10 inhibitors, and both inhibitors are found to bind to NAT10 proteins. Inhibiting NAT10 suppresses osteosarcoma progression in vivo. Combined treatment using paliperidone and AG-401 produces synergistic inhibition for osteosarcoma in patient-derived xenograft (PDX) models. Our findings demonstrate that NAT10 facilitates osteosarcoma progression through the ATF4/ASNS/Asn axis, and pharmacological inhibition of NAT10 may be a feasible therapeutic approach for osteosarcoma.

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Factor de Transcripción Activador 4 , Asparagina , Aspartatoamoníaco Ligasa , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/genética , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Animales , Línea Celular Tumoral , Aspartatoamoníaco Ligasa/metabolismo , Aspartatoamoníaco Ligasa/genética , Aspartatoamoníaco Ligasa/antagonistas & inhibidores , Ratones , Asparagina/metabolismo , Progresión de la Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Masculino , Femenino

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Greenhouse gas (GHG) detection plays an important role in climate change research and industry applications. A novel photoacoustic spectroscopy (PAS) sensor based on multiple resonators has been developed for the detection of GHGs. The major GHGs CO2, CH4, and N2O were measured simultaneously using only one acoustic sensor by coupling three acoustic resonators into a photoacoustic cell. A sinusoidal voltage signal-driven noise source was integrated into a multiresonator photoacoustic cell, allowing convenient calibration of the resonant frequency of the photoacoustic cell. The performance of the sensor was further enhanced by reflecting a laser beam four times in the photoacoustic cell. Allan deviation analysis showed that the minimum detection limits of 2.7 ppm, 90 ppb, and 1 ppb could be achieved for CO2, CH4, and N2O, respectively, over a 300 s integration time. The feasibility of the system was confirmed by continuous measurements of the three major GHGs from different sources for up to 10 h.

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The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.

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Sugarcane smut fungus Sporisorium scitamineum produces polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) to regulate sexual mating/filamentous growth critical for pathogenicity. Besides de novo biosynthesis, intracellular levels of polyamines could also be modulated by oxidation. In this study, we identified two annotated polyamine oxidation enzymes (SsPAO and SsCuAO1) in S. scitamineum. Compared to the wild type (MAT-1), the ss1paoΔ and ss1cuao1Δ mutants were defective in sporidia growth, sexual mating/filamentation, and pathogenicity. The addition of a low concentration of cAMP (0.1 mM) could partially or fully restore filamentation of ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ. cAMP biosynthesis and hydrolysis genes were differentially expressed in the ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ cultures, further supporting that SsPAO- or SsCuAO1-based polyamine homeostasis regulates S. scitamineum filamentation by affecting the cAMP/PKA signalling pathway. During early infection, PUT promotes, while SPD inhibits, the accumulation of reactive oxygen species (ROS) in sugarcane, therefore modulating redox homeostasis at the smut fungus-sugarcane interface. Autophagy induction was found to be enhanced in the ss1paoΔ mutant and reduced in the ss1cuao1Δ mutant. Exogenous addition of cAMP, PUT, SPD, or SPM at low concentration promoted autophagy activity under a non-inductive condition (rich medium), suggesting a cross-talk between polyamines and cAMP signalling in regulating autophagy in S. scitamineum. Overall, our work proves that SsPAO- and SsCuAO1-mediated intracellular polyamines affect intracellular redox balance and thus play a role in growth, sexual mating/filamentation, and pathogenicity of S. scitamineum.

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Oxidación-Reducción , Poliaminas , Poliaminas/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , AMP Cíclico/metabolismo , Saccharum/microbiología , Regulación Fúngica de la Expresión Génica , Ustilaginales/patogenicidad , Autofagia

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Objective To assess the efficacy and safety of three treatment modalities (rituximab targeted B-cell therapy, calcium-phosphate inhibitor in conjunction with low-dose corticosteroids, and full-dose corticosteroids combined with cyclophosphamide) for patients at intermediate or high risk of idiopathic membranous nephropathy (IMN) and to analyze the factors impacting the remission rates of IMN. Methods A retrospective cohort study was conducted to analyze patients diagnosed with IMN in our nephrology department via renal biopsy, identifying a total of 148 patients at intermediate or high risk. These patients were categorized into three treatment groups: a RTX group with 60 patients receiving rituximab, a CNI group with 42 patients receiving calcineurin inhibitors, and a CTX group with 46 patients received cyclophosphamide. Baseline measurements of 24-hour urine protein, serum albumin, blood creatinine, uric acid, estimated glomerular filtration rate (eGFR), and serum anti-phospholipase A2 receptor antibody levels were recorded at the onset of the follow-up. Subsequently, changes in 24-hour urine protein, eGFR, remission rates, and occurrence of adverse events among the three patient groups were compared at 6, 12, and 18 months post-treatment. Moreover, COX regression analysis was employed to ascertain factors influencing the remission rate of IMN. Results At the outset of the follow-up period, no significant difference existed in baseline characteristics such as gender, age, 24-hour urine protein quantification, serum albumin, serum creatinine, uric acid, eGFR, serum anti-PLA2R antibody levels, body mass index (BMI), and systolic blood pressure among the patients, indicating the comparability of three groups. After 6 months, there were no notable changes in 24-hour urine protein quantification and eGFR among the three groups; however, remission rates in the RTX and CTX groups were lower than those in the CNI group. By the 12-month mark, 24-hour urine protein quantification in the RTX group significantly decreased compared to the CTX group, with overall remission rates showing no significant differences among the three groups. By the 18-month milestone, 24-hour urine protein quantification in the RTX group remained notably lower than that in the CTX group, with significantly higher eGFR levels. Additionally, the CTX group exhibited lower 24-hour urine protein quantification compared to the CNI group, with both RTX and CTX groups displaying higher remission rates than the CNI group. Predominant adverse reactions in the RTX group included infusion reactions and infections, whereas the CNI group were associated with metabolic syndrome and elevated serum creatinine, and the CTX group primarily experienced hepatic dysfunction. Multifactorial COX regression analysis revealed an association between baseline anti-PLA2R antibodies and remission rates of IMN (HR=1.162, 95% CI 1.078-1.249). Conclusion RTX therapy for IMN exhibits a gradual onset of action, boasting a superior disease remission rate at 18 months in comparison to CNI. It demonstrates a similarity to CTX in this aspect and offers prolonged maintenance of remission. Conversely, CNI demonstrates a rapid onset of action but poses a risk of exacerbating renal impairment in patients. Notably, elevated levels of serum anti-PLA2R antibodies emerge as an independent risk factor influencing remission in IMN.

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Glomerulonefritis Membranosa , Inmunosupresores , Rituximab , Humanos , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/orina , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Receptores de Fosfolipasa A2/inmunología

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Maintaining bile acid homeostasis is essential for metabolic health. Bile acid homeostasis encompasses a complex interplay between biosynthesis, conjugation, secretion, and reabsorption. Beyond their vital role in digestion and absorption of lipid-soluble nutrients, bile acids are pivotal in systemic metabolic regulation. Recent studies have linked bile acid dysregulation to the pathogenesis of metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). Bile acids are essential signaling molecules that regulate many critical biological processes, including lipid metabolism, energy expenditure, insulin sensitivity, and glucose metabolism. Disruption in bile acid homeostasis contributes to metabolic disease via altered bile acid feedback mechanisms, hormonal dysregulation, interactions with the gut microbiota, and changes in the expression and function of bile acid transporters and receptors. This review summarized the essential molecular pathways and regulatory mechanisms through which bile acid dysregulation contributes to the pathogenesis and progression of obesity, T2DM, and MASLD. We aim to underscore the significance of bile acids as potential diagnostic markers and therapeutic agents in the context of metabolic diseases, providing insights into their application in translational medicine.

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A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment.

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Proliferación Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Largo no Codificante , Receptores Acoplados a Proteínas G , Neoplasias del Cuello Uterino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Animales , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Femenino , Ratones , Proliferación Celular/genética , Progresión de la Enfermedad , Ratones Noqueados , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Movimiento Celular/genética

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Applying chemical enhanced oil recovery (EOR) to shale and tight formations is expected to accelerate China's Shale Revolution as it did in conventional reservoirs. However, its screening and modeling are more complex. EOR operations are faced with choices of chemicals including traditional surfactant solutions, surfactant solutions in the form of micro-emulsions (nano-emulsions), and nano-fluids, which have similar effects to surfactant solutions. This study presents a systematic comparative analysis composed of laboratory screening and numerical modeling. It was conducted on three scales: tests of chemical morphology and properties, analysis of micro-oil-displacing performance, and simulation of macro-oil-increasing effect. The results showed that although all surfactant solutions had the effects of reducing interfacial tension, altering wettability, and enhancing imbibition, the nano-emulsion with the lowest hydrodynamic radius is the optimal selection. This is attributed to the fact that the properties of the nano-emulsion match well with the characteristics of these shale and tight reservoirs. The nano-emulsion is capable of integrating into the tight matrix, interacting with the oil and rock, and supplying the energy for oil to flow out. This study provides a comprehensive understanding of the role that surfactant solutions could play in the EOR of unconventional reservoirs.

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Immunotherapy has been an advanced and effective approach to treating various types of solid tumors in recent years, and the most successful strategy is immune checkpoint inhibitors (ICIs), which have shown beneficial effects in patients with colorectal cancer (CRC). Drug resistance to ICIs is usually associated with CD8+ T-cells targeting tumor antigens; thus, CD8+ T-cells play an important role in immunotherapy. Unfortunately, Under continuous antigen stimulation, tumor microenvironment(TME), hypoxia and other problems it leads to insufficient infiltration of CD8+ T-cells, low efficacy and mechanism exhaustion, which have become obstacles to immunotherapy. Thus, this article describes the relationship between CRC and the immune system, focuses on the process of CD8+ T-cells production, activation, transport, killing, and exhaustion, and expounds on related mechanisms leading to CD8+ T-cells exhaustion. Finally, this article summarizes the latest strategies and methods in recent years, focusing on improving the infiltration, efficacy, and exhaustion of CD8+ T-cells, which may help to overcome the barriers to immunotherapy.

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Antituberculosis drugs induce pharmacologic cholestatic liver injury with long-term administration. Liver injury resulting from rifampicin is potentially related to the bile acid nuclear receptor Farnesoid X Receptor (FXR). To investigate this, cholestasis was induced in both wild-type (C57BL/6N) mice and FXR knockout (FXR-null) mice through administration of rifampicin (200 mg/kg) via gavage for 7 consecutive days. Compared with C57BL/6N mice, FXR-null mice exhibited more severe liver injury after rifampicin administration, characterized by enlarged liver size, elevated transaminases, and increased inflammation. Moreover, under rifampicin treatment, FXR knockout impairs lipid secretion and exacerbates hepatic steatosis. Significantly, the expression of metabolism molecules BSEP increased, while NTCP and CYP7A1 decreased following rifampicin administration in C57BL/6N mice, whereas these changes were absent in FXR knockout mice. Furthermore, rifampicin treatment in both C57BL/6N and FXR-null mice was associated with elevated c-Jun N-terminal kinase phosphorylation (p-JNK) levels, with a more pronounced elevation in FXR-null mice. Our study suggests that rifampicin-induced liver injury, steatosis, and cholestasis are associated with FXR dysfunction and altered bile acid metabolism, and that the JNK signaling pathway is partially implicated in this injury. Based on these results, we propose that FXR might be a novel therapeutic target for addressing drug-induced liver injury.

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Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares , Rifampin , Animales , Rifampin/efectos adversos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/genética , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/metabolismo , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , Simportadores/genética , Simportadores/metabolismo , Ácidos y Sales Biliares/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Colestasis/inducido químicamente , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo

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The micro-arc oxidation (MAO) technique was used to grow in situ oxidation coating on the surface of R60705 zirconium alloy in Na2SiO3, Na2EDTA, and NaOH electrolytes. The thickness, surface morphology, cross-section morphology, wear resistance, composition, and structure of the micro-arc oxidation coating were analyzed by an eddy current thickness measuring instrument, XPS, XRD, scanning electron microscopy, energy spectrometer, and wear testing machine. The corrosion resistance of the coating was characterized by a polarization curve and electrochemical impedance spectroscopy (EIS). The results show that, with the increase in frequency, the single-pulse discharge energy decreases continuously, and the coating thickness shows a decreasing trend, from the highest value of 152 µm at 400 Hz to the lowest value of 87.5 µm at 1000 Hz. The discharge pore size on the surface of the coating gradually decreases, and the wear resistance and corrosion resistance of the coating first increase and then decrease. The corrosion resistance is the best when the frequency is 400 Hz. At this time, the corrosion potential is -0.215 V, and the corrosion current density is 2.546 × 10-8 A·cm-2. The micro-arc oxidation coating of zirconium alloy is mainly composed of monoclinic zirconia (m-ZrO2) and tetragonal zirconia (t-ZrO2), in which the content of monoclinic zirconia is significantly more than that of tetragonal zirconia.

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Bacterial community is strongly associated with activated sludge performance, but there still remains a knowledge gap regarding the rare bacterial community assembly and their influence on the system performance in industrial wastewater treatment plants (IWWTPs). Here, we investigated bacterial communities in 11 full-scale IWWTPs with similar process designs, aiming to uncover ecological processes and functional traits regulating abundant and rare communities. Our findings indicated that abundant bacterial community assembly was governed by stochastic processes; thereby, abundant taxa are generally present in wastewater treatment compartments across different industrial types. On the contrary, rare bacterial taxa were primarily driven by deterministic processes (homogeneous selection 61.9%-79.7%), thus they only exited in specific IWWTPs compartments and wastewater types. The co-occurrence networks analysis showed that the majority of keystone taxa were rare bacterial taxa, with rare taxa contributing more to network stability. Furthermore, rare bacteria rather than abundant bacteria in the oxic compartment contributed more to the degradation of xenobiotics compounds, and they were main potential drivers of pollutant removal. This study demonstrated the irreplaceable roles of rare bacterial taxa in maintaining system performance of IWWTPs, and called for environmental engineers and microbial ecologists to increase their attention on rare biosphere.

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Bacterias , Eliminación de Residuos Líquidos , Aguas Residuales , Aguas Residuales/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Aguas del Alcantarillado/microbiología , Residuos Industriales , Biodegradación Ambiental

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Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the "sweating" primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

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We report on a Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser with in-band pumping of the Tm ions by a spatially single-mode 1678 nm Raman fiber laser. The structurally disordered CaGdAlO4 host crystal is also codoped also with the passive Lu ion for additional inhomogeneous line broadening. The Tm,Ho,Lu:CaGdAlO4 laser generates soliton pulses as short as 79 fs at a central wavelength of 2073.6 nm via soft-aperture Kerr-lens mode-locking. The corresponding average output power amounts to 91 mW at a pulse repetition rate of ∼86 MHz. The average output power can be scaled to 842 mW at the expense of slightly longer pulses of 155 fs at 2045.9 nm, which corresponds to a peak power of ∼58 kW. To the best of our knowledge, this represents the first demonstration of an in-band pumped Kerr-lens mode-locked Tm,Ho solid-state laser at ∼2 µm.

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We report on the growth, polarized spectroscopy and first laser operation of an orthorhombic (space group Pnma) Tm3+,Ho3+-codoped gadolinium orthoscandate (GdScO3) perovskite-type crystal. A single crystal of 3.76 at.% Tm, 0.35 at.% Ho:GdScO3 was grown by the Czochralski method. Its polarized absorption and fluorescence properties were studied revealing a broadband emission around 2 µm. The parameters of the Tm3+ ↔ Ho3+ energy transfer was quantified, P28 = 1.30 × 10-22 cm3µs-1, and P71 = 0.99 × 10-23 cm3µs-1, and the thermal equilibrium lifetime was measured to be 3.5 ms. The crystal-field splitting of Tm3+ and Ho3+ multiplets in Cs symmetry sites of the perovskite structure was determined by low-temperature spectroscopy and the mechanism of spectral line broadening is discussed. The continuous-wave Tm,Ho:GdScO3 laser generated 1.16 W at ∼2.1 µm with a slope efficiency of 50.5%, a laser threshold of 184 mW, a linear laser polarization (E || c) and a spatially single-mode output. The Tm,Ho:GdScO3 crystal is promising for broadly tunable and femtosecond mode-locked lasers emitting above 2 µm.

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PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residues→3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ 2,6)-α-D-Galp-(1→6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ , while branching occurred at ß-D-Glcp-(1→, α-D-Manp-(1→, and α-L-Fucp-(1 â†’ 3)- α-L-Fucp-(1→. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-ß, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily dock onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.

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FN-kappa B , Polisacáridos , Transducción de Señal , Receptor Toll-Like 4 , Wolfiporia , Animales , Ratones , Receptor Toll-Like 4/metabolismo , Células RAW 264.7 , FN-kappa B/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Transducción de Señal/efectos de los fármacos , Wolfiporia/química , Antígeno 96 de los Linfocitos/metabolismo , Antígeno 96 de los Linfocitos/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Simulación del Acoplamiento Molecular

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OBJECTIVE: Surgical site infection (SSI) after spinal surgery is still a persistent worldwide health concern as it is a worrying and devastating complication. The number of samples in previous studies is limited and the role of conservative antibiotic therapy has not been established. This study aims to evaluate the clinical efficacy and feasibility of empirical antibiotic treatment for suspected early-onset deep spinal SSI. METHODS: We conducted a retrospective study to identify all cases with suspected early-onset deep SSI after lumbar instrumented surgery between January 2009 and December 2018. We evaluated the potential risks for antibiotic treatment, examined the antibiotic treatment failure rate, and applied logistic regression analysis to assess the risk factors for empirical antibiotic treatment failure. RESULTS: Over the past 10 years, 45 patients matched the inclusion criteria. The success rate of antibiotic treatment was 62.2% (28/45). Of the 17 patients who failed antibiotic treatment, 16 were cured after a debridement intervention and the remaining one required removal of the internal fixation before recovery. On univariate analysis, risk factors for antibiotic treatment failure included age, increasing or persisting back pain, wound dehiscence, localized swelling, and time to SSI (cut-off: 10 days). Multivariate analysis revealed that infection occurring 10 days after primary surgery and wound dehiscence were independent risk factors for antibiotic treatment failure. CONCLUSION: Appropriate antibiotic treatment is an alternative strategy for suspected early-onset deep SSI after lumbar instrumented surgery. Antibiotic treatment for suspected SSI occurring within 10 days after primary surgery may improve the success rate of antibiotic intervention. Patients with wound dehiscence have a significantly higher likelihood of requiring surgical intervention.

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Antibacterianos , Vértebras Lumbares , Infección de la Herida Quirúrgica , Humanos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/etiología , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Vértebras Lumbares/cirugía , Anciano , Adulto , Factores de Riesgo , Insuficiencia del Tratamiento , Desbridamiento

RESUMEN

We report on a polarization-resolved study of mid-infrared emission properties of Er3+-doped orthorhombic yttrium aluminum perovskite YAlO3 single crystal. For the 4I11/2 → 4I13/2 Er3+ transition, the stimulated emission cross section is 0.20 × 10-20 cm2 at 2919 nm for light polarization E ‖ c. Pumped by an Yb-fiber laser at 976 nm, the 10 at.% Er:YAlO3 laser delivered 1.36 W at 2919 nm with a slope efficiency of 31.4%, very close to the Stokes limit, a laser threshold as low as 33 mW and a linear polarization. Pump-induced polarization switching between E || b and E || c eigen states was observed and explained by excited-state absorption from the terminal laser level.

RESUMEN

OBJECTIVES: The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer's disease (AD) rats. METHODS: The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism. KEY FINDINGS: The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats. CONCLUSIONS: TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.

Asunto(s)

Abietanos , Enfermedad de Alzheimer , Apoptosis , Disfunción Cognitiva , Modelos Animales de Enfermedad , Emulsiones , Neuronas , Estrés Oxidativo , Pirazinas , Ratas Sprague-Dawley , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Abietanos/farmacología , Pirazinas/farmacología , Pirazinas/uso terapéutico , Masculino , Disfunción Cognitiva/tratamiento farmacológico , Ratas , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Caspasa 3/metabolismo , Nanopartículas , Proteína X Asociada a bcl-2/metabolismo