RESUMEN
The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.
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Virus de la Encefalitis Japonesa (Especie) , Proteínas del Envoltorio Viral , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/fisiología , Virus de la Encefalitis Japonesa (Especie)/efectos de los fármacos , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/química , Animales , Línea Celular , Virulencia , Replicación Viral , Encefalitis Japonesa/virología , Humanos , Heparina/farmacología , Sustitución de Aminoácidos , Mutación Missense , Ratones , Mutación , Factores de Virulencia/genética , Glicoproteínas de MembranaRESUMEN
BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.
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Biomarcadores Farmacológicos/análisis , Enfermedad de Graves/radioterapia , Radioisótopos de Yodo/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Yodo/química , Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Glándula Tiroides/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Activation of TGFB (transforming growth factor ß) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers. METHODS: We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Δhep). ECM1 or soluble TGFBR2 (TGFB receptor 2) were expressed in livers of mice after injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy livers were analyzed by immunohistochemistry and in situ hybridization. RESULTS: ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with αv integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Δhep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. CONCLUSIONS: ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.
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Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Proteínas de la Matriz Extracelular/metabolismo , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática Experimental/prevención & control , Hígado/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Animales , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Proteínas de la Matriz Extracelular/deficiencia , Proteínas de la Matriz Extracelular/genética , Células Estrelladas Hepáticas/patología , Hepatitis Alcohólica/metabolismo , Hepatitis Alcohólica/patología , Hepatitis Viral Humana/metabolismo , Hepatitis Viral Humana/patología , Humanos , Hígado/patología , Cirrosis Hepática Alcohólica/metabolismo , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Experimental/genética , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Miembro 4 de la Subfamilia B de Casete de Unión a ATPRESUMEN
Staphylococcus aureus, including MRSA strains, poses significant health risks, imposing a significant disease burden and mortality. We investigate butyrolactone I (BL-1), a marine-derived metabolite from Aspergillus terreus, enhancing aminoglycoside efficacy against MRSA. A promising synergy is observed with BL-1 and various aminoglycosides, marked by low fractional inhibitory concentration indexes (FICIs < 0.5). Comprehensive studies utilizing USA300 MRSA and gentamicin reveal a remarkable one-fourth reduction in minimum inhibitory concentration (MIC) with 20 µg/mL BL-1. A relative abundance assay indicates that BL-1 enhances gentamicin uptake while restraining extracellular presence, involving intricate transmembrane signaling and molecular interactions. RNA-Seq analysis yielded an unexpected revelation, unveiling a distinctive gene expression profile and distinguishing it from other treatment approaches. Furthermore, meticulous analyses validated the extensive perturbations induced by BL-1 exposure, affecting diverse biological functions, encompassing glycolysis, amino acid metabolisms, substance transmembrane transport, and virulence generation. These valuable insights inspired further confirmation of bacterial virulence and the modulation of membrane permeability resulting from BL-1 treatment. Phenotypic validations corroborated our observations, revealing reduced membrane permeability and hemolytic toxicity, albeit demanding a deeper comprehension of the intricate interplay underlying these actions. Our study contributes crucial mechanistic insights to the development of therapeutic strategies against this notorious pathogen and the judicious employment of aminoglycosides. Additionally, it elucidates marine-derived metabolites' ecological and functional roles, exemplified by fungal quorum sensing signals. These compounds could give producers a competitive edge, inhibiting microorganism proliferation and suggesting novel approaches for combating resistant pathogens.
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4-Butirolactona/análogos & derivados , Staphylococcus aureus Resistente a Meticilina , Gentamicinas/farmacología , Antibacterianos/farmacología , Aminoglicósidos/farmacologíaRESUMEN
Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.
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Biomarcadores , Remodelación Ósea , Enfermedad de Graves , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/metabolismo , Adulto , Biomarcadores/sangre , Estudios Retrospectivos , Persona de Mediana Edad , Glándula Tiroides/metabolismo , Huesos/metabolismo , Hormonas Tiroideas/sangre , Estudios de Casos y Controles , Pronóstico , Antitiroideos/uso terapéutico , Tiroxina/sangre , Triyodotironina/sangre , Estudios de SeguimientoRESUMEN
Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Subunidad gamma Común de Receptores de Interleucina/metabolismo , Receptores de Interleucina-21/genética , Receptores de Interleucina-21/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T CD8-positivosRESUMEN
BACKGROUND: Podocyte injury is very important process in diabetic nephropathy (DN) progression. Circular RNA (circRNA) takes part in regulating the advancement of DN. Herein, we explored the role and mechanism of circGAB1 in DN progression. METHODS: The abundances of circGAB1, microRNA-346 (miR-346) and mitogen-activated protein kinase 6 (MAPK6) were detected by qRT-PCR in DN serum samples and podocyte HGPC. Moreover, cell viability and apoptosis were determined using CCK8 assay and flow cytometry. Also, the protein levels of MAPK6, proliferation-related markers and apoptosis-related markers were analyzed by western blot. ELISA assay was used to measure the levels of inflammatory factors, and corresponding kits were used to detect the levels of oxidative stress-related markers. The relationship between miR-346 and circGAB1 or MAPK6 was distinguished by dual-luciferase reporter assay. RESULTS: CircGAB1 expression was increased in DN serum samples and HG-treated HGPC cells. CircGAB1 knockdown inhibited HG-induced apoptosis, inflammatory response and oxidative stress in HGPC cells. In terms of mechanism, circGAB1 sponged miR-346, and miR-346 targeted MAPK6. The inhibition effect of circGAB1 knockdown on HG-induced podocyte injury could be reversed by miR-346 inhibitor. Moreover, miR-346 overexpression repressed HG-induced podocyte injury by targeting MAPK6. CircGAB1 served as miR-346 sponge to positively regulate MAPK6. CONCLUSION: CircGAB1 contributed to podocyte injury through mediating miR-346/MAPK6 axis, suggesting that circGAB1 might promote DN progression.
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OBJECTIVE: The purpose of this study was to evaluate the curative effect of external therapies of traditional Chinese medicine on constipation in patients with chronic renal failure and to provide scientific theoretical basis for clinical practice. METHOD: We searched the English database of PubMed, EMBASE, the Cochrane Library and the Web of Science and Chinese database of CNKI, Wan fang database, VIP Database and China Biomedical Literature Database up to December 2022. Randomized controlled trials (RCTs) involving constipation in patients with CRF that compared external therapies of traditional Chinese medicine and routine treatment to routine treatment were eligible for the analysis. A meta-analysis of the outcome indicators including total efficiency, weekly defecation times, defecation time, defecation difficulty score, patient-assessment of constipation quality of life and adverse events of treatment were performed. The analysis was performed by using Review Manager version 5.3. RESULT: A total of 23 studies were included, with 1764 patients. Meta-analysis results showed that compared with the control group, the test group could significantly increase weekly defecation times(MD = 0.94, 95%CI(0.70, 1.18), Z = 7.74, P < 0.00001), reduce defecation time(MD = -2.92, 95%CI(-3.69, -2.16), Z = 7.49, P < 0.00001), reduce defecation difficulty score(MD = -1.92, 95%CI(-2.45, -1.39), Z = 7.11, P < 0.00001), improve the quality of life in patients with constipation(MD = -7.57, 95%CI(-10.23, -4.91), Z = 5.58, P < 0.00001) and obtain a higher total effective rate of treatment(OR = 4.53, 95%CI(3.27, 6.29), Z = 9.07, P < 0.00001). In terms of safety, there was no statistical significance in the incidence of adverse events between two groups(OR = 0.35, 95%CI(0.04, 2.95), Z = 0.96, P = 0.34). CONCLUSION: The combination of external therapies of traditional Chinese medicine and routine treatment could achieve an excellent curative effect, and there was no specific adverse event. However because of the limited level of current evidence, more high-quality trials are needed in the future.5.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Medicina Tradicional China , Estreñimiento/tratamiento farmacológico , ChinaRESUMEN
Citrus peel polyphenols have possess the distinct anti-inflammatory activities. However, its underlying mechanism on ulcerative colitis have not been elucidated. The aim of this research was to investigate the anti-inflammatory effect and action mechanisms of citrus peel polyphenols. Total citrus peel polyphenols were concentrated using macroporous resins and separated into water-soluble citrus polyphenols and ester-soluble citrus peel polyphenols. These extracts were then gavaged to acute colitis mice induced by dextran sulfate sodium for 14 days using a dose of 300 mg/kgâªbw. High performance liquid chromatography results showed that the extracts contained flavanones, flavonoids, and phenolic acids. Compared to the dextran sulfate sodium group, total citrus peel polyphenols, water-soluble citrus polyphenols, and ester-soluble citrus peel polyphenols significantly ameliorated the severity of colitis symptoms. Additionally, citrus peel polyphenols reduced the activity of myeloperoxidase, lowered secretion of tumor necrosis factor-α and interleukin-6, and increased interleukin-10. Meanwhile, total citrus peel polyphenols, water-soluble citrus polyphenols, and ester-soluble citrus peel polyphenols effectively blocked the activation of the nuclear factor-kappa B. These results demonstrated that citrus peel polyphenols alleviated ulcerative colitis in mice by damping pro-inflammatory cytokine secretion and suppressing the nuclear factor-kappa B pathway activation.
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Nitrogen pollution, especially ammonia, and its impacts on aquatic ecosystems are always hot topics worldwide. Evaluating the toxicity effect of ammonia on aquatic organisms is the essential basis for nitrogen management. Benthic macroinvertebrates are widely used to evaluate ammonia toxicity based on acute and chronic lab tests. In comparison, responses of macroinvertebrates under field and controlled conditions were rarely studied. To explore the effect of ammonia on macroinvertebrate assemblages and the underlying mechanisms under field conditions, a 5-year fertilization experiment was conducted in 5 quasi-natural ponds located in the Yangtze River floodplain. One control (TN0, no artificial ammonia loading) and four treatments (TN2, TN10, TN20, TN100; ordered by artificial ammonia loading from low to high) were set. The results showed that (1) species number of macroinvertebrates differed little among the ponds, while total density and biomass were positively correlated with unionized ammonia concentration (NH3), indicating that increased ammonia loading had no adverse impact on macroinvertebrate abundance; (2) all ponds were dominated by gathering collectors and the biomass was higher in the ponds with higher ammonia loading resulting from the more phytoplankton promoted by ammonia loading and improved internal phosphorus release; (3) the biomass of predators also increased with the increasing NH3 which may be due to the bottom-up effect through their prey; (4) some species, such as Limnodrilus hoffmeisteri, survived and were dominant species in the ponds with higher NH3 compared with 96 h median lethal concentration from acute lab test. The results suggested that higher ammonia loading increased macroinvertebrate abundance, mainly contributed by gathering collectors and predators. Unlike previous acute and chronic lab tests, macroinvertebrates showed extremely high tolerance to NH3 in field conditions. This study supported that ammonia toxicity to aquatic organisms was scale-dependent and should be evaluated at multiple scales.
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Ecosistema , Invertebrados , Animales , Amoníaco/toxicidad , Estanques , Organismos Acuáticos , Ríos , Nitrógeno , FertilizaciónRESUMEN
The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.
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As a typical filamentous fungus, Aspergillus species are highly adaptive to diverse ecological habitats, represented by their occurrence in both terrestrial and marine environments; this could plausibly be ascribed to their preeminent biological diversity and metabolic variability. In this context, marine-derived Aspergillus fungi have recently attracted great interest as a promising potential source of biologically active compounds. The present study depicts the genomic and chemical profiles of M7, a strain of Aspergillus terreus isolated from mussels in the South China Sea; the crude extracts of its soybean fermentation exhibit potent growth-inhibitory properties against A. baumannii and P. aeruginosa. Subsequently, functional genomics analysis based on sequences implied a considerable biosynthetic potential of the strain, which is substantiated by the 75 biosynthetic gene clusters (BGCs) identified via genome mining; the majority (49 BGCs) were functionally unknown. Representatively, the putative biosynthetic pathways of terramide A and terramide B, the bacteriostatic products obtained through chemical separation and characterized from the fermentation, could not be allocated to any known BGC, highlighting the metabolic potency and diversity of this strain. Meanwhile, based on a comprehensive analysis of fermentation conditions, we confirmed that the presence of environmental iron was inversely correlated with antimicrobial characteristics of the strain M7, presumably due to the interference in the biosynthetic pathway or bioactive mechanisms of the antimicrobial components, e.g., terramide A and B. Our observations provide genomic and biochemical insight into the metabolic and ecological novelties of this strain, underpinning the diversity of biosynthetic flexibility and adaptive strategies of marine Aspergillus fungi.
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This study presented the first insights into the genomic and chemical profiles of B9, a specific Penicillium strain derived from sponges of the South China Sea that demonstrated the closest morphological and phylogenetic affinity to P. paxillin. Via the Illumina MiSeq sequencing platform, the draft genome was sequenced, along with structural assembly and functional annotation. There were 34 biosynthetic gene clusters (BGCs) predicted against the antiSMASH database, but only 4 gene clusters could be allocated to known BGCs (≥50% identities). Meanwhile, the comparison between B9 and P. paxillin ATCC 10480 demonstrated clear distinctions in morphology, which might be ascribed to the unique environmental adaptability of marine endosymbionts. In addition, two novel pyridinones, penicidihydropyridone A (2) and penicidihydropyridone B (3), were isolated from cultures of B9, and structurally characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The absolute configurations were confirmed by comparison of experimental and calculated electronic circular dichroism (ECD) curves. In addition, structure-based molecular docking indicated that both neo-pyridinones might block the programmed cell death protein 1(PD-1) pathway by competitively binding a programmed cell death 1 ligand 1(PD-L1) dimer. This was verified by the significant inhibition rates of the PD-1/L1 interaction. These indicated that Penicillium sp. B9 possessed a potential source of active secondary metabolites.
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An effective biological index should meet two criteria: (1) the selected parameters have clear relationships with ecosystem health and can be measured simply by standard methods and (2) reference conditions can be defined objectively and simply. Species richness is a widely used estimate of ecosystem condition, although it is increased by nutrient enrichment, a common disturbance. Based on macrobenthos data from 91 shallow Yangtze lakes disconnected from the mainstem, we constructed an observed species (SO)-area (A) model to predict expected species richness (SE), and then developed an observed to expected index (O/E-SA) by calculating the SO/SE ratio. We then compared O/E-SA with three other commonly used indices regarding their ability to discriminate cultivated and urban lakes: (1) River Invertebrate Prediction and Classification System (RIVPACS; O/E-RF), (2) Benthic Index of Biotic Integrity (B-IBI), and (3) Average Score Per Taxon (ASPT). O/E-SA showed significant positive linear relationships with O/E-RF, B-IBI and ASPT. Quantile regressions showed that O/E-SA and O/E-RF had hump-shape relationships with most eutrophication metrics, whereas B-IBI and ASPT had no obvious relationships. Only O/E-SA, O/E50 and B-IBI significantly discriminated cultivated from urban lakes. O/E-SA had comparable or higher performance with O/E-RF, B-IBI and ASPT, but was much simpler. Therefore, O/E-SA is a simple and reliable index for lake ecosystem health bioassessment. Finally, a framework was proposed for integrated biological assessment of Yangtze-disconnected lakes.
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Ecosistema , Lagos , China , Monitoreo del Ambiente/métodos , Eutrofización , RíosRESUMEN
Objective: The objective of this study was to explore the risk factors of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and to establish a nomogram model evaluate the probability of OHSS in PCOS patients. Methods: We retrospectively analyzed clinical data from 4,351 patients with PCOS receiving IVF/ICSI in our reproductive medical center. The clinical cases were randomly divided into a modeling group (3,231 cases) and a verification group (1,120 cases) according to a ratio of about 3:1. The independent risk factors correlation with the occurrence of OHSS was identified by logistic regression analysis. Based on the selected independent risk factors and correlated regression coefficients, we established a nomogram model to predict the probability of OHSS in PCOS patients, and the predictive accuracy of the model was measured using the area under the receiver operating curve (AUC). Results: Univariate and multivariate logistic regression analyses showed that FSH (OR, 0.901; 95% CI, 0.847-0.958; P<0.001), AMH (OR, 1.259; 95% CI, 1.206-1.315; P<0.001), E2 value on the day of hCG injection (OR, 1.122; 95% CI, 1.021-1.253; P<0.001), total dosage of Gn used (OR, 1.010; 95% CI, 1.002-1.016; P=0.041), and follicle number on the day of hCG injection (OR, 0.134; 95% CI, 1.020-1.261; P=0.020) are the independent risk factors for OHSS in PCOS patients. The AUC of the modeling group is 0.827 (95% CI, 0.795-0.859), and the AUC of the verification group is 0.757 (95% CI, 0.733-0.782). Conclusion: The newly established nomogram model has proven to be a novel tool that can effectively, easily, and intuitively predict the probability of OHSS in the patients with PCOS, by which the clinician can set up a better clinical management strategies for conducting a precise personal therapy.
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Nomogramas , Síndrome de Hiperestimulación Ovárica/complicaciones , Síndrome del Ovario Poliquístico/terapia , Adulto , Área Bajo la Curva , Femenino , Fertilización In Vitro/métodos , Humanos , Folículo Ovárico , Síndrome de Hiperestimulación Ovárica/diagnóstico , Inducción de la Ovulación , Síndrome del Ovario Poliquístico/complicaciones , Embarazo , Índice de Embarazo , Probabilidad , Curva ROC , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Inyecciones de Esperma Intracitoplasmáticas/métodosRESUMEN
Background: Serum thyroglobulin (Tg) serves as a sensitive and easily available tumor marker for patients with metastatic differentiated thyroid carcinoma (m-DTC). The aim of the present study was to evaluate the predictive value of suppressed Tg changes (Δsup-Tg) and/or stimulated Tg changes (Δsti-Tg) to evaluate the efficacy of radioiodine therapy (RT). Methods: We studied 117 patients with m-DTC who received RT. Δsup-Tg and Δsti-Tg were compared after the first RT in different therapeutic response groups and a receiver-operating characteristic (ROC) curve was used to determine the cut-off values to predict non-remission. Univariate and multivariate analyses were used to investigate the effects of 17 observed factors on the efficacy of RT. Results: A total of 218 RT events in 117 patients with m-DTC were analyzed. After the last RT, the remission rate was 70.94% (83/117), and the proportion of remission events accounted for 74.77% (163/218). ROC curve analysis showed that the cut-off values for Δsup-Tg and Δsti-Tg after the first RT to predict the non-remission of RT were 21.54% and 27.63%, respectively. Age, the size of the metastasis, the maximum count of target metastatic lesions and the average count of contralateral non-target tissue on tomographic imaging (Tmax/NTmean) of the first RT, and Δsup-Tg after the first RT were identified as independent factors associated with RT efficacy. Conclusions: Tg response was valuable to predict RT efficacy for patients with m-DTC. Age, the size of the metastasis, Tmax/NTmean, and Δsup-Tg after the first RT were verified as independent predictive factors of RT efficacy.
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Adenocarcinoma/patología , Biomarcadores de Tumor/sangre , Radioisótopos de Yodo/uso terapéutico , Tiroglobulina/sangre , Neoplasias de la Tiroides/patología , Adenocarcinoma/sangre , Adenocarcinoma/radioterapia , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Inducción de Remisión , Estudios Retrospectivos , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/radioterapiaRESUMEN
Background: There are no definite recommendations on the optimal time of initiating radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC) patients in current relevant guidelines. This study aimed to investigate the relationship between the timing of initiating radioiodine adjuvant therapy (RAT) and the clinical outcomes based on dynamic follow-ups and assessments in intermediate- to high-risk DTC patients. Methods: A total of 206 patients with intermediate- to high-risk DTC receiving RAT of 150 mCi were retrospectively reviewed. According to the time interval (TI: between thyroidectomy and initial RAT), the patients were divided into 2 groups: Group 1: TI < 3 months (n=148), and Group 2: TI ≥ 3 months (n=58). The RAT therapy response was evaluated as excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), structural incomplete response (SIR). The univariate and multivariate analyses were conducted to screen out factors associated with incomplete response (IR= BIR+SIR). Finally, the prognostic nomogram was used to explain IR rates as a valuable tool in clinical practice. Results: Response to initial RAT was significantly different between 2 groups during dynamic follow-ups (all P<0.05). Group 2 had significantly lower ER rates (37.9 vs 63.5, 52.0 vs 73.9, 64.4 vs 80.3, all P<0.05, respectively) and higher IR rates (39.7 vs 14.9, 36.0 vs 9.7, 12.2 vs 3.9, all P<0.05, respectively) than group 1 during dynamic follow-ups. By univariate and multivariate analyses, prolonged TI (HR: 6.67, 95%CI: 2.241-19.857, P=0.001), soft tissue invasion (HR: 7.35, 95%CI: 1.624-33.296, P=0.010), higher sTg (HR: 7.21, 95%CI: 1.991-26.075, P=0.003) were manifested to be independent risk factors for IR. The nomogram showed that soft tissue invasion, sTg, and TI were the top 3 contributors to the IR. Conclusions: Early RAT is associated with greater biochemical response but has no impact on SIR. Delayed initial RAT (≥3 months after thyroidectomy) related to IR in intermediate- to high-risk DTC.
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Radioisótopos de Yodo/uso terapéutico , Radioterapia Adyuvante/métodos , Neoplasias de la Tiroides/radioterapia , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Nomogramas , Estudios Retrospectivos , Riesgo , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.
RESUMEN
BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are the most common GISTs. The risk, incidence, and outcome of cancer are different between the sexes. Whether gender is related to the prognosis of gastric stromal tumors is unclear. Therefore, this study aims to explore the relationship between gender and gastric GIST prognosis. METHODS: Data from gastric GIST patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce confounding factors, and the clinicopathological features and prognosis of GIST patients were comprehensively evaluated. RESULTS: There were 512 male patients and 538 female patients with gastric GIST. The gender of gastric GIST patients was associated with marital status, surgical treatment, tumor size, and mitotic index (P < 0.05). The Kaplan-Meier analysis and log-rank test revealed that male patients had a higher mortality rate than female patients (P = 0.0024). After matching all the potential confounding factors, the survival of the female gastric GIST patients was better than that of the male gastric GIST patients (P = 0.042). Cox regression analysis revealed that gender was an independent risk factor for overall survival. The risk of death was higher for males than for females (HR 1.677, 95% CI 1.150-2.444, P = 0.007). CONCLUSION: Gender could be a prognostic factor for gastric GIST survival, and male patients had a higher risk of death.
Asunto(s)
Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
OBJECTIVE: To explore the effect of syndecan-1 (Sdc-1) in the pathogenesis of colitis. METHODS: Thirty BALB/c mice were forced to drink 4% dextran sodium sulphate (DSS) in distilled water as the sole source of drinking fluid for 7 days, distilled water for 10 days, and 4% DSS in distilled water for another 7 days so as to establish colitis models and then were randomly divided into 3 equal groups: model groups 1, 2, and 3 to be killed 8, 18, and 25 days after the DSS drinking respectively to take their colons. Another 10 mice were fed with distilled water as control group and were killed on Day 8. Microscopy was used to evaluate the histological score of the colon. RT-PCR was used to detect the expression of Sdc-1 mRNA and IL-1 mRNA in the colon mucosa. Immunohistochemistry was conducted to detect the Sdc-1 protein level. RESULTS: The histological scores of the 3 model groups were all significantly higher than that of the control group (F = 448.717, P < 0.01) and the score was the highest in the model group 1 and then gradually decreased. There was not significant differences in the Sdc-1 mRNA expression among different groups (F = 0.822, P > 0.05). The levels of Sdc-1 protein of the 3 model groups were all significantly lower than that of the control group (F = 865.586, P < 0.01), and the Sdc-1 protein level was the lowest level in the model group1, and then increased gradually. The expression of IL-1 mRNA of the 3 model groups were all significantly higher than that of the control group (F = 103.833, P < 0.01), and the IL-1 mRNA level was the highest in the model group1 and then decreased gradually. CONCLUSION: The severity of colitis is associated with the reduction of Sdc-1 protein level, but not with the Sdc-1 mRNA level in the colon mucosa. The reduction of Sdc-1 protein level may be associated to increase of IL-1 level.