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Wnt/ß-catenin signaling is frequently activated in advanced prostate cancer and contributes to therapy resistance and metastasis. However, activating mutations in the Wnt/ß-catenin pathway are not common in prostate cancer, suggesting alternative regulations may exist. Here, we report that the expression of endothelial cell-specific molecule 1 (ESM1), a secretory proteoglycan, is positively associated with prostate cancer stemness and progression by promoting Wnt/ß-catenin signaling. Elevated ESM1 expression correlates with poor overall survival and metastasis. Accumulation of nuclear ESM1, instead of cytosolic or secretory ESM1, supports prostate cancer stemness by interacting with the ARM domain of ß-catenin to stabilize ß-catenin-TCF4 complex and facilitate the transactivation of Wnt/ß-catenin signaling targets. Accordingly, activated ß-catenin in turn mediates the nuclear entry of ESM1. Our results establish the significance of mislocalized ESM1 in driving metastasis in prostate cancer by coordinating the Wnt/ß-catenin pathway, with implications for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in prostate cancer.
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Núcleo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/secundario , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/patología , Neoplasias de la Próstata/patología , Proteoglicanos/metabolismo , beta Catenina/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/metabolismo , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteoglicanos/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/genéticaRESUMEN
Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.
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Neoplasias de la Mama , Doxorrubicina , Resistencia a Antineoplásicos , Exosomas , Regulación Neoplásica de la Expresión Génica , MicroARNs , Receptor Notch1 , Humanos , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Doxorrubicina/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Células MCF-7 , Femenino , Receptor Notch1/metabolismo , Receptor Notch1/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Ferrate (Fe(VI)) is an emerging green disinfectant and has received increasing attention nowadays. This study conducted systematic analyses of Fe(VI) disinfection on six typical bacteria in different water matrices. The results showed that Fe(VI) was more effective in inactivating Gram-negative (G-) bacteria than Gram-positive (G+) bacteria, and the disinfection performance of Fe(VI) was better in a phosphate buffer than that in a borate buffer and secondary effluent. The inactivation rate constants of G- bacteria were significantly higher than those of G+ bacteria. The cell membrane damage of G- bacteria was also more severe than that of G+ bacteria after Fe(VI) treatment. The cell wall structure, especially cell wall thickness, might account for the difference of the inactivation efficiency between G- bacteria and G+ bacteria. Moreover, it is revealed that Fe(VI) primarily reacted with proteins rather than other biological molecules (i.e., phospholipids, peptidoglycan, and lipopolysaccharide). This was further evidenced by the reduction of bacterial autofluorescence due to the destruction of bacterial proteins during Fe(VI) inactivation. Overall, this study advances the understanding of Fe(VI) disinfection mechanisms and provides valuable information for the Fe(VI) application in water disinfection.
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Contaminantes Químicos del Agua , Purificación del Agua , Agua , Purificación del Agua/métodos , Hierro/química , Contaminantes Químicos del Agua/análisis , Bacterias , Oxidación-ReducciónRESUMEN
INTRODUCTION: Non-ketotic hyperglycaemic hemichorea-hemiballismus (NHHH) is often secondary to middle-aged and elderly diabetic people with poor-controlled diabetes; Fahr's disease (FD) is another rare neurological disorder characterized by abnormal calcified deposits in the brain that control movement. We described a rare case of NHHH combined with a heterozygous mutation (SLC20A2) resulting in one family with FD. CASE PRESENTATION: The patient has a 30-day history of involuntary choreic movements of the left limbs and left face. In addition, he had a bit of speech slurred and walked unsteadily. He was diagnosed with type 2 diabetes mellitus two months ago. Over the past two months, he had noticed that urination, appetite, and water volume increased obviously and weight loss drastically. Other problems such as dizziness, headache, difficulty swallowing, nausea, and vomiting did not occur. T1- weighted MRI indicts characteristic contralateral basal ganglia hyper-intensity. During hospitalization, he was injected insulin and oral haloperidol. And the clinical symptoms improved, but parkinsonism symptoms emerge soon after discharge. The parkinsonism symptoms were gradually improved after adjusting medications. Combined with the subsequent genetic test results, we attribute it to NHHH with FD. CONCLUSION: It is relatively rare that NHHH or FD is both presents. We should use antipsychotics with caution in these patients to avoid parkinsonism symptoms.
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The understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low-dose streptozotocin combined with a high-fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)-1ß, IL-6, transforming growth factor ß1 (TGF-ß1), and tumor necrosis factor α (TNF-α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator-activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element-binding protein 1 (SREBP-1), TGF-ß1, nuclear factor (NF)-κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock-down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF-κB signaling pathway.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , PPAR alfa/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Hígado , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , FN-kappa B/metabolismo , Lípidos , Ratones Endogámicos C57BL , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/farmacología , Proteínas del Tejido Nervioso/uso terapéuticoRESUMEN
BACKGROUND: Insulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD. METHODS: NAFLD patients and healthy participants (n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed. RESULTS: Patients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861. CONCLUSIONS: It is possible for serum IL-38 to be a biomarker for NAFLD.
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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Biomarcadores , Humanos , Interleucinas , Lípidos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
OBJECTIVES: Even today, tuberculosis (TB) remains a leading public health problem; yet, the current diagnostic methods still have a few shortcomings. Lipoarabinomannan (LAM) provides an opportunity for TB diagnosis, and urine LAM detection seems to have a promising and widely applicable prospect. DESIGN OR METHODS: Four databases were systematically searched for eligible studies, and the quality of the studies was evaluated using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2). Graphs and tables were created to show sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), the area under the curve (AUC), and so on. RESULTS: Based on the included 67 studies, the pooled sensitivity of urine LAM was 48% and specificity was 89%. In the subgroup analyses, the FujiLAM test had higher sensitivity (69%) and specificity (92%). Furthermore, among patients infected with human immunodeficiency virus (HIV), 50% of TB patients were diagnosed using a urine LAM test. Besides, the CD4+ cell count was inversely proportional to the sensitivity. CONCLUSIONS: Urine LAM is a promising diagnostic test for TB, particularly using the FujiLAM in HIV-infected adults whose CD4+ cell count is ≤100 per µl. Besides, the urine LAM test shows various sensitivities and specificities in different subgroups in terms of age, HIV infection status, CD4+ cell count, and testing method.
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Lipopolisacáridos/orina , Tuberculosis/diagnóstico , Adulto , Recuento de Linfocito CD4 , Niño , Infecciones por VIH/complicaciones , Humanos , Mycobacterium tuberculosis , Sensibilidad y Especificidad , Tuberculosis/complicaciones , Tuberculosis/orinaRESUMEN
The excessive expression of reactive oxygen species is closely connected to many diseases. Considerable studies have demonstrated dandelion as well as its ingredients exhibited antioxidant activity. However, specific material basis reflecting the antioxidant activity has not been comprehensively investigated. In this study, a spectrum-effect relationship study on dandelion between fingerprinting and antioxidant activity was analyzed in detail, while a UHPLC quantification method developed and completely validated for simultaneous determination of active ingredients in dandelion. With the establishment of dandelion fingerprints of different regions, 24 common peaks were characterized. The classic FRAP method and ABTS methods were then used to detect their antioxidant activity. Partial least squares regression analysis, bivariate correlation analysis and grey correlation method were used to accomplish the spectrum-effect relationship. Eventually, the ingredients with antioxidant activity which could be considered as candidate quality markers of dandelion were discovered through spectrum-effect relationship analysis. The six compounds including caftaric acid, chlorogenic acid, caffeic acid, chicoric acid, isochlorogenic acid A, and isochlorogenic acid C were quantitatively determined. The developed UHPLC assay method was accurate, precise, and reliable. The study has elucidated the antioxidant material basis of dandelion and provided a scientific basis for the quality control of dandelion.
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Medicamentos Herbarios Chinos , Taraxacum , Antioxidantes/análisis , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/análisis , Análisis MultivarianteRESUMEN
OBJECTIVE: To investigate the application value of RigiScan monitoring in assisting tadalafil medication. METHODS: This self-control study included 89 ED patients (IIEF-5 < 21) treated in our hospital from August 2019 to July 2020. The patients underwent audiovisual sexual stimulation (AVSS), nocturnal penile tumescence and rigidity (NPTR) test, scoring on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-Item Scale (GAD-7), blood routine test, blood biochemical analysis, and hormone secretion examination, which confirmed 21 cases of psychogenic, 28 cases of organic and 40 cases of mixed ED. We treated the patients with tadalafil at 5 mg/d for 30 days, followed by examination of their erectile function by IIEF-5 scoring and AVSS and comparison of their erectile function with the baseline. For some of the patients that responded poorly to tadalafil at 5 mg/d, we increased the dose to 20 mg and detected the efficacy by AVSS at 1 h after medication. For those with organic or mixed ED irreponsive to tadalafil at 20 mg, we performed screening for corpora cavernosal venous leakage (CCVL) by intracavernosal injectionof alprostadil and penile color Doppler duplex ultrasonography or used dynamic infusion cavernosometry and cavernosography (DICC) to confirm the diagnosis of CCVL. RESULTS: The effectiveness rates of 5 mg/d tadalafil on mild, moderate and severe ED were 85.4%, 53.1% and 43.8%, respectively, significantly higher on mild than on moderate and severe ED (P = 0.002), and its effectiveness rates on psychogenic, organic and mixed ED were 90.5%, 60.7% and 57.5%, respectively, remarkably higher on psychogenic than on organic and mixed ED (P = 0.026). For those with organic or mixed ED irresponsive to 5 mg/d tadalafil, the increased dose of 20 mg achieved an effectiveness rate of 64.3%. (P = 0.033). The results of DICC did not encourage tadalafil medication for the cases of organic or mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil. CONCLUSION: RigiScan monitoring plays a guiding role in tadalafil medication of ED and helps distinguish organic from psychogenic ED. Tadalafil at 5 mg/d produces a better effect on mild than on moderate and severe ED, and so does it on psychogenic than on organic and mixed ED. The dose of medication can be increased to 20 mg for organic and mixed ED irresponsive to 5 mg tadalafil, but tadalafil is not recommended for organic and mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil.
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Disfunción Eréctil , Masculino , Humanos , Disfunción Eréctil/diagnóstico , Tadalafilo/uso terapéutico , Pene , Erección Peniana/fisiología , Ultrasonografía Doppler en ColorRESUMEN
BACKGROUND AND OBJECTIVE: Patients with non-alcoholic fatty liver disease (NAFLD) have insulin resistance and are at an increased risk of diabetes. Recent evidence suggests that asprosin-a novel hormone secreted by white adipose tissue-may play a role in the pathogenesis of insulin resistance. However, the role of asprosin in NAFLD remains unclear. This study aimed to determine whether serum asprosin level could be used as a biochemical marker for NAFLD diagnosis. METHODS: Forty-three untreated NAFLD patients and 50 sex- and age-matched healthy controls were included. Circulating serum asprosin and adiponectin (another adipokine) levels were detected by ELISA. Other metabolic parameters related to NAFLD were also determined. RESULTS: Increased circulating serum asprosin and decreased serum adiponectin levels were found in NAFLD patients unlike in healthy controls. A positive correlation was observed between asprosin and platelet counts (PLT) (r = 0.3653, p = 0.015), fasting blood glucose (FBG) (r = 0.3592, p = 0.017), triglyceride (TG) levels (r = 0.3383, p = 0.025), serum albumin (ALB) levels (r = 0.3273, p = 0.030), and insulin resistance (HOMA-IR) (r = 0.4799, p = 0.001), whereas a negative correlation existed between adiponectin and TG levels in the NAFLD group. Multivariate linear regression showed that FBG and HOMA-IR were independently related to asprosin levels. Receiver operating characteristic (ROC) curves showed that asprosinAUC and adiponectinAUC were 0.735 (95%CI 0.633-0.836, P < 0.0001) and 0.702 (95%CI 0.597-0.807, p = 0.0007) respectively. Moreover, the combination of both biomarkers showed good sensitivity and specificity with AUC of 0.827, which was better than the single detection of asprosin or adiponectin. CONCLUSION: High serum asprosin and low adiponectin level might be associated with the presence of insulin resistance in NAFLD, and the combination of asprosin and adiponectin could be a novel biomarker for diagnosing NAFLD. These data needed to be confirmed and extended in further large-population, well-designed clinical studies.
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Adiponectina/sangre , Fibrilina-1/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
Understanding the factors that may affect behavioural thermoregulation of endangered reptiles is important for their conservation because thermoregulation determines body temperatures and in turn physiological functions of these ectotherms. Here we measured seasonal variation in operative environmental temperature (Te), body temperature (Tb), and microhabitat use of endangered crocodile lizards (Shinisaurus crocodilurus) from a captive population, within open and shaded enclosures, to understand how they respond to thermally challenging environments. Te was higher in open enclosures than in shaded enclosures. The Tb of lizards differed between the open and shaded enclosures in summer and autumn, but not in spring. In summer, crocodile lizards stayed in the water to avoid overheating, whereas in autumn, crocodile lizards perched on branches seeking optimal thermal environments. Crocodile lizards showed higher thermoregulatory effectiveness in open enclosures (with low thermal quality) than in shaded enclosures. Our study suggests that the crocodile lizard is capable of behavioural thermoregulation via microhabitat selection, although overall, it is not an effective thermoregulator. Therefore, maintaining diverse thermal environments in natural habitats for behavioural thermoregulation is an essential measure to conserve this endangered species both in the field and captivity.
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Conducta Animal , Temperatura Corporal , Lagartos/fisiología , Termotolerancia , Animales , Ecosistema , Especies en Peligro de Extinción , Estaciones del AñoRESUMEN
Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplant (LT). Ischemia-reperfusion injury (IRI) promotes chronic rejection (CR) and CLAD, but the underlying mechanisms are not well understood. To examine mechanisms linking IRI to CR, a mouse orthotopic LT model using a minor alloantigen strain mismatch (C57BL/10 [B10, H-2b ] â C57BL/6 [B6, H-2b ]) and isograft controls (B6âB6) was used with antecedent minimal or prolonged graft storage. The latter resulted in IRI with subsequent airway and parenchymal fibrosis in prolonged storage allografts but not isografts. This pattern of CR after IRI was associated with the formation of B cell-rich tertiary lymphoid organs within the grafts and circulating autoantibodies. These processes were attenuated by B cell depletion, despite preservation of allograft T cell content. Our observations suggest that IRI may promote B cell recruitment that drives CR after LT. These observations have implications for the mechanisms leading to CLAD after LT.
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Autoanticuerpos/inmunología , Linfocitos B/inmunología , Fibrosis/patología , Rechazo de Injerto/patología , Supervivencia de Injerto/inmunología , Trasplante de Pulmón/efectos adversos , Daño por Reperfusión/complicaciones , Aloinjertos , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Fibrosis/etiología , Rechazo de Injerto/etiología , Masculino , Ratones , Daño por Reperfusión/patologíaRESUMEN
A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.
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The escalating proliferation of cyanobacteria poses significant taste and odor (T/O) challenges, impacting freshwater ecosystems, public health, and water treatment costs. We examined monthly variations in four T/O compounds from September 2011 to August 2012 in Chaohu Lake's eastern drinking water source (DECL). More importantly, we compared the reported T/O occurrence and the related factors in freshwater bodies worldwide. The assessment of T/O issues indicated a severe and widespread problem, with many cases surpassing odor threshold values. Remarkably, China reported the highest frequency and severity of odor-related problems. A temporal analysis revealed variations in odor occurrences within the same water body across different years, emphasizing the need to consider high values in all seasons for water safety. Globally, T/O issues were widespread, demanding attention to variations within the same water body and across different layers. Algae were crucial contributors to odor compounds, necessitating targeted interventions due to diverse odorant sources and properties. A correlation analysis alone lacked definitive answers, emphasizing the essential role of further validation, such as algae isolation. Nutrients are likely to have influenced the T/O, as GSM and MIB correlated positively with nitrate and ammonia nitrogen in DECL, resulting in proposed control recommendations. This study offers recommendations for freshwater ecosystem management and serves as a foundation for future research and management strategies to address T/O challenges.
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Agua Potable , Lagos , Odorantes , Gusto , Odorantes/análisis , China , Agua Potable/análisis , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Cianobacterias , Estaciones del Año , Agua DulceRESUMEN
Ferrate (Fe(VI)) is an emerging green oxidant which has great potential and prospect in water disinfection. However, the effects of water quality on Fe(VI) disinfection remain unclear. This study systematically investigated the effects of pH, organic matters and inorganic ions on Fe(VI) inactivation of Escherichia coli (E. coli). Results showed that pH was the dominant influencing factor and the inactivation efficiency as well as inactivation rate constant was negatively correlated with pH (6.8-8.4). HFeO4- was found to be the critical Fe(VI) species contributing to the inactivation. As for organic matters (0-5 mg C/L), protein and humic acid significantly accelerated the decay of Fe(VI) and had negative effects on the inactivation efficiency, while polysaccharide slightly inhibited the inactivation due to the low reactivity with Fe(VI). As for inorganic ions, bicarbonate (0-2 mM) could stabilize Fe(VI) and decreased the inactivation rate constant, while ammonium (0-1 mM) had little effect on the inactivation of E. coli. In addition, the comprehensive effects of water quality on Fe(VI) disinfection in actual reclaimed water were also evaluated. The inactivation of E. coli in secondary effluent and denitrifying effluent was found to be inhibited compared to that in phosphate buffer. Overall, this study is believed to provide valuable information on Fe(VI) disinfection for water and wastewater treatment practices.
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Contaminantes Químicos del Agua , Purificación del Agua , Escherichia coli , Calidad del Agua , Hierro/química , Oxidantes/química , Purificación del Agua/métodos , Oxidación-Reducción , Contaminantes Químicos del Agua/análisisRESUMEN
Chlorination is the most widely used disinfection technology due to its simplicity and continuous disinfection ability. However, the drawbacks of disinfection by-products and chlorine-resistant bacteria have gained increasing attention. Nowadays, ferrate (Fe(VI)) is a multifunctional and environmentally friendly agent which has great potential in wastewater reclamation and reuse. This study investigated synergistic Fe(VI) and chlorine technology for reclaimed water disinfection in terms of microbial control and chlorine decay mitigation. Specifically, synergistic disinfection significantly improved the inactivation efficiency on total coliform, Escherichia coli and heterotrophic bacteria compared to sole chlorination. Synergistic disinfection also exhibited superior performance on controlling the relative abundance of chlorine-resistant bacteria and pathogenic bacteria. In addition, the decay rate of residual chlorine was relatively lower after Fe(VI) pretreatment, which was beneficial for microbial control during the reclaimed water distribution process. Technical and economic analyses revealed that synergistic Fe(VI) and chlorine disinfection was suitable and feasible. Results of this study are believed to provide useful information and alternative options on the optimization of reclaimed water disinfection.
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Cloro , Desinfección , Hierro , Eliminación de Residuos Líquidos , Purificación del Agua , Cloro/farmacología , Desinfección/métodos , Purificación del Agua/métodos , Eliminación de Residuos Líquidos/métodos , Desinfectantes/farmacología , Aguas Residuales/microbiología , Escherichia coli/efectos de los fármacos , Microbiología del AguaRESUMEN
Background: Both Sophora flavescens (SF) and Astragalus mongholicus (AM) are known for their anti-inflammatory, antifibrotic, and anticancer activities. However, the efficacy, multi-target mechanisms, and therapeutic substances of SF-AM herb pair on the progression of hepatitis-cirrhosis-hepatocellular carcinoma hepatocellular carcinoma (HCC) remain unclear. Purpose: To investigate the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the progression of hepatitis-cirrhosis-HCC. Methods: Firstly, diethylnitrosamine was used to establish the hepatitis-cirrhosis-HCC model. HE staining and non-targeted metabolomics were used to evaluate the efficacy of SF-AM herb pair. Subsequently, the absorbed components of SF-AM herb pair in the plasma of rats were determined through HPLC-Q-TOF-MS/MS analysis. Flow cytometry, Western blot, and qRT-PCR were then employed to assess CD4+ and CD8+ T lymphocytes, PI3K/Akt signaling pathway-related proteins, and their corresponding mRNAs. Simultaneously, the efficacy and mechanism of SF-AM herb pair on HCC were confirmed by in vitro experiments. Finally, Pearson correlation analysis was performed between pharmacodynamic indicators and in vivo components to identify the potential therapeutic substances of SF-AM herb pair. Results: SF-AM herb pair can alleviate the pathological damage and reverse metabolic abnormalities in hepatitis, cirrhosis, and HCC rats, particularly during the hepatitis and cirrhosis stages. Pharmacological researches have demonstrated that SF-AM herb pair can increase the proportion of CD8+ T lymphocytes, inhibit the expression of PI3K, Akt, p-Akt, NF-κB p65, NF-κB pp65, and Bcl-2, as well as increase the expression of IκBα, Bax, and cleaved caspase-3. These findings suggest that SF-AM herb pair has the ability to enhance immunity, anti-inflammation and promote apoptosis. Cell experiments have shown that SF-AM herb pair can inhibit the proliferation of HepG2 cell and regulate the PI3K/Akt signaling pathway. Moreover, 23 absorbed prototypical components and 53 metabolites of SF-AM herb pair were identified at different stages of HCC rats. Pearson correlation analysis revealed that matrine, cytisine, wogonoside, and isoastragaloside are potential therapeutic substances in SF-AM herb pair for the prevention and treatment of hepatitis, cirrhosis, and HCC. Conclusion: In summary, this study revealed the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the hepatitis-cirrhosis-HCC axis and provided a reference for its clinical application.
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Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.
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Envejecimiento , Perfilación de la Expresión Génica , Glucólisis , Obesidad , Envejecimiento/metabolismo , Envejecimiento/genética , Obesidad/metabolismo , Obesidad/genética , Obesidad/patología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Fibras Musculares Esqueléticas/metabolismo , Transcriptoma/genética , Fibras Musculares de Contracción Lenta/metabolismo , HumanosRESUMEN
Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. Lect2 inhibited EOC cells' invasive phenotype and suppressed EOC's transcoelomic metastasis by targeting c-Met signaling. In addition, Lect2 downregulation induced the accumulation and activation of myeloid-derived suppressor cells (MDSCs). This fostered an immunosuppressive microenvironment in EOC by inhibiting T-cell activation and skewing macrophages toward an M2 phenotype. The therapeutic efficacy of programmed cell death-1 (PD-1)/PD-L1 pathway blockade for the ID8 model was significantly hindered. Overall, our data highlight multiple functions of Lect2 during EOC progression and reveal a rationale for synergistic immunotherapeutic strategies by targeting Lect2.
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Neoplasias Ováricas , Humanos , Ratones , Animales , Femenino , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/metabolismo , Macrófagos/metabolismo , Transducción de Señal , Inmunosupresores , Modelos Animales de Enfermedad , Microambiente Tumoral/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismoRESUMEN
We determined the effects of nitrification capacity and environmental factors on landfill methane oxidation potential (MOP) using an aged refuse in laboratory batch assays and compared it with two different types of soils. The nitrogen conversion in the three experimental materials after 120 h incubation yielded first-order reaction kinetics at an initial concentration of 200 mg kg(-1) NH4(+)-N. The net nitrification rate for the aged refuse was 1.50 (p < 0.05) and 2.08 (p < 0.05) times that of the clay soil and the sandy soil, respectively. The net NO3(-)-N generation rate by the aged refuse was 1.93 (p < 0.05) and 2.57 (p < 0.05) times that of the clay soil and the sandy soil, respectively. When facilitated by ammonia-oxidizing bacteria during CH4 co-oxidation, the average value of the MOP in the aged refuse at a temperature range of 4-45 °C was 2.34 (p < 0.01) and 4.71 (p < 0.05) times greater than that of the clay soil and the sandy soil, respectively. When the moisture content ranged from 8 to 32% by mass, the average values for the MOP in the aged refuse were 2.08 (p < 0.01) and 3.15 (p < 0.01) times greater than that of the clay soil and the sandy soil, respectively. The N2O fluxes in the aged refuse at 32% moisture content were 5.33 (p < 0.05) and 12.00 (p < 0.05) times more than in the clay and the sandy soil, respectively. The increase in N2O emissions from a municipal solid waste landfill can be neglected after applying an aged refuse bio-cover because of the much higher MOP in the aged refuse. The calculated maximum MOP value in the aged refuse was 12.45 µmol g(-1) d.w. h(-1), which was much higher than the documented data.