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Sweating is a basic skin function in body temperature control. In sweat glands, salt excretion and reabsorption are regulated to avoid electrolyte imbalance. To date, the mechanism underlying such regulation is not fully understood. Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), a cardiac hormone essential for normal blood volume and pressure. Here, we report an unexpected role of corin in sweat glands to promote sweat and salt excretion in regulating electrolyte homeostasis. In human and mouse eccrine sweat glands, corin and ANP are expressed in the luminal epithelial cells. In corin-deficient mice on normal- and high-salt diets, sweat and salt excretion is reduced. This phenotype is associated with enhanced epithelial sodium channel (ENaC) activity that mediates Na+ and water reabsorption. Treatment of amiloride, an ENaC inhibitor, normalizes sweat and salt excretion in corin-deficient mice. Moreover, treatment of aldosterone decreases sweat and salt excretion in wild-type (WT), but not corin-deficient, mice. These results reveal an important regulatory function of corin in eccrine sweat glands to promote sweat and salt excretion.
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Glándulas Ecrinas/fisiología , Serina Endopeptidasas/metabolismo , Cloruro de Sodio/metabolismo , Animales , Factor Natriurético Atrial/metabolismo , Glándulas Ecrinas/metabolismo , Electrólitos/metabolismo , Folículo Piloso/metabolismo , Homeostasis/fisiología , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Serina Endopeptidasas/genética , Sudor/química , Agua/metabolismoRESUMEN
Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Krüppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to the CORIN promoter and enhances the promoter activity. Disruption of the KLF17 gene in the endometrial cells abolishes CORIN expression. In mice, Klf17 is up-regulated in the pregnant uterus. Klf17 deficiency prevents uterine Corin expression in pregnancy. Moreover, Klf17-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulating Corin expression and uterine physiology in pregnancy.
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Arterias/fisiología , Serina Endopeptidasas/genética , Factores de Transcripción/metabolismo , Útero/fisiología , Animales , Células Cultivadas , Femenino , Fertilidad/genética , Regulación de la Expresión Génica , Humanos , Hipertensión Inducida en el Embarazo/genética , Masculino , Ratones , Ratones Noqueados , Embarazo , Regiones Promotoras Genéticas , Proteinuria/genética , Serina Endopeptidasas/metabolismo , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Útero/irrigación sanguínea , Útero/metabolismo , Remodelación VascularRESUMEN
BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.
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Vía de Señalización Hippo/fisiología , Hepatopatías , Proteínas Serina-Treonina Quinasas/metabolismo , Daño por Reperfusión , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Animales , Proliferación Celular , Descubrimiento de Drogas , Hepatocitos/fisiología , Humanos , Inflamación/metabolismo , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Ratones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Regulación hacia ArribaRESUMEN
BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Hepáticas/patología , Inflamación/patología , Linfocitos/patología , NeutrófilosRESUMEN
BACKGROUND: The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis) in patients with genital tract diseases in Jiangsu, China. METHODS: A total of 3,321 patients suspected with genital tract infectious diseases were enrolled in this study from September 2017 to September 2020. The Mycoplasma detection and antimicrobial susceptibility were tested using the commercially available Mycoplasma kit. RESULTS: Among the 3,321 specimens tested, 1,503 (45.3%) were positive for Mycoplasmas, and the proportion of mono-infection of U. urealyticum is highest (79.5%). The overall infection rate has been increasing in the past 3 years. The positive rate in females (68.7%) was higher than in males (25.0%), and the main infection age group was 20 - 39 (81.2%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to gatifloxacin, josamycin, minocycline, and doxycycline (6.0%, 6.5%, 3.1%, and 3.2%, respectively). However, the antimicrobial resistance rates to azithromycin, clindamycin, roxithromycin, sparfloxacin, and ofloxacin were relatively high (45.4%, 42.1%, 34.9, 36.0, and 65.5%, respectively). Antimicrobial resistance of U. urealyticum and M. hominis to these 14 drugs have been changing in the past 3 years. CONCLUSIONS: In total, these preliminary data showed the prevalence and antimicrobial resistance status of U. urealyticum and M. hominis in patients suspected with genital tract infectious diseases, which has use for reference on both prevention and treatment of diseases caused by them.
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Enfermedades Transmisibles , Infecciones por Mycoplasma , Mycoplasma , Infecciones del Sistema Genital , Infecciones por Ureaplasma , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/epidemiología , Mycoplasma hominis , Prevalencia , Infecciones del Sistema Genital/tratamiento farmacológico , Infecciones del Sistema Genital/epidemiología , Infecciones por Ureaplasma/diagnóstico , Infecciones por Ureaplasma/tratamiento farmacológico , Infecciones por Ureaplasma/epidemiología , Ureaplasma urealyticumRESUMEN
A three-dimensional (3D) printed biodegradable hydrogel scaffold with a strong self-expanding ability to conform to the contour of irregular bone defects and be closely adjacent to host tissues is reported herein. The scaffold has a triple cross-linked network structure consisting of photo-cross-linked polyacrylamide (PAAM) and polyurethane (PU) as the primary IPN network and chemical cross-linked gelatin (Gel) as the secondary network, which confers the scaffold with good mechanical properties. The addition of PU in the polymerization process of acrylamide (AAM) can improve the ultraviolet (UV) photocuring efficiency of the hydrogel and incorporate abundant hydrogen bonds between the PAAM copolymer chain and the PU chain. The results show that the hydrogel scaffold contains regular structures with smooth morphology, excellent dimensional stability, and uniform aperture. The degradation rate of the hydrogel scaffold is controllable through adjusting cross-linking agents and can be up to about 60% after degradation for 28 days. More importantly, the rapid self-inflating characteristic of the scaffold in water, that is, the volume of hydrogel scaffold can increase to about 8 times that of their own in an hour and can generate a slight compressive stress on the surrounding host tissue, thus stimulating the reconstruction and growth of new bone tissues. The in vitro experiment indicates that the scaffold is nontoxic and biocompatible. The in vivo experiment shows that the PU/PAAM/Gel chemically cross-linked scaffold displays the desirable osteogenic capability. This UV-curable 3D printed self-adaptive and degradable hydrogel scaffold holds great potential for nonload-bearing bone repair.
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Implantes Absorbibles , Resinas Acrílicas/química , Gelatina/química , Poliuretanos/química , Impresión Tridimensional , Andamios del Tejido , Células 3T3 , Animales , Regeneración Ósea/efectos de los fármacos , Huesos/lesiones , Supervivencia Celular , Femenino , Hidrogeles , Ratones , Microscopía Electrónica de Rastreo , Osteoblastos/fisiología , RatasRESUMEN
Corin is a transmembrane serine protease that activates atrial natriuretic peptide, a cardiac hormone essential for normal blood pressure. Corin is synthesized as a zymogen and activated on the cell surface. In previous studies, we identified a CORIN variant allele with an adenine insertion in the 5'-end of the coding region in â¼5% of hypertensive individuals in a Chinese population. The protein, named insA, encoded by the CORIN variant allele has a shortened cytoplasmic tail and reduced atrial natriuretic peptide processing activity. It remains unknown how a shortened cytoplasmic tail impairs corin function. In this study, we expressed a series of corin mutants with different N-terminal sequences and analyzed them by Western blotting, flow cytometry, protein chase, and immunostaining. Our results revealed that a Gly-Asn sequence after the initiating Met at the newly generated N-terminus was responsible for delaying corin trafficking in the Golgi. Deletion of the N-terminal Gly and Asn residues increased the intracellular trafficking, cell surface expression, and activation cleavage of the insA variant. These results help to explain how the CORIN variant allele impairs corin structure and function as an underlying mechanism in hypertension.
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Hipertensión/metabolismo , Serina Endopeptidasas/metabolismo , Células HEK293 , Humanos , Hipertensión/genética , Mutación , Dominios Proteicos , Transporte de Proteínas , Serina Endopeptidasas/análisis , Serina Endopeptidasas/genéticaRESUMEN
B-cell lymphoma 2 (Bcl-2)-associated transcription factor 1 (Bclaf1) is known to be involved in diverse biological processes, but, to date, there has been no evidence for any functional role of Bclaf1 in hepatocellular carcinoma (HCC) progression. Here, we demonstrate that Bclaf1 is frequently up-regulated in HCC and that Bclaf1 up-regulation is associated with Edmondson grade, lower overall survival rates, and poor prognosis. Overexpression of Bclaf1 in HCC cell lines HepG2 and Huh7 promoted proliferation considerably, whereas Bclaf1 knockdown had the opposite effect. Xenograft tumors grown from Bclaf1 knockdown Huh7 cells had smaller tumor volumes than tumors grown from control cells. Furthermore, our study describes MYC proto-oncogene (c-Myc) as a downstream target of Bclaf1, given that Bclaf1 regulates c-MYC expression posttranscriptionally by its RS domain. To exert this function, Bclaf1 must interact with the molecular chaperone, heat shock protein 90 alpha (Hsp90α). In HCC tissue samples, Hsp90α levels were also increased significantly and Hsp90α-Bclaf1 interaction was enhanced. Bclaf1 interacts with the C-terminal domain of Hsp90α, and this interaction is disrupted by the C-terminal domain inhibitor, novobiocin (NB), resulting in proteasome-dependent degradation of Bclaf1. Moreover, NB-induced disruption of Hsp90α-Bclaf1 interaction dampened the production of mature c-MYC mRNA and attenuated tumor cell growth in vitro and in vivo. Conclusion: Our findings suggest that Bclaf1 affects HCC progression by manipulating c-MYC mRNA stability and that the Hsp90α/Bclaf1/c-Myc axis might be a potential target for therapeutic intervention in HCC.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Represoras/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , China/epidemiología , Femenino , Genes myc , Proteínas HSP90 de Choque Térmico/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Masculino , Ratones Desnudos , Persona de Mediana Edad , Estabilidad Proteica , Proto-Oncogenes MasRESUMEN
Virus-induced flowering (VIF) exploits RNA or DNA viruses to express flowering time genes to induce flowering in plants. Such plant virus-based tools have recently attracted widespread attention for their fundamental and applied uses in flowering physiology and in accelerating breeding in dicotyledonous crops and woody fruit-trees. We now extend this technology to a monocot grass and a cereal crop. Using a Foxtail mosaic virus (FoMV)-based VIF system, dubbed FoMViF, we showed that expression of florigenic Flowering Locus T (FT) genes can promote early flowering and spikelet development in proso millet, a C4 grass species with potential as a nutritional food and biofuel resource, and in non-vernalized C3 wheat, a major food crop worldwide. Floral and spikelet/grain induction in the two monocot plants was caused by the virally expressed untagged or FLAG-tagged FT orthologs, and the florigenic activity of rice Hd3a was more pronounced than its dicotyledonous counterparts in proso millet. The FoMViF system is easy to use and its efficacy to induce flowering and early spikelet/grain production is high. In addition to proso millet and wheat, we envisage that FoMViF will be also applicable to many economically important monocotyledonous food and biofuel crops.
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Fitomejoramiento , Potexvirus , Productos Agrícolas/genética , TriticumRESUMEN
Escherichia coli (E. coli) O1-induced diarrhea is associated with intestinal microbial imbalance, however, the results of using oral antibiotics still remain poor. To overcome such problem, our study investigates the role of metabolites from stable flies (MSF) in the occurrence of diarrhea. The amino acid composition and molecular weight analysis of MSF by RP-HPLC and GPC, respectively. Besides the normal control group, SPF mice in other group were inoculated with E. coli O1 received treatment as follows over a period of 7 days saline solution (E. coli control), ciprofloxacin (0.13â¯g/kg; positive control) and MSF (2, 4 and 8â¯mg/kg) dosage. Throughout the experiment, defecation and body weights were examined and recorded. On the eighth day, after administering anesthesia, blood, tissue of small intestine samples were obtained for immunological and anti-oxidant. Small intestinal tissues and cecum contents samples were used for histopathological and 16S rDNA sequencing analysis. Our showed that MSF was rich in isoleucine, and its molecular weight less than 400â¯Da is 60.03%. MSF (4 and 8â¯mg/kg) and ciprofloxacin, significantly decreased IL-6, IL-8 and TNF-α levels, whereas, increased IL-2, IL-4, IL-10, INF-γ, IgA and IgG levels in mice having diarrhea. These treatments also reversed intestinal flora imbalance as indicated by the increased in Firmicutes-to-Bacteroidetes ratio and Clostridium levels (Pâ¯<â¯0.05) and improved 5-HT, CAT and SOD levels. MSF favored diarrhea management as compared to ciprofloxacin, suggesting that MSF can be used in the management of E. coli O1-induced diarrhea, in normal gut microbiota and normal intestinal antioxidant function.
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Diarrea/tratamiento farmacológico , Sistema Inmunológico/inmunología , Muscidae/química , Animales , Antioxidantes/uso terapéutico , Peso Corporal , Ciego , Ciprofloxacina/farmacología , Citocinas/sangre , Citocinas/metabolismo , Diarrea/patología , Diarrea/prevención & control , Modelos Animales de Enfermedad , Escherichia coli Enterotoxigénica/inmunología , Infecciones por Escherichia coli/patología , Microbioma Gastrointestinal/efectos de los fármacos , Intestino Delgado , Intestinos/efectos de los fármacos , Intestinos/patología , Larva/química , Masculino , RatonesRESUMEN
The effects of nisin on the neurochemicals, Aquaporin-3 (AQP-3) and intestinal microorganisms in the brain-gut axis of mice were analyzed by using enzyme linked immune sorbent assay (ELISA) and high throughput sequencing in this investigation, to further revealed the relationship between intestinal flora abundance in mice and neurochemicals in the brain-gut axis. Using HE staining found damage of structure of small intestine villi in the model group (Escherichia coli O1, E. coli O1). Compared with normal control and ciprofloxacin groups, using ELISA showed that nisin increased the highest norepinephrine (NE) expression in the brain, expression of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the duodenum, and increased the expression of AQP-3 in jejunum. Using high-throughput sequencing showed the highest diversity of cecal microflora in nisin group (ACE-indexâ¯=â¯1417.25, Chao1-indexâ¯=â¯1378.45), but the cecal microflora in the negative control group (ACE-indexâ¯=â¯969.54, Chao1-indexâ¯=â¯340.29) exhibited the lowest species diversity. Our data indicated that nisin regulates neurochemicals, AQP-3 and cecal microflora imbalance in mice.
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Encéfalo/efectos de los fármacos , Diarrea/metabolismo , Diarrea/microbiología , Escherichia coli/patogenicidad , Microbioma Gastrointestinal/efectos de los fármacos , Nisina/farmacología , Animales , Acuaporina 3/sangre , Acuaporina 3/efectos de los fármacos , Biodiversidad , Ciego/efectos de los fármacos , Ciego/microbiología , Ciego/patología , ADN Bacteriano/análisis , Dopamina/sangre , Dopamina/farmacología , Duodeno/metabolismo , Duodeno/patología , Íleon/metabolismo , Íleon/patología , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Yeyuno/patología , Masculino , Ratones , Norepinefrina/sangre , Norepinefrina/farmacología , Serotonina/sangre , Serotonina/metabolismoRESUMEN
Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum. Because of nonspecific clinical manifestations, diagnosis of HGA highly depends on laboratory tests. Identification of immunoreactive proteins is prerequisite for development of specific and sensitive immunoassays for HGA. In this study, we identified novel immunoreactive proteins of A. phagocytophilum. Previous studies indicated that secreted proteins of A. phagocytophilum and other bacteria can be immunoreactive antigens. Here we in silico screened A. phagocytophilum genome for encoding proteins which bear features of type IV secretion system substrates. Among seventy seven predicted proteins, fourteen proteins were determined for antigenicity and nine proteins were showed to be immunoreactive antigens. In addition, an APH1384 peptide harboring a B cell epitope predicted by bioinformatics was found specifically reacting with anti-A. phagocytophilum sera. Hereby, we identified novel immunoreactive proteins and delineated a specific epitope of A. phagocytophilum, which might be employed for HGA diagnosis.
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Anaplasma phagocytophilum/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Ehrlichiosis/diagnóstico , Epítopos/inmunología , Anaplasma phagocytophilum/genética , Proteínas Bacterianas/genética , Biología Computacional , Ehrlichiosis/inmunología , Epítopos/genética , Humanos , Factores de Virulencia/genética , Factores de Virulencia/inmunologíaRESUMEN
Corin is a serine protease that activates atrial natriuretic peptide (ANP). CORIN gene variants have been reported in patients with hypertension. To date, however, the prevalence of CORIN variants in hypertensive patients remains unknown. To understand the prevalence and functional significance of CORIN variants in hypertension, we sequenced CORIN exons in 300 normal and 401 hypertensive individuals in a Chinese population and identified nine nonsynonymous variants, of which eight were not characterized previously. Among them, variants c.131A > G (p.Tyr13Cys), c.376G > T (p.Asp95Tyr), c.1094T > G (p.Leu334Trp), and c.1667G > A (p.Arg525His) occurred similarly in both normal and hypertensive individuals. Variants c1139G > A (p.Arg349His), c.2689C > T (p.Pro866Ser), and c.2864C > T (p.Thr924Met) were found once each in hypertensive individuals. Variant c.1683G > T (p.Arg530Ser) occurred preferentially in hypertensive individuals [10/401 (2.5%) vs. 1/300 (0.3%) in normal individuals; P = 0.023], which was confirmed in another independent cohort [9/368 (2.44%) in hypertensive and 2/377 (0.53%) in normal individuals; P = 0.033]. In biochemical and cell-based functional studies, variants p.Arg530Ser and p.Thr924Met, but not p.Tyr13Cys, p.Asp95Tyr, p.Leu334Trp, p.Arg349His, p.Arg525His, and p.Pro866Ser, exhibited reduced pro-ANP processing activity, which was caused by endoplasmic reticulum retention and poor zymogen activation, respectively. These results indicate that genetic variants impairing corin function are not uncommon in general populations and that such variants may be an important contributing factor in hypertension.
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Precursores Enzimáticos/metabolismo , Variación Genética , Hipertensión/genética , Modelos Moleculares , Serina Endopeptidasas/genética , Factor Natriurético Atrial/genética , Factor Natriurético Atrial/metabolismo , China , Estudios de Cohortes , Exones/genética , Humanos , Hipertensión/metabolismo , Transporte de Proteínas , Análisis de Secuencia de ADN , Serina Endopeptidasas/metabolismoRESUMEN
Salmonella enterica serovar typhimurium (S. typhimurium) is globally distributed and causes massive morbidity and mortality in humans and animals. S. typhimurium carries Salmonella plasmid virulence (spv) locus, which is highly conserved and closely related to bacterial pathogenicity, while its exact role in host immune responses during infection remains to be elucidated. To counteract the invaders, the host has evolved numerous strategies, among which the innate immunity and autophagy act as the first defense. Recently, zebrafish has been universally accepted as a valuable and powerful vertebrate model in analyzing bacteria-host interactions. To investigate whether spv locus enhances the virulence of Salmonella by exerting an effect on the host early defense, zebrafish larvae were employed in this study. LD50 of S. typhimurium to zebrafish larvae and bacterial dissemination were analyzed. Sudan black B and neutral red staining were performed to detect the responses of neutrophils and macrophages to Salmonella infection. Autophagy agonist Torin1 and inhibitor Chloroquine were used to interfere in autophagic flux, and the protein level of Lc3 and p62 were measured by western blotting. Results indicated that spv locus could decrease the LD50 of S. typhimurium to zebrafish larvae, accelerate the reproduction and dissemination of bacteria by inhibiting the function of neutrophils and macrophages. Moreover, spv locus restrained the formation of autophagosomes in the earlier stage of autophagy. These findings suggested the virulence of spv locus involving in suppressing host innate immune responses for the first time, which shed new light on the role of spv operon in Salmonella pathogenicity.
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Proteínas Bacterianas/genética , Infecciones por Salmonella/microbiología , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidad , Factores de Virulencia/genética , Animales , Proteínas Bacterianas/metabolismo , Modelos Animales de Enfermedad , Humanos , Infecciones por Salmonella/fisiopatología , Virulencia , Factores de Virulencia/metabolismo , Pez CebraRESUMEN
The infections of Mycoplasmas and Chlamydiae are still severe in patients with genital tract diseases and antimicrobial resistance for these organisms has been changing in recent years. In this study, we reported the prevalence status of Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis in 965 patients with genital tract infection in Shanghai from January 2011 to December 2014 and analyzed the antimicrobial resistance of U. urealyticum and M. hominis to 12 kinds of antimicrobial drugs by using commercial kits and SPSS13.0 software. Here, we found the infection of U. urealyticum was the most frequent among these three organisms. The total infection rate for containing any organisms of them was 49.5%, and it has been increasing in recent 4 years. Positive rate in female (53.3%) was higher than male's (34.8%), and the high risk population was 20-39 years old (56.7%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to minocycline, doxycycline, josamycin and gatifloxacin (6.5%, 7.2%, 13.5% and 8.6%, respectively). However, for erythromycin, roxithromycin, thiamphenicol and clindamycin, the resistance rates were relatively high (41.9%, 47.2%, 62.3% and 74.9%, respectively). U. urealyticum and M. hominis displayed a declined trend of the antimicrobial resistance to 12 kinds of drugs detected in this study. In total, these preliminary data showed the prevalence of Mycoplasmas and Chlamydiae in patients and the antimicrobial resistance status of Mycoplasmas, which has use for reference on both prevention and treatment of diseases caused by them.
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Infecciones por Chlamydia/epidemiología , Infecciones por Mycoplasma/epidemiología , Infecciones del Sistema Genital/epidemiología , Infecciones del Sistema Genital/microbiología , Infecciones por Ureaplasma/epidemiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Niño , Preescolar , China , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/aislamiento & purificación , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/microbiología , Mycoplasma hominis/aislamiento & purificación , Prevalencia , Infecciones del Sistema Genital/tratamiento farmacológico , Infecciones por Ureaplasma/tratamiento farmacológico , Infecciones por Ureaplasma/microbiología , Ureaplasma urealyticum/aislamiento & purificación , Adulto JovenRESUMEN
As a new type of high-performance material, gradient structural steel is widely used in engineering fields due to its unique microstructure and excellent mechanical properties. For the prevalent fatigue failure problem, the rate of change in the local grain size gradients along the structure (referred to as the gradient rate) is a key parameter in the design of gradient structures, which significantly affects the fatigue performance of gradient structural steel. In this study, a new method of 'Voronoi primary + secondary modeling' is adopted to successfully establish three typical high-strength steel models corresponding to the convex-, linear-, and concave-type gradient rates for gradient structures, focusing on the stress-strain response and crack propagation in structural steel with different gradient rates under cyclic loading. It was found that the concave gradient rate structural model is dominated by finer grains with larger volume fraction, which is conducive to hindering fatigue crack propagation and has the longest fatigue life, which is 16.16% longer than that of the linear gradient rate structure and 23.66% longer than that of the convex gradient rate structure. The simulation results in this study are consistent with the relevant experimental phenomena. Therefore, when regulating the gradient rate, priority should be given to increasing the volume fraction of fine grains and designing a gradient rate structure dominated by fine grains to improve the fatigue life of the material. This study presents a new strategy for designing engineering materials with better service performance.
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Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.
The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (antiPD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 34 weeks after IMRT initiation and platelet-to-lymphocyte ratio 34 weeks after IMRT initiation demonstrated good reliability.
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Based on previous literature, the present study examines the effects of background music on English reading comprehension using eye tracking techniques. All the participants, whose first language was Chinese, were selected from a foreign language college and all of them were sophomores who majored in English. The experiment in this study was a 2 (music tempo: fast and slow) × 2 (text difficulty: difficult and easy) × 2 (background music preference: high and low) mixed design. Both musical tempo and English reading passage were within-subjects factors, and the level of music listening preference was a between-subjects factor. The results showed that the main effect of the music tempo was statistically significant, which indicated that participants read texts more quickly in the fast-tempo music condition than in the slow-tempo music condition. Furthermore, the main effect of the text difficulty was statistically significant. Additionally, the interaction between the text difficulty and music tempo was statistically significant. The music tempo had a greater effect on easy texts than on difficult texts. The results of this study reveal that it is beneficial for people who have a stronger preference for music listening to conduct English reading tasks with fast-tempo music. It is detrimental for people who have little preference for background music listening to complete difficult English reading tasks with slow-tempo music.
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One of the effective methods for the long-term preservation of mammalian genetic resources is the cryopreservation of semen. However, a number of parameters, including diluents, the rate of freezing and thawing, cryoprotectants, etc., can easily alter the survival of frozen-thawed sperm. Numerous studies have documented the addition of a variety of zinc compounds, to the diluents used to cryopreserve sperm. The primary objective of this review is to briefly describe that adding zinc to diluents as an antioxidant significantly enhances frozen-thawed sperm quality. Second, a summary of the present understanding of zinc's molecular mechanism on semen cryopreservation is provided. Thirdly, this study addresses that nanoparticles of zinc can offer suggestions for raising cryopreservation effectiveness.
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Semen , Zinc , Masculino , Animales , Zinc/farmacología , Criopreservación/veterinaria , Crioprotectores/farmacología , Espermatozoides , MamíferosRESUMEN
BACKGROUND: The effects of Arula-7 powder (ASP) on diarrhea and intestinal barrier function associated with its regulation of intestinal microflora in calves infected with pathogenic Escherichia coli O1 (E. coli O1) were studied. METHOD: Twenty Holstein calves were randomly divided into four treatment groups: normal control (NC), model control (MC), 0.5 mg/kg ciprofloxacin (CIP) and 2.50 g/kg ASP groups. RESULTS: ASP inhibited the relative abundance of Proteobacteria, Selenomonadales, and Enterobacteriales, and increased the relative abundance of Lactobacillus, Faecalibacterium, and Alloprevotella. Moreover, we demonstrated for the first time that the ASP and CIP promoted weight gain, reduced the diarrhea rate (P < 0.05), and enhanced antioxidant capacity (P < 0.05) due to the increase in average daily gain (ADG), total protein (TP), and albumin (ALB). In addition, ASP and CIP increased the expression of Zunola occludens-1 (ZO-1), Occludin, and Claudin-1 in the ileum (P < 0.05), and improved immunity due to increase levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-γ (IFN-γ), immunoglobulin A (IgA), and immunoglobulin G (IgG) in the serum, strengthened CD4+T levels in the ileal mucosa and reducing CD8+T and CD11c+T (P < 0.05). CONCLUSION: Hence, The intestinal microbiota environment formed by early intervention of ASP powder has a protective effect on the intestinal mucosal function of calves infected with pathogenic E. coli. Video Abstract.