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The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.
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Intestinos , Análisis de la Célula Individual , Humanos , Diferenciación Celular/genética , Cromatina/genética , Células Epiteliales/citología , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Mucosa Intestinal/citología , Intestinos/citología , Intestinos/inmunología , Análisis de Expresión Génica de una Sola CélulaRESUMEN
The existing body of research underscores the critical impact of intratumoral microbiomes on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly in reshaping the tumor microenvironment and influencing gemcitabine resistance. However, peritumoral tissues' microbiome, distinct from PDAC tumors, remain understudied, and Western-centric analyses overlooking potential variations in dietary-influenced microbiomes. Our study addresses this gap by 16â¯S rRNA sequencing of PDAC tumors and matched peritumoral tissues from Chinese Mainland patients. Our research has uncovered that the microbiome composition within tumors and paired peritumoral tissues exhibits a high degree of similarity, albeit with certain discrepancies. Notably, Exiguobacterium is found to be more abundant within the tumor tissues. Further investigations have revealed that a lower Exiguobacterium/Bacillus ratio in both the tumor and peritumoral tissues of PDAC patients is indicative of a more favorable prognosis. Further exploration utilizing an orthotopic tumor model demonstrates that the probiotic Bacillus Coagulans impedes PDAC progression, accompanied by an increased infiltration of inflammatory neutrophils in tumors. Additionally, in the subgroup with a low Exiguobacterium/Bacillus ratio, whole-exome sequencing reveals elevated missense mutations in ABL2 and MSH2. The elevated expression of ABL2 and MSH2 has been correlated with poorer prognostic outcomes in PDAC patients. Together, these insights shed light on risk factors influencing PDAC progression and unveil potential therapeutic targets, alongside probiotic intervention strategies.
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Progresión de la Enfermedad , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/microbiología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , China/epidemiología , Masculino , Femenino , Animales , Pronóstico , Carcinoma Ductal Pancreático/microbiología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/genética , Bacillus/genética , Bacillus/aislamiento & purificación , Persona de Mediana Edad , Anciano , Microambiente Tumoral , Probióticos/uso terapéutico , Ratones , Microbiota , Línea Celular Tumoral , Microbioma GastrointestinalRESUMEN
The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Microbiota , Humanos , Ratones , Animales , Microbioma Gastrointestinal/genética , Neoplasias Colorrectales/metabolismo , Multiómica , Heces , Microbiota/genéticaRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is a liver disease syndrome. The prevalence of NAFLD has continued to increase globally, and NAFLD has become a worldwide public health problem. Glucosamine (GLC) is an amino monosaccharide derivative of glucose. GLC has been proven to not only be effective in anti-inflammation applications, but also to modulate the gut microbiota effectively. Therefore, in this study, the therapeutic effect of GLC in the NAFLD context and the mechanisms underlying these effects were explored. Specifically, an NAFLD model was established by feeding mice a high-fat and high-sugar diet (HFHSD), and the HFHSD-fed NAFLD mice were treated with GLC. First, we investigated the effect of treating NAFLD mice with GLC by analyzing serum- and liver-related indicator levels. We found that GLC attenuated insulin resistance and inflammation, increased antioxidant function, and attenuated serum and liver lipid metabolism in the mice. Then, we investigated the mechanism underlying liver lipid metabolism, inflammation, and intestinal barrier function in these mice. We found that GLC can improve liver lipid metabolism and relieve insulin resistance and oxidative stress levels. In addition, GLC treatment increased intestinal barrier function, reduced LPS translocation, and reduced liver inflammation by inhibiting the activation of the LPS/TLR4/NF-κB pathway, thereby effectively ameliorating liver lesions in NAFLD mice.
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Hepatitis , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Metabolismo de los Lípidos , Glucosamina/farmacología , Lipopolisacáridos/farmacología , Hígado , Inflamación/metabolismo , Hepatitis/metabolismo , Azúcares/metabolismo , Dieta , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: The patient of hypertension and its complication increase fast in the past years. Obesity is thought to be a risk factor for hypertension, and BMI (body mass index) is widely used to evaluate the obesity and hypertension risk. However, the abdominal obesity and visceral fat accumulation are more obvious in the East Asian population. The aim of this study was to evaluate the predictive value of fatty liver for hypertension in the Chinese population. METHOD: We compared the predictive value of BMI and fatty liver for the hypertension and its complication in 1386 patients with hypertension in Shanghai China. RESULTS: In the analysis of 1386 patients with hypertension in Shanghai China, we found that the prevalence and risk of hypertension and its complications were higher in the fatty liver group than that in the group of BMI≥24. Furthermore, the areas under the ROC curve of fatty liver for hypertension and its complications were superior to that of BMI. CONCLUSION: These results suggested that fatty liver is a more sensitive early warning for hypertension and its complication than BMI in Chinese population.
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Hígado Graso , Hipertensión , Humanos , Pueblos del Este de Asia , China/epidemiología , Hígado Graso/complicaciones , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa Corporal , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiologíaRESUMEN
Low loading is one of the bottlenecks limiting the performance of quantum dot sensitized solar cells (QDSCs). Although previous QD secondary deposition relying on electrostatic interaction can improve QD loading, due to the introduction of new recombination centers, it is not capable of enhancing the photovoltage and fill factor. Herein, without the introduction of new recombination centers, a convenient QD secondary deposition approach is developed by creating new adsorption sites via the formation of a metal oxyhydroxide layer around QD presensitized photoanodes. MgCl2 solution treated Zn-Cu-In-S-Se (ZCISSe) QD sensitized TiO2 film electrodes have been chosen as a model device to investigate this secondary deposition approach. The experimental results demonstrate that additional 38% of the QDs are immobilized on the photoanode as a single layer. Due to the increased QD loading and concomitant enhanced light-harvesting capacity and reduced charge recombination, not only photocurrent but also photovoltage and fill factor have been remarkably enhanced. The average PCE of resulted ZCISSe QDSCs is boosted to 15.31% (Jsc = 26.52 mA cm-2, Voc = 0.802 V, FF = 0.720), from the original 13.54% (Jsc = 24.23 mA cm-2, Voc = 0.789 V, FF = 0.708). Furthermore, a new certified PCE record of 15.20% has been obtained for liquid-junction QDSCs.
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Dielectric particles in weakly conducting fluids rotate spontaneously when subject to strong electric fields. Such Quincke rotation near a plane electrode leads to particle translation that enables physical models of active matter. In this Letter, we show that Quincke rollers can also exhibit oscillatory dynamics, whereby particles move back and forth about a fixed location. We explain how oscillations arise for micron-scale particles commensurate with the thickness of a field-induced boundary layer in the nonpolar electrolyte. This work enables the design of colloidal oscillators.
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Calorie restriction can modulate the gut microbiota and protect against many diseases including ischemic stroke. However, the role of calorie-restriction-induced microbiota alteration remained unknown in ischemic stroke rehabilitation. Here we conducted 30% reduction of caloric intake on mice for four weeks, to evaluate its role on ischemic stroke rehabilitation. Significantly, this calorie restriction led to better long-term rehabilitation in comparison of normal control. Notably, the transplantation of gut microbiome from calorie-restriction-treated mice to post-stroke mice was eligible to obtain better long-term rehabilitation of stroke mice. Bifidobacterium identified by 16â¯S ribosomal RNA sequencing were enriched in those of calorie-restriction mice. Then we administrated Bifidobacterium to stroke mice and found Bifidobacterium treatment could successfully improve the long-term rehabilitation of cerebral ischemia mice. Furthermore, the metabolomics analysis revealed a panel of upshifting metabolites, suggesting that calorie restriction greatly altered the gut microbiota composition and its metabolism. Hence, we discovered the novel effect of CR on long-term rehabilitation of ischemic stroke and the underlying role of gut microbiota, which might provide novel thoughts for the clinical post-stroke rehabilitation.
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Bacterias/crecimiento & desarrollo , Eje Cerebro-Intestino , Encéfalo/fisiopatología , Restricción Calórica , Microbioma Gastrointestinal , Accidente Cerebrovascular Isquémico/rehabilitación , Rehabilitación de Accidente Cerebrovascular , Animales , Bacterias/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Disbiosis , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/microbiología , Accidente Cerebrovascular Isquémico/fisiopatología , Ratones , Recuperación de la Función , Factores de TiempoRESUMEN
In this study, zinc-gallium oxynitrides with a Zn:Ga mole ratio of 1:1 [(GaN)0.5(ZnO)0.5] were synthesized from a Zn/Ga/CO3 layered double hydroxide (LDH) precursor. The microstructure and photoactivity of the (GaN)0.5(ZnO)0.5 particles were tuned by adjusting the nitridation conditions of the LDH. It is revealed that the quantity of the LDH, or, equivalently, the partial pressure of the water during nitridation, plays a pivotal role in the defect structure of the obtained oxynitrides. A reduction in the quantity of the LDH precursor can effectively suppress the formation of defects including Ga(Zn)-O bonding, bulk anion vacancies, and surface-deposited Ga/ON···VGa complexes, leading to a better charge-separation efficiency for the photogenerated electron-hole pairs in the oxynitride. Furthermore, a suitable introduction of methane during nitridation would not only increase the crystallinity of the bulk materials but also enhance the density of the surface oxygen vacancy (VO), which would raise the charge-injection efficiency by working as an electron trap and a reaction site to form O2â¢-. O2â¢-, as well as photogenerated holes, have been proven to be the dominant active species for the photodegradation of phenol. 25CH4-ZnGaNO, with the lowest density of bulk defects and the highest density of surface VO, exhibited the best photoactivity under visible-light irradiation for the photodegradation of Rhodamine B and phenol. The obtained surface-VO-rich (GaN)0.5(ZnO)0.5 particles can be applied as a high-performance visible-light-driven photocatalyst in the photodegradation of organic pollutants.
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Neutrophil extracellular traps (NETs) are characterized as extracellular DNA fibers comprised of histone and cytoplasmic granule proteins. NETs were first described as a form of innate response against pathogen invasion, which can capture pathogens, degrade bacterial toxic factors, and kill bacteria. Additionally, NETs also provide a scaffold for protein and cell binding. Protein binding to NETs further activate the coagulation system which participates in thrombosis. In addition, NETs also can damage the tissues due to the proteins they carry. Many studies have suggested that the excessive formation of NETs may contribute to a range of diseases, including thrombosis, atherosclerosis, autoimmune diseases, and sepsis. In this review, we describe the structure and components of NETs, models of NET formation, and detection methods. We also discuss the molecular mechanism of NET formation and their disease relevance. Modulation of NET formation may provide a new route for the prevention and treatment of releated human diseases.
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Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Animales , Aterosclerosis/metabolismo , Enfermedades Autoinmunes/metabolismo , HumanosRESUMEN
ADMSCs were isolated from subcutaneous adipose tissue, characterized and cultured in vitro. GFP-labeled ADMSCs can grow and proliferate well on the Atelocollagen scaffolds, and induced by 5-aza the cells can differentiate into cardio-like cells. 3D cultured ADMSCs on Atelocollagen scaffolds were transplanted into mice ischemia myocardium, and have good biocompatibility with host cardio tissue.
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Adipocitos/citología , Colágeno/química , Células Madre Mesenquimatosas/citología , Células Madre/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Adipogénesis , Tejido Adiposo , Animales , Materiales Biocompatibles/química , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Proteínas Fluorescentes Verdes/metabolismo , Corazón , Integrina beta1/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/patología , OsteogénesisRESUMEN
It remains controversial whether renal allografts from donation after circulatory death (DCD) have a higher risk of acute rejection (AR). In the porcine large animal kidney transplant model, we investigated the AR and function of DCD renal allografts compared to the non-DCD renal allografts and the effects of increased immunosuppression. We found that the AR was significantly increased along with elevated MHC-I expression in the DCD transplants receiving low-dose immunosuppression; however, AR and renal function were significantly improved when given high-dose immunosuppressive therapy postoperatively. Also, high-dose immunosuppression remarkably decreased the mRNA levels of ifn-g, il-6, tgf-b, il-4, and tnf-a in the allograft at day 5 and decreased serum cytokines levels of IFN-g and IL-17 at day 4 and day 5 after operation. Furthermore, Western blot analysis showed that higher immunosuppression decreased phosphorylation of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells-p65, increased phosphorylation of extracellular-signal-regulated kinase, and reduced the expression of Bcl-2-associated X protein and caspase-3 in the renal allografts. These results suggest that the DCD renal allograft seems to be more vulnerable to AR; enhanced immunosuppression reduces DCD-associated AR and improves early allograft function in a preclinical large animal model.
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Funcionamiento Retardado del Injerto/prevención & control , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Tolerancia Inmunológica/inmunología , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Aloinjertos , Animales , Muerte , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/patología , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto/efectos de los fármacos , Porcinos , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodosRESUMEN
Aim: To evaluate the impact of socioeconomic factors (SEFs) on survival of renal cell carcinoma (RCC) patients. Materials & methods: RCC patients diagnosed between 2007 and 2015 were collected from the SEER database. The crude and multivariate Cox regression analysis was used to identify the independent prognostic factors and quantity the mortality risks for overall survival (OS). Results: Three SEFs including marital status, insurance status and median household income were identified as prognostic factors for OS. SEF-stage was built based on the three SEFs. Moreover, the SEF-stage 1 had superior OS than SEF-stage 2 within the respective American Joint Committee on Cancer stages. Conclusion: The SEF-stage was an independently prognostic factor for OS in RCC. Incorporation of SEF-stage into the American Joint Committee on Cancer staging system might be beneficial for better survival prediction and clinical management. However, further studies were needed to validate these findings in other populations.
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Carcinoma de Células Renales/mortalidad , Neoplasias Renales/mortalidad , Adolescente , Adulto , Carcinoma de Células Renales/diagnóstico , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/diagnóstico , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Vigilancia en Salud Pública , Programa de VERF , Factores Socioeconómicos , Carga Tumoral , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated. METHODS: Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV+EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed. RESULTS: Hepatic steatosis was significantly more severe in the HBV+EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV+EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV+EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR)=1.43, P<0.01). CONCLUSIONS: Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.
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Depresores del Sistema Nervioso Central/farmacología , Dieta Alta en Grasa , Etanol/farmacología , Hígado Graso/patología , Hepatitis B Crónica/patología , Hígado/efectos de los fármacos , Consumo de Bebidas Alcohólicas/epidemiología , Animales , Modelos Animales de Enfermedad , Hígado Graso/epidemiología , Hígado Graso/virología , Hepatitis B Crónica/epidemiología , Humanos , Hígado/patología , Hígado/virología , RatonesRESUMEN
Modulation of nitric oxide activity through blockade of CD47 signaling has been shown to reduce ischemia-reperfusion injury (IRI) in various models of tissue ischemia. Here, we evaluate the potential effect of an antibody-mediated CD47 blockade in a syngeneic and an allogeneic DCD rat kidney transplant model. The donor organ was subjected to 1 hour of warm ischemia time after circulatory cessation, then flushed with a CD47 monoclonal antibody (CD47mAb) in the treatment group, or an isotype-matched immunoglobulin in the control group. We found that CD47mAb treatment improved survival rates in both models. Serum markers of renal injury were significantly decreased in the CD47mAb-treated group compared with the control group. Histologically the CD47mAb-treated group had significantly reduced scores of acute tubular injury and acute tubular necrosis. The expression of biomarkers related to mitochondrial stress and apoptosis also were significantly lower in the CD47mAb-treated groups. Overall, the protective effects of CD47 blockade were greater in the syngeneic model. Our data show that CD47mAb blockade decreased the IRI of DCD kidneys in rat transplant models. This therapy has the potential to improve DCD kidney transplant outcomes in the human setting.
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Anticuerpos Monoclonales/farmacología , Antígeno CD47/antagonistas & inhibidores , Muerte , Rechazo de Injerto/prevención & control , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Daño por Reperfusión/prevención & control , Animales , Apoptosis , Antígeno CD47/inmunología , Tasa de Filtración Glomerular , Supervivencia de Injerto , Inflamación/prevención & control , Pruebas de Función Renal , Masculino , Estrés Oxidativo , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Transducción de SeñalRESUMEN
We investigated whether blockade of the CD47 signaling pathway could reduce ischemia-reperfusion injury (IRI) of renal allografts donated after cardiac death (DCD) in a porcine animal model of transplantation. Renal allografts were subjected to 30 minutes of warm ischemia, 3.5 hours of cold ischemia, and then perfused with a humanized anti-CD47 monoclonal antibody (CD47mAb) in the treatment group or HTK solution in the control group (n = 4/group). The animals were euthanized five days after transplantation. At the time of reperfusion, indocyanine green-based in vivo imaging showed that CD47mAb-treated organs had greater and more uniform reperfusion. On post-transplant days 3-5, the treatment group had lower values compared to the control for creatinine and blood urea nitrogen. Histological examination of allograft tissues showed a significant decrease of acute tubular injury in the CD47mAb-treated group compared to control. Compared to the control group, CD47mAb treatment significantly decreased genes expression related to oxidative stress (sod-1, gpx-1, and txn), the inflammatory response (il-2, il-6, inf-g, and tgf-b), as well as reduced protein levels of BAX, Caspase-3, MMP2, and MMP9. These data demonstrate that CD47mAb blockade decreases IRI and subsequent tissue injury in DCD renal allografts in a large animal transplant model.
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Anticuerpos Monoclonales/farmacología , Antígeno CD47/antagonistas & inhibidores , Muerte , Rechazo de Injerto/prevención & control , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Daño por Reperfusión/prevención & control , Animales , Apoptosis , Antígeno CD47/inmunología , Modelos Animales de Enfermedad , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Inflamación/prevención & control , Pruebas de Función Renal , Estrés Oxidativo , Transducción de Señal , PorcinosRESUMEN
CCDC39 and CCDC40 were first identified as causative mutations in primary ciliary dyskinesia patients; cilia from patients show disorganized microtubules, and they are missing both N-DRC and inner dynein arms proteins. In Chlamydomonas, we used immunoblots and microtubule sliding assays to show that mutants in CCDC40 (PF7) and CCDC39 (PF8) fail to assemble N-DRC, several inner dynein arms, tektin, and CCDC39. Enrichment screens for suppression of pf7; pf8 cells led to the isolation of five independent extragenic suppressors defined by four different mutations in a NIMA-related kinase, CNK11. These alleles partially rescue the flagellar length defect, but not the motility defect. The suppressor does not restore the missing N-DRC and inner dynein arm proteins. In addition, the cnk11 mutations partially suppress the short flagella phenotype of N-DRC and axonemal dynein mutants, but do not suppress the motility defects. The tpg1 mutation in TTLL9, a tubulin polyglutamylase, partially suppresses the length phenotype in the same axonemal dynein mutants. In contrast to cnk11, tpg1 does not suppress the short flagella phenotype of pf7. The polyglutamylated tubulin in the proximal region that remains in the tpg1 mutant is reduced further in the pf7; tpg1 double mutant by immunofluorescence. CCDC40, which is needed for docking multiple other axonemal complexes, is needed for tubulin polyglutamylation in the proximal end of the flagella. The CCDC39 and CCDC40 proteins are likely to be involved in recruiting another tubulin glutamylase(s) to the flagella. Another difference between cnk11-1 and tpg1 mutants is that cnk11-1 cells show a faster turnover rate of tubulin at the flagellar tip than in wild-type flagella and tpg1 flagella show a slower rate. The double mutant shows a turnover rate similar to tpg1, which suggests the faster turnover rate in cnk11-1 flagella requires polyglutamylation. Thus, we hypothesize that many short flagella mutants in Chlamydomonas have increased instability of axonemal microtubules. Both CNK11 and tubulin polyglutamylation play roles in regulating the stability of axonemal microtubules.
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Axonema , Chlamydomonas/fisiología , Flagelos/fisiología , Proteínas Quinasas/metabolismo , Chlamydomonas/enzimología , Chlamydomonas/genética , Genes de Plantas , Movimiento , Mutación , TemperaturaRESUMEN
In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.
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PURPOSE: Ovarian cancer is one of the most malignant tumors in the female reproductive system. With the widespread application of chemotherapeutic drugs, many ovarian cancer patients develop drug resistance. The aim of this study was to explore the function of HOTAIR in the treatment of ovarian cancer with cisplatin and its underlying mechanism. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect HOTAIR expressions in tissues and cells of ovarian cancer. Cell counting kit-8 (CCK-8) assay was used to examine the viability of ovarian cancer cells. Besides, small interfering (si) RNA was transfected to knockdown HOTAIR so as to explore its biological function. Western blot was performed to detect the expression levels of autophagy-related proteins. Flow cytometry was applied to detect apoptosis of ovarian cancer cells. RESULTS: HOTAIR was upregulated in ovarian cancer. Meanwhile, expression levels of autophagy-related proteins Atg7 and LC3 II/I in ovarian cancer cells increased with the increase of cisplatin concentration. Transfection of si-Atg7 could improve the therapeutic effect of cisplatin on ovarian cancer via inhibiting autophagy. Additionally, HOTAIR knockdown could increase the sensitivity of cisplatin in ovarian cancer treatment by inhibiting cisplatin-induced autophagy. CONCLUSIONS: Knockdown of long non-coding (lnc) RNA HOTAIR could increase the sensitivity of cisplatin in ovarian cancer by inhibiting cisplatin-induced autophagy. Our research attempts to find a more effective treatment and provides new ideas for the clinical treatment of ovarian cancer.
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Cisplatino/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , ARN Largo no Codificante/genética , Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Autofagia/genética , Línea Celular Tumoral , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Ováricas/patología , Transfección , Regulación hacia ArribaRESUMEN
OBJECTIVE: The immune system is critical for controlling the progression of HPV cervical disease and the development of cancer. This study aimed to identify cervical cancer susceptibility alleles in candidate immune-modulating genes. METHODS: Our family-based study involved a cohort of 641 probands (women with ICC/CIN III) and their biologic parents or siblings (641 trios). In the discovery phase (stage 1), involving 288 of the trios, 80 tag single nucleotide polymorphisms (SNPs) in 11 immune-modulating genes (IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1, STAT6, IL12A, TNF, LTA and LTB) were evaluated on the GoldenGate platform. We used the combined dataset for a total of 641 trios (stage 2) and the Taqman platform to validate the SNPs that had proved significant in the discovery dataset. The transmission disequilibrium test was used to detect significant shifts in allelic transmissions in the datasets. RESULTS: Two SNPs in JAK2 and one SNP in STAT6 showed significant allelic association with cervical cancer in the stage 1 discovery dataset and were replicated in the larger joint analysis stage 2 dataset (JAK2 rs10815144, P=0.0029 and rs12349785, P=0.0058; and STAT6 rs3024971, P=0.0127). An additional SNP in exon 19 of JAK2 (rs2230724) was also examined in the combined dataset due to its strong linkage disequilibrium (LD) with rs10815144. It was also significant (P=0.0335). CONCLUSIONS: Our results suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This association should be investigated in additional cervical cancer populations.