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Aqueous Zn-ion batteries are the ideal candidate for large-scale energy storage systems owing to their high safety and low cost. However, the uncontrolled deposition and parasitic reaction of Zn metal anode hinder their commercial application. Here, the 2D metal-organic-framework (MOF) nanoflakes covered on the surface of Zn are proposed to enable dendrite-free for long lifespan Zn metal batteries. The MOF can facilitate the desolvation process to accelerate reaction kinetic due to its special channel structure. The abundant zincopilicity sites of MOF can realize the homogenous Zn2+ deposition. Consequently, their synergetic effect makes the MOF protected Zn anode good electrochemical performance with a long cycle life of 1400 h at 1 mA cm-2 and a high depth of discharge of 30 mAh cm-2 (DOD ≈ 54%) continued for over 700 h. This work provides a novel strategy for high-performance rechargeable Zn-ion batteries.
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Solid-state symmetrical battery represents a promising paradigm for future battery technology. However, its development is hindered by the deficiency of high-performance bipolar electrodes and compatible solid electrolytes. Herein, a quasi-solid-state all-V2O5 battery constructed by a binder-free carbon fabric-V2O5 nanowires@graphene (CVOG) bipolar electrode and a softly cross-linked polyethylene oxide-based solid polymer electrolyte (SPE) is reported. The synergetic effect of nano-structuring of V2O5, hierarchical conductive network, and graphene wrapping endows the CVOG electrode with boosted reaction kinetics and suppressed vanadium dissolution. The cathodic and anodic reactions of CVOG are decoupled by electrochemical analysis, conceiving the feasibility of constructing all-V2O5 full battery. In manifesting the solid-state all-V2O5 battery, the robust and elastic SPE exhibits high ionic conductivity, tight/self-adaptable electrolyte-electrode contact, and a low charge-transfer barrier. The resultant solid-state full battery exhibits a high reversible capacity of 158 mAh g-1 at 0.1 C, good capacity retention of over 61% from 0.1 C to 2 C, and remarkable cycling stability of 77% capacity retention after 1000 cycles at 1 C, which surpass other solid-state symmetrical batteries. Hence, this work provides a practice of high-performance solid-state batteries with symmetrical configuration and is constructive for next-generation battery technology.
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BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.
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Proteínas de Transferencia de Ésteres de Colesterol , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Apnea Obstructiva del Sueño , Apnea Obstructiva del Sueño/genética , Humanos , Proteínas de Transferencia de Ésteres de Colesterol/genética , LDL-Colesterol/sangre , Dislipidemias/genética , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Dislipidemias/sangre , Sitios de Carácter Cuantitativo , Hipolipemiantes/uso terapéutico , Factores de Riesgo , Polimorfismo de Nucleótido SimpleRESUMEN
AIM: To investigate the effect of a nurse support using a proactive mobile app to enhance parental self-efficacy in symptom management for children with medical complexity. DESIGN: A single-blinded, randomized controlled trial with a two-armed repeated measures design. METHODS: Eligible parents and the children will be recruited from the special schools and non-government offices. They will be randomly assigned either to the intervention or control groups. Subjects in the study group will receive nurse parental support using a symptom management mobile app for 3 months. The control group will receive the usual care that is available in the community. Data will be collected pre-intervention (T1), immediately after the intervention (T2), and three-month after intervention (T3). The primary outcome is parental self-efficacy. The secondary outcomes include child's symptom burden and their health service utilization. Primary outcome will be compared across two groups in T2 and T3 using with control for the pre-test value of parental self-efficacy. Generalized estimating equation (GEE) will be used to address secondary objectives from T1 to T3 with appropriate link function. DISCUSSION: As a result of the successful implementation of this nurse-led symptom management, parental self-efficacy will be enhanced. Both the symptoms reported by the children and their health service utilization will be reduced. Findings of this study will help in service delivery improvements because it maximizes the availability and accessibility of paediatric health service to parents and the children in local communities. IMPACT: The evidence produced in this study will enlarge the knowledge base that supports evidence-based paediatric home nursing service with the use of health technology in symptom management. This evidence will also contribute to the development of other symptom management programs for other paediatric patient groups. TRIAL REGISTRATION: NCT05765643 (ClinicalTrials.gov identifier). PATIENT OR PUBLIC CONTRIBUTION: Parents of children with medical complexity contributed in mobile application development by giving comments on the usability of mobile application. IMPACT WILL BE GENERATED THROUGH THE FOLLOWING BENEFITS: Improve health service delivery: Home nursing service may not be sustainable in a long run in Hong Kong, as the health care system has been facing a serious nursing workforce shortage in recent years. Besides, these services are affected or even suspended during the community outbreak of infectious disease, like recent coronavirus disease pandemic. Nurse parental support in symptom management for the CMC using a proactive mobile health application will help in service delivery improvements because it maximizes the availability and accessibility of paediatric health service to parents and their CMC in local communities. Improve physical and psychological health of parents and their CMC: The success of program implementation will help to increase parental self-efficacy in symptom management for their CMC, as a result of decrease of children's symptom burden. Improve knowledge base: The evidence produced in this study will (1) enlarge the knowledge base that supports evidence-based paediatric community nursing service related to symptom management for the CMC. This evidence will contribute to the development of other symptom management programs for other paediatric patient groups.
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Aplicaciones Móviles , Padres , Humanos , Niño , Masculino , Femenino , Padres/psicología , Preescolar , Método Simple Ciego , Autoeficacia , Adolescente , Adulto , LactanteRESUMEN
Mucosal melanoma (MM) represents an uncommon form of melanoma. Primary gastrointestinal tract (GIT) melanoma is even rarer. A 70-year-old male visited the Liaoning Cancer Hospital and Institute, China, due to upper abdominal discomfort for the past two months. His endoscopy revealed a prominent, 6-cm ulcerated neoplasm in the gastroesophageal junction (GEJ). Lesion endoscopic biopsy showed diffusely distributed tumour cells. He underwent subtotal gastrectomy with lymph node dissection (LND). Postoperative histopathology revealed a diffuse distribution of tumour cells with numerous tumourinfiltrating lymphocytes (TILs) and pigment granules. Immunohistochemical (IHC) results were positive for both S-100 and HMB-45. Molecular analysis showed KIT gene exon 11 mutations. Although the clinicians emphasised the necessity of systemic chemotherapy and immunotherapy with the patient and his family, the patient did not receive any adjuvant therapy and died 36 months after surgery. Primary malignant melanoma of GEJ should be considered in a differential diagnosis for gastrointestinal malignancies, especially after excluding the source of metastasis through a systemic examination.
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Unión Esofagogástrica , Exones , Melanoma , Mutación , Proteínas Proto-Oncogénicas c-kit , Neoplasias Gástricas , Humanos , Masculino , Melanoma/genética , Melanoma/patología , Melanoma/cirugía , Anciano , Unión Esofagogástrica/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Proteínas Proto-Oncogénicas c-kit/genética , Exones/genética , Gastrectomía , Resultado FatalRESUMEN
White matter hyperintensity (WMH) is associated with vascular hemodynamic alterations and reflects white matter injury. To date, the sex difference of tract-specific WMH and the relationship between high blood pressure (BP) and tract-specific WMH remain unclear. We recruited 515 subjects from the Shanghai Changfeng study (range 53-89 years, mean age 67.33 years). Systolic and diastolic blood pressure (SBP and DBP) were collected and used to calculate pulse pressure (PP). Magnetic resonance T1 and T2 FLAIR images were acquired to measure WMH and calculate WMH index. The ANCOVA test was performed to test the difference between sexes, and the linear regression model was used to examine the associations between BP and WMH index. Men showed higher WMH index than women in all white matter tracts (p < .001, respectively) except for the bilateral superior longitudinal fasciculus (SLF) and its left temporal part (tSLF). High SBP and PP was associated with a lower WMH index on the left corticospinal tract (CST), SLF, tSLF and right cingulum in hippocampus (p ≤ .001, respectively) in women, while high DBP was associated with a higher WMH index on the bilateral CST (left p < .001; right p = .001), left inferior longitudinal fasciculus (p < .001) and inferior fronto-occipital fasciculus (p = .002) in men. Men tend to have more WMH compared to women. A high SBP/PP relates to a lower WMH burden in women. This suggests that women could benefit from higher blood pressure in older age.
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Hipertensión , Caracteres Sexuales , Sustancia Blanca , Anciano , Femenino , Humanos , Masculino , Envejecimiento/fisiología , China , Hipertensión/diagnóstico por imagen , Imagen por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
AIM: Postoperative spindle cell nodule (PSCN) is a pseudosarcomatous proliferative lesion of unclear molecular genetic origins. METHODS AND RESULTS: We examined seven patients with PSCN, using routine haematoxylin-eosin (H&E) slide preparations and a series of immunostains. The latter targeted keratin, vimentin, α-smooth muscle actin (SMA), anaplastic lymphoma kinase (ALK [D5F3]), and other proteins. Ubiquitin-specific peptidase 6 (USP6) and anaplastic lymphoma kinase (ALK) gene rearrangements were also analysed by fluorescence in situ hybridization (FISH). There were histories of prior surgical intervention (n = 6) or trauma (n = 1) in all seven patients. All lesions were highly cellular and mitotically active spindle cell proliferations, with no cytologic atypia, nuclear pleomorphism, or aberrant mitoses. Immunohistochemical (IHC) staining disclosed focal, weak keratin positivity in two lesions, whereas vimentin (diffuse, strongly positive) and SMA (tram-track pattern) were present in each instance, and ALK (D5F3) was entirely negative. FISH analysis confirmed USP6 gene rearrangements in all seven cases, showing no ALK gene rearrangements. RNA sequencing results showed an MYH9::USP6 gene fusion in only one lesion (No. 6). CONCLUSION: A subset of PSCN is marked by USP6 gene rearrangements, a genetic feature of nodular fasciitis (NF). Given its similarity to NF, a designation as USP6-associated neoplasm (UAN) seems reasonable, signifying a transient clonal neoplastic lesion.
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Fascitis , Neoplasias , Humanos , Quinasa de Linfoma Anaplásico/genética , Reordenamiento Génico , Vimentina/genética , Proteínas Proto-Oncogénicas/genética , Hibridación Fluorescente in Situ , Fascitis/genética , Neoplasias/genética , Queratinas , Ubiquitina Tiolesterasa/genéticaRESUMEN
OBJECTIVE: A significant proportion of patients can not benefit from neoadjuvant chemotherapy (NCT) due to drug resistance. Cancer-associated fibroblasts (CAFs) influence many biological behaviours of tumors, including chemo-resistance. This study aims to explore whether CAFs expressing FAP, CD10, and GPR77 affect the efficacy of NCT and the prognosis of patients with gastric cancer, and its mechanism. METHODS: One hundred seventy-one patients with locally progressive gastric adenocarcinoma who had undergone NCT and radical surgery were collected. Immunohistochemistry was used to detect the expression of FAP, CD10, and GPR77 in CAFs; the EMT markers (N-cadherin, Snail1, and Twist1) and the CSC markers (ALDH1, CD44, and LGR5) in gastric cancer cells. The χ2 test was used to analyze the relationship between the expression of CAF, EMT, and CSC markers and the clinicopathological factors, as well as the relationship between CAF markers and EMT, and CSC markers. Logistic regression and Cox risk regression were used to analyze the relationship between the expression of CAF, EMT, and CSC markers and TRG grading and OS; Kaplan-Meier analysis was used for survival analysis and plotting the curves. RESULTS: The expression of CAF markers FAP, CD10, and GPR77 was closely associated with that of EMT markers; FAP and CD10 were closely related to CSC markers. In the univariate analysis of pathological response, CAF markers (FAP, CD10, GPR77), EMT markers (N-cadherin, Snail1, Twist1), and CSC markers (ALDH1, LGR5, CD44), were all closely associated with pathological response (all p < 0.05). Only Twist1 was an independent factor affecting pathological response in multifactorial analysis (p = 0.001). In a univariate analysis of OS, expression of FAP and CD10 in CAF, as well as expression of EMT biomarkers (N-cadherin, Snail1), were significant factors influencing patient prognosis (all p < 0.05). Multifactorial analysis revealed N-cadherin (p = 0.032) and Snail1 (p = 0.028), as independent prognostic factors affecting OS. CONCLUSION: FAP, CD10, and GPR77 labeled CAF subgroup may lead to NCT resistance and poor prognosis by inducing EMT and CSC of gastric cancer cells in locally advanced gastric cancer patients.
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Fibroblastos Asociados al Cáncer , Neoplasias Gástricas , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Terapia Neoadyuvante , Biomarcadores/metabolismo , Cadherinas/metabolismoRESUMEN
The tumor microenvironment is one of the important drivers of tumor development. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and actively participate in tumor development, invasion, metastasis, drug resistance, and other biological behaviors. CAFs are a highly heterogeneous group of cells, a reflection of the diversity of their origin, biomarkers, and functions. The diversity of CAF origin determines the complexity of CAF biomarkers, and CAF subpopulations expressing different biomarkers may play contrasting roles in tumor progression. In this review, we provide an overview of these emerging CAF biomarkers and the biological functions that they suggest, which may give a better understanding of the relationship between CAFs and tumor cells and be of great significance for breakthroughs in precision targeted therapy for tumors. Video Abstract.
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Fibroblastos Asociados al Cáncer , Neoplasias , Humanos , Fibroblastos Asociados al Cáncer/patología , Biomarcadores , Neoplasias/patología , Microambiente Tumoral , Biomarcadores de Tumor , Fibroblastos/patologíaRESUMEN
We conducted first-principles calculations to investigate the dynamic braiding of local edge states and the spin topological transport mechanism in a strong topological MoS1.75Te0.25 matrix. The presence of type-II Van Hove singularity in the middle of the X-S path indicates a strong cohesive interaction and a paring condensation mechanism within the matrix. The surface state data of MoS1.75Te0.25 clearly demonstrate the characteristic features of strong regular loop braiding in spin transport. The spin Hall conductivity of the matrix was determined from the anisotropic characteristics of the spin Berry curvature. The phase transition of the spin Hall conductivity was evidenced by the positive sign of local spin polarization strength, primarily contributed by the dz2 orbital of Mo atoms, and the negative sign of spin polarization strength, mainly contributed by the p-px orbitals of S atoms. Moreover, the inclusion of Te selectively tuned the spin transport efficiency of the dz2 and px orbitals. Comprehensive braiding and readout of edge states can be achieved using an artificially designed MoS1.75Te0.25 spintronic device. This 2D fractional braiding holds significant potential for applications in topological quantum computation.
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We theoretically demonstrate how the competition between band inversion and spin-orbit coupling (SOC) results in the nontrivial topology of band evolution, using two-dimensional (2D) Mn16B16 as a matrix. This study utilizes the ab initio method with the generalized gradient approximation (GGA+U scheme) and Wannier functions to investigate the topological and transport properties of the Ni-doped structure. The Ni atom induces dynamical antilocalization, which appears due to the phase accumulation between time-reversed fermion loops. A key observation is that when band inversion dominates over SOC, "twin" Weyl cones appear in the band structure, in which the Weyl cones caused by the large Berry curvature coupling with the net magnetization lead to the significantly enhanced anomalous Hall conductivity (AHC). Interestingly, the nested small polaron and energy band inversion coexist with SOC. An analysis of the projected energy band shows that the doped Ni atom induces a strong spin wave for both spin up and spin down.
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A highly densified electrode material is desirable to achieve large volumetric capacity. However, pores acting as ion transport channels are critical for high utilization of active material. Achieving a balance between high volume density and pore utilization remains a challenge particularly for hollow materials. Herein, capillary force is employed to convert hollow fibers to a bamboo-weaving-like flexible electrode (BWFE), in which the shrinkage of hollow space results in high compactness of the electrode. The volume of the electrode can be decreased by 96% without sacrificing the gravimetric capacity. Importantly, the conductivity of BWFE after thermal treatment can reach up to 50,500 S/m which exceeds that for most other carbon materials. Detailed mechanical analysis reveals that, due to the strong interaction between nanoribbons, Young's modulus of the electrode increases by 105 times. After SnO2 active materials is impregnated, the BWFE/SnO2 electrode exhibits an exceptionally ultrahigh volumetric capacity of 2000 mAh/cm3.
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BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1â³HBS ) against NAFLD. APPROACH AND RESULTS: FGF1â³HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1â³HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1â³HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1â³HBS . In palmitate-treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1â³HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1â³HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1â³HBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1â³HBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. CONCLUSIONS: These findings indicate that FGF1â³HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.
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Proteínas Quinasas Activadas por AMP/metabolismo , Factor 1 de Crecimiento de Fibroblastos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Animales , Diabetes Mellitus Experimental , Dieta Alta en Grasa , Células Hep G2 , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado , Masculino , Ratones , Ratones Noqueados , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Oxidativo , Palmitatos/farmacología , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
AIMS: JAZF1 translocation is the most common genetic change in low-grade (LG) endometrial stromal sarcoma (ESS), and YWHAE and BCOR translocations are common in high-grade (HG) ESS. Primary extrauterine ESS is rare, and there are limited data on molecular alterations in these tumours. METHODS AND RESULTS: Cases of primary extrauterine ESS, comprising eight LG-ESS cases and five HG-ESS cases were collected. Haematoxylin and eosin and immunohistochemical staining were used to observe the histomorphology and analyse related protein expression. JAZF1, YWHAE and BCOR rearrangements were explored with fluorescence in-situ hybridisation (FISH). In LG-ESS, the tumour cells resembled normal proliferative-phase endometrial stromal cells; CD10, oestrogen receptor and progesterone receptor were expressed in all eight cases. In HG-ESS, the tumour cells had uniform HG round and/or spindle morphology, sometimes with an LG component; CD10 was fully expressed in one case and focally expressed in four cases; BCOR was expressed in all five cases, and cyclin D1 in four of five cases. FISH analysis showed JAZF1 translocation in one of eight LG-ESS cases (12.5%). YWHAE translocation occurred in four of five HG-ESS cases, with a positivity rate of 80%. BCOR translocation was absent in all five cases. CONCLUSIONS: In extrauterine LG-ESS, the rate of JAZF1 rearrangement was significantly lower than in uterine LG-ESS. This result limited the value of JAZF1 translocation for diagnosis. YWHAE rearrangement is a common genetic change in extrauterine HG-ESS. Further studies are required to confirm these findings, especially in LG-ESS.
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Proteínas 14-3-3/genética , Proteínas Co-Represoras/genética , Proteínas de Unión al ADN/genética , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma Estromático Endometrial/genética , Sarcoma Estromático Endometrial/patología , Adulto , Neoplasias Endometriales/diagnóstico , Tumores Estromáticos Endometriales/diagnóstico , Tumores Estromáticos Endometriales/genética , Tumores Estromáticos Endometriales/patología , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoma Estromático Endometrial/diagnóstico , Translocación GenéticaRESUMEN
BACKGROUND: Adenomatoid tumors (ATs) are benign tumors originating from the mesothelium. ATs of the ovary are rare, and can easily be confused with malignancy due to the histomorphological diversity. Thus, it is difficult in histopathological and differential diagnosis, especially during intraoperative frozen pathological diagnosis, which directly affects the resection scope of surgery. CASE PRESENTATION: In this study, we reported two patients (58 and 41 year old) with ovarian ATs. AT of patient 1 occurred in both ovaries at different time points and she had been diagnosed with Hashimoto's thyroiditis. AT of patient 2 occurred in right ovary. Intraoperative frozen pathological diagnosis was performed in both cases and laparoscopic salpingo-oophorectomy was undergone on the lesion side according to benign freezing diagnostic result. Ovarian ATs, the final diagnoses of the 2 cases were concluded after histological, extensive immunohistochemical (IHC), histochemical, and fluorescence in situ hybridization analyses. CONCLUSIONS: Our results show that ovarian ATs may not be related to BAP1 or CDKN2A/p16 mutations. In addition, the case 1 suggests that ATs may be associated with immune dysregulation. When encountering such similar lessions, we recommend that a series of immunohistochemical, histochemical and molecular biological techniques should be used for diagnosis and differential diagnosis to avoid misdiagnosis. Improving understanding of the rare ovarian ATs which mimic malignancy is necessary to prevent overresection.
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Tumor Adenomatoide , Neoplasias Ováricas , Femenino , Humanos , Tumor Adenomatoide/diagnóstico , Tumor Adenomatoide/cirugía , Tumor Adenomatoide/patología , Hibridación Fluorescente in Situ , Neoplasias Ováricas/patología , Errores DiagnósticosRESUMEN
BACKGROUND AND AIMS: Hepatic macrophages can be activated by many factors such as gut-derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell-cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored. APPROACH AND RESULTS: In the present study, we reported that lipotoxic injury-induced release of hepatocyte exosomes enriched with miR-192-5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR-192-5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR-192-5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high-fat high-cholesterol diet-fed rat models. Lipotoxic hepatocytes released more miR-192-5p-enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b-positive [CD11b+ ]/CD86+ ) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte-derived exosomal miR-192-5p inhibited the protein expression of the rapamycin-insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response. CONCLUSIONS: Hepatocyte-derived exosomal miR-192-5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR-192-5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.
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Exosomas/metabolismo , Factores de Transcripción Forkhead/fisiología , Hepatocitos/metabolismo , Activación de Macrófagos/fisiología , MicroARNs/fisiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Proteína Asociada al mTOR Insensible a la Rapamicina/fisiología , Transducción de Señal/fisiología , Animales , Masculino , MicroARNs/biosíntesis , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND AIMS: STAT3, a member of the signal transducer and activator of transcription (STAT) family, is strongly associated with liver injury, inflammation, regeneration, and hepatocellular carcinoma development. However, the signals that regulate STAT3 activity are not completely understood. APPROACH AND RESULTS: Here we characterize CREB/ATF bZIP transcription factor CREBZF as a critical regulator of STAT3 in the hepatocyte to repress liver regeneration. We show that CREBZF deficiency stimulates the expression of the cyclin gene family and enhances liver regeneration after partial hepatectomy. Flow cytometry analysis reveals that CREBZF regulates cell cycle progression during liver regeneration in a hepatocyte-autonomous manner. Similar results were observed in another model of liver regeneration induced by intraperitoneal injection of carbon tetrachloride (CCl4 ). Mechanistically, CREBZF potently associates with the linker domain of STAT3 and represses its dimerization and transcriptional activity in vivo and in vitro. Importantly, hepatectomy-induced hyperactivation of cyclin D1 and liver regeneration in CREBZF liver-specific knockout mice was reversed by selective STAT3 inhibitor cucurbitacin I. In contrast, adeno-associated virus-mediated overexpression of CREBZF in the liver inhibits the expression of the cyclin gene family and attenuates liver regeneration in CCl4 -treated mice. CONCLUSIONS: These results characterize CREBZF as a coregulator of STAT3 to inhibit regenerative capacity, which may represent an essential cellular signal to maintain liver mass homeostasis. Therapeutic approaches to inhibit CREBZF may benefit the compromised liver during liver transplantation.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Regulación de la Expresión Génica , Regeneración Hepática/genética , Hígado/fisiología , Factor de Transcripción STAT3/genética , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Tetracloruro de Carbono/toxicidad , Ciclo Celular/genética , Eliminación de Gen , Hepatocitos/efectos de los fármacos , Hepatocitos/fisiología , Hígado/efectos de los fármacos , Hígado/lesiones , Redes y Vías Metabólicas , Ratones , Ratones NoqueadosRESUMEN
The novel HNO3-modifitied biochar (NBC) was synthesized from walnut shell. The NBC was characterized from scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Raman spectrum. The NBC was then used in the adsorption of sulfadiazine, sulfamethazine and sulfachloropyridazine from aqueous solution. The material surface has carbon/oxygen-contained groups, which is benefit for the adsorption. The results showed the adsorption ability of NBC on three sulfonamides were 32, 46, and 40 mg g-1, respectively. The kinetic was found to follow the Elovich model and the isotherm conformed Freundlich. Adsorption was more favorable at weak acidic solution. The interactions mainly include π-π EDA, electrostatic interaction, Lewis acid-base interaction, hydrophobic interaction and H-bond.
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Juglans , Contaminantes Químicos del Agua , Adsorción , Antibacterianos , Carbón Orgánico , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Sulfonamidas , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. METHODS: Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). RESULTS: Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. CONCLUSIONS: Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH. TRIAL REGISTRATION: Registration ID: ChiCTR-DDT-13003983 . Data of registration: 13 May, 2013, retrospectively registered.
Asunto(s)
Autofagia/efectos de los fármacos , Ceramidas/metabolismo , Dislipidemias/tratamiento farmacológico , Ácidos Grasos Monoinsaturados/farmacología , Hipolipemiantes/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adulto , Animales , Autofagia/genética , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Estudios de Casos y Controles , Ceramidas/antagonistas & inhibidores , Dieta Alta en Grasa/efectos adversos , Dislipidemias/etiología , Dislipidemias/genética , Dislipidemias/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatitis B Crónica/genética , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácido Oléico/antagonistas & inhibidores , Ácido Oléico/farmacología , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Ácido Palmítico/antagonistas & inhibidores , Ácido Palmítico/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Zn2SnO4-reduced graphene oxide photocatalysts were synthesized by using SnCl4 5H2O, Zn(NO3)2 · 6H2O and graphene oxide via hydrothermal process. The structure, morphology, specific surface area and photo response of the as-prepared nanocomposites were characterized by X-ray diffraction, Transmission electron microscopy, UV-vis diffuse reflectance spectra, Brunauer-emmett-teller surface area measurement and Photoluminescence emission spectra. Experimental results showed that the Zn2SnO4 nanoparticles, with 20-30 nm a size range, were uniformly dispersed on the surfaces of reduced graphene oxide. Moreover, the as-prepared Zn2SnO4-reduced graphene oxide photocatalysts exhibited enhanced photocatalytic activities for degradation of Rhodamine B compared to those of pure Zn2SnO4. When the amount of reduced graphene oxide was 4 wt%, it showed the highest photocatalytic efficiency of 99.7% for 240 min, and the photocatalytic efficiency was still 98.5% after it was recycled 4 times. It also possessed the band gap of 2.48 eV and specific surface area of 58.1 m2 g-1.