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Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.
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BACKGROUND: Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. RESULTS: In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3'H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6''-O-acetyl)-glucoside, cosmosiin and apigenin-4'-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. CONCLUSION: The findings are helpful for genetic improvement of varieties in L.macranthoides.
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Lonicera , Lonicera/genética , Apigenina , Quempferóis , Perfilação da Expressão Gênica , Flavonoides , Flores/genética , GlucosídeosRESUMO
The utilization of layered oxides as cathode materials has significantly contributed to the advancement of the lithium-ion batteries (LIBs) with high energy density and reliability. However, the structural and interfacial instability triggered by side reactions when charged to high voltage has plagued their practical applications. Here, this work reports a novel multifunctional additive, id est, 7-Anilino-3-diethylamino-6-methyl fluoran (ADMF), which exhibits unique characteristics such as preferential adsorption, oxygen scavenging, and electropolymerization protection for high-voltage cathodes. The ADMF demonstrates the capability to ameliorate the growth of cathode-electrolyte interphase (CEI), effectively diminishing the dissolution of transition metal (TM) ions, reducing the interface impedance, and facilitating the Li+ transport. As a result, ADMF additive with side reaction-blocking ability significantly enhances the cycling stability of MCMB||NCM811 full-cells at 4.4 V and MCMB||LCO full-cells at 4.55 V, as evidenced by the 80% retention over 600 cycles and 87% retention after 750 cycles, respectively. These findings highlight the potential of the additive design strategy to modulate the CEI chemistry, representing a new paradigm with profound implications for the development of next-generation high-voltage LIBs.
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INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy and esophagogastric devascularization (LSED) are minimally invasive, effective, and safe in treating esophageal-fundic variceal bleeding with portal hypertension (PHT). The study aimed to assess the learning curve of LSED by cumulative summation (CUSUM) analysis. The 10-year follow-up data for LSED and open surgery were also examined. PATIENTS AND METHODS: Five hundred and ninety-four patients were retrospectively analyzed. Operation time, intraoperative blood loss, open operation conversion, and postoperative complications were selected as the evaluation indicators of surgical ability. The learning curve of LESD was assessed by the CUSUM approach. Patient features, perioperative indices, and 10-year follow-up data were examined. RESULTS: Totally 236 patients underwent open surgery, and 358 underwent LSED. Patient characteristics were similar between groups. The LSED patients experienced less intraoperative blood loss, fewer complications, and faster recovery compared to the open surgery cohort. The learning curve of LESD was maximal for a case number of 50. Preoperative general characteristics were comparable for both stages. But the skilled stage had decreased operation time, reduced blood loss, less postoperative complications, and better recovery compared to the learning stage. The LSED group had higher recurrent hemorrhage-free survival rate and increased overall survival in comparison with cases administered open surgery in the 10-year follow-up. Free-liver cancer rates were similar between two groups. CONCLUSIONS: About 50 cases are needed to master the LSED procedure. Compared to open surgery, LSED is a safer, feasible, and safe procedure for PHT patients, correlating with decreased rebleeding rate and better overall survival.
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Cathepsin G (CTSG) plays an important role in the regulation of immune processes. Accumulated studies show that CTSG is involved in the onset and development of type 1 diabetes mellitus (T1DM). As the genetic background of T1DM varies widely among populations, we aimed to study the relationship between genetic polymorphisms in CTSG and T1DM susceptibility in Chinese populations. A total of 141 patients with T1DM and 200 healthy controls were enrolled in the study. Serum CTSG expression was detected using enzyme-linked immunosorbent assay (ELISA). Genotyping of two selected single nucleotide polymorphisms (SNPs) (rs2236742 and rs2070697) of CTSG was performed using PCR and Sanger sequencing. CTSG expression in patients with T1DM was significantly higher than in the control group. Alleles C and T of CTSG SNP rs2236742 were increased in T1DM. No significant associations were found for the SNP rs2070697. Our results indicate that the CTSG rs2236742 allele (C/T) is associated with T1DM in Chinese children and may serve as a new biomarker for predicting T1DM susceptibility.
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Alelos , Povo Asiático , Diabetes Mellitus Tipo 1 , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Humanos , Diabetes Mellitus Tipo 1/genética , Feminino , Masculino , Criança , Estudos de Casos e Controles , Povo Asiático/genética , China/epidemiologia , Pré-Escolar , Frequência do Gene , Ensaio de Imunoadsorção Enzimática , Adolescente , Reação em Cadeia da Polimerase , Biomarcadores/sangue , População do Leste AsiáticoRESUMO
In order to safeguard and restore ecological security in ecologically fragile regions, a regionally appropriate land use structure and ecological security pattern should be constructed. Previous ecological security research models for ecologically fragile areas are relatively homogenous, and it is necessary to establish a multi-modeling framework to consider integrated ecological issues. This study proposes a coupled "PLUS-ESI-Circuit Theory" framework for multi-scenario ecological security assessment of the Ningxia Hui Autonomous Region (NHAR). Firstly, the PLUS model was used to complete the simulation of four future development scenarios. Secondly, a new ecological security index (ESI) is constructed by synthesizing ecological service function, ecological health, and ecological risk. Finally, the Circuit Theory is applied to construct the ecological security pattern under multiple scenarios, and the optimization strategy of ecological security zoning is proposed. The results show that (1) from 2000 to 2030, the NHAR has about 80% of grassland and farmland. The built-up area is consistently growing. (2) Between 2000 and 2030, high ecological security areas are primarily located in Helan Mountain, Liupan Mountain, and the central part of NHAR, while the low ecological security areas are dominated by Shapotou District and Yinchuan City. (3) After 2010, the aggregation of high-security areas decreases, and the fragmentation of patches is obvious. Landscape fragmentation would increase under the economic development (ED) scenario and would be somewhat ameliorated by the ecological protection (EP) and balanced development (BD) scenarios. (4) The number of sources increases but the area decreases from 2000 to 2020. The quantity of ecological elements is on the rise. Ecological restoration and protection of this part of the country will improve its ecological security.
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Planejamento de Cidades , Monitoramento Ambiental , Simulação por Computador , Desenvolvimento Econômico , FazendasRESUMO
Reactive astrocytes can be transformed into new neurons. Vascular endothelial growth factor (VEGF) promotes the transformation of reactive astrocytes into neurons in ischemic brain. Therefore, in this study, the molecular mechanism of VEGF's effect on ischemia/hypoxia-induced astrocyte to neuron transformation was investigated in the models of rat middle cerebral artery occlusion (MCAO) and in astrocyte culture with oxygen and glucose deprivation (OGD). We found that VEGF enhanced ischemia-induced Pax6, a neurogenic fate determinant, expression and Erk phosphorylation in reactive astrocytes and reduced infarct volume of rat brain at 3 days after MCAO, which effects could be blocked by administration of U0126, a MAPK/Erk inhibitor. In cultured astrocytes, VEGF also enhanced OGD-induced Erk phosphorylation and Pax6 expression, which was blocked by U0126, but not wortmannin, a PI3K/Akt inhibitor, or SB203580, a MAPK/p38 inhibitor, suggesting VEGF enhanced Pax6 expression via activation of MAPK/Erk pathway. OGD induced the increase of miR365 and VEGF inhibited the increase of OGD-induced miR365 expression. However, miR365 agonists blocked VEGF-enhanced Pax6 expression in hypoxic astrocytes, but did not block VEGF-enhanced Erk phosphorylation. We further found that VEGF promoted OGD-induced astrocyte-converted to neuron. Interestingly, both U0126 and Pax6 RNAi significantly reduced enhancement of VEGF on astrocytes-to-neurons transformation, as indicated Dcx and MAP2 immunopositive signals in reactive astrocytes. Moreover, those transformed neurons become mature and functional. We concluded that VEGF enhanced astrocytic neurogenesis via the MAPK/Erk-miR-365-Pax6 signal axis. The results also indicated that astrocytes play important roles in the reconstruction of neurovascular units in brain after stroke.
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Astrócitos , Fator A de Crescimento do Endotélio Vascular , Ratos , Animais , Astrócitos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sistema de Sinalização das MAP Quinases , Transdiferenciação Celular , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Infarto da Artéria Cerebral Média/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Neurônios/metabolismo , Glucose/metabolismoRESUMO
Electrostatic capacitors are emerging as a highly promising technology for large-scale energy storage applications. However, it remains a significant challenge to improve their energy densities. Here, an effective strategy of introducing non-isovalent ions into the BiFeO3 -based (BFO) ceramic to improve energy storage capability via delaying polarization saturation is demonstrated. Accordingly, an ultra-high energy density of up to 7.4 J cm-3 and high efficiency ≈ 81% at 680 kV m-1 are realized, which is one of the best energy storage performances recorded for BFO-based ceramics. The outstanding comprehensive energy storage performance is attributed to inhibiting the polarization hysteresis resulting from generation ergodic relaxor zone and random field, and generating highly-delayed polarization saturation with continuously-increased polarization magnitudes with the electric field of supercritical evolution. The contributions demonstrate that delaying the polarization saturation is a consideration for designing the next generation of lead-free dielectric materials with ultra-high energy storage performance.
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BACKGROUND: Activated hepatic stellate cells (HSCs) are primarily involved in liver fibrosis and portal hypertension (PHT). We aimed to investigate the effect of miR-20b-5p on HSCs, liver fibrosis, and PHT. METHODS: MiR-20b-5p expression in HSCs and in mouse liver fibrosis was determined by qPCR. Further, the effects of miR-20b-5p mimic on HSCs migration, proliferation, and apoptosis were investigated in vitro. A dual-luciferase reporter assay was performed to confirm the direct interaction between miR-20b-5p and STAT3. In vivo, mouse liver fibrosis was established by common bile duct ligation and intervened by agomiR-20b-5p. Sirius red staining and hydroxyproline content were used to evaluate collagen deposition. The α-SMA expression in the liver was detected by IHC and Western blotting. The STAT3 signaling pathway and its downregulated cytokines as well as portal pressure and angiogenesis were explored. RESULTS: MiR-20b-5p was significantly downregulated during HSCs activation and in mouse liver fibrosis. The functional analyses demonstrated that miR-20b-5p inhibited cell proliferation, activation, and promoted apoptosis in HSCs in vitro. Moreover, miR-20b-5p regulated STAT3 expression by binding to the 3'UTR of its miRNA directly. Overexpression of miR-20b-5p facilitated HSC activation and proliferation by inhibiting the STAT3 signaling pathway. MiR-20b-5p overexpression suppressed the STAT3 and its downstream cytokines and ameliorated liver fibrosis in mice. The intra- and inter-hepatic angiogenesis were also effectively inhibited. The inhibition of liver fibrosis and neoangiogenesis contributed to the decrease of portal pressure. CONCLUSIONS: MiR-20b-5p plays an important role in the fibrosis and angiogenesis of liver fibrosis by targeting the STAT3 signaling pathway.
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Cirrose Hepática , MicroRNAs , Camundongos , Animais , Regulação para Baixo , Cirrose Hepática/patologia , MicroRNAs/genética , Transdução de Sinais/genética , Fibrose , Proliferação de Células/genética , Citocinas/metabolismo , Células Estreladas do Fígado/metabolismoRESUMO
Previously, we identified a series of steroids (1-6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3ß,5α-dihydroxycholest-6-one, named as (25R)-5, in seven steps from a commercially available compound diosgenin (7), with a total yield of 2.8%. Unfortunately, compound (25R)-5 and the intermediates only showed slight inhibitions against RSV replication at the concentration of 10 µM, but they possessed potent cytotoxicity activities against human bladder cancer 5637 (HTB-9) and hepatic cancer HepG2, with IC50 values ranging from 3.0 to 15.5 µM without any impression of normal liver cell proliferation at 20 µM. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC50 values of 4.8 µM and 15.5 µM, respectively. Further studies indicated that compound (25R)-5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25R-isomer of compound 5; the biological results suggested that compound (25R)-5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer.
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Antineoplásicos , Diosgenina , Esteroides/farmacologia , Diosgenina/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células , Estrutura MolecularRESUMO
Microblood perfusion of isolated single umbilical artery (ISUA) foetus placenta was evaluated using three-dimensional power Doppler ultrasound (3D-PDU). Vascular endothelial growth factor (VEGF) protein expression in the placenta was also semi-quantitative and qualitatively analysed. Differences between ISUA and control groups were compared. 3D-PDU was used to detect placental blood flow parameters, including vascularity index (VI), flow index, and vascularity flow index (VFI), in 58 foetuses in the ISUA group and 77 normal foetuses in the control group. Immunohistochemistry and polymerase chain reaction were employed to analyse the VEGF expression in placental tissues of 26 foetuses in the ISUA group and 26 foetuses in the control group. The control group exhibited higher VI and VFI than the ISUA group (p < 0.05). Meanwhile, the ISUA group showed a higher positivity rate of VEGF protein expression than the control group (χ2=28.013, pË0.001). The ISUA group also presented a higher VEGF mRNA protein expression than the control group (pË0.001). 3D-PDU can be used to quantitatively analyse microblood perfusion of the placenta and provide an objective assessment of ISUA foetuses.Impact statementWhat is already known on this subject? Colour Doppler flow can be used to evaluate placental and maternal circulation and remains an ideal method for evaluating high-risk placental function. Three-dimensional power Doppler ultrasound (3D-PDU) can be used to quantify blood vessels and blood flow in placental parenchyma via the measurement of the amplitude of blood vessels and blood flow in normal foetuses, respectively.What do the results of this study add? 3D-PDU can be used to quantitatively analyse micro blood perfusion of the placenta and conduct an objective assessment of isolated single umbilical artery foetuses. The isolated single umbilical artery foetuses exhibited a higher positivity rate of vascular endothelial growth factor (VEGF) protein expression and higher VEGF mRNA protein expression than the normal foetuses.What are the implication of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal-foetal monitoring during pregnancy in the isolated single umbilical artery foetuses. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.
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Placenta , Artéria Umbilical Única , Gravidez , Feminino , Humanos , Placenta/diagnóstico por imagem , Fator A de Crescimento do Endotélio Vascular , Circulação Placentária , Feto , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Doppler/métodos , Artérias Umbilicais/diagnóstico por imagemRESUMO
Accumulating evidence has demonstrated that microRNA-519a (miR-519a) acts as the tumor suppressor in various cancers, but little is known regarding its intrinsic regulatory mechanisms in non-small cell lung cancer (NSCLC). Here, we aimed to investigate the role of miR-519a-targeted ephrinA2 receptor (EphA2) in radiosensitivity of NSCLC. MiR-519a and EphA2 expression in NSCLC and paracancerous tissues were detected using RT-qPCR and western blot analysis. A549 cell line was cultured and radiation-resistant cell line A549R was constructed using fractionated X-ray irradiation of these cells at 60 Gy. Colony formation ability and radioresistance of parent strain A549 and resistant strain A549R were detected with restored miR-519a and depleted EphA2. MTT assay was used to measure cell proliferation, flow cytometry was performed for determination of cell cycle distribution and apoptosis. The migration and invasion abilities were assessed by Transwell assay. The target relationship between miR-519a and EphA2 was verified. Results suggested that miR-519a was downregulated and EphA2 was upregulated in NSCLC tissues and cells, and miR-519a targeted EphA2. MiR-519a expression declined, while EphA2 expression elevated in A549R cells versus A549 cells. Upregulated miR-519a and downregulated EphA2 suppressed D0, Dq, survival fraction (SF2) and N-value, arrested cells at G0/G1 phase, advanced the apoptosis and attenuated migration, proliferation, and invasion of A549 and A549R cells. Overexpression of EphA2 reversed the promotion of upregulated miR-519a on radiosensitivity of NSCLC cells. Our results revealed that miR-519a enhances radiosensitivity of NSCLC by inhibiting EphA2 expression. Moreover, miR-519a serves as a target for NSCLC treatment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Receptor EphA2 , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Tolerância a Radiação/genética , Células A549 , Receptor EphA2/genéticaRESUMO
BACKGROUND: This meta-analysis was designed to systematically assess the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with surgery for different stages of advanced gastric cancer (AGC) during the last 12 years. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched online, and papers were retrieved from other sources. Next, randomized controlled trials (RCTs) and high-quality nonrandomized controlled trials (NRCTs) were selected for this analysis. The meta-analysis was conducted with RevMan5.4 software. RESULT: The 10 RCTs and 13 NRCTs selected for the study included 1892 patients. The overall survival rates were higher in the HIPEC group at 1 year (risk ratio [RR], 0.52; P = 0.004) and 3 years (RR, 0.63; P < 0.00001) than in the control group for the patients without peritoneal cancer, and the HIPEC group had a significant reduction in the recurrence rate (RR, 0.60; p < 0.00001). Among the patients with peritoneal carcinomatosis (PC), the HIPEC group had significantly higher overall survival rates at 1 year (RR, 0.62; P = 0.00001), 2 years (RR, 0.85; P = 0.002), and 3 years (RR, 0.87; P = 0.0001), with an increase in the overall median survival time of 4.67 months. The two groups showed no statistically significant difference in terms of complications for patients with PC (RR, 1.03; P = 0.93) or without PC (RR, 1.15; P = 0.51). CONCLUSION: For local AGC without PC, standard surgery combined with prophylactic HIPEC could prolong survival and reduce the recurrence rate without more complications. The prognosis of this treatment strategy for patients with PC is closely related to patient selection. Complete cytoreduction combined with therapeutic HIPEC could prolong survival.
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Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
IL-10 is critical for Foxp3+ regulatory T cell (Tregs)-mediated immune suppression, but how to efficiently upregulate IL-10 production in Tregs remains unclear. In this article, we show that human IL-10+ FOXP3+-induced regulatory T cell (iTreg) generation can be dramatically promoted by inhibiting GSK3 activity. IL-10+ FOXP3+ iTregs induced by GSK3 inhibition exhibit classical features of immune-suppressive T cells. We further demonstrate that IL-10+ iTregs exhibit enhanced suppressive function in both IL-10-dependent and -independent manners. The enhanced suppressive function of IL-10+ Tregs is not due to a single factor such as IL-10, although IL-10 may mediate this enhanced suppressive function to some extent. Mechanistically, the increased transcriptional activity of IL-10 promoter and the enhanced expression of C-Maf and BLIMP1 coordinately facilitate IL-10 expression in human iTregs under GSK3 inhibition. Our study provides a new strategy to generate human immune-suppressive IL-10+ FOXP3+ Tregs for immunotherapies.
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Quinase 3 da Glicogênio Sintase/metabolismo , Interleucina-10/metabolismo , Linfócitos T Reguladores/imunologia , Animais , Células Cultivadas , Fatores de Transcrição Forkhead/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/genética , Xenoenxertos , Humanos , Tolerância Imunológica , Indóis/farmacologia , Interleucina-10/genética , Ativação Linfocitária , Maleimidas/farmacologia , Camundongos , Camundongos Knockout , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-maf/genética , Ativação TranscricionalRESUMO
AIMS: The study aimed to investigate the value of autoantibodies in predicting the risk of ketoacidosis or microalbuminuria in children with type 1 diabetes mellitus. METHODS: Clinical data and laboratory indicators of 80 patients with type 1 diabetes admitted to the Department of Endocrinology in Tianjin Children's Hospital, from June 2017 to March 2019, were retrospectively analyzed. The patients were divided into two groups: diabetes without ketoacidosis group (n = 20) and diabetes with ketoacidosis group (n = 60). The differences in general data, laboratory test indexes, and autoantibodies between the two groups were analyzed. Finally, ROC curves and multivariate logistic regression analysis were used to explore the value of autoantibodies in patients with ketoacidosis or microalbuminuria. RESULTS: A total of 80 children with type 1 diabetes were assessed, including 35 boys and 45 girls, ranging in age from 10 months to 15 years. The concentration of GADA, IA2A, and ZnT8A was not statistically different between the two groups, but the positive rate of ZnT8A was statistically significant (p = 0.038) and had a diagnostic value for the occurrence of ketoacidosis (p = 0.025). ZnT8A-positive patients had a higher titer of IA2A and a more frequent prevalence of GADA and IA2A than ZnT8A-negative patients (p < 0.01). In multivariate logistic regression analyses, the presence of positive ZnT8A was associated with a higher risk of microalbuminuria independent of age, sex, and BMI (OR = 4.184 [95% CI 1.034~16.934], p = 0.045). CONCLUSIONS: The positive ZnT8A had diagnostic value for ketoacidosis in children with type 1 diabetes and had the highest specificity among the three kinds of autoantibodies. Moreover, ZnT8A positivity was related to a higher titer of IA2A and more frequent occurrence of multiple diabetes-related autoantibodies. Besides, the presence of positive ZnT8A was an independent risk factor of microalbuminuria in children with type 1 diabetes. Therefore, we can infer that positive ZnT8A may be related to ketoacidosis and microalbuminuria, accelerating the progression of T1DM.
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Albuminúria , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1 , Cetose , Adolescente , Albuminúria/complicações , Albuminúria/epidemiologia , Albuminúria/imunologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Lactente , Cetose/complicações , Cetose/epidemiologia , Cetose/imunologia , Masculino , Curva ROCRESUMO
Centromere protein M (CENPM) is essential for chromosome separation during mitosis. However, its roles in lung adenocarcinoma (LUAD) progression and metastasis remain unknown. In this study, we aimed to explore the effects of CENPM on LUAD progression as well as the underlying mechanisms. We analyzed the expression of CENPM and its correlation with clinicopathological characteristics using GEO LUAD chip datasets and TCGA dataset. We further investigated the impact of CENPM on LUAD and . In silico analysis and qRT-PCR revealed that CENPM is upregulated in LUAD compared with that in normal lung tissues. Via gain/loss-of-function assays, we further found that CENPM promotes the LUAD cell cycle, cell proliferation, migration and invasion, and inhibits cell apoptosis. The study showed that loss of CENPM inhibits the growth of A549 xenografts. Furthermore, we found that CENPM can promote the phosphorylation of mTOR rather than directly affect the mTOR content. Inhibition of mTOR activity abrogates the promoting effects of CENPM on cell cycle progression, cell proliferation, migration and invasion. Taken together, these results show that CENPM plays an important role in the growth and metastasis of LUAD and may be a promising therapeutic target in LUAD.
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Adenocarcinoma de Pulmão , Proteínas de Ciclo Celular/genética , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação para CimaRESUMO
The SmFLS gene was cloned from eggplant and has an ORF of 1014 bp encoding 337 amino acids. The deduced protein sequence of SmFLS was 88.07% and 84.94% identical to homologs encoded by StFLS in Solanum tuberosum and SlFLS in S. lycopersicum, respectively. SmFLS contains typical DIOX_N and 2OG-Fe (II)_Oxy functional domains, as well as five strictly conserved amino acid residues (H223, D225, H279, R289, and S291) related to FLS enzyme activity. Phylogenetic tree analysis showed that SmFLS had the closest genetic relationship with the FLS genes in potato and tomato. At a high temperature of 35 °C, the expression level of SmFLS was higher than that of the control in the same period, and it reached extremely significant levels on 15DAF and 20DAF, at which the eggplant peel color became lighter accordingly. Upon overexpression of SmFLS in eggplant, the flavonol content of transformed plants was significantly higher than that of untransformed plants, and the peel color was lighter than that of the control. The results indicate that SmFLS negatively regulates eggplant peel coloration under high temperature.
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Frutas/genética , Pigmentação/genética , Solanum melongena , Solanum lycopersicum/genética , Filogenia , Solanum melongena/genética , Solanum tuberosum/genética , TemperaturaRESUMO
BACKGROUND AND PURPOSE: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disease. In addition to the traditional clinical triad, there is also a diversity of clinical signs, and it may be related to other systemic diseases. METHODS: In the present study, we report a case of MRS with endocrine disorders that exhibits extraordinary therapeutic efficiency by using hydroxychloroquine (HCQ), explore whether there is an internal connection between MRS and endocrine disorders, and discuss the mechanism of the therapeutic efficiency of using HCQ. The hypothesis proposed for the first time is that MRS may essentially be a systemic granulomatous disease. RESULTS: The physical examination revealed orofacial swelling and fissured tongue. The histopathologic examination showed epithelioid granulomas. Combined with the other examination, this case was diagnosed as incomplete MRS. HCQ and local drugs were introduced. The patient achieved clinical recovery and psychological cure by the 18-week follow-up, and the 1-year follow-up found no reactivation of MRS. Moreover, the levels of cortisol and adrenocorticotropic were within normal ranges. CONCLUSIONS: After the drug therapy was targeted at granuloma, not only did all of the symptoms related to MRS disappear, but the endocrine system also returned to normal. It is speculated that the endocrine disorder in this patient may be related to MRS. We further propose the first-time hypothesis that MRS may essentially be a systemic granulomatous disease. It provides a new medication method with high-level efficiency.
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Hidroxicloroquina , Síndrome de Melkersson-Rosenthal , Adolescente , Feminino , Granuloma , Humanos , Síndrome de Melkersson-Rosenthal/tratamento farmacológicoRESUMO
Gouty arthritis is an inflammatory disease that is triggered by abnormal uric acid metabolism, which is usually attributed to obesity, a risk factor of hyperuricemia and gout attack. A high level of leptin in plasma is a marker of individuals with obesity. Population studies show that leptin promotes obesity-related arthritis, such as osteoarthritis, but it is unknown whether leptin contributes to gouty arthritis, another form of obesity-related arthritis. Our present study showed that the levels of leptin and leptin receptor in patients with active gouty arthritis were elevated. Leptin facilitates the stimulation of human synoviocytes, mouse peritoneal macrophages, and HL-60 cells induced by monosodium urate, leading to higher levels of acute gout-related proinflammatory factors. Leptin obviously exacerbates the inflammation of monosodium urate-induced acute gouty arthritis in wild-type mice, whereas that in leptin-deficient C57BL6/Job/ob mice is markedly alleviated. The proinflammatory effect of leptin in acute gouty arthritis is partly mediated by mTORC1 signaling pathway. Our study reveals that leptin may serve as a novel prevention and treatment target in acute gouty arthritis.
Assuntos
Artrite Gotosa/imunologia , Leptina/imunologia , Sinoviócitos/imunologia , Ácido Úrico/toxicidade , Animais , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/patologia , Modelos Animais de Doenças , Feminino , Células HL-60 , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Leptina/efeitos adversos , Leptina/farmacologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/imunologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Sinoviócitos/patologiaRESUMO
INTRODUCTION: Birth defects are a leading cause of infant death. Pregnant women spend a large amount of time indoors, and little research from population-based studies has investigated the association between indoor air pollution and birth defects. We aimed to examine whether using coal, biomass, or electromagnetic stoves for cooking is associated with risk of birth defects compared to using gas stoves. METHODS: A birth cohort study was conducted from 2010 to 2012 in Lanzhou, China. Cases (n = 264) were singleton births with birth defects, which were defined as abnormalities of structure or function, including metabolism, presented at birth based on the International Classification of Diseases (ICD)-10 codes. Controls (n = 9926) were defined as singleton live births without birth defects. Unconditional logistic regression models were employed to estimate the association adjusting for confounding variables. RESULTS: Compared to gas stoves for cooking, biomass (OR = 2.66, 95%CI: 1.38-5.13), and electromagnetic stove (OR = 1.90, 95%CI: 1.26-2.88) for cooking were associated with an increased risk of birth defects. The significant associations remained among non-congenital heart disease (CHD) defects but not CHDs. CONCLUSIONS: Using biomass or electromagnetic stoves for cooking during pregnancy was associated with an increased risk of birth defects. Additional studies are warranted to confirm these novel findings. Studies with larger sample size or greater statistical power are also warranted to better estimate the associations for individual birth defects.