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High energy density and flexible electrodes, which have high mechanical properties and electrochemical stability, are critical to the development of wearable electronics. In this work, a free-standing MXene bonded SnS2 composited nitrogen-doped carbon fibers (MXene/SnS2 @NCFs) film is reported as a flexible anode for sodium-ion batteries. SnS2 nanoparticles with high-capacity properties are covalently decorated in bio-derived nitrogen-doped 1D carbon fibers (SnS2 @NCFs) and further assembled with highly conductive MXene sheets. The addition of bacterial cellulose (BC) can further improve the flexibility of the film. The unique 3D structure of points, lines, and planes can not only offset the disadvantage of low conductivity of SnS2 nanoparticles but also expand the distance between MXene sheets, which is conducive to the penetration of electrolytes. More importantly, the MXene sheets and N-doped 1D carbon fibers (NCFs) can accommodate the large volume expansion of SnS2 nanoparticles and trap polysulfide during the cycle. The MXene/SnS2 @NCFs film exhibits better sodium storage and excellent rate performance compared to the SnS2 @NCFs. The in situ XRD and ex situ (XRD, XPS, and HRTEM) techniques are used to analyze the sodiation process and to deeply study the reaction mechanism of the films. Finally, the quasi-solid-state full cells with MXene/SnS2 @NCFs and Na3 V2 (PO4 )3 @carbon cloth (NVP@CC) fully demonstrate the application potential of the flexible electrodes.
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Heme has attracted considerable attention due to its indispensable biological roles and applications in healthcare and artificial foods. The development and utilization of edible microorganisms instead of animals to produce heme is the most promising method to promote the large-scale industrial production and safe application of heme. However, the cytotoxicity of heme severely restricts its efficient synthesis by microorganisms, and the cytotoxic mechanism is not fully understood. In this study, the effect of heme toxicity on Saccharomyces cerevisiae was evaluated by enhancing its synthesis using metabolic engineering. The results showed that the accumulation of heme after the disruption of heme homeostasis caused serious impairments in cell growth and metabolism, as demonstrated by significantly poor growth, mitochondrial damage, cell deformations, and chapped cell surfaces, and these features which were further associated with substantially elevated reactive oxygen species (ROS) levels within the cell (mainly H2O2 and superoxide anion radicals). To improve cellular tolerance to heme, 5 rounds of laboratory evolution were performed, increasing heme production by 7.3-fold and 4.2-fold in terms of the titer (38.9 mg/L) and specific production capacity (1.4 mg/L/OD600), respectively. Based on comparative transcriptomic analyses, 32 genes were identified as candidates that can be modified to enhance heme production by more than 20% in S. cerevisiae. The combined overexpression of 5 genes (SPS22, REE1, PHO84, HEM4 and CLB2) was shown to be an optimal method to enhance heme production. Therefore, a strain with enhanced heme tolerance and ROS quenching ability (R5-M) was developed that could generate 380.5 mg/L heme with a productivity of 4.2 mg/L/h in fed-batch fermentation, with S. cerevisiae strains being the highest producers reported to date. These findings highlight the importance of improving heme tolerance for the microbial production of heme and provide a solution for efficient heme production by engineered yeasts.
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OBJECTIVE: To investigate the efficacy and safety of mini-track, mini-nephroscopy and mini-ultrasonic probe percutaneous nephrolithotomy (3mPCNL) for the treatment of 1.5-2.5 cm kidney stones. METHODS: The perioperative data and postoperative follow-up data of a total of 25 patients with about 1.5-2.5 cm kidney stones who underwent 3mPCNL under ultrasound guidance in Peking University People's Hospital from November 2023 to January 2024 were retrospectively analyzed. During the matching period, the 25 patients with 1.5-2.5 cm kidney stones receiving standard percutaneous nephrolithotomy (sPCNL) were matched one-to-one according to the criterion that the absolute difference of the maximum diameter of stones between the two groups was less than 1 mm. The operative time, renal function changes, postoperative stone-free rate, hemoglobin changes, and complication rate of the two treatments were compared, and then the effectiveness and safety of 3mPCNL were preliminarily analyzed. RESULTS: There were no significant differences in mean age, preoperative median creatinine, preoperative mean hemoglobin, preoperative mean hematocrit, median stone maximum diameter, and median stone CT density between the 3mPCNL group and the sPCNL group. The median operation time in the 3mPCNL group was 60.0 (45.0-110.0) min, with no statistical significance compared with the sPCNL group, and all the patients underwent single-channel operations. The mean hemoglobin after operation in the 3mPCNL group was (115.3±15.5) mmol/L, and there was no significant difference between the preoperative group and the sPCNL group, and the mean hemoglobin decreased significantly between the sPCNL group and the sPCNL group [(9.5±2.2) mmol/L vs. (10.1±1.9) mmol/L]. The mean hematocrit after operation was (28.0±5.2)%, and the difference was statistically significant compared with that before operation (t=2.414, P=0.020). The mean hematocrit drop was not statistically signi-ficant compared with the sPCNL group (2.3% vs. 2.7%). The median serum creatinine in the 3mPCNL group was 74.0 (51.0-118.0) µmol/L after operation, and the difference was statistically significant compared with that before operation (Z=-2.980, P=0.005). The stone-free rate in the 3mPCNL group and the sPCNL group was 96.0% and 97.3%, respectively, and the mean hospital stay was (4.3± 1.4) d and (5.5±2.0) d, respectively, with the statistical significance (t=0.192, P=0.025). After the operation, one patient in sPCNL group had massive hemorrhage after the nephrostomy tube was removed, which was improved after selective renal artery embolization. One patient in the 3mPCNL group developed mild perirenal hematoma, which was improved after conservative treatment, and no complications were observed in the other patients. CONCLUSION: 3mPCNL in the treatment of 1.5-2.5 cm kidney stones can achieve an effective rate comparable to sPCNL, and can achieve the ideal stone-free rate in a shorter operative time with a lower rate of surgery-related complications.
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Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Duração da Cirurgia , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Traditional approaches in studying the genetics of complex traits have focused on identifying specific genetic variants. However, the collective effects of variants have remained largely unexplored. Here, we evaluated whether traits could be influenced by the collective effects of variants across the entire protein coding-region of the genome or the entire genome. We studied the UK Biobank exome sequencing data of 167,246 individuals as well as the genome-wide SNP array data of 408,868 individuals. We calculated for each individual four different measures of genetic variation such as heterozygosity and number of variants and two different measures of the overall deleteriousness of all variants, and performed correlations with 17 representative traits that have been studied previously. Linear regression analysis was performed with adjustment for age, sex, and genetic principal components. The results showed a high correlation among the six different measures and an inverse association of two well-correlated traits (educational attainment and height) with the total number of all variants as well as the overall deleteriousness of all variants. We have also categorized the genes based on whether they are expressed in the brain and found that the association with educational attainment only held for the brain-expressed genes. No other traits examined showed a significant correlation with the brain-expressed genes. The study demonstrates that common traits could be studied by analyzing the overall genetic variation and suggests that educational attainment is inversely related to genetic variation.
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Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Herança Multifatorial/genética , Fenótipo , Sequenciamento do Exoma , Exoma , Polimorfismo de Nucleotídeo Único , Variação GenéticaRESUMO
BACKGROUND: Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. METHODS: PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). RESULTS: Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001). CONCLUSIONS: SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.
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Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Nefroureterectomia , Carcinoma de Células de Transição/patologia , Estudos Retrospectivos , Neoplasias Ureterais/patologiaRESUMO
Selectively anchoring active centers on the external surface for forming highly exposed acid sites is a highly desirable but challenging task in zeolite catalyst synthesis. Herein, a defect-guided etching-regrowth strategy is rationally designed for facilely positioning Sn Lewis acid sites on the outer surface of the Sn-B-Beta while fabricating a bifunctional hierarchical structure. The synthesis was conducted by hydrothermal treatment of the as-made B-Beta (uncalcined), which has intrinsic defects of the BEA structure, with Sn source and basic organic structure directing agent (SDA). Under a moderate SDA concentration, with blocked micropore channels, such SDA-triggered etching-regrowth will proceed along the defect defined pathway, which ensures Sn selectively anchored on the external surface. Moreover, this methodology has exclusively introduced tetrahedrally coordinated framework Sn with open Sn sites as the predominated species. Mono- and disaccharide isomerizations in ethanol over different Sn-Beta catalysts proved the prominent advantages of the hierarchical structure with highly exposed and synergetic acid sites.
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BACKGROUND: Ambient air pollution has been characterized as a leading cause of mortality worldwide and has been associated with cardiovascular and respiratory diseases. There is increasing evidence that short-term exposure to nitrogen dioxide (NO2), is related to adverse health effects and mortality. METHODS: We conducted a systematic review of short-term NO2 and daily mortality, which were indexed in PubMed and Embase up to June 2021. We calculated random-effects estimates by different continents and globally, and tested for heterogeneity and publication bias. RESULTS: We included 87 articles in our quantitative analysis. NO2 and all-cause as well as cause-specific mortality were positively associated in the main analysis. For all-cause mortality, a 10 ppb increase in NO2 was associated with a 1.58% (95%CI 1.28%-1.88%, I2 = 96.3%, Eggers' test p < 0.01, N = 57) increase in the risk of death. For cause-specific mortality, a 10 ppb increase in NO2 was associated with a 1.72% (95%CI 1.41%-2.04%, I2 = 87.4%, Eggers' test p < 0.01, N = 42) increase in cardiovascular mortality and a 2.05% (95%CI 1.52%-2.59%, I2 = 78.5%, Eggers' test p < 0.01, N = 38) increase in respiratory mortality. In the sensitivity analysis, the meta-estimates for all-cause mortality, cardiovascular and respiratory mortality were nearly identical. The heterogeneity would decline to varying degrees through regional and study-design stratification. CONCLUSIONS: This study provides evidence of an association between short-term exposure to NO2, a proxy for traffic-sourced air pollutants, and all-cause, cardiovascular and respiratory mortality.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análiseRESUMO
The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.
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Portadores de Fármacos/síntese química , Excipientes/síntese química , Impressão Tridimensional , Comprimidos/síntese química , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Excipientes/farmacocinética , Álcool de Polivinil/síntese química , Álcool de Polivinil/farmacocinética , Propranolol/síntese química , Propranolol/farmacocinética , Comprimidos/farmacocinética , Difração de Raios X/métodosRESUMO
To study the effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy. A total of 205 cases of patient with early diabetic nephropathy treated in our hospital from March 2014 to April 2016 were selected and divided into two groups according to the admitted order, with 103 cases in clinical group and 102 in control group. Patients in control group were treated with melbine and captopril, which may be adjusted according to the clinical symptom. The clinical group was given Shenqi Dihuang decoction. Then the clinical efficady, inflammatory factors, renal function, endothelial function and hemorheology index were compared. Compared with 77.45% in the control group, the total effective rate of the clinical group was 92.23%. There was a significant increase (P<0.05). The comparison of the values of IL-6, IL-8, TNF-α and CRP between the two groups before and after treatment showed significant differences. The values of inflammatory factors in treatment group were lower than in control group (P<0.05). The comparison of the values of ß2-MG, Cys-C and urine m-ALB between the two groups before and after treatment showed significant differences. The values of renal function in treatment group were lower than those in control group (P<0.05). Compared with before treatment, ET-1 of the two groups after treatment decreased, while NO increased (P<0.05). Compared with the control group, the value of ET-1 in patients of the experimental group was lower after treatment, while NO was higher (P<0.05). The comparison of the values of whole blood viscosity, plasma viscosity, whole blood reduction viscosity, platelet aggregation rate and fibrinogen between the two groups before and after treatment showed significant differences. The value of hemorheology index in treatment group was lower than that in control group (P<0.05). Shenqi Dihuang decoction has a better effect on patients with early diabetic nephropathy. It can significantly intervene with inflammatory response, reduce proteinuria, protect the renal function of patients, and improve the patient's vascular endothelial function and blood rheology, so as to make microcirculation to recover to the normal level.
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Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Microcirculação , ProteinúriaRESUMO
Tumour suppressor protein 53 (p53) plays a central role in apoptosis, cell proliferation and death. Previously studies found contribution of functional p53 Arg72Pro polymorphism (TP53 rs1042522G/C polymorphism) in the development of systemic lupus erythematosus (SLE) remains controversial. In this study, for the first time, we evaluated its association with SLE in a Chinese Han population. This case-control study enrolled 1470 SLE patients and 2283 healthy controls. The genotyping of TP53 rs1042522 polymorphism was determined by Sequenom Mass ARRAY technology. Statistical analysis was conducted by Chi-square test (χ 2 test). Odds ratio (OR) with 95% confidence interval (CI) was calculated using unconditional logistic regression with adjusting age and sex. Allele and genotype frequencies of TP53 rs1042522G/C polymorphism showed statistically significant difference between the SLE patients and the normal controls (C vs. G: OR = 0.89, 95% CI 0.89-0.97, p = 0.01; (GC + CC) vs. GG using recessive model: OR = 0.84, 95% CI 0.73-0.96, p = 0.01; GC vs. GG using co-dominant model: OR = 0.86, 95% CI 0.74-0.99, p = 0.04; CC vs. GG using co-dominant model: OR = 0.80, 95% CI 0.66-0.96, p = 0.02; GC vs. GG using co-dominant model: OR = 0.86, 95% CI 0.74-0.99, p = 0.02). In addition, there was weak association between discoid rash and distribution of TP53 rs1042522G/C polymorphism in SLE patients (C vs. G: OR = 1.25, 95% CI 1.00-1.55, p = 0.04; CC vs. GG using co-dominant model: OR = 1.54, 95% CI 1.10-2.36, p = 0.04). Our finding suggests a significant relationship between the TP53 rs1042522G/C polymorphism and SLE. TP53 rs1042522G/C polymorphism would be promising as an indicator of SLE as well as the therapeutic target if its functions and mechanisms could be further investigated.
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Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of this study was to explore the association between the IL7R T244I polymorphism (rs6897932) and susceptibility of multiple sclerosis (MS). A comprehensive literature search for relevant studies was conducted on Google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated. Seventeen case-control studies were included in this meta-analysis. In total, 17 articles provided data for 15,270 cases and 17,971 controls. The results showed significant association between the IL7R T244I polymorphism and susceptibility to MS (OR = 1.125, 95 % CI: 1.016-1.245, p = 0.024 for C vs. T; OR = 1.176, 95 % CI: 1.078-1.282, p < 0.001 for CC + CT vs. TT; OR = 1.243, 95 % CI: 1.088-1.421, p = 0.001 for CC vs. TT). Stratified analysis of ethnicities also showed significant association in Europeans. However, no association was found in Asians. This study suggested that the IL7R C allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the roles played by the IL7R T244I polymorphism during the pathogenesis of MS.
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Predisposição Genética para Doença/genética , Interleucina-7/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Bases de Dados Bibliográficas/estatística & dados numéricos , Estudos de Associação Genética , Genótipo , Humanos , Fatores de RiscoRESUMO
Nucleotide-binding oligomerization domain 2 (NOD2) is one of the most prominent member of the NOD-like receptors protein family that functions as intracellular pattern recognition receptors. Numerous studies have suggested the importance of NOD2 in defensing against microbial infections, regulation of the inflammatory process. It is shown that NOD2 contributes to the pathogenesis of various autoimmune and chronic inflammatory diseases, such as Crohn's disease, rheumatoid arthritis. The aim of this study is to summarize our current understandings of NOD2 function and the role of NOD2 in systemic lupus erythematosus (SLE). The following databases were searched: Pubmed, EMBASE and Web of Science for English-language sources, using the terms "lupus," "systemic lupus erythematosus," ''SLE," "immunity," "inflammatory" and "NOD2." Emerging data evidences that NOD2 has important biological effects in autoimmunity and inflammatory and might take part in the pathogenesis of SLE. Studies exploring the relationship between NOD2 and SLE are very limited. Whether NOD2 could be a potentially valuable therapeutic target for treatment for SLE, more understanding of the mechanism of NOD2 is needed in the future in SLE.
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Autoimunidade/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismoRESUMO
OBJECTIVE: To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy. MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS). RESULTS: Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% ( n =5658) were considered primary MIBC patients, and 16.7% ( n =974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P <0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant ( P =0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P <0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P =0.089). CONCLUSION: CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses.
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Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Cistectomia/métodos , Pontuação de Propensão , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Estudos de Coortes , Músculos/patologia , Invasividade Neoplásica/patologia , Estudos RetrospectivosRESUMO
Background: Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Methods: Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Results: Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Conclusions: Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.
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Kidney stones and infections significantly affect patients' health-related quality of life (HRQOL); however, the relationship between urinary tract infections (UTIs) and HRQOL in patients with kidney stones remains unclear. This study aimed to investigate the relationship using the validated Chinese version of the Wisconsin Stone Quality of Life questionnaire (C-WISQOL). We prospectively recruited 307 patients with kidney stones to complete the C-WISQOL before and after stone removal. The participants were diagnosed with UTI based on the presence of pyuria or bacteriuria with or without clinical symptoms. The psychometric properties of the C-WISQOL were statistically analyzed. Multivariate linear regression was used to predict the risk factors for impaired HRQOL in patients with stones and UTIs. The questionnaire is a reliable and robust tool for evaluating HRQOL in Chinese-speaking patients with urolithiasis. The UTI and kidney stone co-occurrence was significantly associated with female sex, diabetes mellitus, more previous stone events, higher antibiotic usage, positive stone- or UTI-related symptoms, and postoperative residual stones. The preoperative C-WISQOL scores and improvement in the HRQOL after stone removal in patients clinically diagnosed with UTI were significantly inferior to those in patients without UTI. The regression analyses showed that worse HRQOL was predicted by more previous stone events and positive stone- or UTI-related symptoms. In contrast, the presence of diabetes mellitus and postoperative residual stone fragments predicted a lower improvement in the HRQOL. These findings underscore UTI's harmful impact on perioperative HRQOL in patients with kidney stones and could help strategies benefit those patients.
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Cálculos Renais , Qualidade de Vida , Infecções Urinárias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cálculos Renais/complicações , Cálculos Renais/cirurgia , Infecções Urinárias/psicologia , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Estudos Prospectivos , Adulto , Inquéritos e Questionários/estatística & dados numéricos , Fatores de Risco , Idoso , PsicometriaRESUMO
The current generation of wearable sensors often experiences signal interference and external corrosion, leading to device degradation and failure. To address these challenges, the biomimetic superhydrophobic approach has been developed, which offers self-cleaning, low adhesion, corrosion resistance, anti-interference, and other properties. Such surfaces possess hierarchical nanostructures and low surface energy, resulting in a smaller contact area with the skin or external environment. Liquid droplets can even become suspended outside the flexible electronics, reducing the risk of pollution and signal interference, which contributes to the long-term stability of the device in complex environments. Additionally, the coupling of superhydrophobic surfaces and flexible electronics can potentially enhance the device performance due to their large specific surface area and low surface energy. However, the fragility of layered textures in various scenarios and the lack of standardized evaluation and testing methods limit the industrial production of superhydrophobic wearable sensors. This review provides an overview of recent research on superhydrophobic flexible wearable sensors, including the fabrication methodology, evaluation, and specific application targets. The processing, performance, and characteristics of superhydrophobic surfaces are discussed, as well as the working mechanisms and potential challenges of superhydrophobic flexible electronics. Moreover, evaluation strategies for application-oriented superhydrophobic surfaces are presented.
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BACKGROUND: The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. METHODS: The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. RESULTS: PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. CONCLUSIONS: Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.
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Neoplasias da Mama , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Feminino , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Biomarcadores , Prognóstico , Microambiente Tumoral/genética , Proteína Tirosina Fosfatase não Receptora Tipo 3RESUMO
Sodium-ion batteries (SIBs) have great potential as electrochemical energy storage systems; however, their commercial viability is limited by the lack of anode materials with fast charge/discharge rates and long lifetimes. These challenges were addressed by developing a multi-interface design strategy using FCSe (FeSe2/CoSe2) nanoparticles on V4C3Tx MXene nanosheets as conductive substrates. The heterogeneous interface created between the two materials provided high-speed transport of sodium ions, suppressed the chalking-off of nanoparticles, and improved the cycling stability. Additionally, the Fe-Co bonds generated at the interface effectively relieved mechanical stress, further enhancing the electrode durability. The C@FCSe@V4C3 electrode exhibited high-speed charging and discharging characteristics, and maintained a high specific capacity of 260.5 mAh g-1 even after 15,000 cycles at 10 A g-1, with a capacity retention rate of 50.2% at an ultrahigh current density of 20 A g-1. Furthermore, the composite displayed a good cycling capability in the fast discharge and slow charge mode. This demonstrates its promising commercial potential. This multi-interface design strategy provides insights and guidance for solving the reversibility and cycling problems of transformed selenide anode materials.
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Exploring the relationship between neuronal dynamics and ethologically relevant behaviour involves recording neuronal-population activity using technologies that are compatible with unrestricted animal behaviour. However, head-mounted microscopes that accommodate weight limits to allow for free animal behaviour typically compromise field of view, resolution or depth range, and are susceptible to movement-induced artefacts. Here we report a miniaturized head-mounted fluorescent mesoscope that we systematically optimized for calcium imaging at single-neuron resolution, for increased fields of view and depth of field, and for robustness against motion-generated artefacts. Weighing less than 2.5 g, the mesoscope enabled recordings of neuronal-population activity at up to 16 Hz, with 4 µm resolution over 300 µm depth-of-field across a field of view of 3.6 × 3.6 mm2 in the cortex of freely moving mice. We used the mesoscope to record large-scale neuronal-population activity in socially interacting mice during free exploration and during fear-conditioning experiments, and to investigate neurovascular coupling across multiple cortical regions.
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Comportamento Animal , Neurônios , Animais , Neurônios/fisiologia , Camundongos , Comportamento Animal/fisiologia , Camundongos Endogâmicos C57BL , Miniaturização , Masculino , Cálcio/metabolismo , Medo/fisiologiaRESUMO
Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood-brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.