Glucose metabolism reprogramming in gynecologic malignant tumors.

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, as well as social and economic pressures. Consequently, it has emerged as a significant threat to women's health. Numerous studies have revealed the remarkable metabolic activity of tumor cells in glycolysis and its ability to influence malignant biological behavior through specific mechanisms. Therefore, it is crucial for patients and gynecologists to comprehend the role of glycolytic proteins, regulatory molecules, and signaling pathways in tumorigenesis, progression, and treatment. This article aims to review the correlation between abnormal glucose metabolism and gynecologic tumors including cervical cancer (CC), endometrial carcinoma (EC), and ovarian cancer (OC). The findings from this research will provide valuable scientific insights for early screening, timely diagnosis and treatment interventions while also aiding in the prevention of recurrence among individuals with gynecological tumors.

Predictors of Perioperative Complications During Leo Baby Stent Treatment for Acutely Ruptured Intracranial Aneurysms: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: Stent-assisted coiling (SAC) of acutely ruptured aneurysms has been controversial. Moreover, for aneurysms originating from small diameter vessels, the SAC presents more challenges. This study aimed to investigate the predictors of perioperative complications after SAC with Leo baby stent of acutely ruptured aneurysms. METHODS: We performed a retrospective multicenter analysis of 425 patients with acutely ruptured aneurysms treated with Leo baby. We compared clinical characteristics and outcomes among patients with perioperative complications and those without. Subgroup analysis, including thromboembolic and hemorrhagic complications, was also performed. RESULTS: Immediate postoperative angiograms showed Raymond 1 in 357 aneurysms (84.2%), 2 in 53 (12.5%), and 3 in 14 (3.3%). A total of 372 patients (87.5%) were independent (modified Rankin Scale [mRS] score 0-2) at discharge. Perioperative complications occurred in 18 cases (4.2%) harboring 13 cases (3.1%) of thromboembolic complications and 5 cases (1.2%) of hemorrhagic complications. Patients with perioperative complications had a higher rate of unfavorable outcomes at discharge (P = .018), especially with thromboembolic complications (P = .043). Multivariate analysis showed that higher preoperative mRS score (P = .004), irregular shape (P = .017), and larger aneurysms (P = .049) were independent predictors of the overall complications, whereas higher preoperative mRS score (P = .022) was an independent predictor for ischemic complications. The follow-up angiogram was available for 245 patients, and the follow-up angiograms revealed Raymond 1 in 223 aneurysms (91.0%), 2 in 19 (7.8%), and 3 in 3 (1.2%). CONCLUSION: Worse clinical condition, irregular shape, and larger aneurysms were independently associated with overall complications, whereas worse clinical condition was viewed as an independent predictor for thromboembolic complications. Attention to these factors is essential for the safe treatment and prognosis of patients with acutely ruptured aneurysms.

Low temperature multi-catalytic growth and growth mechanism of carbon nanotubes on carbon fiber surfaces.

In order to reduce the etching effect of the catalysts to carbon fibers caused by high temperature during the chemical vapor deposition (CVD) process, four multi-element catalysts, Fe-Co, Fe-Ni, Co-Ni and Fe-Co-Ni, were used to realize the low temperature growth of carbon nanotubes (CNTs) on carbon fibers at 350 °C-400 °C. The results show that the growth state of CNTs has a great relationship with the type of catalysts. The catalytic efficiency of Fe-Co catalysts is low, but the graphitization degree of CNTs is relatively high. The Fe-Co-Ni catalysts has high catalytic efficiency but low graphitization degree of CNTs. The tensile strength of carbon fiber/CNTs reinforcements prepared by Fe-Ni catalysts at 400 °C is the highest, reaching 3.99 GPa, which is 11.14% higher than that of desized fiber. The melt drop phenomenon of the catalysts was found by TEM, indicating the formation of the liquid phase catalysts during the growth of CNTs. This phenomenon can change the diffusion mode of carbon atoms in the catalyst and significantly reduce the growth activation energy of CNTs, so that CNTs can grow at lower temperatures. Based on the detailed analysis of the CVD process, a low temperature growth model of CNTs on carbon fibers was proposed.

The application of exosomes in the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and invasive breast cancer (BC) subtype that is estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (Her2)-negative. So far, the treatment of TNBC is still ineffective due to the lack of well-defined molecular targets. Exosomes are nanosized extracellular vesicles composed of lipid bilayers. They originate from various types of donor cells and release a complex mixture of contents including diverse nucleic acid types (miRNA, LnRNA, siRNA, and DNA) and proteins; after binding to recipient cells the exosomes release their contents that execute their biological functions. Exosomes have been reported to play an important role in the tumorigenesis of TNBC, including tumor initiation, metastasis, angiogenesis, cell proliferation, immune escape, and drug resistance. On the other hand, exosomes can be valuable biomarkers for diagnosis, monitoring, and treatment of TNBC. More interestingly, exosomes can be harnessed as a nanosized drug-delivery system specifically targeting TNBC. In this review, we present the most recent mechanistic findings and clinical applications of exosomes in TNBC therapy, focusing on their use as diagnostic and prognostic biomarkers, nanoscale drug delivery platforms, and immunotherapeutic agents. In addition, the associated challenges and future directions of using exosomes for TNBC treatment will be discussed.

A Flexible Circularly Polarized Luminescence Switching Device Based on Proton-Coupled Electron Transfer.

Flexible circularly polarized luminescence (CPL) switching devices have been long-awaited due to their promising potential application in wearable optoelectronic devices. However, on account of the few materials and complicated design of manufacturing systems, how to fabricate a flexible electric-field-driven CPL-switching device is still a serious challenge. Herein, a flexible device with multiple optical switching properties (CPL, circular dichroism (CD), fluorescence, color) is designed and prepared efficiently based on proton-coupled electron transfer (PCET) mechanism by optimizing the chiral structure of switching molecule. More importantly, this device can maintain the switching performance even after 300 bending-unbending cycles. It has a remarkable comprehensive performance containing bistable property, low open voltage, and good cycling stability. Then, prototype devices with designed patterns have been fabricated, which opens a new application pattern of CPL-switching materials.

A MOF derived bifunctional electrocatalyst Ni3ZnC0.7-Mo2C with enhanced performance for overall water splitting.

The efficiency and cost of electrocatalysts are critical factors restricting their application in water electrochemical decomposition. In recent years, transition metal carbides (TMCs) have been highlighted due to their unique characteristics for water splitting: good conductivity and stability. However, their electrochemical performance required further optimization. In this work, a distinct non-solvent method was utilized to achieve a Ni3ZnC0.7-Mo2C/Ni foam (NF) catalyst, which exhibited a nanoflower structure with efficient exposed active sites. Moreover, the synergistic effect between the Mo and Ni species greatly affected its HER and OER performance. Ni3ZnC0.7-Mo2C/NF showed excellent electrocatalytic performance with small overpotentials of 58 mV and 257 mV at 10 mA cm-2 for the HER and OER, respectively. To our delight, the overall water splitting could be driven by only 1.56 V. This work not only demonstrates an excellent bifunctional electrocatalyst for overall water splitting but also provides another method for polymetallic carbide preparation and activity optimization.

Bifunctional catalysts of Ni nanoparticle coupled MoO2 nanorods for overall water splitting.

The development of active and cost-effective bifunctional catalysts is crucial for water dissociation through electrolysis. In this study, bifunctional catalysts with Ni nanoparticles (NPs) anchored on MoO2 nanorods have been synthesized via in situ dissolution of NiMoO4-ZIF under an inert atmosphere without using hydrogen gas. The Ni-MoO2 catalyst exhibits high electrocatalytic activity by modulating the calcination temperature. Benefitingfrom the MOF transformation and accompanying Ni particles' outward diffusion, a precisely designed interface heterostructure between Ni and MoO2 was constructed. As a result, the optimized Ni-MoO2 catalyst achieves extremely low overpotentials of only 24 mV and 275 mV at 10 mA cm-2 for the hydrogen evolution reaction and oxygen evolution reaction, respectively. Furthermore, the catalyst required a small cell voltage of 1.55 V to deliver a current density of 10 mA cm-2 and remained stable over 20 h for overall water splitting. The proposed MOF-derived heterojunction protocol provides a general approach for designing and fabricating transition metal oxide catalysts for water electrolysis.

Self-aligned stitching growth of centimeter-scale quasi-single-crystalline hexagonal boron nitride monolayers on liquid copper.

Two-dimensional hexagonal boron nitride (hBN) atomic crystals are excellent charge scattering screening interlayers for advanced electronic devices. Although wafer-scale single crystalline hBN monolayer films have been demonstrated on liquid Au and solid Cu (110) and (111) vicinal surfaces, their reproducible growth still remains challenging. Here, we report the facile self-aligned stitching growth of centimeter-scale quasi-single-crystalline hBN monolayer films through synergistic chemical vapor deposition growth kinetics and liquid Cu rheological kinetics control. The sublimation temperature of the ammonia borane precursor, H2 content and melting temperature of the Cu substrate are revealed to be the dominant factors that regulate hBN nucleation, growth and alignment. The flowing liquid Cu catalytic surface promotes efficient rotation of floating triangular hBN domains and provokes uniform self-alignment upon merging at a critical high temperature of 1105 °C. Identical aligned grains are constantly observed at multiple regions, which corroborate the homogeneous in-plane orientation and uniform stitching over the whole growth area. Continuous quasi-single-crystalline hBN monolayer films are produced by seamless stitching of aligned domains with the same polarity. The quasi-single-crystalline hBN monolayers are successfully included as charge scattering and trap site screening interlayers in the hBN/SiO2 gate insulator stack to build high performance InGaZnO field-effect transistors (FETs). Full suppression of hysteresis and twofold enhancement of field-effect mobility are realized for InGaZnO FETs built with hBN as the interface dielectric. The facile growth of large quasi-single-crystalline hBN monolayers on liquid Cu paves the way for future high-performance electronics.

Effect of Microstructures of Carbon Nanoproducts Grown on Carbon Fibers on the Interfacial Properties of Epoxy Composites.

Two kinds of carbon nanoproducts with different microstructures, namely, carbon nanotubes (CNTs) and carbon nanofibers (CNFs), were grown on the surface of carbon fibers (CFs) by chemical vapor deposition (CVD) at low temperatures to improve the interface bonding between fibers and resins. The short-beam method and the micro-debonding method were used to test the interlaminar shear strength (ILSS) and interfacial shear strength (IFSS) of the composites. The results showed that the contribution of CNTs to the improvement of interfacial properties was better than that of CNFs. Specifically, the ILSS and IFSS of the CF-CNFs/epoxy composites increased by 18.59 and 24.39%, respectively, while the ILSS and IFSS of the CF-CNTs/epoxy composites increased by 26.97 and 47.79%, respectively. Compared with CNFs, the high degree of graphitization of CNTs and the π-interactions with the resin can better induce the formation of an interphase between the fiber and the resin, which suppressed the initiation of cracks and extended the propagation path of the cracks in the composites.

A Bioinformatic Analysis of Immune-Related Prognostic Genes in Clear Cell Renal Cell Carcinoma Based on TCGA and GEO Databases.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a commonly occurring tumor. Through a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, immunotherapy may serve as a potential treatment for cancer patients. This study aimed at identifying the survival-related immune cells and hub genes, which could be potential targets for immunotherapy in ccRCC. METHODS: The gene expression profiles and clinical data of ccRCC patients were extracted from UCSC Xena and Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were utilized to select the survival-related tumor-infiltrating immune cells. Multivariate Cox regression was utilized to develop a signature based on the tumor-infiltrating immune cells (TIICs). Based on the signature, the risk score was calculated, following which the samples were divided into high-risk and low-risk groups. Differentially expressed genes (DEGs) between the two risk groups were identified. Functional enrichment analysis was performed and cytoHubba plug-in of Cytoscape was used to identify the hub genes. Multiple datasets were utilized to validate these hub genes, including the Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and the Human Protein Atlas (HPA), and the GEO datasets. Finally, a correlation analysis was performed to evaluate the relationship between the hub genes and TIICs. RESULTS: Four immune survival-related cells, including T cell CD4 memory-activated, T cell regulatory (Tregs), eosinophils, and mast cell resting were identified. Nine immune-specific hub genes were identified, which included APOE, CASR, CTLA4, CXCL8, EGF, F2, KNG1, MMP9, and IL6. Furthermore, these hub genes were significantly correlated with clinical traits and closely associated with some TIICs. CONCLUSION: A total of four survival-related immune cell types and nine hub genes were found to be closely associated with ccRCC. These findings may have implications for the development of novel potential immunotherapeutic targets for ccRCC.

Wnt2 Contributes to the Development of Atherosclerosis.

Atherosclerosis, is a chronic inflammatory disease, characterized by the narrowing of the arteries resulting from the formation of intimal plaques in the wall of arteries. Yet the molecular mechanisms responsible for maintaining the development and progression of atherosclerotic lesions have not been fully defined. In this study, we show that TGF-ß activates the endothelial-to-mesenchymal transition (EndMT) in cultured human aortic endothelial cells (HAECs) and this transition is dependent on the key executor of the Wnt signaling pathway in vitro. This study presents the first evidence describing the mechanistic details of the TGF-ß-induced EndMT signaling pathway in HAECs by documenting the cellular transition to the mesenchymal phenotype including the expression of mesenchymal markers α-SMA and PDGFRα, and the loss of endothelial markers including VE-cadherin and CD31. Furthermore, a short hairpin RNA (shRNA) screening revealed that Wnt2 signaling is required for TGF-ß-mediated EndMT of HAECs. Also, we found that LDLR-/- mice fed on a high-fat western-type diet (21% fat, 0.2% cholesterol) expressed high levels of Wnt2 protein in atherosclerotic lesions, confirming that this signaling pathway is involved in atherosclerosis in vivo. These findings suggest that Wnt2 may contribute to atherosclerotic plaque development and this study will render Wnt2 as a potential target for therapeutic intervention aiming at controlling atherosclerosis.

Construction of a novel mRNA-signature prediction model for prognosis of bladder cancer based on a statistical analysis.

BACKGROUND: Bladder cancer (BC) is a common malignancy neoplasm diagnosed in advanced stages in most cases. It is crucial to screen ideal biomarkers and construct a more accurate prognostic model than conventional clinical parameters. The aim of this research was to develop and validate an mRNA-based signature for predicting the prognosis of patients with bladder cancer. METHODS: The RNA-seq data was downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened in three datasets, and prognostic genes were identified from the training set of TCGA dataset. The common genes between DEGs and prognostic genes were narrowed down to six genes via Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox regression. Then the gene-based risk score was calculated via Cox coefficient. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic power of risk score. Multivariate Cox regression analysis was applied to construct a nomogram. Decision curve analysis (DCA), calibration curves, and time-dependent ROC were performed to assess the nomogram. Finally, functional enrichment of candidate genes was conducted to explore the potential biological pathways of candidate genes. RESULTS: SORBS2, GPC2, SETBP1, FGF11, APOL1, and H1-2 were screened to be correlated with the prognosis of BC patients. A nomogram was constructed based on the risk score, pathological stage, and age. Then, the calibration plots for the 1-, 3-, 5-year OS were predicted well in entire TCGA-BLCA patients. Decision curve analysis (DCA) indicated that the clinical value of the nomogram was higher than the stage model and TNM model in predicting overall survival analysis. The time-dependent ROC curves indicated that the nomogram had higher predictive accuracy than the stage model and risk score model. The AUC of nomogram time-dependent ROC was 0.763, 0.805, and 0.806 for 1-year, 3-year, and 5-year, respectively. Functional enrichment analysis of candidate genes suggested several pathways and mechanisms related to cancer. CONCLUSIONS: In this research, we developed an mRNA-based signature that incorporated clinical prognostic parameters to predict BC patient prognosis well, which may provide a novel prognosis assessment tool for clinical practice and explore several potential novel biomarkers related to the prognosis of patients with BC.

Integrative analysis of immune molecular subtypes and microenvironment characteristics of bladder cancer.

The emergence of immunotherapy has provided an option of treatment methods for bladder cancer (BC). However, the beneficiaries of immunotherapy are still limited to small-scale patients, and immunotherapy-related adverse events often occur. It is a major challenge for clinical work to study the immune subtypes of BC and the molecular mechanism of immune escape, and identify the immune responders accurately. Here, we explore the immune molecular subtypes of bladder cancer and potential escape mechanisms. First, we screened the expression profiles of 303 differentially expressed immune-related genes in BC patients from the Cancer Genome Atlas (TCGA) database, and successfully identified 4 molecular subtypes of BC. By comparing the clinical characteristics, immune cells infiltration, the expression of checkpoint genes, human leukocyte antigen (HLA) genes, and gene mutation status of different subtypes, we identified different clinical and immunological characteristics of 4 subtypes. Among 4 subtypes, Cluster 2 met the general characteristics of immunotherapy responders and responded well to immunotherapy, while Cluster 4 had the highest expression of immune characteristics, and is similar to the immune environment of normal bladder tissue. Then, the weighted gene co-expression network analysis (WGCNA) of immune-related genes revealed that brown module was positively correlated with subtypes. Pathway enrichment analysis explored the major pathways associated with subtypes, which are also associated with immune escape mechanisms. Moreover, the decision tree model, which was constructed by the principle of random forest screening factors, was also validated in internal validation set and external validation set from the Gene Expression Omnibus (GEO) cohort (GSE133624), and could achieve accurate subtypes prediction for BC patients with high-throughput sequencing. Taken together, we explored the immune molecular subtypes and their mechanisms of BC, and these results may provide guidance for the development of new BC immunotherapy strategies.

Analysis on the spatio-temporal characteristics of COVID-19 in mainland China.

COVID-19 has brought many unfavorable effects on humankind and taken away many lives. Only by understanding it more profoundly and comprehensively can it be soundly defeated. This paper is dedicated to studying the spatial-temporal characteristics of the epidemic development at the provincial-level in mainland China and the civic-level in Hubei Province. Moreover, a correlation analysis on the possible factors that cause the spatial differences in the epidemic's degree is conducted. After completing these works, three different methods are adopted to fit the daily-change tendencies of the number of confirmed cases in mainland China and Hubei Province. The three methods are the Logical Growth Model (LGM), Polynomial fitting, and Fully Connected Neural Network (FCNN). The analysis results on the spatial-temporal differences and their influencing factors show that: (1) The Chinese government has contained the domestic epidemic in early March 2020, indicating that the number of newly diagnosed cases has almost zero increase since then. (2) Throughout the entire mainland of China, effective manual intervention measures such as community isolation and urban isolation have significantly weakened the influence of the subconscious factors that may impact the spatial differences of the epidemic. (3) The classification results based on the number of confirmed cases also prove the effectiveness of the isolation measures adopted by the governments at all levels in China from another aspect. It is reflected in the small monthly grade changes (even no change) in the provinces of mainland China and the cities in Hubei Province during the study period. Based on the experimental results of curve-fitting and considering the time cost and goodness of fit comprehensively, the Polynomial(Degree = 18) model is recommended in this paper for fitting the daily-change tendency of the number of confirmed cases.

Influencing factors and growth kinetics analysis of carbon nanotube growth on the surface of continuous fibers.

Carbon nanotubes (CNTs) were continuously grown on the surface of the moving carbon fiber by chemical vapor deposition method using a custom-designed production line to prepare composite reinforcements on a large-scale. The systematic study of different parameters affecting the CNT growth revealed simple growth kinetics, which helps to control the surface morphology and structural quality of CNTs. Since hydrogen maintains the activity of the catalyst, it promotes the growth of CNTs in a continuous process. The increase of acetylene partial pressure promotes the accumulation of amorphous or graphite carbon on the catalyst surface, resulting in the decrease of CNT growth rate when acetylene concentration reaches 40%. The growth temperature significantly affects the CNT diameter and structural quality. As the temperature increases, the crystallinity of the tube wall increases obviously, and the CNT diameter increases due to the aggregate growth of the catalyst particles. According to the Arrhenius formula, the apparent activation energy is observed to be 0.67 eV, which proves that both bulk diffusion and surface diffusion exist when activated carbon passes through the catalyst to form CNTs.

Transcriptomics analysis for the identification of potential age-related genes and cells associated with three major urogenital cancers.

Age is one of the most important risk factors of the occurrence for tumor patients. The majority of patients with urogenital cancers are the elderly, whose clinical characteristics are greatly affected by age and ageing. Our study aimed to explore age-related genes, cells, and biological changes in three common urogenital cancers via integrative bioinformatics analysis. First, mRNA (count format) and clinical data for bladder cancer, prostate cancer and renal cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA). Through the comparison of clinicopathological characteristics, genes expression and cells infiltration between the old group and the young group, it was found that the clinical characteristics, genes and cells in the tumor microenvironment of different ages were quite different. And 4 key cells, 14 hub genes and some potential pathways were identified and considered as important factors. More importantly, we analyzed the differential landscape of the genes and cells from different perspectives, and confirmed its importance. In conclusion, we identified genes and cell types associated with age-related changes in the tumour microenvironment in urogenital cancer patients. These genes and cell types may play a critical role in the age-associated differences in clinicopathological characteristics among urogenital cancers, thus providing a link between ageing and cancer occurrence. The findings of this study may pave the way for the development of age-tailored approaches to treat cancer and other age-related diseases.

Qualitative and Quantitative Wall Enhancement on Magnetic Resonance Imaging Is Associated With Symptoms of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Aneurysmal wall enhancement (AWE) on vessel wall magnetic resonance imaging (VW-MRI) has been described as a new imaging biomarker of unstable unruptured intracranial aneurysms (UIAs). Previous studies of symptomatic UIAs are limited due to small sample sizes and lack of AWE quantification. Our study aims to investigate whether qualitative and quantitative assessment of AWE can differentiate symptomatic and asymptomatic UIAs. METHODS: Consecutive patients with UIAs were prospectively recruited for vessel wall magnetic resonance imaging at 3T from October 2014 to October 2019. UIAs were categorized as symptomatic if presenting with sentinel headache or oculomotor nerve palsy directly related to the aneurysm. Evaluation of wall enhancement included enhancement pattern (0=none, 1=focal, and 2=circumferential) and quantitative wall enhancement index (WEI). Univariate and multivariate analyses were used to identify the parameters associated with symptoms. RESULTS: Two hundred sixty-seven patients with 341 UIAs (93 symptomatic and 248 asymptomatic) were included in this study. Symptomatic UIAs more frequently showed circumferential AWE than asymptomatic UIAs (66.7% versus 17.3%, P<0.001), as well as higher WEI (median [interquartile range], 1.3 [1.0-1.9] versus 0.3 [0.1-0.9], P<0.001). In multivariate analysis, both AWE pattern and WEI were independent factors associated with symptoms (odds ratio=2.03 across AWE patterns [95% CI, 1.21-3.39], P=0.01; odds ratio=3.32 for WEI [95% CI, 1.51-7.26], P=0.003). The combination of AWE pattern and WEI had an area under the curve of 0.91 to identify symptomatic UIAs, with a sensitivity of 95.7% and a specificity of 73.4%. CONCLUSIONS: In a large cohort of UIAs with vessel wall magnetic resonance imaging, both AWE pattern and WEI were independently associated with aneurysm-related symptoms. The qualitative and quantitative features of AWE can potentially be used to identify unstable intracranial aneurysms.

Subanesthetic isoflurane abates ROS-activated MAPK/NF-κB signaling to repress ischemia-induced microglia inflammation and brain injury.

Isoflurane (ISO) elicits protective effects on ischemia-induced brain injury. We investigated whether sub-anesthetic (0.7%) ISO post-conditioning attenuates the inflammation and apoptosis in oxygen-glucose deprivation (OGD)-insulted co-cultures (microglia and neurons) in vitro and the brain injury of the middle cerebral arterial occlusion (MCAO) rat. We demonstrated that ISO augmented the viability of OGD-treated microglia and neurons. ISO reduced the expression and activation of COX2 and iNOS in OGD-challenged microglia. ISO repressed the production of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and monocyte chemoattractant protein-1 in OGD-exposed microglia. ISO also decreased nucleosomal fragmentation and caspase-3 activity but increased mitochondrial membrane potential in OGD-stimulated microglia and neurons. Mechanistically, ISO suppressed OGD-induced microglial inflammation by blocking ROS-regulated p38 MAPK/NF-κB signaling pathway and hampered OGD-triggered microglial apoptosis in a ROS- or NO-dependent fashion. In vivo results with MCAO rats were partly consistent with the in vitro observation. These findings indicate that sub-anesthetic ISO post-conditioning abates the inflammation and apoptosis in OGD-stimulated rat microglia and the apoptosis of OGD-exposed neurons and the brain injuries of MCAO rats, suggesting it as a potentially effective therapeutic approach for ischemic brain damages.

Graded Channel Junctionless InGaZnO Thin-Film Transistors with Both High Transporting Properties and Good Bias Stress Stability.

InGaZnO (IGZO) is currently the most prominent oxide semiconductor complement to low-temperature polysilicon for thin-film transistor (TFT) applications in flat panel displays. However, the compromised transport performance and bias stress instability are critical issues inhibiting its application in ultrahigh-resolution optoelectronic displays. Here, we report the fabrication of graded channel junctionless IGZO:O|N TFTs with both high transporting properties and good bias stress stability by systematic manipulation of oxygen vacancy (VO) defects through sequential O antidoping and O/N codoping of the continuous IGZO framework. The transporting properties and bias stress stability of the graded channel IGZO:O|N TFTs, which exhibited high field-effect mobilities close to 100 cm2 V-1 s-1, negligible performance degradations, and trivial threshold voltage shifts against gate bias stress and photobias stress, are simultaneously improved compared to those of the controlled single-channel uniformly doped IGZO:O TFTs, IGZO:N TFTs, and double-channel barrier-confined IGZO:O/IGZO:N TFTs. The synergistic improvements are attributed to the sequential mobility and stability enhancement effects of O antidoping and O/N codoping where triple saturation currents are induced by O antidoping of the front-channel regime while the trapped electrons and photoexcited holes in the back-channel bulk and surface regions are suppressed by O/N codoping. More importantly, fast accumulation and barrier-free full depletion are rationally realized by eliminating the junction interface within the graded channel layer. Our observation identifies that graded channel doping could be a powerful way to synergistically boost up the transport performance and bias stress stability of oxide TFTs for new-generation ultrahigh-definition display applications.

Identification of prognostic biomarkers associated with stromal cell infiltration in muscle-invasive bladder cancer by bioinformatics analyses.

Muscle-invasive bladder cancer (MIBC) is one of the common malignant tumors. Patients with MIBC still have high tumor recurrence and progression rates after surgery. Bioinformatics analysis of stromal infiltration-related genes in the tumor microenvironment (TME) of MIBC patients was performed in this study to determine the major stromal cells types and biomarkers for their progression and poor prognosis. The ESTIMATE algorithm was applied to evaluate the stromal score and immune score of samples from MIBC patients in The Cancer Genome Atlas (TCGA) and found that stromal score was closely related to the clinical characteristics of the patients. The Gene Set Enrichment Analysis (GSEA) further revealed that stromal cells were involved in biological processes such as activation of leukocytes and positive regulation of cell migration during MIBC progression, as well as PI3K-Akt, MAPK, and Rap1 signaling pathways. Five hub genes related to prognosis, including ACTA2, COL5A1, DCN, LUM, and PRRX1 were identified by the Weighted Gene Co-Expression Network Analysis (WGCNA), Protein-Protein Interaction (PPI), survival analysis, and Oncomine, Gene Expression Omnibus (GEO) database validation. Besides, we identified five stromal cell types associated with overall survival time, among which chondrocytes and fibroblasts were identified as the major stromal cell types through correlation analysis. Finally, the Receiver Operating Characteristic (ROC) curve and immunohistochemistry were used to verify the diagnostic value and expression of hub genes in different invasive tumors. In summary, we investigated the biological behavior of stromal cells in the TME of MIBC to promote tumor progression obtained hub genes associated with progression and poor prognosis and identified the main stromal cells types in the TME.