Magnetotransport spectroscopy of electroburnt graphene nanojunctions.

We have reported the precise methodology for fabricating graphene quantum dots through electroburning and performed measurements on the Coulomb blockade and oscillation phenomena. The diameters of graphene quantum dots can be estimated to range from several to tens of nanometers, utilizing the disk capacitance model and the two-dimensional quantum well model. By subjecting the quantum dots to a vertical magnetic field, an obvious alteration in conductance can be detected at the point of resonance tunneling. This observed phenomenon can be attributed to the modification in the density of states of Landau levels within the graphene leads. Moreover, by manipulating the gate voltage, it is possible to regulate the Fermi level of the lead, resulting in distinct magnetoresistance of different electron states. The presence of this lead effect may potentially disrupt the magnetic response analysis of graphene-based single-molecule transistors, necessitating a comprehensive theoretical examination to mitigate such interference.

Electrically controlled nonvolatile switching of single-atom magnetism in a Dy@C84 single-molecule transistor.

Single-atom magnetism switching is a key technique towards the ultimate data storage density of computer hard disks and has been conceptually realized by leveraging the spin bistability of a magnetic atom under a scanning tunnelling microscope. However, it has rarely been applied to solid-state transistors, an advancement that would be highly desirable for enabling various applications. Here, we demonstrate realization of the electrically controlled Zeeman effect in Dy@C84 single-molecule transistors, thus revealing a transition in the magnetic moment from 3.8 µ B to 5.1 µ B for the ground-state GN at an electric field strength of 3 - 10 MV/cm. The consequent magnetoresistance significantly increases from 600% to 1100% at the resonant tunneling point. Density functional theory calculations further corroborate our realization of nonvolatile switching of single-atom magnetism, and the switching stability emanates from an energy barrier of 92 meV for atomic relaxation. These results highlight the potential of using endohedral metallofullerenes for high-temperature, high-stability, high-speed, and compact single-atom magnetic data storage.

A "Prediction - Detection - Judgment" framework for sudden water contamination event detection with online monitoring.

The contamination detection technology helps in water quality management and protection in surface water. It is important to detect sudden contamination events timely from dynamic variations due to various interference factors in online water quality monitoring data. In this study, a framework named "Prediction - Detection - Judgment" is proposed with a method framework of "Time series increment - Hierarchical clustering - Bayes' theorem model". Time to detection is used as an evaluation index of contamination detection methods, along with the probability of detection and false alarm rate. The proposed method is tested with available public data and further applied in a monitoring site of a river. Results showed that the method could detect the contamination events with a 100% probability of detection, a 17% false alarm rate and a time to detection close to 4 monitoring intervals. The proposed index time to detection evaluates the timeliness of the method, and timely detection ensures that contamination events can be responded to and dealt with in time. The site application also demonstrates the feasibility and practicability of the framework proposed in this study and its potential for extensive implementation.

Justice at the Forefront: Cultivating felt accountability towards Artificial Intelligence among healthcare professionals.

The advent of AI has ushered in a new era of patient care, but with it emerges a contentious debate surrounding accountability for algorithmic medical decisions. Within this discourse, a spectrum of views prevails, ranging from placing accountability on AI solution providers to laying it squarely on the shoulders of healthcare professionals. In response to this debate, this study, grounded in the mutualistic partner choice (MPC) model of the evolution of morality, seeks to establish a configurational framework for cultivating felt accountability towards AI among healthcare professionals. This framework underscores two pivotal conditions: AI ethics enactment and trusting belief in AI and considers the influence of organizational complexity in the implementation of this framework. Drawing on Fuzzy-set Qualitative Comparative Analysis (fsQCA) of a sample of 401 healthcare professionals, this study reveals that a) focusing justice and autonomy in AI ethics enactment along with building trusting belief in AI reliability and functionality reinforces healthcare professionals' sense of felt accountability towards AI, b) fostering felt accountability towards AI necessitates ensuring the establishment of trust in its functionality for high complexity hospitals, and c) prioritizing justice in AI ethics enactment and trust in AI reliability is essential for low complexity hospitals.

Nonlinear relationship between untraditional lipid parameters and the risk of prediabetes: a large retrospective study based on Chinese adults.

BACKGROUND: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. METHODS: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. RESULTS: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. CONCLUSION: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

Upregulation of the key biomarker kinesin family member 20A (KIF20A) is associated with pulmonary artery hypertension.

OBJECTIVE: Pulmonary artery hypertension (PAH) is a complex, fatal disease with limited treatments. This study aimed to investigate possible key targets in PAH through bioinformatics. METHODS: GSE144274 were obtained from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) between idiopathic pulmonary hypertension (IPAH) and healthy subjects were identified and analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed, and a protein-protein interaction (PPI) network was constructed using STRING. The hub genes were identified by MCODE method. The expression levels of hub genes were validated in vitro and in vivo models. Finally, the ROC analysis was performed based on the level of hub genes in clinical plasma samples. RESULTS: A total of 363 DEGs were identified. GO analysis on these DEGs were mainly enriched in cell division, inflammatory response, among others. In the KEGG pathways analysis, DEGs mainly involved in cytokine-cytokine receptor interaction, rheumatoid arthritis, and IL-17 signaling pathways were enriched. The DEGs were analyzed with the STRING for PPI network analysis, and 62 hub genes were identified by MCODE. Finally, 6 central genes, KIF18B, SPC25, DLGAP5, KIF20A, CEP55 and ANLN, were screened out due to their novelty role in PAH. The expression of KIF20A was validated to be significantly upregulated both in the lung tissue of hypoxia-induced pulmonary hypertension (HPH) mice and proliferative PASMCs. Additionally, KIF20A levels is evelated in PAH plasma and the area under the curve (AUC) to identify PAH was 0.8591 for KIF20A. CONCLUSION: The level of KIF20A elevates during the progression of PAH, which suggestes it could be a potential diagnostic and therapeutic target for the PAH.

Prognostic value of cell division cycle-associated protein-3 in prostate cancer.

BACKGROUND: The study was aimed to explore cell division cycle-associated protein-3 (CDCA3) expression and its correlation with clinicopathological characteristics, and identification of co-expressed genes of CDCA3 in prostate cancer (PCa). METHODS: Data for CDCA3 mRNA expression in PCa were obtained from The Cancer Genome Atlas database. Furtherly, CDCA3 protein expression was examined by immunohistochemistry in 80 cases, including 20 normal prostate samples and 60 PCa samples. Then we used "survival" package to obtain the differentially expressed CDCA3 mRNA associated with prognosis of PCa patients. "pROC" package was used to analyze receiver operating characteristic of CDCA3. We used chi-square test, Kruskal-Wallis test and Wilcoxon rank sum test to identify clinicopathological parameters that correlated with CDCA3 expression. In order to determine the effects of CDCA3 expression and clinicopathological parameters on survival, univariate cox regression analysis was performed. Finally, the co-expressed genes of CDCA3 in PCa were explored by search tool for the retrieval of interacting genes, Kyoto encyclopedia of genes and genomes enrichment analysis and Spearman correlation analysis. RESULTS: In this study, we found that CDCA3 expression was increased in PCa. PCa patients with higher CDCA3 expression had poor outcomes. In terms of receiver operating characteristic, CDCA3 had an area under the curve of 0.857. High CDCA3 expression was positively correlated with advanced T stage, N stage, Gleason score, and served as an independent predictor of progress free interval in PCa patients. Then 20 proteins closely related to CDCA3 were screened through STRING website. Functional enrichment analysis revealed that, Kyoto encyclopedia of genes and genomes pathway was mainly enriched in cell cycle, including 6 genes, BUB1, CCNA2, CDK1, CDC20, TTK, and CCNB2. CONCLUSION: CDCA3 is significantly associated with the prognosis of PCa, which may be an indicator of the diagnosis and prognosis of PCa and a new therapeutic target.

De Ritis Ratio is Associated with Contrast-Associated Acute Kidney Injury Prediction and Long-Term Clinical Outcomes in Patients Undergoing Emergency Percutaneous Coronary Intervention.

Contrast-associated acute kidney injury (CA-AKI) is a familiar complication following percutaneous coronary intervention (PCI). The present study evaluated the predictive value of the De Ritis ratio for CA-AKI and its association with long-term clinical outcomes in patients undergoing emergency PCI. Overall, 546 patients were included in this study. The De Ritis ratio was calculated by aspartate aminotransferase/alanine aminotransferase activity. The De Ritis ratios in the CA-AKI patients were significantly higher than the non-CA-AKI patients [3.74 (2.32, 4.90) vs 1.61 (1.02, 2.53); P < .001]. The De Ritis ratio was an independent risk factor for CA-AKI [odds ratio, 2.243; 95% confidence interval (CI), 1.823-2.759; P < .001]. The area under the ROC curve was .813 (95% CI, .763-.862; P < .001), and the sensitivity and specificity were 67.0% and 82.4%, respectively, when the optimum cut-off value was 2.97. Furthermore, patients in the high De Ritis ratio group (≥1.76) had a significantly greater incidence of primary endpoints [26.7% (73/273) vs 13.2% (36/273); P < .001], and the high De Ritis ratio was an independent predictor for primary endpoints (hazard ratio, 1.888, 95% CI, 1.235-2.887; P = .003). In conclusion, the De Ritis Ratio is associated with CA-AKI prediction and long-term clinical outcomes in patients undergoing emergency PCI.

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis.

Background: To identify the potential key genes of ferroptosis in the pathogenesis of lung cancer with bone metastasis (LCBM) by bioinformatics analysis to provide new targets for treating LCBM and an indicator for early monitoring. Methods: We first obtained differentially expressed genes (DEGs) associated with ferroptosis from the Gene Expression Omnibus (GEO) database. MiRWalk 2.0 was used to predict the key microRNAs (miRNAs) and construct related gene-miRNA interaction networks. The functional enrichment analysis of key miRNAs was performed using the miEAA database. Finally, the clinical data of 105 lung cancer patients were retrospectively analyzed, and logistic regression analysis was conducted to assess the relationship between serum alkaline phosphatase (ALP), neuron-specific enolase (NSE), and bone metastasis in lung cancer patients, and a receiver operating characteristic (ROC) curve was drawn. Results: We identified 15 ferroptosis-related genes that were differentially expressed in lung cancer bone metastasis. GO and KEGG enrichment analyses suggested that these genes may affect the oxidative stress response, hypoxia response, rough endoplasmic reticulum, mitochondrial outer membrane, iron-sulfur cluster binding, virus receptor activity, central carbon metabolism in cancer, the interleukin-17 (IL-17) signaling pathway, and other aspects to participate in the occurrence and development of lung cancer bone metastasis. Among the 105 lung cancer patients included in the study, 39 cases had bone metastasis, and the incidence rate was 37.14%. A high Eastern Cooperative Oncology Group (ECOG) score and serum ALP and NSE overexpression were associated with bone metastasis in patients with lung cancer. By assessing the risk of bone metastasis in patients with lung cancer, we found that the Area Under Curves (AUCs) of serum ALP and NSE alone and combined were >0.70. Conclusions: The differentially expressed ferroptosis-related genes and predicted miRNA regulatory network in lung cancer bone metastasis and the related functional enrichment analysis provide new targets for the treatment of lung cancer bone metastasis. At the same time, from a serological perspective, it was found that early monitoring of serum ALP and NSE expression in patients with lung cancer could be considered to assess the risk of bone metastasis in the future.

Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a common cancer of the adult urological system. Recent developments in tumor immunology and pyroptosis biology have provided new directions for kidney cancer treatment. Therefore, there is an urgent need to identify potential targets and prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy. METHODS: The expression of immune-pyroptosis-related differentially expressed genes (IPR-DEGs) between KIRC and healthy tissues was examined using the Gene Expression Omnibus datasets. The GSE168845 dataset was selected for subsequent analyses. Data of 1793 human immune-related genes were downloaded from the ImmPort database (https://www.immport.org./home), while those of 33 pyroptosis-related genes were extracted from previous reviews. The independent prognostic value of IPR-DEGs was determined using differential expression, prognostic, and univariate and multivariate Cox regression analyses. The GSE53757 dataset was used to further verify the GSDMB and PYCARD levels. In our cohorts, the association among DEGs and clinicopathological features and overall survival was analyzed. The least absolute shrinkage and selection operator Cox regression model was established to evaluate the correlation of IPR-DEGs with the immune score, immune checkpoint gene expression, and one-class logistic regression (OCLR) score. KIRC cells and clinical tissue samples were subjected to quantitative real-time polymerase chain reaction to examine the GSDMB and PYCARD mRNA levels. The GSDMB and PYCARD levels in a healthy kidney cell line (HK-2 cells) and two KIRC cell lines (786-O and Caki-1 cells) were verified. The tissue levels of GSDMB and PYCARD were evaluated using immunohistochemical analysis. GSDMB and PYCARD were knocked down in 786-O cells using short-interfering RNA. Cell proliferation was examined using the cell counting kit-8 assay. Cell migration was measured by transwell migration assays RESULTS: GSDMB and PYCARD were determined to be IPR-DEGs with independent prognostic values. A risk prognostic model based on GSDMB and PYCARD was successfully established. In the GSE53757 dataset, the GSDMB and PYCARD levels in KIRC tissues were significantly higher than those in healthy tissues. The GSDMB and PYCARD expression was related to T stage and OS in our cohort. The GSDMB and PYCARD levels were significantly correlated with the immune score, immune checkpoint gene expression, and OCLR score. The results of experimental studies were consistent with those of bioinformatics analysis. The GSDMB and PYCARD levels in KIRC cells were significantly upregulated when compared with those in healthy kidney cells. Consistently, GSDMB and PYCARD in KIRC tissues were significantly upregulated when compared with those in adjacent healthy kidney tissues. GSDMB and PYCARD knockdown significantly decreased 786-O cell proliferation (p < 0.05). Transwell migration result reflects that silencing GSDMB and PYCARD inhibited 786-O cell migration (p < 0.05) . CONCLUSIONS: GSDMB and PYCARD are potential targets and effective prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy in KIRC.

Electrical devices designed based on inorganic clusters.

The idea of exploring the bottom brink of material science has been carried out for more than two decades. Clusters science is the frontmost study of all nanoscale structures. Being an example of 0-dimensional quantum dot, nanocluster serves as the bridge between atomic and conventionally understood solid-state physics. The forming mechanism of clusters is found to be the mutual effects of electronic and geometric configuration. It is found that electronic shell structure influences the properties and geometric structure of the cluster until its size becomes larger, where electronic effects submerge in geometric structure. The discrete electronic structures depend on the size and conformation of clusters, which can be controlled artificially for potential device applications. Especially, small clusters with a size of 1-2 nm, whose electronic states are possibly discrete enough to overcome thermal fluctuations, are expected to build a single-electron transistor with room temperature operation. However, exciting as the progress may be seen, cluster science still falls within the territory of merely the extension of atomic and molecular science. Its production rate limits the scientific and potential application research of nanoclusters. It is suggested in this review that the mass-produce ability without losing the atomic precision selectivity would be the milestone for nanoclusters to advance to material science.

The omega-3 hydroxy fatty acid 7(S)-HDHA is a high-affinity PPARα ligand that regulates brain neuronal morphology.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is emerging as an important target in the brain for the treatment or prevention of cognitive disorders. The identification of high-affinity ligands for brain PPARα may reveal the mechanisms underlying the synaptic effects of this receptor and facilitate drug development. Here, using an affinity purification-untargeted mass spectrometry (AP-UMS) approach, we identified an endogenous, selective PPARα ligand, 7(S)-hydroxy-docosahexaenoic acid [7(S)-HDHA]. Results from mass spectrometric detection of 7(S)-HDHA in mouse and rat brain tissues, time-resolved FRET analyses, and thermal shift assays collectively revealed that 7(S)-HDHA potently activated PPARα with an affinity greater than that of other ligands identified to date. We also found that 7(S)-HDHA activation of PPARα in cultured mouse cortical neurons stimulated neuronal growth and arborization, as well as the expression of genes associated with synaptic plasticity. The findings suggest that this DHA derivative supports and enhances neuronal synaptic capacity in the brain.

Bioinformatics analysis of the clinical relevance of CDCA gene family in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the second most frequent cancer in men worldwide, and its mortality rate is increasing every year. The cell division cycle-associated (CDCA) gene family plays vital roles in the cell cycle process, but an analysis of these proteins in PCa is still lacking. METHODS: UALCAN and GEPIA were used to examine the transcriptional data and survival of the CDCA gene family in PCa patients. CDCA genetic alterations, prognostic value of genetic alterations, and correlations of CDCAs with each other in PCa were downloaded from cBioPortal. The functional enrichment data of CDCA-related genes were analyzed using DAVID. RESULTS: Six CDCA genes were upregulated in PCa tissues relative to those in normal tissues (P < .001), including NUF2, CDCA2, CDCA3, CDCA5, CBX2, and CDCA8. The expression levels of the 6 CDCAs were related to the tumor Gleason score (P < .05). In addition, survival analysis using GEPIA suggested that PCa patients with increased NUF2, CBX2, and CDCA2/3/5/8 expression levels had poor relapse-free survival (P < .05). Distinct patterns of genetic alterations of the 6 CDCAs were observed in PCa, and pairwise comparison of the mRNA expression of the 6 CDCAs displayed a close relationship. The biological functions of CDCA-related genes are principally associated with the activation of the following pathways: cell cycle, Fanconi anemia pathway, microRNAs in cancer, oocyte meiosis, and homologous recombination. CONCLUSIONS: Upregulated CDCA (NUF2, CBX2, and CDCA2/3/5/8) expression in PCa tissues may play a crucial role in the occurrence of PCa. These CDCAs can predict relapse-free survival prognosis and the Gleason score of patients with PCa. Moreover, CDCAs probably exert their functions in tumorigenesis through the cell cycle and miRNAs in the cancer pathway.

Electroacupuncture alleviates neuropathic pain caused by spared nerve injury by promoting AMPK/mTOR-mediated autophagy in dorsal root ganglion macrophage.

Background: Dorsal root ganglia (DRG) plays an important role in mediating the peripheral sensation transduction through the primary afferent neurons in pain research. Neuropathic pain (NP) is a syndrome of hyperalgesia, spontaneous pain and allodynia caused by central or peripheral nerve injury. Recent trends of study are turning towards the development of therapies for the management of NP. Activation of autophagy in glial cells in the spinal cord has been reported to be associated with attenuation of NP, but the autophagic process in DRG is rarely studied. Methods: The analgesic effect of electroacupuncture (EA) was evaluated in NP-induced rats developed using spared nerve injury (SNI). Acupuncture or EA was performed after 7 days of SNI at Zusanli (ST36) and Huantiao (GB30) acupoints. Then, the activation status of autophagy process in DRGs of rats treated with SNI and EA were investigated, and the possible mechanism of the analgesic effect of EA were explored. Results: Application of EA has been found to reduce mechanical hyperalgesia. Autophagy indicator p62 was colocalized with the marker proteins for macrophages (CD11b), but not with NeuN (marker protein for neurons) or GFAP (marker protein for satellite glial cells), as shown by immunofluorescence. Western blots results indicate that the expression levels of p62, Beclin-1 and LC3-II in the L4-L6 DRG of rats in the SNI group were increased, compared with that in the control group. EA treatment resulted in decreased expression of p62 and increased expression of Beclin-1 and LC3-II/LC3-I. Furthermore, we explored the causal relationship between EA-induced suppression of NP and increased levels of autophagy in DRG using electron microscopy and the AMPK (AMP-activated protein kinase) inhibitor compound C. Conclusions: SNI achieved a significant upregulation of autophagy levels in DRG macrophages. Furthermore, EA attenuated NP, which may contribute to the promotion of AMPK/mTOR (mammalian target of rapamycin)-mediated autophagy in DRG macrophages. Therefore, this strategy provides a new target for therapeutic intervention of NP.

Suppression of CDCA3 inhibits prostate cancer progression via NF­κB/cyclin D1 signaling inactivation and p21 accumulation.

Dysregulation of the cell cycle contributes to tumor progression. Cell division cycle­associated 3 (CDCA3) is a known trigger of mitotic entry and has been demonstrated to be constitutively upregulated in tumors. It is therefore associated with carcinogenic properties reported in various cancers. However, the role of CDCA3 in prostate cancer is unclear. In the present study, western blotting and analysis of gene expression profiling datasets determined that CDCA3 expression was upregulated in prostate cancer and was associated with a poor prognosis. CDCA3 knockdown in DU145 and PC­3 cells led to decreased cell proliferation and increased apoptosis, with increased protein expression levels of cleaved­caspase3. Further experiments demonstrated that downregulated CDCA3 expression levels induced G0/G1 phase arrest, which was attributed to increased p21 protein expression levels and decreased cyclin D1 expression levels via the regulation of NF­κB signaling proteins (NFκB­p105/p50, IKKα/ß, and pho­NFκB­p65). In conclusion, these results indicated that CDCA3 may serve a crucial role in prostate cancer and consequently, CDCA3 knockdown may be used as a potential therapeutic target.

Quantitative Proteomics Analysis of Susceptibility and Resilience to Stress in a Rat model of PTSD.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder and sometimes deadly consequence of exposure to severe psychological trauma. However, there has been little known about the definitive molecular changes involved in determining vulnerability to PTSD. In the current study, we used proteomics to quantify protein changes in the hippocampus of foot shocks rats. A total of 6151 proteins were quantified and 97 proteins were significantly differentially expressed. The protein-protein interaction (PPI) analysis showed that oxidation-reduction process and glutathione homeostasis may be the potential key progress of being vulnerable to PTSD. The Gene Ontology analysis revealed enriched GO terms in the protein groups of Susceptible group vs Control group rats for glutathione binding,oligopeptide binding,modified amino acid binding,and glutathione transferase activity for their molecular functions (MF) and in the process of cellular response to toxic substance,xenobiotic metabolic process, urea metabolic process, and response to drug for the biological process (BP).SIGNIFICANCE:In recent years, there has been a growing interest in mental illness associated with trauma exposure. We found that stress susceptibility was associated with increased expression of arginase 1 indicated as a potential treatment target. Our results also proposed that carbonic anhydrases 3 could be a biomarker for the development of PTSD. This research helps to explain the potential molecular mechanism in PTSD and supply a new method for ameliorating PTSD.

Factors Associated with Survival From Xp11.2 Translocation Renal Cell Carcinoma Diagnosis-A Systematic Review and Pooled Analysis.

Purpose: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients. Methods: Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model. Results: There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; p = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; p = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; p < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; p = 0.027) were all associated with OS, with a median follow-up time of 198 months. Conclusion: T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.

Bioinformatics analysis identified hub genes in prostate cancer tumorigenesis and metastasis.

OBJECTIVE: Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. To discover key molecular changes in PCa development and metastasis, we analyzed microarray data of localized PCa, metastatic PCa and normal prostate tissue samples from clinical specimens. METHODS: Gene expression profiling datasets of PCa were analyzed online. The DAVID was used to perform GO functional and KEGG pathway enrichment analyses. CytoHubba in Cytoscape software was applied to identify hub genes. Survival data were downloaded from GEPIA. Gene expression data were obtained from ONCOMINE and UALCAN. RESULTS: We obtained 4 sets of differentially expressed genes (DEGs), DEGs 1: a comparison of the gene expression between 4 normal prostate and 5 localized PCa samples in GSE27616; DEGs 2: a comparison of the gene expression between 6 normal prostate and 7 localized PCa samples in GSE3325; DEGs 3: a comparison of the gene expression between 5 localized PCa and 4 metastatic PCa samples in GSE27616; DEGs 4: a comparison of the gene expression between 7 localized PCa and 6 metastatic PCa samples in GSE3325. A comparison of these 4 sets of genes revealed 51 overlapped genes. GO function analysis revealed enrichment of the 51 DEGs in functions related to the proteinaceous extracellular matrix and centrosome, protein homodimerization activity and chromatin binding were the main functions of these genes, which participated in regulating cell division, mitotic nuclear division, proteinaceous extracellular matrix, cell adhesion and apoptotic process. KEGG pathway analysis indicated that these identified DEGs were mainly enriched in progesterone-mediated oocyte maturation, oocyte meiosis and cell cycle. We defined the 16 genes with the highest degree of connectivity as the hub genes in the 51 overlapped DEGs. Cox regression revealed TOP2A, CCNB2, BUB1, CDK1 and EZH2 were related to Disease-free survival (DFS). The expression levels of the 5 genes were 2.232-, 1.786-, 2.303-, 1.699-, and 1.986-fold higher in PCa than the levels in normal tissues, respectively (P < 0.05). We obtained 20 hub genes from DEGs by the comparison of normal prostate tissue vs. localized cancer tissue. Among them, KIF20A, CDKN3, PBK and CDCA2, were expressed higher in PCa than in normal tissues, and were associated with the DFS of PCa patients. Meanwhile, we obtained 20 hub genes from DEGs by the comparison of localized cancer tissue vs. metastatic cancer tissue. Cox regression revealed PLK1, CCNA2 and CDC20, were associated with both the DFS and overall survival of PCa patients. CONCLUSIONS: The results suggested that the functions of KIF20A, CDKN3, PBK and CDCA2 may contribute to PCa development and the functions of PLK1, CCNA2 and CDC20 may contribute to PCa metastasis. Meanwhile, the functions of TOP2A, CCNB2, BUB1, CDK1 and EZH2 may contribute to both PCa development and metastasis.

Reversible engineering of topological insulator surface state conductivity through optical excitation.

Despite the broadband response, limited optical absorption at a particular wavelength hinders the development of optoelectronics based on Dirac fermions. Heterostructures of graphene and various semiconductors have been explored for this purpose, while non-ideal interfaces often limit the performance. The topological insulator (TI) is a natural hybrid system, with the surface states hosting high-mobility Dirac fermions and the small-bandgap semiconducting bulk state strongly absorbing light. In this work, we show a large photocurrent response from a field effect transistor device based on intrinsic TI Sn-Bi1.1Sb0.9Te2S (Sn-BSTS). The photocurrent response is non-volatile and sensitively depends on the initial Fermi energy of the surface state, and it can be erased by controlling the gate voltage. Our observations can be explained with a remote photo-doping mechanism, in which the light excites the defects in the bulk and frees the localized carriers to the surface state. This photodoping modulates the surface state conductivity without compromising the mobility, and it also significantly modify the quantum Hall effect of the surface state. Our work thus illustrates a route to reversibly manipulate the surface states through optical excitation, shedding light into utilizing topological surface states for quantum optoelectronics.

Inclined Ultrathin Bi2O2Se Films: A Building Block for Functional van der Waals Heterostructures.

As an emerging ultrathin semiconductor material, Bi2O2Se exhibits prominent performances in electronics, optoelectronics, ultrafast optics, etc. However, until now, the in-plane growth of Bi2O2Se thin films is mostly fulfilled on atomically flat mica substrates with interfacial electrostatic forces setting obstacles for Bi2O2Se transfer to fabricate functional van der Waals heterostructures. In this work, controlled growth of inclined Bi2O2Se ultrathin films is realized with apparently reduced interfacial contact areas upon mica flakes. Consequently, the transfer of Bi2O2Se could be facile by overcoming weaker electrostatic interactions. From cross-sectional characterizations at the Bi2O2Se/mica interfaces, it is found that there are no oxide buffer layers in existence for both in-plane and inclined growths, while the un-neutralized charge density is apparently decreased for inclined films. By mechanical pressing, inclined Bi2O2Se could be transferred onto SiO2/Si substrates, and back-gated Bi2O2Se field effect transistors are fabricated, outperforming previously reported in-plane Bi2O2Se devices transferred with the assistance of corrosive acids and adhesive polymers. Furthermore, Bi2O2Se/graphene heterostructures are fulfilled by a probe tip to fabricate hybrid phototransistors with pristine interfaces, exhibiting highly efficient photoresponses. The results in this work demonstrate the potential of inclined Bi2O2Se to act as a building block for prospective van der Waals heterostructures.