Single Atom Catalysts Remodel Tumor Microenvironment for Augmented Sonodynamic Immunotherapy.

The immunosuppressive tumor microenvironment (TME) is a huge hurdle in immunotherapy. Sono-immunotherapy is a new treatment modality that can reverse immunosuppressive TME, but the sonodynamic effects are compromised by overexpressed glutathione (GSH) and hypoxia in the TME. Herein, this work reports a new sono-immunotherapy strategy using Pdδ+ single atom catalysts to enhance positive sonodynamic responses to the immunosuppressive and sono-suppressive TME. To demonstrate this technique, this work employs rich and reductive Ti vacancies in Ti3-xC2Ty nanosheets to construct the atomically dispersed Pd-C3 single atom catalysts (SAC) with Pd content up to 2.5 wt% (PdSA/Ti3-xC2Ty). Compared with Pd nanoparticle loaded Ti3-xC2Ty, PdSA/Ti3-xC2Ty single-atom enzyme showed augmented sonodynamic effects that are ascribed to SAC facilitated electron-hole separation, rapid depletion of overexpressed GSH by ultrasound (US) excited holes, and catalytic decomposition of endogenous H2O2 for relieving hypoxia. Importantly, the sono-immunotherapy strategy can boost abscopal antitumor immune responses by driving maturation of dendritic cells and polarization of tumor-associated macrophages into the antitumoral M1 phenotype. Bilateral tumor models demonstrate the complete eradication of localized tumors and enhance metastatic regression. Th strategy highlights the potential of single-atom catalysts for robust sono-immunotherapy by remodeling the tumor microenvironment.

Boosting the Cell Performance of the SiO/Cu and SiO/PPy Anodes via In-Situ Reduction/Oxidation Coating Strategies.

Silicon monoxide (SiO) has attracted great attention due to its high theoretical specific capacity as an alternative material for conventional graphite anode, but its poor electrical conductivity and irreversible side reactions at the SiO/electrolyte interface seriously reduce its cycling stability. Here, to overcome the drawbacks, the dicharged SiO anode coated with Cu coating layer is elaborately designed by in-situ reduction method. Compared with the pristine SiO anode of lithium-ion battery (293 mAh g-1 at 0.5 A g-1 after 200 cycles), the obtained SiO/Cu composite presents superior cycling stability (1206 mAh g-1 at 0.5 A g-1 after 200 cycles). The tight combination of Cu particles and SiO significantly improves the conductivity of the composite, effectively inhibits the side-reaction between the active material and electrolyte. In addition, polypyrrole-coated SiO composites are further prepared by in-situ oxidation method, which delivers a high reversible specific capacity of 1311 mAh g-1 at 0.5 A g-1 after 200 cycles. The in-situ coating strategies in this work provide a new pathway for the development and practical application of high-performance silicon-based anode.

A prognostic model based on necroptosis-related genes for prognosis and therapy in bladder cancer.

Bladder cancer, one of the most prevalent malignant cancers, has high rate of recurrence and metastasis. Owing to genomic instability and high-level heterogeneity of bladder cancer, chemotherapy and immunotherapy drugs sensitivity and lack of prognostic markers, the prognosis of bladder cancer is unclear. Necroptosis is a programmed modality of necrotic cell death in a caspase-independent form. Despite the fact that necroptosis plays a critical role in tumor growth, cancer metastasis, and cancer patient prognosis, necroptosis-related gene sets have rarely been studied in bladder cancer. As a result, the development of new necroptosis-related prognostic indicators for bladder cancer patients is critical. Herein, we assessed the necroptosis landscape of bladder cancer patients from The Cancer Genome Atlas database and classified them into two unique necroptosis-related patterns, using the consensus clustering. Then, using five prognosis-related genes, we constructed a prognostic model (risk score), which contained 5 genes (ANXA1, DOK7, FKBP10, MAP1B and SPOCD1). And a nomogram model was also developed to offer the clinic with a more useful prognostic indicator. We found that risk score was significantly associated with clinicopathological characteristics, TIME, and tumor mutation burden in patients with bladder cancer. Moreover, risk score was a valid guide for immunotherapy, chemotherapy, and targeted drugs. In our study, DOK7 was chosen to further verify our prognosis model, and functional assays indicated that knockdown the expression of DOK7 could prompt bladder cancer proliferation and migration. Our work demonstrated the potential role of prognostic model based on necroptosis genes in the prognosis, immune landscape and response efficacy of immunotherapy of bladder cancer.

Compressive strain induced superior HER performance of nickel in alkaline solution.

The HER requires a highly efficient, cost-effective, and stable catalyst to adapt to the large-scale hydrogen industry. Nickel has been confirmed to be useful to drive the water splitting reaction, but the intrinsic performance remains unsatisfactory. In this work, nickel (EG-Ni) with compressive strain was prepared through a one-step electrochemical deposition strategy. It shows an outstanding enhancement for the HER, and it achieves a current density of 10 mA cm-2 at a low overpotential of 85.9 mV. A long-term durability test proves that the EG-Ni can tolerate a large current density of 100 mA cm-2, and the overpotential remains steady without dramatically increasing. Such a low overpotential and superior stability are attributed to the optimized adsorption energy on the catalyst surface, as evidenced by the downshifted position of the d-band center.

Establishment of an optimized orthotopic bladder cancer model in mice.

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Animal models offer an important tool to explore tumour initiation, progression, and therapeutic mechanisms. Our aim is to construct an optimized orthotopic BC model which is predictable, reproducible, and convenient. METHODS: The optimized orthotopic BC model was constructed in male C57BL/6 mice utilizing microsyringes to inoculate them with a murine BC cell line (MB49). Anesthetised mice were inoculated with an MB49 cell suspension (10 µL) at approximately 5 × 106/mL. The whole process of modelling was observed and monitored every 3 days for 21 days utilizing HE staining and transabdominal ultrasonography (TUS). RESULTS: In this study, the model showed excellent success rates for tumour formation (96.67%) and metastatic rate (89.66%). Compared to the control group (sham operation), mice in the modelling group had serous cachexia, visible haematuresis and weight loss (all P < 0.05). The lungs, liver, ureter and kidneys were found to have tumour metastasis. Moreover, the average survival time (19.73 ± 1.69 d) of modelling mice was significantly shorter than that of the control mice (P < 0.05), which remained alive. CONCLUSION: Our study established a method using microsyringes to inject murine BC cells into the bladder wall, creating a stable transplantable BC model in mice.

Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer.

BACKGROUND: Enolase is an essential enzyme in the process of glycolysis and has been implicated in cancer progression. Though dysregulation of ENOs has been reported in multiple cancers, their prognostic value and specific role in bladder cancer (BLCA) remain unclear. METHODS: Multiple databases were employed to examine the expression of ENOs in BLCA. The expression of ENO1 was also validated in BLCA cell lines and tissue samples by western blotting and immunohistochemistry. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression were performed to evaluate the predictive capability of the ENO1. Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) analysis were employed to perform the biological processes enrichment. Function experiments were performed to explore the biological role of ENO1 in BLCA. The correlation of ENO1 with immune cell infiltration was explored by CIBERSORT. RESULTS: By analyzing three ENO isoforms in multiple databases, we identified that ENO1 was the only significantly upregulated gene in BLCA. High expression level of ENO1 was further confirmed in BLCA tissue samples. Aberrant ENO1 overexpression was associated with clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ENO1 depletion inhibited cancer cell aggressiveness. Furthermore, the expression level of ENO1 was correlated with the infiltration levels of immune cells and immune-related functions. CONCLUSIONS: Taken together, our results indicated that ENO1 might serve as a promising prognostic biomarker for prognosticating prognosis associated with the tumor immune microenvironment, suggesting that ENO1 could be a potential immune-related target against BLCA.

Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress.

BACKGROUND: The current drug treatments for benign prostatic hyperplasia (BPH) have negative side effects. Therefore, it is important to find effective alternative therapies with significantly fewer side effects. Our previous study revealed that Rauwolfia vomitoria (RWF) root bark extract reversed BPH development in a rat model. However, the molecular mechanism of its inhibitory effects on BPH remains largely unknown. METHODS: BPH-1 and WPMY-1 cell lines derived from BPH epithelial and prostatic stromal compartments were selected to investigate how RWF extract inhibits BPH in vitro by MTT and flow cytometry assays. Microarray, quantitative real-time PCR, immunoblotting, and GFP-LC3 immunofluorescence assays were performed to evaluate the effects of RWF extract on endoplasmic reticulum stress (ER stress) and autophagic apoptosis pathways in two cell lines. A human BPH ex vivo explant assay was also employed for validation. RESULTS: RWF extract treatment decreased cell viability and induced apoptotic cell death in both BPH-1 and WPMY-1 cells in a concentration-dependent manner with the increase of pro-apoptotic PCDC4 protein. RWF extract induced autophagy by enhancing the levels of autophagic genes (ULK2 and SQSTM1/p62) and the LC3II:LC3I ratio, with the increase of GFP-LC3 puncta. Moreover, RWF extract activated PERK- and ATF6-associated ER stress pathways by inducing the transcriptional levels of EIF2AK3/PERK, DDIT3/CHOP and ATF6, accompanied by the reduction of BiP protein level, but not its mRNA level. Another ER stress pathway was not induced by RWF extract, as manifested by the lack of XBP1 splicing. Pharmacological inhibition of autophagy by 3-methyladenine abrogated apoptosis but not ER stress; while inhibition of ER stress by 4-phenylbutyrate alleviated the induction of autophagy and apoptosis. In addition, pretreatments with either 3-methyladenine or 4-phenylbutyrate suppressed RWF extract-induced cytotoxicity. Notably, the inductions of PERK- and ATF6-related stress pathways and autophagic apoptosis were confirmed in a human BPH ex vivo explant. CONCLUSIONS: Our data have demonstrated that RWF extract significantly suppressed the viabilities of BPH epithelial cells and BPH myofibroblasts by inducing apoptosis via upregulating ER stress and autophagy. These data indicate that RWF extract is a potential novel alternative therapeutic approach for BPH.

Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer.

Background: Bladder cancer (BC) is a leading cause of death from malignancy, with significant heterogeneity in the immunotherapeutic responsiveness of advanced status. Pyroptosis, a newly discovered inflammatory programmed cell death, is confirmed to play an indispensable role in tumorigenesis and anti-tumor activity. However, the effect of pyroptosis on the tumor-immune landscape remodeling and immunotherapy in BC remains elusive. Methods: We comprehensively evaluated the mRNA expression and genomic alterations of 33 pyroptosis-related genes (PRGs) in BC and evaluated the patterns of pyroptosis in publicly available BC datasets. An unsupervised clustering method was used to classify patients into distinct patterns. Then, we established a pyroptosis-related signature score (PS-score) model to quantify the pyroptosis-related patterns of individual BC patients using principal component analysis. Furthermore, we correlated the patterns with the immune landscape and response efficacy of immunotherapy. Results: Two pyroptosis-related patterns were identified in BC, and distinct patterns showed various immune characteristics. Patterns with a high expression level of PRGs exhibited a survival advantage and showed higher infiltration of cytotoxic lymphocytes. Tumors with a low PS-score were characterized by high tumor-infiltrating lymphocytes and considered "hot." Further analysis revealed that the PS-score was an independent prognostic factor and could predict the response to immunotherapy for patients with advanced BC. We found a significant positive association between AHNAK2, AHNAK nucleoprotein 2, expression, and PS-score. Functional assays showed that AHNAK2 knockdown was correlated with attenuated invasive ability. Conclusion: This work comprehensively demonstrated the potential function of pyroptosis-related patterns in the bladder tumor-immune landscape and identified their therapeutic liability in immunotherapy. Our study enhanced our understanding of the immune landscape and provided a new approach toward more effective immunotherapy strategies.

A novel cuproptosis-related lncRNA signature predicts prognosis and therapeutic response in bladder cancer.

Bladder cancer (BC) ranks the tenth in the incidence of global tumor epidemiology. LncRNAs and cuproptosis were discovered to regulate the cell death. Herein, we downloaded transcriptome profiling, mutational data, and clinical data on patients from The Cancer Genome Atlas (TCGA). High- and low-risk BC patients were categorized. Three CRLs (AL590428.1, AL138756.1 and GUSBP11) were taken into prognostic signature through least absolute shrinkage and selection operator (LASSO) Cox regression. Worse OS and PFS were shown in high-risk group (p < 0.05). ROC, independent prognostic analyses, nomogram and C-index were predicted via CRLs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated IncRNAs play a biological role in BC progression. Immune-related functions showed the high-risk group received more benefit from immunotherapy and had stronger immune responses, and the overall survival was better (p < 0.05). Finally, a more effective outcome (p < 0.05) was found from clinical immunotherapy via the TIDE algorithm and many potential anti-tumor drugs were identified. In our study, the cuproptosis-related signature provided a novel tool to predict the prognosis in BC patients accurately and provided a novel strategy for clinical immunotherapy and clinical applications.

Development and Validation of Prognostic Model in Transitional Bladder Cancer Based on Inflammatory Response-Associated Genes.

BACKGROUND: Bladder cancer is a common malignant type in the world, and over 90% are transitional cell carcinoma. While the impact of inflammatory response on cancer progression has been reported, the role of inflammatory response-associated genes (IRAGs) in transitional bladder cancer still needs to be understood. METHODS: In this study, IRAGs were download from Molecular Signature Database (MSigDB). The transcriptional expression and matched clinicopathological data were separately obtained from public databases. The TCGA-BLCA cohort was used to identify the differentially expressed IRAGs, and prognostic IRAGs were filtrated by univariate survival analysis. The intersection between them was displayed by Venn diagram. Based on least absolute shrinkage and selection operator (LASSO) regression analysis method, the TCGA-BLCA cohort was used to construct a risk signature. Survival analysis was conducted to calculate the overall survival (OS) in TCGA and GSE13507 cohort between two groups. We then conducted univariate and multivariate survival analyses to identify independently significant indicators for prognosis. Relationships between the risk scores and age, grade, stage, immune cell infiltration, immune function, and drug sensitivity were demonstrated by correlation analysis. The expression level of prognostic genes in vivo and in vitro were determined by qRT-PCR assay. RESULTS: Comparing with normal tissues, there were 49 differentially expressed IRAGs in cancer tissues, and 12 of them were markedly related to the prognosis in TCGA cohort for transitional bladder cancer patients. Based on LASSO regression analysis, a risk model consists of 10 IRAGs was established. Comparing with high-risk groups, survival analysis showed that patients in low-risk groups were more likely to have a better survival time in TCGA and GSE13507 cohorts. Besides, the accuracy of the model in predicting prognosis is acceptable, which is demonstrated by receiver operating characteristic curve (ROC) analysis. Age, stage, and risk scores variables were identified as the independently significant indicators for survival in transitional bladder cancer. Correlation analysis represented that the risk score was identified to be significantly related to the above variables except gender variable. Moreover, the expression level of prognostic genes in vivo and in vitro was markedly upregulated for transitional bladder cancer. CONCLUSIONS: A novel model based on the 10 IRAGs that can be used to predict survival time for transitional bladder cancer. In addition, this study may provide treatment strategies according to the drug sensitivity in the future.

A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer.

Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling.

The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.

Loss of polarity protein Par3, via transcription factor Snail, promotes bladder cancer metastasis.

Bladder cancer (BLCA) remains the leading cause of cancer-related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2-box (CAGGTG) of PARD3 promoter-proximal. Inhibition of GSK-3ß promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936-1356 aa) and ZO-1 (1372-1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK-3ß/Snail/Par3/ZO-1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA.

TEAD4 as a Prognostic Marker Promotes Cell Migration and Invasion of Urinary Bladder Cancer via EMT.

PURPOSE: As a member of TEA Domain Transcription Factors (TEADs), TEAD4 was found to be upregulated in urinary bladder cancer (UBC). This study focused on investigating the clinical value and potential functions of TEAD4 in UBC. MATERIALS AND METHODS: Patients' samples, TCGA-BLCA and multiple GEO datasets were applied to explore the expression pattern of TEAD4 in UBC. Cox regression and Kaplan-Meier survival analyses were carried out to evaluate the prognostic significance of TEAD4 in UBC. Wound healing and transwell assays were performed to explore the biological functions of TEAD4 in UBC cells. RESULTS: The results of TCGA-BLCA, GEO datasets, Western blotting and immunohistochemistry staining (IHC) indicated that TEAD4 was strikingly elevated in UBC tissues as compared to their normal counterparts, and upregulation of TEAD4 was significantly correlated with clinical stage, pathological grade and poor clinical outcome. Functional studies demonstrated that TEAD4 knockdown suppressed cell migration and invasion by reducing the expression of epithelial-mesenchymal transition (EMT) related markers and transcription regulators. CONCLUSION: Our results suggest that TEAD4 may serve as a novel prognostic biomarker and a promising therapeutic target for UBC, and act as a pro-tumorigenic gene to promote cell migration and invasion by inducing EMT.

Identification of a novel immune microenvironment signature predicting survival and therapeutic options for bladder cancer.

Few studies have investigated the potential of tumor immune microenvironment genes as indicators of urinary bladder cancer. Here, we sought to establish an immune-related gene signature for determining prognosis and treatment options. We developed a ten-gene tumor immune microenvironment signature and evaluated its prognostic capacity on internal and external cohorts. Multivariate Cox regression and nomogram analyses revealed the prognostic risk model as an independent and effective indicator of prognosis. We observed lower proportions of CD8+ T cells, dendritic cells, regulatory T cells, higher proportions of macrophages and neutrophils in high UBC risk group. UBC tissues with high-risk score tend to exhibit high TP53 and RB1 mutation rates, high PD1/PD-L1 expression and poor-survival basal squamous subtypes, while those with low-risk score tend to have high FGFR3 mutation rates and luminal papillary subtypes. Unexpectedly, we found a highly significant positive correlation between glycolytic genes and risk score, highlighting metabolic competition in tumor ecosystem and potential therapeutic avenues. Our study thus revealed a tumor immune microenvironment signature for predicting prognostic and response to immune checkpoint inhibitors against bladder cancer. Prospective studies are required to further test the predictive capacity of this model.

Two-dimensional polymer formation on surfaces: insight into the roles of precursor mobility and reactivity.

We report on a combined scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) study on the surface-assisted assembly of the hexaiodo-substituted macrocycle cyclohexa-m-phenylene (CHP) toward covalently bonded polyphenylene networks on Cu(111), Au(111), and Ag(111) surfaces. STM and XPS indicate room temperature dehalogenation of CHP on either surface, leading to surface-stabilized CHP radicals (CHPRs) and coadsorbed iodine. Subsequent covalent intermolecular bond formation between CHPRs is thermally activated and is found to proceed at different temperatures on the three coinage metals. The resulting polyphenylene networks differ significantly in morphology on the three substrates: On Cu, the networks are dominated by "open" branched structures, on the Au surface a mixture of branched and small domains of compact network clusters are observed, and highly ordered and dense polyphenylene networks form on the Ag surface. Ab initio DFT calculations allow one to elucidate the diffusion and coupling mechanisms of CHPRs on the Cu(111) and Ag(111) surfaces. On Cu, the energy barrier for diffusion is significantly higher than the one for covalent intermolecular bond formation, whereas on Ag the reverse relation holds. By using a Monte Carlo simulation, we show that different balances between diffusion and intermolecular coupling determine the observed branched and compact polyphenylene networks on the Cu and Ag surface, respectively, demonstrating that the choice of the substrate plays a crucial role in the formation of two-dimensional polymers.

Atomically precise bottom-up fabrication of graphene nanoribbons.

Graphene nanoribbons-narrow and straight-edged stripes of graphene, or single-layer graphite-are predicted to exhibit electronic properties that make them attractive for the fabrication of nanoscale electronic devices. In particular, although the two-dimensional parent material graphene exhibits semimetallic behaviour, quantum confinement and edge effects should render all graphene nanoribbons with widths smaller than 10 nm semiconducting. But exploring the potential of graphene nanoribbons is hampered by their limited availability: although they have been made using chemical, sonochemical and lithographic methods as well as through the unzipping of carbon nanotubes, the reliable production of graphene nanoribbons smaller than 10 nm with chemical precision remains a significant challenge. Here we report a simple method for the production of atomically precise graphene nanoribbons of different topologies and widths, which uses surface-assisted coupling of molecular precursors into linear polyphenylenes and their subsequent cyclodehydrogenation. The topology, width and edge periphery of the graphene nanoribbon products are defined by the structure of the precursor monomers, which can be designed to give access to a wide range of different graphene nanoribbons. We expect that our bottom-up approach to the atomically precise fabrication of graphene nanoribbons will finally enable detailed experimental investigations of the properties of this exciting class of materials. It should even provide a route to graphene nanoribbon structures with engineered chemical and electronic properties, including the theoretically predicted intraribbon quantum dots, superlattice structures and magnetic devices based on specific graphene nanoribbon edge states.

Porous graphenes: two-dimensional polymer synthesis with atomic precision.

We demonstrate, by surface-assisted coupling of specifically designed molecular building blocks, the fabrication of regular two-dimensional polyphenylene networks with single-atom wide pores and sub-nanometer periodicity.

[Relationship between atrial fibroblast proliferation/fibrosis and atrial fibrillation in patients with rheumatic heart disease].

OBJECTIVE: To investigate the association between gene expressions of basic fibroblast growth factor (bFGF), smooth muscle alpha-actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) and atrial fibrosis in patients with atrial fibrillation (AF). METHODS: The right atrial tissue samples were taken from 75 patients with rheumatic heart disease underwent heart valve replacement surgery (34 patients with sinus rhythm, 11 patients with paroxysmal AF and 30 patients with persistent AF) and stained with picrosirius red for quantitative analysis of collagen accumulation. The mRNA and protein levels of bFGF, alpha-SMA and PCNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. RESULTS: The percent volume fraction of collagen (CVF) was the highest in persistent AF group and the lowest in the sinus rhythm group (all P < 0.01). CVF significantly correlated with AF duration (r = 0.390, P = 0.010) and left atria (LA) dimension (r = 0.320, P = 0.005). The mRNA and protein levels of bFGF, alpha-SMA and PCNA were significantly higher in the persistent AF group than those in the paroxysmal AF group (all P < 0.05) and significantly higher in both AF groups than those in the sinus rhythm group (P < 0.05-0.01). The mRNA and protein levels of bFGF were positively correlated with CVF (r = 0.330, P = 0.004 and r = 0.292, P = 0.013, respectively), AF duration (r = 0.330, P = 0.005 and r = 0.299, P = 0.010, respectively) and left atrial dimension (r = 0.342, P = 0.003 and r = 0.285, P = 0.015, respectively). CONCLUSION: The increased gene expressions of bFGF, alpha-SMA and PCNA in atrium during AF may contribute to atrial fibrosis by promoting fibroblast proliferation in AF patients.