The long-term outcomes of local tumor destruction versus partial nephrectomy for cT1a non-clear cell renal cell carcinoma and development of prognostic nomograms.

PURPOSE: There is a lack of authoritative opinions on local tumor destruction (LTD) for clinical T1a (cT1a) non-clear cell renal cell carcinoma (nccRCC). We aim to compare the outcomes of cT1a nccRCC after partial nephrectomy (PN) or LTD and explore prognostic factors. METHODS: Patients diagnosed with cT1a nccRCC receiving LTD or PN between 2000 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. A 1:1 propensity score matching (PSM) was performed for patients receiving LTD and PN. Kaplan-Meier survival analysis, Cox regression analysis, competing risk regression models, and subgroup analysis were used to compare outcomes and identify prognostic factors. Prognostic nomograms were established and evaluated based on the multivariate models. RESULTS: A total of 3664 cT1a nccRCC patients were included. The LTD group had poorer overall survival (OS) and similar cancer-specific survival (CSS) compared with the PN group before and after PSM (p < 0.05), while the other-cause mortality rate of the LTD group was higher than that of the PN group. Age, marital status, household income, prior tumor history, interval between diagnosis and treatment, treatments, and tumor size were identified as independent predictive factors for OS. Age, tumor size, prior tumor history, and histological type were identified as independent predictive factors for CSS. Then the nomograms predicting OS and CSS were constructed based on these prognostic factors, which showed excellent performance in risk stratification and accuracy. CONCLUSION: LTD could achieve comparable cancer-control effects as PN among cT1a nccRCC patients. The OS and CSS nomograms worked effectively for prognosis assessment.

Design Strategy of High Stability Vertically Aligned RGO@V2O5 Heterostructure Cathodes for Flexible Quasi-Solid-State Aqueous Zinc-Ion Batteries.

Among various cathodes for aqueous zinc-ion batteries (AZIBs), vanadium-based oxides have garnered significant attention in research circles owing to their exceptionally high theoretical specific capacity. However, the outstanding zinc storage capacity of vanadium pentoxide is constrained by its irreversible dissolution in an aqueous solution. Here, we propose a laser reduction of graphene oxide and construct a heterostructure of V2O5 coated with vertically aligned reduced graphene oxide (VrGO). The VrGO nanosheets effectively suppress the dissolution of V2O5 and provide channels for the efficient transport of zinc ions and electrons, so the electrochemical reaction kinetics of the electrode are improved. The AZIB based on the VrGO@V2O5 heterostructure cathode has a high specific capacity of 254.9 mAh g-1 at 0.2 A g-1 and excellent cycle stability with a capacity retention rate of 90.1% after 5000 cycles of charge and discharge. When assembled into a flexible quasi-solid-state AZIB, the capacity of the device is reduced by only 2% after 1000 bending cycles, showing good potential for wearable applications. This work provides a reliable strategy for designing flexible AZIB with high electrochemical performance and structural stability.

The long-term outcome of nephron-sparing surgery versus radical nephroureterectomy for organ-localized upper urinary tract urothelial carcinoma: a population-based study of 1969 patients.

PURPOSE: To compare the long-term outcomes after nephron-sparing surgery (NSS) and radical nephroureterectomy (RNU) and investigate prognostic factors for organ-localized upper urinary tract urothelial carcinoma (UTUC) as the role of NSS for UTUC remains unclear. METHODS: Patients diagnosed with organ-localized UTUC between 2004 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score overlap weighting (PSOW) process, Cox regression analysis, Kaplan‒Meier analysis, competing-risks models, and subgroup analysis were employed to compare the outcomes and identify prognostic factors. The overall survival (OS) and cancer-specific survival (CSS) nomograms were developed and evaluated using the concordance index (C-index) and calibration curve. RESULTS: A total of 1969 patients were included. After the process of PSOW, baseline data were well balanced. RNU was associated with similar OS and CSS than NSS in the overall cohort. Age, T stage, and histologic grade were independent prognostic factors for OS and CSS, while marital status was an independent prognostic factor only for OS. Four and three predictors were identified for developing the OS and CSS nomograms, respectively. C-index (OS 0.637, CSS 0.670), calibration curve, and Kaplan-Meier analysis proved excellent predictive accuracy of nomograms. CONCLUSION: Patients accepting RNU had a comparative or better outcome in each sample group. NSS achieved a similar oncologic control for selected patients with organ-localized UTUC.

Metabolomics and Proteomics Responses of Largemouth Bass (Micropterus salmoides) Muscle under Organic Selenium Temporary Rearing.

Organic selenium has been widely studied as a nutritional supplement for animal feed. However, there are few studies on the effect of organic selenium on flesh quality. In this study, the effects of organic selenium (yeast selenium (YS), Se 0.002 mg/L) on the metabolism and protein expression in Micropterus salmoides muscle under temporary fasting condition (6 weeks) were investigated. The muscle structure was observed through a microscope, and regulatory pathways were analyzed using proteomics and metabolomics methods. Electron microscopy showed that YS made the muscle fibers of M. salmoides more closely aligned. Differential analysis identified 523 lipid molecules and 268 proteins. The numbers of upregulated and downregulated proteins were 178 and 90, respectively, including metabolism (46.15%), cytoskeleton (11.24%) and immune oxidative stress (9.47%), etc. Integrated analyses revealed that YS enhanced muscle glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation metabolism. In the YS group, the content of eicosapentaenoic acid was increased, and that of docosahexaenoic acid was decreased. YS slowed down protein degradation by downregulating ubiquitin and ubiquitin ligase expression. These results suggest that organic selenium can improve M. salmoides muscle quality through the aforementioned pathways, which provides potential insights into the improvement of the quality of aquatic products, especially fish.

TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma.

BACKGROUND: The management of advanced clear cell renal cell carcinoma (ccRCC) remains a major challenge in clinical practice, and the construction of more reliable prognostic prediction models and the further elucidation of key molecular mechanisms of tumor progression are topics in urgent need of in-depth investigation. METHODS: We used CIBERSORT to estimate the proportion of 22 tumor-infiltrating immune cell types in the TCGA-KIRC cohort. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator regression analysis were used to build risk prediction models. Expression patterns and clinical significance of TRAF2 were determined through bioinformatics analysis, real-time qPCR, Western Blot, immunohistochemistry. GSEA analysis, transmission electron microscopy, 2D/3D colony formation assay, cell migration and invasion assay, and tube-formation assay were used to investigate the underlying function and mechanism of the TRAF2/M2 macrophage/autophagy axis. RESULTS: We constructed a novel prognostic prediction model based on M2 macrophage-related genes, which was identified as an accurate, independent and specific prognostic risk model for ccRCC patients. A reliable nomogram was constructed to predict 1-, 3-, and 5-year overall survival for patients with ccRCC. As one of the constituent genes of the risk model, TRAF2 was determined to be upregulated in ccRCC and associated with poor clinical prognosis. We found that TRAF2 promotes malignant progression of ccRCC by regulating macrophage polarization, migration and angiogenesis. Mechanistically, we found that TRAF2 promotes the polarization of M2 macrophages, and this chemotaxis is achieved in an autophagy-dependent pathway. Orthotopic tumor growth assay results revealed that TRAF2 plays a key role as a promotor of ccRCC growth and metastasis. CONCLUSIONS: In conclusion, this risk model is highly predictive of prognostic in ccRCC patients, which is expected to promote improved treatment evaluation and comprehensive management of ccRCC. Moreover, our findings reveal that the TRAF2/M2 macrophage/autophagy axis plays a key regulatory role in the malignant progression of ccRCC, and suggest that TRAF2 is a potential novel therapeutic target for advanced ccRCC.

Clinical characteristics analysis and prognostic nomogram for predicting survival in patients with second primary prostate cancer: a population study based on SEER database.

BACKGROUND AND AIMS: Second primary prostate cancer (SPPCa) is a common type of secondary malignancy that negatively impacts patient prognosis. This study aimed to identify prognostic factors for SPPCa patients and develop nomograms to assess their prognosis. METHODS: Patients diagnosed with SPPCa between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The study cohort was randomly divided into a training set and a validation set. Cox regression analysis, Kaplan‒Meier survival analysis, and least absolute shrinkage and selection operator regression analysis were used to identify independent prognostic factors and develop the nomogram. The nomograms were evaluated using the concordance index (C-index), calibration curve, area under the curve (AUC), and Kaplan-Meier analysis. RESULTS: A total of 5342 SPPCa patients were included in the study. Independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were identified as age, interval between diagnoses, first primary tumor site, and AJCC stage, N stage, M stage, PSA, Gleason score, and SPPCa surgery. Nomograms were constructed based on these prognostic factors, and the performance was evaluated using the C-index (OS: 0.733, CSS: 0.838), AUC, calibration curve, and Kaplan-Meier analysis, which demonstrated excellent predictive accuracy. CONCLUSION: We successfully established and validated nomograms to predict OS and CSS in SPPCa patients using the SEER database. These nomograms provide an effective tool for risk stratification and prognosis assessment in SPPCa patients, which will aid clinicians in optimizing treatment strategies for this patient population.

Wide-Potential-Window Bimetallic Hydrated Eutectic Electrolytes with High-Temperature Resistance for Zinc-Ion Hybrid Capacitors.

Aqueous zinc-ion hybrid capacitors (ZHCs) are considered ideal energy-storage devices. However, the common aqueous Zn2+ -containing electrolytes used in ZHCs often cause parasitic reactions during charging-discharging owing to free water molecules. Hydrated eutectic electrolytes (HEEs) that bind water molecules through solvation shells and hydrogen bonds can be applied at high temperatures and within a wide potential window. This study reports a novel bimetallic HEE (ZnK-HEE), consisting of zinc chloride, potassium chloride, ethylene glycol, and water, which enhances the capacity and electrochemical reaction kinetics of ZHCs. The bimetallic solvation shell in ZnK-HEE is studied by molecular dynamics and density functional theory, confirming its low step-by-step desolvation energy. A Zn//activated carbon ZHC in ZnK-HEE shows a high operating voltage of 2.1 V, along with an ultrahigh capacity of 326.9 mAh g-1 , power density of 2099.7 W kg-1 , and energy density of 343.2 Wh kg-1 at 100 °C. The reaction mechanisms of charging-discharging process are investigated by ex situ X-ray diffraction. This study reports a promising electrolyte for high-performance ZHCs, which exhibits high-temperature resistance and is operable within a wide potential window.

Tetris-Style Stacking Process to Tailor the Orientation of Carbon Fiber Scaffolds for Efficient Heat Dissipation.

As the miniaturization of electronic devices and complication of electronic packaging, there are growing demands for thermal interfacial materials with enhanced thermal conductivity and the capability to direct the heat toward heat sink for highly efficient heat dissipation. Pitch-based carbon fiber (CF) with ultrahigh axial thermal conductivity and aspect ratios exhibits great potential for developing thermally conductive composites as TIMs. However, it is still hard to fabricate composites with aligned carbon fiber in a general approach to fully utilize its excellent axial thermal conductivity in specific direction. Here, three types of CF scaffolds with different oriented structure were developed via magnetic field-assisted Tetris-style stacking and carbonization process. By regulating the magnetic field direction and initial stacking density, the self-supporting CF scaffolds with horizontally aligned (HCS), diagonally aligned and vertically aligned (VCS) fibers were constructed. After embedding the polydimethylsiloxane (PDMS), the three composites exhibited unique heat transfer properties, and the HCS/PDMS and VCS/PDMS composites presented a high thermal conductivity of 42.18 and 45.01 W m-1 K-1 in fiber alignment direction, respectively, which were about 209 and 224 times higher than that of PDMS. The excellent thermal conductivity is mainly ascribed that the oriented CF scaffolds construct effective phonon transport pathway in the matrix. In addition, fishbone-shaped CF scaffold was also produced by multiple stacking and carbonization process, and the prepared composites exhibited a controlled heat transfer path, which can allow more versatility in the design of thermal management system.

The physicochemical, antioxidant, hypoglycemic and prebiotic properties of γ-irradiated polysaccharides extracted from Lentinula edodes.

In this study, the influence of γ-irradiation with different dose (0, 4, 8, and 16 kGy) on chemical composition, physicochemical features and bioactivities of polysaccharides extracted from Lentinula edodes (LEP) were investigated. The carbohydrate content (from 59.47 to 70.96%), the solubility, the ⋅OH and DPPH scavenging ability of LEP increased with the increased γ-irradiation dose, while the protein content, the weight-average and number-average molecular weight of LEP were significantly decreased with the increased γ-irradiation dose. Moreover, γ-irradiation treatment caused LEP color changes and surface topography destroyed. γ-Irradiated LEP showed higher hypoglycemic activities in vitro than that of non-irradiated LEP. Moreover, γ-irradiated LEP had better proliferation promoting effects on Lactobacillus rhamnosus and L. plantarum. These results showed that γ-irradiation treatment changes the physicochemical features of LEP, thus affects its antioxidant, hypoglycemic and prebiotic properties, which suggests that γ-irradiated LEP has potential application in the pharmaceutical industries and functional foods. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01234-5.

Preparation of Bis-Thiophene Schiff Alkali-Copper Metal Complex for Metal Corrosion Inhibition.

Due to the obvious numerous economic and technical consequences of the corrosion process, its inhibition is one of the most critical aspects of current research. A corrosion inhibitor for the bis-thiophene Schiff base copper-metal complex Cu(II)@Thy-2 was investigated here, which was synthesized via a coordination reaction with a bis-thiophene Schiff base (Thy-2) as a ligand and copper chloride (CuCl2-2H2O) as a ligand metal salt. When the corrosion inhibitor concentration was increased to 100 ppm, the self-corrosion current density Icoor reached a minimum of 2.207 × 10-5 A/cm2, the charge transfer resistance reached a maximum of 932.5 Ω·cm2, and the corrosion inhibition efficiency reached a maximum of 95.2%, with the corrosion inhibition efficiency showing a trend of increasing first and then decreasing with concentration increase. After adding Cu(II)@Thy-2 corrosion inhibitor, a uniformly distributed dense corrosion inhibitor adsorption film formed on the surface of the Q235 metal substrate, significantly improving the corrosion profile compared to both before and after the addition of the corrosion inhibitor. Before and after the addition of corrosion inhibitor, the metal surface's contact angle CA increased from 54.54° to 68.37°, showing that the adsorbed corrosion inhibitor film decreased the metal surface's hydrophilicity and increased its hydrophobicity.

Genotype-phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions.

BACKGROUND: Approximately 20%-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype-phenotype correlations and clinical outcomes in VHL patients with LDs. METHODS: In this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy. RESULTS: The overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy. CONCLUSION: The number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.

A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy of the urological system with poor prognosis. Cuproptosis is a recently discovered novel manner of cell death, and the hub gene FDX1 could promote cuproptosis. However, the potential roles of cuproptosis-related genes (CRGs) and FDX1 for predicting prognosis, the immune microenvironment, and therapeutic response have been poorly studied in ccRCC. In the present study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were downloaded. CRGs were subjected to prognosis analysis, and three of them were used to construct the prognostic model by least absolute shrinkage and selection operator (LASSO) regression. The CRGs prognostic model showed excellent performance. Moreover, based on the risk score of the model, the nomogram was developed to predict 1-year, 3-year, and 5-year survival. Furthermore, the hub gene of cuproptosis, FDX1, was an independent prognostic biomarker in multivariate Cox regression analysis. The pan-cancer analysis showed that FDX1 was significantly downregulated and closely related to prognosis in ccRCC among 33 cancer types. Lower FDX1 was also correlated with worse clinicopathologic features. The lower expression of FDX1 in ccRCC was verified in the external database and our own database, which may be caused by DNA methylation. We further demonstrated that the tumor mutational burden (TMB) and immune cell infiltration were related to the expression of FDX1. Immune response and drug sensitivity analysis revealed that immunotherapy or elesclomol may have a favorable treatment effect in the high FDX1 expression group and sunitinib or axitinib may work better in the low FDX1 expression group. In conclusion, we constructed a CRGs prognostic model and revealed that FDX1 could serve as a prognostic biomarker and predict therapeutic response in ccRCC. The study will provide a novel, precise, and individual treatment strategy for ccRCC patients.

Rice straw cellulose microfiber reinforcing PVA composite film of ultraviolet blocking through pre-cross-linking.

Rice straw cellulose microfiber (CMF) was obtained through the gentle low-temperature phase transition method. Then, NaIO4 was utilized to modify CMF by selective oxidation to prepare aldehyde CMF (a-CMF) to improve the reactivity of the CMF. Finally, the a-CMF reinforced polyvinyl alcohol (PVA) composite films were prepared through a pre-cross-linking and solvent casting approach. The cross-linking network formed by a-CMF and PVA through the aldolization reaction significantly improved the mechanical properties of the a-CMF/PVA composite film. The tensile strength of a-CMF-2/PVA was 37.54 ± 0.77 MPa, which was higher than 25.88 ± 2.97 MPa of the pure PVA. SEM results showed that the fracture surface of the a-CMF/PVA composite film with the cross-linking network was smooth. In addition, prepared a-CMF-2/PVA composite films had a transmittance of over 80 % in the visible light range, and also possessed excellent UV blocking property.

Claudin-10 overexpression suppresses human clear cell renal cell carcinoma growth and metastasis by regulating ATP5O and causing mitochondrial dysfunction.

Our previous study has proved that down-regulation of CLDN10 (Claudin-10) in ccRCC (clear cell renal cell carcinoma) was closely related to tumor metastasis and predicted an unfavorable prognosis by analyzing TCGA-KIRC data. However, the effects of CLDN10 on the progression of ccRCC and its mechanisms of action remain elusive. During the study, a large number of clinical samples were utilized to verify the reduced expression of CLDN10 in ccRCC and its association with tumor metastasis and poor prognosis, and our results confirmed that lower CLDN10 expression was an independent predictor of shorter OS (HR: 4.0860, 95%CI: 2.4737-6.7490, P<0.0001) and DFS (HR: 4.3680, 95%CI: 2.2800-8.3700, P<0.0001) in metastatic ccRCC patients. CLDN10 overexpression accelerated cell apoptosis and restrained cell proliferation, migration and invasion in vitro. Besides, CLDN10 overexpression suppressed ccRCC growth and lung metastasis and promoted apoptosis in orthotopic models. Mechanistically, we found that CLDN10 overexpression up-regulated the acetylation and expression levels of ATP5O (ATP synthase subunit O, mitochondrial), leading to the dysfunction of mitochondrial, thereby suppressing the growth and metastasis of ccRCC through increasing the levels of NDUFS2, ROS, Cleaved-Caspase 3, E-cadherin and SDHB and decreasing the levels of N-cadherin and mitochondrial membrane potential. Moreover, knockdown of ATP5O expression based on the overexpression of CLDN10 could reverse the increase in NDUFS2, ROS, Cleaved-Caspase 3, E-cadherin and SDHB levels, the decrease in N-cadherin and mitochondrial membrane potential levels and the inhibition of ccRCC phenotypes caused by CLDN10 overexpression. Taken together, these findings for the first time illuminate the mechanism by which CLDN10 overexpression suppresses the growth and metastasis of ccRCC.

Synthesis of Sodium Carboxymethyl Cellulose/Poly(acrylic acid) Microgels via Visible-Light-Triggered Polymerization as a Self-Sedimentary Cationic Basic Dye Adsorbent.

In this study, sodium carboxymethyl cellulose/poly(acrylic acid) (CMC/PAA) microgels were successfully synthesized via visible-light-triggered free-radical polymerization to remove methylene blue (MB) from water. The microgels had a loose and porous 3-D network structure, exhibiting excellent adsorption performance. The equilibrium adsorption capacity and the removal efficiency of the microgels reached approximately 1479 mg/g and 97%, respectively, when the initial concentration of MB was 300 mg/L. The adsorption kinetics was well described by the pseudo-second-order model, and the adsorption isotherms followed the Langmuir isothermal model. Notably, CMC/PAA microgels could naturally settle and be separated from the MB solution. Furthermore, the recovery efficiency of the regenerated CMC/PAA microgels reached approximately 94% after five adsorption-desorption cycles. Therefore, the microgels could be used as promising adsorbents due to the advantages of high adsorption capacity, fast removal rate, and reusability.

Pavement Properties and Predictive Durability Analysis of Asphalt Mixtures.

The actual lifetimes of many highways are lower than that expected based on the initial pavement design, which brings increasingly prohibitive costs of pavement maintenance and repair. Although many works have been done, the real service lifetimes are still disappointing, and the researchers are also trying their best to increase the projects' life span. In this study, to comprehensively predict the durability and lifetime of newly designed asphalt mixture structures, an asphalt pavement project consisting of three hot mix asphalt (HMA) mixtures were evaluated. The mixtures were constructed in the pavement project of the Weiwu expressway in Gansu Province. Pavement properties of the asphalt mixtures, rutting and temperature fatigue factors of the dynamic modulus are discussed. The fatigue resistance is supposed to improve on increasing the vehicles' speed below the freezing point, which may be more suitable for applications in expressways. Meanwhile, the lifetime is measured according to the number of fatigue axle loads calculated, which were corrected between the specimens in the lab and the field core samples. Durability analysis prediction can be obtained based on the fatigue lifetime predictive model accordingly, which can provide more information about the fatigue lifetime and the rehabilitation planning of existing pavements in the future accordingly.

Natural history of Von Hippel-Lindau disease-associated and sporadic clear cell renal cell carcinoma: a comparative study.

PURPOSE: To compare the tumor growth kinetics between sporadic clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau disease-associated renal cell carcinoma (VHL-associated RCC). To analyze predictive markers for the growth rate of these two types of RCC. METHODS: The clinical data of patients with renal tumors who received active surveillance were collected retrospectively. Immunohistochemical staining was utilized to analyze the expression levels of VHL, PBRM1, H3K36me3, and BAP1 in the postoperative specimens. RESULTS: The age of the VHL group was significantly younger than that of the sporadic group (P < 0.0001). The mean linear growth rate (LGR) was significantly faster in the sporadic group (P = 0.0004). The tumors of those in the sporadic group tended to have a higher histologic grade (P = 0.0011). In the sporadic group, tumor histologic grade was an independent predictor for rapid mean LGR (P = 0.0022). In the VHL group, initial maximal tumor diameter (MTD) was the only independent predictor for rapid mean LGR (P < 0.0001). Tumors with low VHL expression and negative PBRM1 expression showed a faster growth rate in the sporadic group (P = 0.001 and P = 0.008, respectively). The expression levels of the four biomarkers showed no impact on the tumor growth rate in the VHL group. CONCLUSION: Sporadic ccRCC grew faster than VHL-associated RCC. High histologic grade, low VHL expression and negative PBRM1 expression were predictors of faster growth in sporadic ccRCC. A large initial MTD was a predictor of faster growth for VHL-associated RCC.

Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors. METHODS: In this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: The estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group. CONCLUSION: This study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

Decreased interferon regulatory factor 6 expression due to DNA hypermethylation predicts an unfavorable prognosis in clear cell renal cell carcinoma.

Background: Emerging evidences have indicated that IRF6, as a member of the Interferon regulatory factors (IRFs) family, plays important roles in a variety of tumors. However, the expression status of IRF6 and its prognostic value in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods: In this study, we used TCGA-KIRC, GEO and TIP databases and immunohistochemistry staining to determine the expression profile, clinico-pathological features and prognostic value of IRF6 in ccRCC. MSP and demethylation analysis were utilized to verify the regulatory effect of DNA methylation on IRF6 expression. Results: Our results found that IRF6 expression was downregulated in ccRCC tissues and cell lines, and decreased IRF6 expression was associated with worse clinicopathological features and poorer prognosis. Besides, the results of multivariate Cox regression analysis also confirmed that decreased IRF6 expression was an independently risk factor predictor of shorter Overall Survival (OS) (HR: 0.8524, 95%CI: 0.7614-0.9543, P=0.0056) and Disease Free Survival (DFS) (HR: 0.7024, 95%CI: 0.6087-0.8104, P<0.0001) in ccRCC patients. Moreover, the results of MSP and demethylation analysis validated that decreased IRF6 expression was caused by DNA hypermethylation. Furthermore, our results showed that IRF6 expression was associated with the infiltration levels of multiple immune cells in ccRCC. Conclusions: These findings demonstrated that IRF6 expression was significantly reduced in ccRCC and DNA hypermethylation played an important role in decreased IRF6 expression. In addition, the decrease of IRF6 was related to the unfavorable prognosis of ccRCC patients and the alterations of tumor immune cells infiltration.

Low-temperature adaptive conductive hydrogel based on ice structuring proteins/CaCl2 anti-freeze system as wearable strain and temperature sensor.

Conductive hydrogels as wearable devices meet the basic demands of mechanical flexibility and smart sensing. However, achieving anti-freeze property in conductive hydrogels is still challengeable. Here, a novel anti-freezing system based on ice structuring proteins and CaCl2 was introduced to enable a conductive hydrogel with low-temperature adaptability. Both formation of ice nuclei and ice growth of the hydrogel at sub-zero temperature could be inhibited. Supported by the anti-freeze system, the hydrogel revealed good flexibility (890% at -20 °C), recovery and conductivity (0.50 S/m at -20 °C) at both room temperature and sub-zero temperature. The low-temperature adaptability enabled the hydrogel to be used as strain and temperature sensors at both room temperature and sub-zero temperature. The anti-freeze system in this work is expected to open up a new avenue to promote the conductive hydrogel with low-temperature adaptability.