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ABSTRACTMolecule interacting with CasL 1 (MICAL1) is a crucial protein involved in cell motility, axon guidance, cytoskeletal dynamics, and gene transcription. This pan-cancer study analyzed MICAL1 across 33 cancer types using bioinformatics and experiments. Dysregulated expression, diagnostic potential, and prognostic value were assessed. Associations with tumor characteristics, immune factors, and drug sensitivity were explored. Enrichment analysis revealed MICAL1’s involvement in metastasis, angiogenesis, metabolism, and immune pathways. Functional experiments demonstrated its impact on renal carcinoma cells. These findings position MICAL1 as a potential biomarker and therapeutic target in specific cancers, warranting further investigation into its role in cancer pathogenesis.

The βʹ-Cu4Ti phase is the major strengthening precipitate in Cu–Ti alloys. Previous research indicates that destabilization of the βʹ-Cu4Ti phase leads to dissolution of Ti atom from precipitates into the Cu matrix. In the present work, Sc was chosen to be alloying elements in Cu–Ti alloys, since stabilization of the βʹ-Cu4Ti phase could be enhanced by formation of βʹ-Cu4(Ti,Sc) phase. Experimental characterization combined with first-principles calculations were used to evaluate the effect of Sc addition. It was found that the bonding between Ti and Sc atoms in the same sublattice of βʹ-Cu4Ti phase increases the diffusion barrier of Ti atoms, and thus dissolution of the βʹ-Cu4Ti phase and further nucleation of the β-Cu4Ti phase were hindered.

Abstract Background Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 μg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. Methods PTB patients who underwent bronchoscopy examination and treatment at The Third People’s Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 μg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon’s up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. Results The ED50 of ciprofol combined with 0.15 μg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. Conclusion The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. Trial registration The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.

Background The intricate task of diagnosing and managing small renal masses (SRMs) has become progressively convoluted within the realm of clinical practice. Contemporary clinical prediction instruments may succumb to a gradual decay in precision, coupled with an absence of unambiguous guidelines to navigate patient management. Methods This investigation was devised to formulate and authenticate nomograms for the overall survival (OS) and cancer- specific survival (CSS) among patients afflicted with SRMs. The study encompassed a cohort of 2558 pediatric patients diagnosed with SRMs over the period of 2000 to 2019. Independent prognostic indicators for OS and CSS, encompassing historical staging, chemotherapy regimens, surgical interventions, and pathological classifications, were ascertained through the employment of multivariate Cox proportional hazards regression analysis and backward stepwise selection. Results Through the utilization of multivariate Cox regression models, nomograms for OS and CSS were meticulously crafted, demonstrating commendable discrimination and calibration within the training set (OS C-index: 0.762, CSS C-index: 0.779). The validation set further corroborated the exemplary discrimination and calibration of the nomograms. Moreover, these nomograms adeptly differentiated between patient groups at elevated and diminished risk levels. Conclusion The nomograms delineated in this research provide propitious predictive accuracy for overall survival and cancer-specific survival in patients suffering from pediatric SRMs, thereby contributing to refined risk stratification and steering the optimal therapeutic course of action. The necessity for supplementary validation prevails before the translation of these findings into clinical practice.

Cu–Al2O3/Cu laminated dual heterogeneous microstructure composites with alternating coarse/fine grain distributions were prepared using a combination of accumulative roll bonding and annealing processes. The average layer thickness of the Al2O3/Cu layers is 2.1 μm and that of the Cu layer is 4.2 μm, and meanwhile, the average grain size of the Al2O3/Cu layers and Cu layers are 0.25 μm, 2.3 μm respectively. The strength of Al2O3/Cu layer is higher than that of the Cu layer because of the additional dispersion strengthening and the stronger grain boundary strengthening. Owing to significant differences in the structural and mechanical properties of the layers in this material, geometrically necessary dislocations accumulated at the interface during the tensile process; this resulted in significant heterogeneous deformation-induced strengthening, which yielded a laminated composite with a tensile strength of 413 MPa, tensile ductility of 27%, and excellent overall performance. This work provides a new design strategy for the preparation of high-strength high-ductility materials.

BackgroundThe therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes.MethodsThis retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders.ResultsThe study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs.ConclusionIn conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

Aims: To provide a comprehensive bibliometric overview of drug resistance in bladder cancer (BC) from 1999 to 2022, aiming to illuminate its historical progression and guide future investigative avenues. Methods: Literature on BC drug resistance between 1999 and 2022 was sourced from the Web of Science. Visual analyses were executed using Vosviewer and Citespace software, focusing on contributions by countries, institutions, journals, authors, references, and keywords. Results: From 2727 publications, a marked growth in BC drug resistance studies was discerned over the two decades. Prominent among all institutions is the University of Texas System. The majority of top-ranked journals were American. In authorship significance, McConkey DJ led in publications, while Bellmunt J dominated in citations. Research topics predominantly spanned cancer demographics, drug efficacy evaluations, molecular features, oncology subtypes, and individualized treatment strategies, with a notable contemporary emphasis on molecular mechanisms behind drug resistance and nuances of ICIs. Conclusions: Our bibliometric analysis charts the landscape of BC drug resistance research from 1999 to 2022. While the study of resistance mechanisms has been robust, there's an evident need for deeper exploration into the molecular intricacies and the potential of ICIs and targeted therapeutic strategies.

The microstructural evolution of a single-phase Cu–12Mn–3Ni alloy during rolling and annealing has been investigated using electron backscatter diffraction and X-ray diffraction techniques. We have established the effects of microstructural characteristics on material strength and the temperature coefficient of resistance (TCR). The yield strength increased to 682 MPa after cold rolling with a strain of 0.87 due to an increase in the density of dislocation and low-angle grain boundary. A significant annealing softening is observed for the cold-rolled Cu–Mn–Ni alloy at temperatures above 400 °C, caused by recrystallization. The difference in yield strength for fully recrystallized alloys is mainly attributed to a difference in grain size, consistent with the Hall–Petch relationship. The addition of Ni and Mn enhanced the degree of difficulty in dislocation passing through the grain boundary, resulting in a higher Hall-Petch constant (274 MPa μm1/2) for Cu–12Mn–3Ni alloys when compared with pure copper. The TCR is related to grain size, dislocation and Cu–12Mn–3Ni alloy texture. Grain coarsening and reduced dislocation density can effectively enhance the resistance temperature stability. In addition, the strong copper texture formed during cold rolling results in a difference in TCR associated with the rolling direction (RD) and transverse direction (TD) of the cold-rolled sheet. The Cu–Mn–Ni alloy crystal exhibits a lower resistance sensitivity to temperature when the [110]Cu direction is parallel to the current direction compared with the [111]Cu direction parallel to the current direction. The absolute value of the TCR in the TD of the cold-rolled sheet is 10.2 × 10−6 °C−1, lower than that in the RD (19.3 × 10−6 °C−1).

BackgroundNeoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the cornerstone of treatment for muscle-invasive bladder cancer (MIBC). While platinum-based regimens have demonstrated benefits in tumor downstaging and improved long-term survival for selected patients, they may pose risks for those who are ineligible or unresponsive to chemotherapy.ObjectiveWe undertook a bibliometric analysis to elucidate the breadth of literature on NAC in bladder cancer, discern research trajectories, and underscore emerging avenues of investigation.MethodsA systematic search of the Web of Science Core Collection (WoSCC) was conducted to identify articles pertaining to NAC in bladder cancer from 1999 to 2022. Advanced bibliometric tools, such as VOSviewer, CiteSpace, and SCImago Graphica, facilitated the examination and depicted the publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and salient keywords, emphasizing the top 25 citation bursts.ResultsOur analysis included 1836 publications spanning 1999 to 2022, indicating a growing trend in both annual publications and citations related to NAC in bladder cancer. The United States emerged as the predominant contributor in terms of publications, citations, and international collaborations. The University of Texas was the leading institution in publication output. “Urologic Oncology Seminars and Original Investigations” was the primary publishing journal, while “European Urology” boasted the highest impact factor. Shariat, Shahrokh F., and Grossman, H.B., were identified as the most prolific and co-cited authors, respectively. Keyword analysis revealed both frequency of occurrence and citation bursts, highlighting areas of concentrated study. Notably, the integration of immunochemotherapy is projected to experience substantial growth in forthcoming research.ConclusionsOur bibliometric assessment provides a panoramic view of the research milieu surrounding neoadjuvant chemotherapy for bladder cancer, encapsulating the present state, evolving trends, and potential future directions, with a particular emphasis on the promise of immunochemotherapy.

Renal interstitial fibrosis/tubular atrophy (IF/TA) is a prominent pathological feature of chronic allograft dysfunction (CAD). Our previous study has demonstrated that epithelial-mesenchymal transition (EMT) plays a significant role in shaping the development of IF/TA. Nuclear SET domain (NSD2), a histone methyltransferase catalyzing methylation at lysine 36 of histone 3, is crucially involved in the development and progression of solid tumors. But its role in the development of renal allograft interstitial fibrosis has yet to be elucidated. Here, we characterize NSD2 as a crucial mediator in the mouse renal transplantation model in vivo and a model of tumor necrosis factor-α (TNF-α) stimulated-human renal tubular epithelial cells (HK-2) in vitro. Functionally, NSD2 knockdown inhibits EMT, dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in mice. Conversely, NSD2 overexpression exacerbates fibrosis-associated phenotypes and mitochondrial fission in tubular cells. Mechanistically, tubular NSD2 aggravated the Drp-1 mediated mitochondrial fission via STAT1/ERK/PI3K/Akt signaling pathway in TNF-α-induced epithelial cell models. Momentously, mass spectrometry (MS) Analysis and site-directed mutagenesis assays revealed that NSD2 interacted with and induced Mono-methylation of STAT1 on K173, leading to its phosphorylation, IMB1-dependent nuclear translocation and subsequent influence on TNF-α-induced EMT and mitochondrial fission in NSD2-dependent manner. Collectively, these findings shed light on the mechanisms and suggest that targeting NSD2 could be a promising therapeutic approach to enhance tubular cell survival and alleviate interstitial fibrosis in renal allografts during CAD.

Abstract Background It has been discovered that tumor-infiltrating lymphocytes (TILs) are essential for the emergence of bladder cancer (BCa). This study aimed to research TIL-related genes (TILRGs) and create a gene model to predict BCa patients' overall survival. Methods The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. Using Pearson correlation analysis, TILRGs were evaluated. Moreover, hub TILRGs were chosen using a comprehensive analysis. By dividing the TCGA-BCa patients into different clusters based on hub TILRGs, we were able to explore the immune landscape between different clusters. Results Here, we constructed a model with five hub TILRGs and split all of the patients into two groups, each of which had a different prognosis and clinical characteristics, TME, immune cell infiltration, drug sensitivity, and immunotherapy responses. Better clinical results and greater immunotherapy sensitivity were seen in the low-risk group. Based on five hub TILRGs, unsupervised clustering analysis identify two molecular subtypes in BCa. The prognosis, clinical outcomes, and immune landscape differed in different subtypes. Conclusions The study identifies a new prediction signature based on genes connected to tumor-infiltrating lymphocytes, providing BCa patients with a new theoretical target.

A series of 3,6-diamino-9-naphthylcarbazole derivatives were synthesized and characterized experimentally and computationally. As the lowest unoccupied molecular orbital of the naphthyl group has lower energy than that of the phenyl group, a charge transfer from carbazole to naphthyl in the excited states occurred causing solvatofluorochromism and solvent-dependency in fluorescence quantum yields. A molecule having two carbazole substituents sandwiching the central naphthyl ring had absorption reaching 470 nm and a high reducing capability in the excited state. This molecule could successfully photosensitize the hydrodehalogenation of haloarenes under visible light irradiation.

Abstract Background Preoperative diagnosis of pheochromocytoma (PHEO) accurately impacts preoperative preparation and surgical outcome in PHEO patients. Highly reliable model to diagnose PHEO is lacking. We aimed to develop a magnetic resonance imaging (MRI)-based radiomic-clinical model to distinguish PHEO from adrenal lesions. Methods In total, 305 patients with 309 adrenal lesions were included and divided into different sets. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. In addition, a nomogram incorporating the obtained radiomics signature and selected clinical predictors was developed by using multivariable logistic regression analysis. The performance of the radiomic-clinical model was assessed with respect to its discrimination, calibration, and clinical usefulness. Results Seven radiomics features were selected among the 1301 features obtained as they could differentiate PHEOs from other adrenal lesions in the training (area under the curve [AUC], 0.887), internal validation (AUC, 0.880), and external validation cohorts (AUC, 0.807). Predictors contained in the individualized prediction nomogram included the radiomics signature and symptom number (symptoms include headache, palpitation, and diaphoresis). The training set yielded an AUC of 0.893 for the nomogram, which was confirmed in the internal and external validation sets with AUCs of 0.906 and 0.844, respectively. Decision curve analyses indicated the nomogram was clinically useful. In addition, 25 patients with 25 lesions were recruited for prospective validation, which yielded an AUC of 0.917 for the nomogram. Conclusion We propose a radiomic-based nomogram incorporating clinically useful signatures as an easy-to-use, predictive and individualized tool for PHEO diagnosis.

Herein, we report the scheme of an optically pumped atomic clock based on a cold cesium atomic beam source. We propose the laser system and physical mechanism of this atomic clock, wherein the atomic beam travels in an upper parabolic trajectory, thereby eliminating the light shift effect. In the experiments, when the length of the free evolution region was 167 mm, the line width of the Ramsey fringe was 37 Hz. When the expected signal-to-noise ratio of the Ramsey fringe that can be achieved is 36,000, the expected short-term frequency stability is about 3.6 × 10–14/√τ, which is significantly higher than that of a conventional optically pumped cesium clock of similar volume.

A beam source is proposed for the production of an intense cold cesium atomic beam that can be used in cesium beam atomic clocks. The source is based on a two-dimensional magneto-optical trap (2D-MOT), but introduces hollow cooling and pushing lights in the axial direction to create a 2D+-MOT, which separates the cooling and pushing functions while the low-power pushing light pushes atoms out to form a cold atomic beam. This cold cesium atomic beam source reduces the light shift due to leakage light and retains longitudinal cooling to increase the flux of the cold atomic beam compared with that of the conventional 2D+-MOT scheme. The specifics of the design are investigated, the atomic velocity and beam flux are calculated, and the results are experimentally verified. The results demonstrate that when the power of the pushing light is 180 µW and when its frequency resonates with the 4 → 5′ transition of the Cs D2 line, the most probable longitudinal velocity of the outgoing cold atomic beam, the width of velocity distribution, and the atomic beam flux are 19.38 m/s, 8.1 m/s, and 1.7 × 1010 atoms/s, respectively.

Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

Abstract Background To compare the safety and efficacy of retrograde intrarenal surgery (RIRS) and modified Ultra-mini percutaneous nephrolithotomy (UMP) in semi-supine combined lithotomy position for the management of 1.5–3.5 cm lower pole renal stones (LPSs). Methods A total of 63 patients with 1.5–3.5 cm LPSs who underwent RIRS (n = 33) or modified UMP (n = 30) in diameter between January 2017 and January 2019 were analyzed retrospectively. Modified UMP was performed in semi-supine combined lithotomy position and a 9.5/11.5 F ureteral access sheath (UAS) was inserted during the procedure in order to maintain low pelvic pressure and to facilitate the removal of stone fragments. Base-line parameters, stone characteristics, illness condition, operation time, postoperative hemoglobin (Hb) drop, postoperative creatinine (Cr) elevation, length of hospital stay, length of postoperative hospital stay, stone-free rate (SFR) and complications were compared between the two groups. Results There were no significant differences between the two groups in base-line parameters, stone characteristics and illness condition. The mean operating time of RIRS group was longer than UMP group (95.61 ± 21.9 vs. 55.0 ± 16.1 min, p

BackgroundSome studies have revealed a close relationship between metabolism-related genes and the prognosis of bladder cancer. However, the relationship between metabolism-related long non-coding RNAs (lncRNA) regulating the expression of genetic material and bladder cancer is still blank. From this, we developed and validated a prognostic model based on metabolism-associated lncRNA to analyze the prognosis of bladder cancer.MethodsGene expression, lncRNA sequencing data, and related clinical information were extracted from The Cancer Genome Atlas (TCGA). And we downloaded metabolism-related gene sets from the human metabolism database. Differential expression analysis is used to screen differentially expressed metabolism-related genes and lncRNAs between tumors and paracancer tissues. We then obtained metabolism-related lncRNAs associated with prognosis by correlational analyses, univariate Cox analysis, and logistic least absolute shrinkage and selection operator (LASSO) regression. A risk scoring model is constructed based on the regression coefficient corresponding to lncRNA calculated by multivariate Cox analysis. According to the median risk score, patients were divided into a high-risk group and a low-risk group. Then, we developed and evaluated a nomogram including risk scores and Clinical baseline data to predict the prognosis. Furthermore, we performed gene-set enrichment analysis (GSEA) to explore the role of these metabolism-related lncRNAs in the prognosis of bladder cancer.ResultsBy analyzing the extracted data, our research screened out 12 metabolism-related lncRNAs. There are significant differences in survival between high and low-risk groups divided by the median risk scoring model, and the low-risk group has a more favorable prognosis than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk score was closely related to the prognosis of bladder cancer. Then we established a nomogram based on multivariate analysis. After evaluation, the modified model has good predictive efficiency and clinical application value. Furthermore, the GSEA showed that these lncRNAs affected bladder cancer prognosis through multiple links.ConclusionsA predictive model was established and validated based on 12 metabolism-related lncRNAs and clinical information, and we found these lncRNA affected bladder cancer prognosis through multiple links.

BackgroundA survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection.MethodsPatients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004–2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model.ResultsA total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan–Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p < 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection.ConclusionsA practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.

Background: Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure. Methods: Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy. Findings: At the global level, albuminuria decreased TH (β = −0.07 mm, 95% CI: −0.12 mm to −0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = −0.11 mm, 95% CI: −0.16 mm to −0.07 mm, P = 3.74×10−6). No pleiotropy was detected. Interpretation: Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. Funding: This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Clinical outcome of adrenocortical carcinoma (ACC) varies because of its heterogeneous nature and reliable prognostic prediction model for adult ACC patients is limited. The objective of this study was to develop and externally validate a nomogram for overall survival (OS) prediction in adult patients with ACC after surgery. Methods Based on the data from the Surveillance Epidemiology, and End Results (SEER) database, adults patients diagnosed with ACC between January 1988 and December 2015 were identified and classified into a training set, comprised of 404 patients diagnosed between January 2007 and December 2015, and an internal validation set, comprised of 318 patients diagnosed between January 1988 and December 2006. The endpoint of this study was OS. The nomogram was developed using a multivariate Cox proportional hazards regression algorithm in the training set and its performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness. The nomogram was then validated using the internal SEER validation, also externally validated using the Cancer Genome Atlas set (TCGA, 82 patients diagnosed between 1998 and 2012) and a Chinese multicenter cohort dataset (82 patients diagnosed between December 2002 and May 2018), respectively. Results Age at diagnosis, T stage, N stage, and M stage were identified as independent predictors for OS. A nomogram incorporating these four predictors was constructed using the training set and demonstrated good calibration and discrimination (C-index 95% confidence interval [CI], 0.715 [0.679–0.751]), which was validated in the internal validation set (C-index [95% CI], 0.672 [0.637–0.707]), the TCGA set (C-index [95% CI], 0.810 [0.732–0.888]) and the Chinese multicenter set (C-index [95% CI], 0.726 [0.633–0.819]), respectively. Encouragingly, the nomogram was able to successfully distinguished patients with a high-risk of mortality in all enrolled patients and in the subgroup analyses. Decision curve analysis indicated that the nomogram was clinically useful and applicable. Conclusions The study presents a nomogram that incorporates clinicopathological predictors, which can accurately predict the OS of adult ACC patients after surgery. This model and the corresponding risk classification system have the potential to guide therapy decisions after surgery.

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

Abstract Background Progression to a castration resistance state is the main cause of deaths in prostate cancer (PCa) patients. Androgen Receptor (AR) signaling plays the central role in progression of Castration Resistant Prostate Cancer (CRPC), therefore understanding the mechanisms of AR activation in the milieu of low androgen is critical to discover novel approach to treat CRPC. Methods Firstly, we explore the CRPC associated lncRNAs by transcriptome microarray. The expression and clinical features of lnc-LBCS are analyzed in three independent large-scale cohorts. The functional role and mechanism of lnc-LBCS are further investigated by gain and loss of function assays in vitro. Results The expression of Lnc-LBCS was lower in CRPC cells lines and tissues. LBCS downregulation was correlated with higher Gleason Score, T stage and poor prognosis of PCa patients. LBCS overexpression decreases, whereas LBCS knockdown increases, the traits of castration resistance in prostate cancer cells under androgen ablated or AR blocked condition. Moreover, knockdown of LBCS was sufficient to activate AR signaling in the absence of androgen by elevating the translation of AR protein. Mechanistically, LBCS interacted directly with hnRNPK to suppress AR translation efficiency by forming complex with hnRNPK and AR mRNA. Conclusions Lnc-LBCS functions as a novel AR translational regulator that suppresses castration resistance of prostate cancer by interacting with hnRNPK. This sheds a new insight into the regulation of CRPC by lncRNA mediated AR activation and LBCS-hnRNPK-AR axis provides a promising approach to the treatment of CRPC.

Bulk Cu/Ag multilayered composites with controlled individual layer thickness (h) varying from several hundred micrometers down to 20 nm were fabricated via cross accumulative roll bonding (CARB). The well-defined, continuous Cu/Ag multilayer structure with flat, planar, and sharp interfaces was found to remain stable when the layer thickness was reduced from several hundred micrometers down to 20 nm. A preferential interface character of {110}Cu[111]//{110}Ag[111] was formed when the layer thickness was reduced to 20 nm. Specifically, high strength, high electrical conductivity and excellent thermal stability were obtained simultaneously in bulk Cu/Ag nanolayered composite with h = 20 nm. Ultimate tensile strength of 938.1 MPa was achieved, corresponding to 2.9 times higher than the rule-of-mixtures estimate based on the strength of the heavily deformed Cu and Ag samples with 95% rolling reduction. Furthermore, a high electrical conductivity higher than that of pure copper was obtained, while high hardness (3.74 GPa) was maintained up to an annealing temperature of 500 °C. Nevertheless, degradation of the mechanical hardness and nanolayered structure occurred once the temperature exceeded 500 °C. Two major mechanisms are responsible for driving the onset of the thermal instability in this CARB-processed Cu/Ag nanolayered composites, namely triple junction motion and Rayleigh instability mechanisms.

ObjectivesTumor enucleation (TE) optimizes parenchymal preservation with promising short-term oncologic outcomes compared with standard partial nephrectomy (SPN). However, researches/literatures about long-term oncologic outcomes for TE after minimally invasive surgery are scarce. We aim to analyze long-term oncologic outcomes after laparoscopic and robotic tumor enucleation for renal cell carcinoma (RCC).Patients and MethodsWe retrospectively analyzed 146 patients who underwent TE with either laparoscopic or robotic approach for localized RCC in our center. Local recurrence, cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were the main outcomes. Survival curves were generated using a Kaplan-Meier method. Perioperative outcomes and pathological outcomes were also analyzed.ResultsOverall, 98 male and 48 female patients were eligible for the study. The median tumor size was 3.4 cm with a median R.E.N.A.L. score of seven. Warm ischemia was used in 143 patients with a median ischemia time of 20 min and three patients had zero ischemia. Five patients (3.4%) had major complications (> Clavien IIIa) and only two were related to urinary system. The median global glomerular filtration rate (GFR) preserved after surgery was 93%. Pseudocapsule invasion was reported in 50 tumors (34%) and positive surgical margins were found in 3/146 (2.1%) tumors. At a median follow-up of 66 months, local recurrence happened in two patients (1.4%), and systemic recurrence happened in six patients (4.2%). The 5-year CSS, RFS, OS were 95.7, 89.6, and 91.9%, and the 10-year CSS, RFS, OS were 93.8, 89.6, and 90.0%, respectively.ConclusionThis study indicates that tumor enucleation with laparoscopic or robotic approach in experienced hands for the treatment of RCC appears oncologically safe with a median follow-up of more than 5 years. Prospective studies with more patients and longer follow-up will be required to further evaluate oncologic safety after TE.

In recent decades, researchers have paid more attention to the indirect tensile test than to the direct tensile test (DTT) of rocks, mainly due to difficulties in the alignment and the stress concentration at the end of an intact cylindrical specimen. In this paper, a new flattened cylinder specimen and a clamp device were designed to obtain the true tensile strength of the rock in DTT. Stress distributions of the specimen with different lengths (l) and cutting thicknesses (t) were analyzed, and damage processes of the specimen were monitored by the Digital Image Correlation (DIC), the fractured sections were also scanned. Different mechanical parameters were also obtained by the DTT of the flattened cylinder specimens and the intact cylinder specimens, as well as the Brazilian disc. Research results show that the tensile strength obtained by DTT is smaller than the Brazilian disc and is slightly greater than the intact cylindrical specimen. The flattened cylinder specimen with 0.20 ≤ 2t/D < 0.68 and 0.10 ≤ l/D ≤ 0.20 is recommended to measure the true tensile strength of rock material in DTT. This new shape of the specimen is promising to be extended in the uniaxial or triaxial direct tension test.

Red shale is widely distributed among the deep mine areas of Kaiyang Phosphate Mine, which is the biggest underground phosphate mine of China. Because of the effect of various factors, such as high stress, ground water and so on, trackless transport roadways in deep mine areas were difficult to effectively support for a long time by using traditional supporting design methods. To deal with this problem, some innovative works were carried out in this paper. First, mineral composition and microstructure, anisotropic, hydraulic mechanical properties and other mechanical parameters of red shale were tested in a laboratory to reveal its deformation and failure characteristics from the aspect of lithology. Then, some numerical simulation about the failure process of the roadways in layered red shale strata was implemented to investigate the change regulation of stress and strain in the surrounding rock, according to the real rock mechanical parameters and in-situ stress data. Therefore, based on the composite failure law and existing support problems of red shale roadways, some effective methods and techniques were adopted, especially a kind of new wave-type bolt that was used to relieve rock expansion and plastic energy to prevent concentration of stress and excess deformation. The field experiment shows the superiorities in new techniques have been verified and successfully applied to safeguard roadway stability.

The microstructure evolution and mechanical property of Cu-25Ni-25Mn alloy after solution treatment and aging treatment are investigated via TEM observation, XRD analysis and Vickers hardness test. The effect of the NiMn precipitates on hardness and its strengthening mechanism in the Cu-25Ni-25Mn alloy is quantitatively analyzed. The results show that in 450 °C aging process, Ni and Mn precipitate from the copper matrix and form nanoscale NiMn phase particle with a face-centered tetragonal (FCT) structure. The XRD analysis indicates that the NiMn precipitates have a lattice constant of a = b = 0.3693 ± 0.0004 nm, c = 0.3570 ± 0.0006 nm, which is fully coherent with the copper matrix. The precipitation of NiMn phase lead to a precipitation strengthening, which provides significant increase in hardness in the peak-aged Cu-25Ni-25Mn alloy. Compared to the solution treated sample, the hardness of peak-aged sample has been increased by 367 HV. The coherency strengthening and modulus strengthening are the dominant strengthening mechanisms. The hardness increment predicted by coherence strengthening and modulus strengthening mechanism has good consistency with the experiment results.

In this paper, the aim is to achieve safe, rapid excavation of an extra-long, large-cross-section highway tunnel in Eastern Tianshan, as well as to reduce production costs, simplify production processes, reduce cycle time, and improve production efficiency. In this study, we explored a new technology for smooth blasting without a detonating cord. A series of sympathetic detonation experiments were conducted in the tunnel face to determine critical distances. The critical distance for No. 2 rock emulsion explosive under blasthole constraints was successfully measured to be approximately 1.0–1.1 m. Based on the critical distance, a new charging structure was designed for tunnel excavation. To assess the influence of the new charging structure on blasting performance, its economic benefits, and its feasibility, full-section tests were performed in the East Tianshan Tunnel. The application of the new charging structure produced good smooth blasting results. It not only simplified the charging process and produced smooth blasting without detonating cord in peripheral holes, but also guaranteed normal excavation, an appropriate tunnel profile, and reasonable overbreak and underbreak volumes. This had remarkable economic benefits and possesses better promotional value.

The softening behavior of a cold-drawn Cu–Cr–In alloy was investigated during annealing between 450 °C and 700 °C. The properties and microstructure evolution of the alloy were characterized using a microhardness tester, electron back-scatter diffraction, and transmission electron microscopy. Elemental In addition was found to hinder the dislocation movement and delay the recovery and recrystallization of the Cu–Cr–In alloy. The experimental data were analyzed using the Johnson–Mehlv–Avramiv–Kolmogorov model. The activation energy of recrystallization of the 60% cold-drawn Cu0.54Cr0.17In alloy was 188.29 ± 18.44 kJ/mol, and the recrystallization mechanism of the alloy was attributed mainly to Cu self-diffusion.

The vacuum horizontal continuous casting method was used for preparing Cu-4.5 wt.% Ag alloy rod containing few oxygen. The evolution of microstructure was observed by metallographic microscope (OM), scanning electron microscope (SEM) and transmission electron microscope (TEM). The results showed that the hardness and electrical conductivity of Cu-4.5 wt.% Ag alloy aged at 450 °C for 12 h were increased by 60 HV and 12 %IACS than solution treated alloy. TEM observation showed that the continuous precipitates of Ag are uniformly distributed in matrix with the form of particles and strips. Through calculation, the strength increment of peak aged Cu-4.5 wt.%Ag alloy from solid solution hardening and precipitation hardening are 86 MPa and 136 MPa, respectively.

WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription (Wysocka et al., 2005 [1]; Sandstrom et al., 2014[2]; Ang et al., 2011[3]). Recently, our study found that WDR5 was upregulated in bladder cancer tissues, promoted bladder cancer cell proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro, and tumor growth in vivo (Chen et al., 2015). To gain a molecular understanding of the role of WDR5 in promoting bladder cancer, we performed a genome-wide analysis on WDR5 knockdown by microarray gene expression profiling. Here we provide detailed experimental methods and analysis for the microarray data, which have been deposited into Gene Expression Omnibus (GEO): GSE59132.

BACKGROUND: The root of Polygala tenuifolia, a traditional Chinese medicine, has been used to improve memory and intelligence, while the underlying mechanisms remain largely unknown. In this study, we investigated the protective effects of senegenin, an component of Polygala tenuifolia root extracts, on cognitive dysfunction induced by hepatic ischemia-reperfusion. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we constructed a rat model of hepatic ischemia-reperfusion (HIR) and found that the memory retention ability of rats in the step-down and Y maze test was impaired after HIR, paralleled by a decrease of N-methyl-D-aspartate (NMDA) receptor NR2B subunit mRNA and protein expressions in hippocampus. Furthermore, we found that administration of senegenin by gavage attenuated HIR-induced cognitive impairment in a dose and time dependent manner, and its mechanisms might partly due to the increasing expression of NR2B in rat hippocampus. CONCLUSIONS/SIGNIFICANCE: Cognitive dysfunction induced by HIR is associated with reduction of NR2B expression. Senegenin plays a neuroprotective role in HIR via increasing NR2B expression in rat hippocampus. These findings suggest that senegenin might be a potential agent for prevention and treatment of postoperative cognitive dysfunction (POCD) or other neurodegenerative diseases.