UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Research on the influencing factors of promoting flipped classroom teaching based on the integrated UTAUT model and learning engagement theory.

With the rapid advancement of educational technology, the flipped classroom approach has garnered considerable attention owing to its potential for enhancing students' learning capabilities. This research delves into the flipped classroom teaching methodology, employing the Unified Theory of Acceptance and Use of Technology (UTAUT), learning engagement theory, and the 4C skills (comprising communication, collaboration, creativity, and critical thinking) to investigate its effects on learning capabilities. The research surveyed 413 students from three universities in Jiangxi Province, employing stratified random sampling. SPSS 24.0 and Amos were used for structural equation modeling and hypothesis testing analysis. The findings indicate that: (1) Performance expectancy, effort expectancy, and peer influence significantly enhance students' learning engagement in the flipped classroom. (2) Students' learning engagement in the flipped classroom notably promotes their learning capabilities. (3) Performance expectancy, effort expectancy, and peer influence can significantly boost learning capabilities by increasing learning engagement. (4) Personality traits significantly moderate the effect of peer influence on learning engagement, highlighting the crucial role of individual differences in learning. (5) The level of students' learning engagement is differentially influenced by performance expectancy and peer influence across various academic disciplines. Ultimately, this research provides valuable insights for educational policymakers and guides improvements in teaching practices, collectively advancing educational quality and equity.

Survival outcomes of segmentectomy and lobectomy for early stage non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The question of whether segmentectomy and lobectomy have similar survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC) is a matter of debate. METHODS: A cohort study and randomized controlled trial were included, comparing segmentectomy and lobectomy, by utilizing computerized access to the Pubmed, Web of Science, and Cochrane Library databases up until July 2022. The Cochrane Collaboration tool was used to evaluate the randomized controlled trials, while the Newcastle-Ottawa Scale (NOS) was used to evaluate the cohort studies. Sensitivity analyses were also carried out. RESULTS: The analysis incorporated 17 literature studies, including one randomized controlled trial and 16 cohort studies, and was divided into a segmentectomy group (n = 2081) and a lobectomy group (n = 2395) based on the type of surgery the patient underwent. Each study was followed up from 27 months to 130.8 months after surgery. Over survival (OS): HR = 1.14, 95%CI(0.97,1.32), P = 0.10; disease-free survival (DFS): HR = 1.13, 95%CI(0.91,1.41), P = 0.27; recurrence-free survival (RFS): HR = 0.95, 95%CI(0.81,1.12), P = 0.54. CONCLUSION: The results of the study suggest that the survival outcomes of the segmentectomy group were not inferior to that of the lobectomy group. Segmentectomy should therefore be considered as a treatment option for early stage NSCLC.

Suitability of the MP1000 Platform for Robot-assisted Prostatectomy: A Prospective Randomised Controlled Trial.

Background and objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP. Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics. Key findings and limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size. Conclusions and clinical implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer. Patient summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery.

Chitinase 3-like 1 expression associated with lymphatic metastasis and prognosis in urothelial carcinoma of the bladder.

Objectives: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways. Conclusion: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend?

Background and Objective: With the emergence of immunotherapy and targeted therapies, there are more options for the perioperative period management of muscle-invasive bladder cancer (MIBC), and various types of clinical studies are emerging, leading to the need to explore ways to choose the optimal treatment modality. This review aims to synthesize past and present treatment modalities and to explore future trends in the perioperative period cares of MIBC for the benefit of clinical practitioners. Methods: A non-systematic, literature search was conducted between March 5, 2023 and November 30, 2023 on PubMed using "perioperative period", "MIBC", "chemotherapy", "radiotherapy", "immunotherapy", "targeted treatment" and "combination" as keywords, along with a search for ongoing clinical studies that were related to the perioperative period of MIBC on classic.clinicaltrials.gov, some latest conference abstracts were also included as references. Key Content and Findings: The trend towards benefit from adjuvant chemotherapy in perioperative chemotherapy is gradually being recognized. Neoadjuvant immunotherapy, including single-agent immunization, like programmed cell death protein 1 (PD-1) inhibitors, programmed cell death 1 ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, and double-immunization, has been confirmed by several clinical studies to be beneficial to clinical remission rates, and the combination regimen is superior to single-agent therapy. Targeted therapies such as antibody-drug conjugate (ADC) are entering MIBC perioperative studies. Multiple sequential and combination clinical studies are gradually disclosing preliminary data on efficacy and safety. Conclusions: Immunotherapy would become an essential perioperative treatment for MIBC, and continuous and integrated perioperative management may become the MIBC treatment mode of the future. ADC medicines will also be a hot research focus in the coming years.

Suitability of the MP1000 system for robot-assisted partial nephrectomy: a multicenter randomized controlled noninferiority trial.

PURPOSE: This study aimed to compare the safety and effectiveness of the MP1000 surgical system with the da Vinci Si robot system in robot-assisted partial nephrectomy (RAPN) through a prospective, single-blinded, randomized controlled trial. MATERIALS AND METHODS: A total of 62 patients who were scheduled to undergo RAPN were randomly assigned to either the da Vinci Si robot or MP1000 group. A noninferiority test was conducted with a noninferior intermediate value of 10%. The study compared installation and operation times, estimated blood loss, warm ischemia time, postoperative surgical margin, rate of conversion to open surgery, eGFR level, complications, and other safety indicators between the two groups. RESULTS: All procedures were successfully completed without the need for conversion to open or laparoscopic surgery, and no major complications were observed during the process. The test of noninferiority was achieved. There were no significant differences in median installation time, operation time, complication rate at 3 months, rate of positive surgical margin, and eGFR level at 3 months between the groups. Additionally, no evidence of recurrence was found on imaging in both groups. No difference in National Aeronautics and Space Administration task load index results for ergonomic considerations. A limitation of this study was its small sample size. CONCLUSIONS: The MP1000 system is a suitable platform for RAPN with safety and effectiveness compared with da Vinci Si system.

SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3'-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer. SIGNIFICANCE: DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer.

Regulation of Cellular Signaling with an Aptamer Inhibitor to Impede Cancer Metastasis.

Tumor invasion and metastasis are the main causes of tumor progression and are the leading causes of death among cancer patients. In the present study, we propose a strategy to regulate cellular signaling with a tumor metastasis-relevant cytoskeleton-associated protein 4 (CKAP4) specific aptamer for the achievement of tumor metastasis inhibition. The designed aptamer could specifically bind to CKAP4 in the cell membranes and cytoplasm to block the internalization and recycling of α5ß1 integrin, resulting in the disruption of the fibronectin-dependent cell adhesion and the weakening of the cell traction force. Moreover, the aptamer is able to impede the interaction between CKAP4 and Dickkopf1 (DKK1) to further block the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which subsequently reduces AKT phosphorylation and inhibits the reorganization of the actin cytoskeleton in cell migration. The synergetic function of the designed aptamer in inhibiting cancer cell adhesion and blocking the PI3K signaling pathway enables efficient tumor cell metastasis suppression. The aptamer with specific targeting ability in regulating cellular signaling paves the way for cancer treatment and further provides a guiding ideology for inhibiting tumor metastasis.

Safety and efficacy of 0.01% hypochlorous acid before cataract phacoemulsification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of 0.01% hypochlorous acid as a conjunctival sac disinfectant before cataract phacoemulsification and its impact on the ocular surface.METHODS: Randomized controlled clinical trial. A total of 285 patients who were scheduled for cataract phacoemulsification surgery were randomly divided into the hypochlorous acid group and the povidone iodine group. Before and after disinfection, conjunctival sac swabs were taken, and bacterial culture and colony-forming units(CFUs)testing were performed using blood agar and chocolate agar media, respectively. All patients were evaluated for ocular symptom scores and pain severity scores 2 h, 1 d, and 1 wk after disinfection, and underwent corneal fluorescein staining, eye redness index, tear meniscus height, and noninvasive breakup time(NIBUT)examination. The incidence of endophthalmitis after surgery was recorded.RESULTS: Conjunctival sac disinfection with 0.01% hypochlorous acid significantly reduced the rate of positive bacterial cultures and colony-forming ability of the conjunctival sac, with statistically significant differences compared with the pre-disinfection period(both P&#x0026;#x003C;0.01), and the disinfecting ability of hypochlorous acid was comparable to that of povidone-iodine(χ2=0.811, P=0.368). The scores of ocular symptoms and pain severity in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(both P&#x0026;#x003C;0.01). The corneal fluorescein staining and eye redness index in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(all P&#x0026;#x003C;0.01). No endophthalmitis occurred in either group of patients. CONCLUSION: As a conjunctival sac disinfectant, 0.01% hypochlorous acid is safe and effective, with minimal discomfort and damage to the ocular surface in patients.

PD-1/L1 inhibitors can improve but not replace chemotherapy for advanced urothelial carcinoma: A systematic review and network meta-analysis.

Background: Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma. Therefore, a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary. Methods: We comprehensively searched PubMed, Web of Science, Embase, and Cochrane Library databases and performed a meta-analysis of randomized controlled trials up to July 2021. We considered overall survival as the primary outcome, and progression-free survival, objective response rate, and treatment-related adverse events as secondary outcomes. Results: Overall, 3584 patients from five studies were evaluated. Compared with first-line chemotherapy, programmed cell death-1/ligand 1 inhibitors were significantly associated with worse progression-free survival (p < 0.001) and adverse objective response rates (p < 0.001). However, the treatments were not significantly different in terms of overall survival (p = 0.33). Compared with second-line chemotherapy, programmed cell death-1/ligand 1 inhibitors significantly improved overall survival (p < 0.001), and there was no statistically significant difference in progression-free survival (p = 0.89) or objective response rate (p = 0.34). Compared with chemotherapy, programmed cell death-1/ligand 1 inhibitors were well tolerated (first-line chemotherapy: p < 0.001; second-line chemotherapy: p < 0.001). Conclusions: The efficacy of programmed cell death-1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first-line platinum-based chemotherapy but is better than second-line chemotherapy; however, programmed cell death-1/ligand 1 inhibitors are safer than first- and second-line chemotherapy and have a broader prospect for use in combination therapy.

Interface-Engineered Field-Effect Transistor Electronic Devices for Biosensing.

Promising advances in molecular medicine have promoted the urgent requirement for reliable and sensitive diagnostic tools. Electronic biosensing devices based on field-effect transistors (FETs) exhibit a wide range of benefits, including rapid and label-free detection, high sensitivity, easy operation, and capability of integration, possessing significant potential for application in disease screening and health monitoring. In this perspective, the tremendous efforts and achievements in the development of high-performance FET biosensors in the past decade are summarized, with emphasis on the interface engineering of FET-based electrical platforms for biomolecule identification. First, an overview of engineering strategies for interface modulation and recognition element design is discussed in detail. For a further step, the applications of FET-based electrical devices for in vitro detection and real-time monitoring in biological systems are comprehensively reviewed. Finally, the key opportunities and challenges of FET-based electronic devices in biosensing are discussed. It is anticipated that a comprehensive understanding of interface engineering strategies in FET biosensors will inspire additional techniques for developing highly sensitive, specific, and stable FET biosensors as well as emerging designs for next-generation biosensing electronics.

The mechanism analysis on the farmers' motivation of using the quality traceability system based on TAM-ECM model.

The quality traceability system for agricultural product plays an important role in tracing the production history or flow of agricultural products in China. At present, the quality traceability system is facing the problem of limited coverage and promotion. Understanding the continuous usage behavior of users can help solve this problem. This study constructed a model integrating TAM-ECM to analyze the mechanisms affecting the continuous usage intention and behavior of users of the quality traceability system, using PLS analysis method and survey data from 197 users of the GanNan navel orange quality traceability system with a usage time of up to two years. The results show that both satisfaction and usage habits directly promote the continuous usage of the quality traceability system. Lowering transaction costs significantly improves perceived value and satisfaction, and has a greater direct impact on satisfaction. Expectation confirmation level has a positive effect on perceived value, and lowering transaction costs also enhances perceived value. Perceived value、transaction cost, and satisfaction are important factors driving the continuous usage of the quality traceability system by users. The research findings provide a reference basis for the government to develop policies to attract users to use the quality traceability system for agricultural product.

Identifying Optimal Candidates for Trimodality Therapy among Nonmetastatic Muscle-Invasive Bladder Cancer Patients.

(1) Background: This research aims to identify candidates for trimodality therapy (TMT) or radical cystectomy (RC) by using a predictive model. (2) Methods: Patients with nonmetastatic muscle-invasive bladder cancer (MIBC) in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. The clinical data of 2174 eligible patients were extracted and separated into RC and TMT groups. To control for confounding bias, propensity score matching (PSM) was carried out. A nomogram was established via multivariable logistic regression. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to assess the nomogram's prediction capacity. Decision curve analysis (DCA) was carried out to determine the nomogram's clinical applicability. (3) Results: After being processed with PSM, the OS of the RC group was significantly longer compared with the TMT group (p < 0.001). This remarkable capacity for discrimination was exhibited in the training (AUC: 0.717) and validation (AUC: 0.774) sets. The calibration curves suggested acceptable uniformity. Excellent clinical utility was shown in the DCA curve. The RC and RC-Beneficial group survived significantly longer than the RC and TMT-Beneficial group (p < 0.001) or the TMT group (p < 0.001). However, no significant difference was found between the RC and TMT-Beneficial group and the TMT group (p = 0.321). (4) Conclusions: A predictive model with excellent discrimination and clinical application value was established to identify the optimal patients for TMT among nonmetastatic MIBC patients.

Characterization and transcriptional expression of ABCG genes in Bactrocera dorsalis: Insights into their roles in fecundity and insecticidal stress response.

The ATP-binding cassette (ABC) transporters are essential for regulating various physiological processes and insecticide resistance across different living organisms. ABCG subfamily genes have diverse functions in insects, but little is known about the function of ABCGs in a serious agricultural pest, Bactrocera dorsalis. In this study, 15 BdABCG genes were identified, and BdABCG6 and BdABCG11 were highly expressed in the pupal and adult stages, especially during the transition period from pupae to adults. Silencing of these two genes resulted in a significant reduction of egg production in B. dorsalis, confirming their importance in reproduction. Analysis of tissue expression patterns showed that most genes, including BdABCG1, 3, 8, and 14, exhibited tissue-specificity, with significantly higher expression levels observed in the intestine, Malpighian tubule, and fat body compared to other tissues. Meanwhile, the induction of malathion and avermectin can significantly upregulate the expression of the above four genes. Furthermore, knockdown of BdABCG3 by RNAi significantly increased the mortality of B. dorsalis upon exposure to avermectin, which suggested that BdABCG3 is involved in the transport or metabolism of avermectin in B. dorsalis. Overall, our work provides valuable insights into the function of BdABCGs involved in the reproduction and detoxification system of B. dorsalis.

Acute kidney injury after infant cardiac surgery: a comparison of pRIFLE, KDIGO, and pROCK definitions.

BACKGROUND: KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. METHODS: We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. RESULTS: Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). CONCLUSIONS: There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.

The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer.

Urothelial bladder cancer (UBC) is one of the most prevalent malignancies worldwide, with striking tumor heterogeneity. Elucidating the molecular mechanisms that can be exploited for the treatment of aggressive UBC is a particularly relevant goal. Protein ubiquitination is a critical post-translational modification (PTM) that mediates the degradation of target protein via the proteasome. However, the roles of aberrant protein ubiquitination in UBC development and the underlying mechanisms by which it drives tumor progression remain unclear. In this study, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 technology, we identified the ubiquitin E3 ligase ANAPC11, a critical subunit of the anaphase-promoting complex/cyclosome (APC/C), as a potential oncogenic molecule in UBC cells. Our clinical analysis showed that elevated expression of ANAPC11 was significantly correlated with high T stage, positive lymph node (LN) metastasis, and poor outcomes in UBC patients. By employing a series of in vitro experiments, we demonstrated that ANAPC11 enhanced the proliferation and invasiveness of UBC cells, while knockout of ANAPC11 inhibited the growth and LN metastasis of UBC cells in vivo. By conducting immunoprecipitation coupled with mass spectrometry, we confirmed that ANAPC11 increased the ubiquitination level of the Forkhead transcription factor FOXO3. The resulting decrease in FOXO3 protein stability led to the downregulation of the cell cycle regulator p21 and decreased expression of GULP1, a downstream effector of androgen receptor signaling. Taken together, these findings indicated that ANAPC11 plays an oncogenic role in UBC by modulating FOXO3 protein degradation. The ANAPC11-FOXO3 regulatory axis might serve as a novel therapeutic target for UBC.

Controlling amorphous silicon in scratching for fabricating high-performance micromixers.

As core parts of microfluidic chip analysis systems, micromixers show robust applications in wide fields. However, restricted by the fabrication technology, it remains challenging to achieve high-quality micromixers with both delicately designed structure and efficient mixing. In this study, based on the theory of chaotic mixing, sinusoidal structures with variable phases were designed and then fabricated through scanning probe lithography (SPL) and post-selective etching. It was found that scratches with phase differences can lead to the periodic formation of amorphous silicon (a-Si), which can resist etching. Consequentially, misaligned sine channels with thick-thin alternating 3D shapes can be generated in situ from the scratched traces after the etching. Further analysis showed that a thicker a-Si layer can be obtained by reducing the line spacing in the scratching, confirmed by Raman detections and simulations. With the proposed method, the misaligned sine micromixer was achieved with higher mixing efficiency than ever. The duplicating process was also investigated for high-precision production of micromixers. The study provided strategies for the miniaturization of high-performance microfluidic chips.

Bladder-sparing approaches for muscle invasive bladder cancer: a narrative review of current evidence and future perspectives.

Background and Objective: In recent years, the application of less-invasive "bladder-sparing" trimodal therapy (TMT) in selected muscle-invasive bladder cancer (MIBC) patients unfit for or who declined radical cystectomy (RC) has been increasing. This review aims to summarize the current evidence and future perspectives of bladder-sparing therapy for MIBC. Methods: A non-systematic Medline/PubMed literature search was conducted on July 2022 with the following keywords 'MIBC', 'bladder-sparing', 'chemotherapy', 'radiotherapy', 'trimodal', 'multimodal', and 'immunotherapy'. Key Content and Findings: All monotherapies are inferior to RC or combination therapy and should not be routinely used for curative intent. Radiotherapy (RT) alone has been shown to have poorer outcomes when compared to chemoradiotherapy. The ideal selection criteria for TMT include good bladder function and capacity, clinical stage within cT2, complete transurethral resection of bladder tumor (TURBT), no prior history of pelvic RT, no extensive carcinoma in situ (CIS), and absence of hydronephrosis. The emergence of immunotherapy may further increase the effect of bladder-sparing therapy. Novel predictive biomarkers are awaited for more precise patient selection and better oncological outcomes. Conclusions: TMT is a well-tolerated and offers a curative alternative approach to RC for selected patients with localized MIBC. Appropriate patient selection and a multi-disciplinary approach is crucial in achieving good oncologic control with bladder-sparing therapy.