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AIM:To establish a model of meibomian gland dysfunction in rats induced by eyeliner tattoo and investigate its potential mechanisms.METHODS:A total of 40 SD rats were selected, with 30 randomly chosen to have eyeliner tattoo applied their right eyes and designated as the eyeliner group. The remaining 10 rats were not given any treatment and served as the normal group. The corneal morphology of both groups was observed using a slit lamp at 1, 2, and 4 wk after establishment, and the tear film break-up time(BUT), Schirmer I test(SIt), corneal fluorescein staining score, and corneal irregularity score were calculated. The corneal Placido rings were examined using an ocular surface analyzer, and the corneal tissue structures of both groups were observed under a confocal microscope. After 4 wk and completion of clinical indicator recording, the eyeballs and upper and lower eyelid tissues were taken for pathological examination. The meibomian gland structures were observed through HE staining, the conjunctival goblet cells were observed using PAS staining, and the lipid droplets were observed with ORO staining.RESULTS:The slit lamp examination results showed that the eyeliner group rats exhibited in situ black pigmentation in the eyelids, with no eyelid deformation or scarring. The corneal epithelium was rough, with positive fluorescein staining, presenting as spotty staining that worsened over time. Compared with the normal group, the BUT was significantly shortened, tear secretion volume was significantly decreased, and the corneal fluorescein staining score and corneal irregularity score were significantly increased at 1, 2, and 4 wk after modeling in the eyeliner group(all P

Objective Shanghai Master Plan (2017-2035) evaluates land use performance using the index of land use area for construction of GDP per unit area across the city. However, since rail transit stations are more concerned with passenger throughput, this index may not be suitable for evaluating land use performance at the stations. Therefore, it is necessary to select appropriate indicators to evaluate the land use performance of rail transit stations. Method By utilizing data on passenger throughput at Shanghai rail transit stations and combining with AOI (area of interest) data, POI (point of interest) data, and surrounding land use planning and utilization situation, the passenger throughput per unit area is defined as the indicator for evaluating the land use performance of stations. The land use performance of rail transit stations in central urban area (within the Outer Ring Inner Region) of Shanghai is evaluated, the performance of general stations and interchange stations is compared, and a causal analysis of the land use performance results of different stations is conducted. Result & Conclusion The type and intensity of land use around the stations have a significant impact on station performance. Rail transit stations located near major transportation hubs, economic development zones, industrial parks, and large commercial districts exhibit higher land use performance. Conversely, stations surrounded by areas with lower land development intensity and dense residential communities demonstrate lower land use performance.

Abstract 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.

Abstract Unprotected gradient exchange in federated learning (FL) systems may lead to gradient leakage-related attacks. CKKS is a promising approximate homomorphic encryption scheme to protect gradients, owing to its unique capability of performing operations directly on ciphertexts. However, configuring CKKS security parameters involves a trade-off between correctness, efficiency, and security. An evaluation gap exists regarding how these parameters impact computational performance. Additionally, the maximum vector length that CKKS can once encrypt, recommended by Homomorphic Encryption Standardization, is 16384, hampers its widespread adoption in FL when encrypting layers with numerous neurons. To protect gradients’ privacy in FL systems while maintaining practical performance, we comprehensively analyze the influence of security parameters such as polynomial modulus degree and coefficient modulus on homomorphic operations. Derived from our evaluation findings, we provide a method for selecting the optimal multiplication depth while meeting operational requirements. Then, we introduce an adaptive segmented encryption method tailored for CKKS, circumventing its encryption length constraint and enhancing its processing ability to encrypt neural network models. Finally, we present FedSHE, a privacy-preserving and efficient Federated learning scheme with adaptive Segmented CKKS Homomorphic Encryption. FedSHE is implemented on top of the federated averaging (FedAvg) algorithm and is available at https://github.com/yooopan/FedSHE . Our evaluation results affirm the correctness and effectiveness of our proposed method, demonstrating that FedSHE outperforms existing homomorphic encryption-based federated learning research efforts in terms of model accuracy, computational efficiency, communication cost, and security level.

Abstract 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.

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.

Background This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC.Methods Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together with in vivo models, have been established to determine the molecular functions of NNMT in CAFs in UBC.Results We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD+) metabolism enzyme NNMT in CAFs (NNMT+ CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT+ CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy.Conclusions NNMT+ CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.

Abstract Demagnetisation fault (DF) is a common rotor fault in the permanent magnet synchronous motor (PMSM). DF can cause obvious changes in the magnetic field of PMSMs. As a result, previous DF diagnosis methods mainly depends on magnetic field analysis. However, conventional analysis methods based on the magnetic potential‐permeability method, sub‐domain method and magnetic equivalent circuit method are not suitable for DF condition. In addition, DF diagnosis is further complicated by various operating conditions. To address these issues, a robust DF diagnosis method is proposed for PMSM based on d‐axis magnetic network model using magnetic field reconstruction. The proposed fault diagnosis method employs magnetic field reconstruction to obtain the radial air‐gap flux density under the open‐circuit condition. Subsequently, a d‐axis magnetic network is established to solve the demagnetisation coefficient matrix in the DF state. Finally, the effectiveness of the proposed method is validated through simulations and experiments. Both results demonstrate that the proposed method can accurately recognise uniform DF and partial DF with multiple demagnetised permanent magnets, exhibiting great robustness against different operating conditions.

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

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.

Abstract 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.

(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.

With the development of the Internet of Things, the rapid development of miniaturized self-powered electronic products and further micro-modulation greatly stimulate the urgent demand for microscale electrochemical energy storage devices. In each electrochemical energy storage device, the supercapacitor based on the plane pattern shape is highly compatible with modern electronic products in terms of functional features such as miniaturization and integration. In this work, the flexible 3D interdigital electrode symmetric micro capacitor was prepared by the combination of semiconductor preparation technology and electrophoresis printing technology, and the 3D printing was carried out by using oxygen enriched activated carbon ink. The 3D interdigital symmetric electrode was prepared by adjusting and optimizing the electric field strength, line width, number of printing layers and other parameters. The energy dispersive spectrometer (EDS), scanning electron microscopy(SEM), rheometer, electrochemical workstation and test system were used to characterize materials, pastes and microcapacitor devices, and to explore the influence of materials and pastes on the performance of 3D interdigital microcapacitor. The results that the 3D interdigital supercapacitor prepared by the combination of semiconductor and electrophoresis printing process has good performances, and its area capacitance can reach 22.3 mF·cm-2. In addition, the device can achieve 96% capacity retention after 2000 cycles through packaging optimization. This simple and controllable 3D jet printing technology provides an effective way to prepare advanced miniaturized electrochemical energy storage devices.

Objective To systematically review the effect of Traditional Chinese Medicine nursing technology in prevention of deep venous thrombosisafter surgery for femoral neck fracture. Methods The CNKI, Wanfang Data, VIP, SinoMed, PubMed, Embase, Cochrane Library and Web of Science were retrieved for random-controlled trails researches about the prevention of deep venous thrombosisafter surgery for femoral neck fracture. These databases were systematically searched from inception up to February 20, 2023. The meta-analysis was conducted using ReMan 5. 4software. Results A total of 12 articles with 942 patients finally were included. The results showed that the Traditional Chinese Medicine nursing technology was associated with a lower incidence of deep venous thrombosisafter surgery［OR=0. 18, 95%CI(0. 10, 0. 33), P＜0. 001］, lower degree of limb swelling［MD=-5. 22, 95%CI(-5. 76, -4. 68), P＜0. 001］ and higher degree of patient satisfaction［OR=7. 73, 95%CI(3. 83, 15. 61), P＜0. 001］ compared with routine intervention. In terms of coagulation indicators, there was no significant difference in APTT［MD=1. 20, 95%CI(-0. 29, 2. 69), P=0. 12］ and FIB［MD=-0. 41, 95%CI(-0. 90, 0. 09), P=0. 11］ between two groups, and there was a significant difference in PT［MD=1. 18, 95%CI(0. 62, 1. 73), P＜0. 001］between two groups. Conclusion Findings of the study showed an advantage of Traditional Chinese Medicine nursing technology in prevention of deep venous thrombosisafter surgery for femoral neck fracture. More high-quality studies with larger sample size are needed to verify the effect of intervention. (目的 系统评价中医护理预防股骨颈骨折术后深静脉血栓形成的效果。方法 计算机检索知网、万方、维普、中国生物医学数据库, PubMed、Embase、Cochrane Library、Web of Science核心数据库有关中医护理预防股骨颈骨折患者术后深静脉血栓形成的临床随机对照研究, 检索时间为从建库至2023年2月20日。采用ReMan 5. 4进行Meta分析。结果 最终纳入12篇文献研究, 共942例患者。Meta分析结果显示: 实验组(中医护理)在术后深静脉血栓的发生率［OR=0. 18, 95%CI(0. 10, 0. 33), P＜0. 001］、术后患肢肿胀程度［MD=-5. 22, 95%CI(-5. 76, -4. 68), P＜0. 001］, 患者满意度［OR=7. 73, 95%CI(3. 83, 15. 61), P＜0. 001］均优于对照组(常规护理); 凝血指标中APTT［MD=1. 20 , 95%CI(-0. 29, 2. 69), P=0. 12］, FIB［MD=-0. 41, 95%CI(-0. 90, 0. 09), P=0. 11］显示两组差异无统计学意义, 而PT［MD=1. 18, 95%CI(0. 62, 1. 73), P＜0. 001］显示两组差异有统计学意义。结论 在预防股骨颈骨折患者术后深静脉血栓中中医护理更有优势。受纳入研究的文献和质量的限制, 上述结论需要更多大样本、高质量的研究予以验证。)

Sensor errors, model uncertainty, changes in the surrounding environment, data loss, or malicious network attacks can all result in outliers, which can pollute the measurement process of the distribution system. In this study, to address this problem, a dynamic state estimation method for distribution systems based on innovation-saturated Koopman Kalman filter (IS-KKF) was proposed. The Koopman Kalman filter (KKF) is model-free and data-driven, and estimates nonlinear dynamics through the conventional linear Kalman filter. To make the Koopman Kalman filter robust to measurement outliers, the innovation saturation mechanism applies a saturation function to it. To correct the state estimation, this mechanism is applied to the filtering process. When outliers occur, the distorted innovation is saturated to prevent the state estimation results from being destroyed. Adaptive adjustment of the saturated boundary is a feature of this mechanism. Extensive simulations were carried out on the IEEE 118-bus test system to verify the effectiveness and robustness of the proposed method. The simulation results demonstrate that the proposed method can effectively reject outliers with different amplitudes, types, and continuous times, has significant computational efficiency, and does not require additional measurement redundancy.

Abstract 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

Lithium-ion capacitors are energy storage devices between lithium-ion batteries and supercapacitors, which have both high energy density and high power density, and are considered as one of the most promising energy storage systems. In this paper, the research progress of carbon-based and lithium-embedded cathode materials in recent years was summarized, and the classification and modification methods of carbon-based and lithium-embedded electrode materials were introduced in detail. In order to further improve the performance of lithium-ion capacitors, researchers further optimized the cathode materials by means of microstructure regulation, surface modification, doping modification and composite materials, and carried out cathode and anode dynamic matching to comprehensively improve the electrochemical performance of lithium-ion capacitors. Finally, the research hotspots and development directions of cathode materials for lithium-ion capacitors in the future were reviewed in order to provide good electrochemical properties for the next generation of cathode materials for commercial applications.

Abstract 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.

Abstract 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.

Abstract Objective Bladder cancer is the 13th most common cancer in China with the predominant histologic type being urothelial carcinoma (UC). Locally advanced and metastatic (la/m) UC accounts for 12% of UC and the five‐year survival rate is only 39.4%, imposing a significant disease and economic burden on the patients. The aim of this scoping review is to synthesize existing evidence of epidemiology, the landscape of treatment options and associated efficacy and safety profiles, as well as treatment‐related biomarkers among Chinese la/mUC patients. Methods A systematic search was conducted on five databases (PubMed, Web of Science, Embase, Wanfang, and CNKI) from January 2011 to March 2022 based on the scoping review criteria in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. Results A total of 6211 records were identified, and further review resulted in 41 relevant studies that met all criteria. Additional searches were conducted on epidemiology and treatment‐related biomarkers of bladder cancer to supplement the evidence. Among 41 studies, 24 reported on platinum‐based chemotherapy, eight on non‐platinum‐based chemotherapy, six on immunotherapy, two on targeted therapy, and one on surgery. Efficacy outcomes were summarized by line of therapy. Treatment‐related biomarkers including PD‐L1, HER2, and FGFR3 alterations were identified, and the alteration rate of FGFR3 of Chinese UC patients was lower than that of the western patients. Conclusions Despite chemotherapy has been the main treatment choice for decades, appealing new therapeutic strategies including ICIs, targeted therapies and ADCs were applied in clinical practice. Further research on epidemiology and treatment‐related biomarkers of la/mUC patients is needed given only a limited number of studies have been identified thus far. High genomic heterogeneity and complexity of molecular features were observed among la/mUC patients; thus, further studies are required to identify critical drivers and promote potential precise therapies.

Abstract Purpose To clarify the necessity and effect of a single intraoperative instillation of chemotherapy during radical cystectomy. Methods Patients who underwent radical cystectomy for bladder cancer between January 2013 and April 2019 were retrospectively evaluated and divided into a non‐instillation group and an instillation group according to the intraoperative instillation of chemotherapy. Univariate and multivariate Cox regression was used to determine the clinical predictors of overall survival and disease‐free survival. Kaplan–Meier analysis and log‐rank tests were performed to analyze overall survival and disease‐free survival. Results Of the 320 patients who were enrolled in the study, 113 underwent radical cystectomy with intraoperative instillation of chemotherapy. Univariate Cox analysis showed that intraoperative instillation was not a risk factor for overall survival or disease‐free survival (HR: 1.04, 95% CI: 0.66–1.63, p = 0.864; HR: 1.11, 95% CI: 0.76–1.62, p = 0.602, respectively). As shown in the Kaplan–Meier analysis, no significant differences were noted in overall survival (p = 0.857) and disease‐free survival (p = 0.600) between the two groups. A subgroup analysis demonstrated that intraoperative instillation was not associated with a statistically better overall survival and disease‐free survival in the nonmuscle invasive (p = 0.852 and 0.836) and muscle‐invasive (p = 0.929 and 0.805) patients. Conclusion A single intraoperative instillation of chemotherapy during radical cystectomy was not related to better disease‐free survival or overall survival. It is unnecessary to consider single instillation of chemotherapy as a regular procedure during radical cystectomy.

Abstract 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

In view of the defects of the new domestic T800 carbon fiber reinforced plastic （CFRP）, such as lamellar tearing and fiber loss, which would be easily caused by large drilling force and torque during cutting, an experimental platform including a vertical ultrasonic machining center and force measurement system was constructed. Carbide twist drill, carbide candle stick drill and carbide dagger drill were used to compare the hole quality of T800 carbon fiber composite. Under the same technological parameters, the influences of three kinds of cutting tool structures on the cutting force, surface morphology of hole inlet and outlet, aperture deviation and surface roughness of T800 composite were compared with those of conventional drilling （CD）. The ultrasonic vibration assisted drilling （UVAD） method was adopted to carry out feasibility experiments on optimum tool structure. The results show that the carbide dagger drill can effectively suppress the surface defects of T800 composite materials, but the entrance aperture accuracy is poor. The ultrasonic vibration assisted dagger drilling can further improve the quality of hole making, especially significantly improve the aperture accuracy by improving the drilling stability.

China’s rapid economic growth and correlating growth of metropolitan areas has attracted young people leaving their hometowns from the rural areas. Revitalizing the rural areas has been a national development strategy in China. College students returning home to start businesses is one way to alleviate the current shortage of young talents in rural areas of China. Based on the model of goal-directed behavior (MGB), this paper takes behavioral attitude, subjective norms, positive expectations of emotion, negative expectations of emotion, perceived behavioral controls, and government support, all as independent variables. The paper uses the desire as the intermediary variable to construct a goal-oriented behavior model about the intention of entrepreneurial initiatives by college students. By using survey data, the empirical analysis shows that the model has a strong explanatory power on the intention of college students. The positive expected emotions, perceived behavioral control, and government support, have a significantly positive influence on college student’s intentions through controlling behavior desire. The perceived behavioral control and behavioral desire of the subjects had a direct positive and significant influence on their intention. This research provides a reference for the government to formulate policies to attract college students to return to their hometowns to start businesses and boost rural revitalization.

Biomineralization is a widespread phenomenon in marine mollusks and is responsible for the production of shells and pearls. However, the regulatory mechanisms governing the adaptive immune responses in the mollusk mantle and visceral mass during mineralization remain unclear. In this work, we examined the mantle and visceral mass immune responses of Hyriopsis cumingii during pearl culture using high-throughput sequencing techniques. A mantle transcriptome database was established using transcriptome sequencing technology and reference to the major databases. Digital gene expression profiling was used to identify the differentially expressed genes of mantle and visceral mass at different insertion periods. Moreover, quantitative real-time PCR was used to verify the expression of five immune-related genes. Transcriptome sequencing results showed 257,457 unigenes were identified. Digital gene expression profiles showed 1389, 3572, 1888, and 2613 differentially expressed genes (DEGs) in the mantle and visceral mass at 5, 20, 50, and 90 d after insertion, respectively, with the highest number at 20 d and the lowest at 5 d after insertion (q < 0.05). A cluster analysis of the DEGs showed similar clustering and expression features in the mantle to the control group, and at 5, 50 and 90 d, after mantle insertion. The DEGs in the visceral mass showed similar clustering and expression features to the control group and at 5, 20 and 50 d after insertion. We also screened 22 immune-related DEGs in the mantle and visceral mass during the same pearl culture period, including serine/threonine-protein kinase NLK, C-type lectin, and galectin. The greatest number of DEGs was found 90 d after insertion. Compared with the mantle, more immune-related DEGs were down-regulated than up-regulated in the visceral mass during pearl culture, indicating that the immune regulatory mechanisms in the visceral mass and the mantle differ during pearl culture, and that the visceral mass is liable to higher infection and mortality rates. Quantitative real-time PCR results showed that the expression of five immune-related genes was consistent with DGE results. Our findings will further knowledge of the immune systems that are present in the mantle and visceral mass during pearl culture.

(1) Purpose: The purpose of this study was to evaluate the prognostic capacity of the pathological N status (pN), lymph node ratio (LNR), and the log odds of positive lymph nodes (LODDS), and to build a prognostic nomogram to predict overall survival (OS) for bladder cancer patients treated by radical cystectomy. (2) Methods: The clinical and pathological characteristics of 10,938 patients with bladder cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017. The predictive capacity was assessed by univariate and multivariate Cox regression analyses, the area under the receiver operating characteristic curve (AUC), and C-index. Calibration curves, decision curve analysis (DCA), and risk-grouping were utilized to evaluate the predictive accuracy and discriminative ability of the nomogram. (3) Results: LODDS was an independent risk factor for bladder cancer (all p < 0.001) and demonstrated the highest values of C-index and AUC. The values of AUCs in the training cohort were 0.747, 0.743, and 0.735 for predicting 1-, 3-, and 5-year OS, respectively. Calibration curves and DCA curves suggested the excellent clinical application value of our nomogram. (4) Conclusions: LODDS is a better predictive indicator for bladder cancer patients compared to pN and LNR. The LODDS-incorporated nomogram has excellent accuracy and promising clinical application value for non-metastatic bladder cancer after radical cystectomy.

Tribotronics represents the modulation of friction via an external electric potential, a field with promising ramifications for intelligent devices, precision manufacturing, and biomedical applications. A profound elucidation of mechanisms that allow for potential-controlled friction is foundational to further research in this tribotronic domain. This article provides a comprehensive review of the research progress in electro-controlled friction over the past few decades, approached from the perspective of the boundary lubrication film at the friction interface, a direct influencer of electro-controlled friction performance. The mechanisms of potential-controlled friction are categorized into three distinct classifications, contingent on the formation mode of the boundary lubrication film: potential-induced interfacial redox reactions, interfacial physical adsorption, and interfacial phase structure transformations. Furthermore, an outlook on the application prospects of electro-controlled friction is provided. Finally, several research directions worth exploring in the field of electro-controlled friction are proposed. The authors hope that this article will further promote the application of electro-controlled friction technology in engineering and provide intellectual inspiration for related researchers.

This study introduces a novel deep modeling approach that utilizes Hamiltonian neural networks to address the challenges of modeling the six degrees of freedom rigid-body dynamics induced by control inputs in various domains such as aerospace, robotics, and automotive engineering. The proposed method is based on the principles of Hamiltonian dynamics and employs an inductive bias in the form of a constructed bias for both conservative and varying energies, effectively tackling the modeling issues arising from time-varying energy in controlled rigid-body dynamics. This constructed bias captures the information regarding the changes in the rigid body’s energy. The presented method not only achieves highly accurate modeling but also preserves the inherent bidirectional time-sliding inference in Hamiltonian-based modeling approaches. Experimental results demonstrate that our method outperforms existing techniques in the time-varying six degrees of freedom dynamic modeling of aircraft and missile guidance, enabling high-precision modeling and feedback correction. The findings of our research hold significant potential for the kinematic modeling of time-varying energy systems, parallel system state prediction and control, inverse motion inference, and autonomous decision-making in military applications.

Gas drilling technology is an effective method to protect low permeability tight sandstone reservoirs from damage. However, using this technology to drill high-pressure fractured reservoirs, the fluid flow characteristics are extremely complex, leading to drilling safety challenges. Therefore, based on the conservation equations of mass, momentum, and energy, a new transient coupled flow model in matrix-fracture is established for high-pressure gas reservoirs opened by gas drilling, considering convection term and energy equation, to research the pressure and flow velocity transient behaviors. This model is solved by Shaher Momani’s algorithm and CyabJiBe format, and the type curves of the pressure and flow velocity are plotted. The three flow stages are developed, and the impact of parameters and equation terms on the transient flow behavior is analyzed and discussed, such as the energy equation, the matrix permeability (k), the fracture aperture (Lf), and the fracture outlet pressure. It is found that the energy equation term of the model has a great influence on the transient characteristics such as velocity and pressure, which cannot be ignored. In the first flow stage, the flow velocity characteristics are not affected by the matrix parameters being extremely unstable, but in the second and third stages, the influence of the gas supplied to fracture cannot be ignored. The proposed transient coupled flow model provides a new understanding of the transient flow behavior in matrix-fracture for high-pressure reservoirs during gas drilling, which can be used to interpret the characteristics of pressure and velocity more realistically, to provide support for safe drilling of gas drilling.

Little is known about the genetic background of pigmented paravenous retinochoroidal atrophy (PPRCA) due to rarity of patients. In this study, we identified two pathogenic variants in RPGRIP1 in a 2-year-old boy with PPRCA screened by whole-exome sequencing (WES). The patient presented to our department with photophobia for 17 months, and then he underwent fundus photography and fluorescein fundus angiography. Genomic DNA was extracted from peripheral blood of the proband and the parents. Trio-WES strategy was utilized to identify the causal variants from the proband and the parents, followed by validation based on Sanger sequencing. The patient was finally diagnosed with PPRCA after differential diagnosis. Two heterozygous pathogenic variants were detected by WES according to the American college of medical genetics and genomics guidelines, including NM_020366.4: c.2592T > G: p.Y864* and NM_020366.4: c.154C > T: p.R52* in RPGRIP1 located in exon 17 and exon 3, leading to termination codon, respectively. This is the first study reporting pathogenic variants within RPGRIP1 as causal for PPRCA.

The risk of hepatitis B virus (HBV) infection is higher in patients with diabetes mellitus, and diabetes mellitus is one of the metabolic complications of HBV infection. However, the cytokine profile of chronic hepatitis B (CHB) patients with type 2 diabetes mellitus (T2DM) is not fully understood. The aim of this study was to investigate the cytokine expression profile in CHB patients with T2DM, and to assess the regulatory function of cytokines to regulatory T cells (Tregs). Forty-four T2DM patients, 39 CHB patients, 17 patients with CHB and T2DM, and 21 control subjects were enrolled. Cytokine levels in the plasma were measured by Luminex multiplex assay. CD4+CD25+CD127dim/- Tregs were detected by flow cytometry. Tregs were purified and stimulated with recombinant human interleukin-15 (IL-15). The regulation of IL-15 on Tregs function was investigated by measuring cell number, IL-10/IL-35 secretion, and mRNA expression of immune checkpoint molecules in a Tregs+PBMC co-culture system. We found that levels of IL-1α, IL-6, and IL-33 were upregulated, while IFN-α, IL-2, IL-7, and IL-15 were downregulated in T2DM and CHB patients. CHB patients with T2DM had even lower plasma IL-7 and IL-15 levels. Tregs percentage was elevated in T2DM and CHB patients. CHB patients with T2DM had increased levels of Tregs, which correlated negatively with IL-15. Tregs showed stronger inhibitory activity in CHB patients with T2DM than in controls, T2DM, and CHB patients, which presented as reduction in cellular proliferation and induction of IL-10/IL-35 secretion. IL-15 suppressed Tregs function and inhibited the expression of immune checkpoint molecules in Tregs. The current data suggest that insufficient IL-15 levels and decreased responsiveness of Tregs to IL-15 signaling might contribute to strong immune dysfunction in CHB patients with T2DM.

Dynamic state estimation (DSE) plays an important role in the real-time control and monitoring of distribution systems, which are high-dimensional space–time systems. The degree of nonlinearity of distribution system increases drastically with the availability of sustainable energy and the diversification of load types, thereby reducing the accuracy of the standard linear model. Under the existing schemes, the measurement noise may not follow a Gaussian distribution. Therefore, a Koopman operator-based Kalman particle filter (KKPF) is proposed herein for estimating the dynamic states of a distribution system. The KKPF performs data-driven dynamic state estimation based on the Koopman operator theory, which does not rely on the distribution system model and can be applied to high-dimensional systems. Furthermore, this method can be applied to dynamic systems and noise with both Gaussian and non-Gaussian distributions. The KKPF method provides accurate estimation results when only a small number of measurements are available. IEEE 141 system and an improved 141 system were used to test the performance of the proposed KKPF compared to the EKF, CKF, and PF. The test revealed that the proposed KKPF can obtain accurate results under high-dimensional and non-Gaussian noise environments.

In light of the challenges posed by the widespread distribution of new energy sources in China and their distance from load centers, the power system must effectively integrate both new energy and thermal power transmission. To address this issue, we propose a dynamic coordinated scheduling model that combines wind, photovoltaic, and thermal power to optimize the profit of the energy complementary delivery system. Additionally, we present an improved ant lion optimization algorithm to investigate the coordinated scheduling and benefit distribution of these three power sources. This paper introduces a cooperative mode for benefit distribution and utilizes an enhanced Shapley value method to allocate the benefits of joint operation among the three parties. The distribution of benefits is based on the contribution of each party to the joint proceeds, considering the profit levels of joint outbound and independent outbound modes. Through our analysis, we demonstrate that the upgraded ant lion optimization algorithm facilitates finding the global optimal solution more effectively within the feasible zone. Furthermore, our suggested three-party combined scheduling model and profit-sharing approach are shown to be superior and feasible.

Sedimentary facies color is an important paleoclimate indicator, but may be unreliable in thick continental red beds. The Danxia Formation is the landscape strata of the Danxia basin, and its color fluctuates between reddish-brown and reddish-purple vertically. This study examined the ferric oxides characteristics, distribution, and mineral composition of the Danxia Formation using a variety of analytical techniques, including optical microscopy, high-resolution scanning electron microscopy, electron probe microanalysis, X-ray diffraction, and micro-Raman spectroscopy. The results indicate that the reddish-brown mineral is composed primarily of fine hematite with traces of goethite, while the reddish-purple mineral consists solely of fine hematite. These hematites exhibit a particle size range of submicron to micron and display various morphologies, including spherical, flake, and fibrous forms. Goethite particles are needle-shaped and often form star-shaped aggregates containing twins. Whole rock geochemical analysis reveals a strong positive correlation between iron and iron group elements, as well as phosphorus and rare earth elements. The findings suggest that the reddening of the Danxia Formation occurs during diagenesis, with fine hematite forming as a result of the alteration of iron-bearing detrital grains. In addition, vertical color variations in Danxia Formation are not attributable to the paleoclimate records, but rather the result of the differentiation of sediment sources. This study provides a novel viewpoint for examining the coloration of thick continental red beds in other regions.

Periodontium regeneration and repair is a controversial and difficult point in the treatment of periodontosis. The proliferation, differentiation, migration and adhesion of periodontal ligament cells and the dynamic relationship between periodontal ligament cells and their extracellular matrix proteins are the basis of periodontium morphological reconstruction, functional maintenance and tissue repair. This article reviews the mechanism of estrogen-regulated periodontal membrane fine repair and periodontal tissue reconstruction to provide the basis for follow-up research on the treatment of periodontitis and the promotion of periodontal tissue repair and reconstruction by exogenous estrogen-mediated periodontal membranes. Under the regulation of certain concentrations of estrogen, the proliferation and differentiation ability of periodontal ligament stem cells (PDLSCs) and bone mesenchymal stem cells (BMSCs) to other periodontal ligament cells were enhanced. At the same time, PDLSCs, BMSCs, human periodontal ligament fibroblasts (HPLFSs), osteoblasts and cementoblasts synthesized and secreted collagen I (COLI), osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OCN) into the extracellular matrix. They interact with fibronectin (FN) and cementum attachment protein (CAP) in the extracellular matrix to form a variety of chain complexes and regulate each other, thus promoting the growth, migration, adhesion and fibrosis of periodontal ligament cells, repairing the collagen fiber skeleton of the periodontal ligament and adhering the two ends to the new cementum and the inherent alveolar bone.

Red ginseng is a steamed and dried processing product of the cultivating root and rhizome of Panax ginseng C. A. Mey., which is one of the most widely used in ginseng products. The main active ingredient of red ginseng is ginsenoside, which is different from the content of ginseng caused by thermal process, such as chemical transformation by hydrolysis reaction and hydrated reaction. In recent years, the treatment of type 2 diabetes mellitus (T2DM) by red ginseng has attracted extensive attention. Ginsenoside has the effect of treating T2DM, but it is not easy to be absorbed directly by oral administration, and the bioavailability is low. Therefore, the metabolism of ginsenoside of red ginseng was studied in this research. The influence of intestinal flora on diseases has been paid more and more attention. Studies have shown that drug molecules can interact with intestinal microorganisms to produce metabolites of intestinal flora and active components of traditional Chinese medicine transformed by intestinal flora, which may be a new way to reveal the potential mechanism of action of red ginseng. Therefore, it is necessary to identify and elucidate ginsenosides in feces. A method of ultra performance liquid chromatography mass spectrometry (UPLC-MS) was established for qualitative and quantitative analysis of ginsenosides in red ginseng, and the content changes of ginsenosides in feces and serum of rats after intragastric administration of total ginsenosides were analyzed. Thermo Syncronis C18 column (100 mm×2.1 mm×1.7 μm) was used, mobile phase A was 0.1% formic acid in water, mobile phase B was acetonitrile, and flow rate was 0.2 mL/min, injection volume was 5 μL, UPLC was equipped with binary linear gradient pump, mass spectrometry was adopted electrospray negative ion mode. Ginsenosides were identified by the information of the retention times, molecular mass, and specific MS/MS fragments. The developed UPLC-MS method for quantitative analysis of ginsenosides was validated with respect to linearity, precision, repeatability, stability, and recovery. The result showed that the detection method of ginsenoside is speedy and accurate. Ginsenosides NotoR1, Rg1, Re, Rf, Rg2, Rh1, Rb1, Rc, Ro, Rb2, Rb3, Rd, Rg3, Rk1 in feces and serum of rats are detected, which show that the intestinal flora did not completely transform ginsenoside, and a part of ginsenosides are absorbed into the blood as prototype components playing a role in the treatment of T2DM. The changes of metabolites of ginsenoside in feces were studied with the prolongation of intervention time, which provided a certain basis for the pharmacodynamics of ginsenosides in red ginseng.

Abstract Background Balloon dilation is a commonly used minimally invasive endourological treatment of ureteral stricture, but the postoperative recurrence rate is relatively high. And factors contributing to recurrence after treatment are poorly understood. Herein, we sought to develop a novel clinical nomogram to predict ureteral stricture-free survival in patients suffering from ureter stricture and performed balloon dilation. Methods The nomogram was established based on a retrospective analysis of 321 patients who received endoscopic balloon dilation alone for ureter strictures from January 2016 to January 2020 in Sun Yat-sen Memorial Hospital using the Cox regression model. Perioperative clinical data and disease outcomes were analyzed. The primary endpoint was the onset of ureteral re-stricture after ureter balloon dilation. Discrimination of the nomogram was assessed by the concordance index (C-index) and the calibration curve. The results were internally validated using bootstrap resampling. Results Overall, 321 patients with a median follow-up of 590 days were enrolled in the study, among which 97 patients (30.2%) developed recurrence of ureteral stricture during follow-up. Five variables remained significant predictors of ureteral re-stricture after multivariable analyses: stricture nature (P

Digital microfluidics (DMF) is a versatile fluid handling tool that is widely used in the biochemical field. There are very high requirements for the volume of single droplet in many biochemical applications. Droplet dispensing and splitting are two main operations to generate a single droplet in DMF. Therefore, the generation of droplets with high volume precision and accuracy in the two droplet operations is one of the keys to the efficient application of DMF in biochemical analysis. We have developed a novel droplet dispensing and splitting scheme where electrode geometry is optimized. The liquid column can contract in a regular shape, which keep the neck shape uniform and stable, and the position of pinch-off point was fixed; meanwhile, the liquid tail is eliminated before pinching off, so that the precision and accuracy of droplet volume were greatly improved. The increase in the radius of the cutting electrodes elongated the droplet neck and increased the neck curvature at the pinch-off point, which further effectively improved the precision and accuracy of droplet volume. The optimized droplet splitting scheme can also be applied to the droplet splitting with unequal volume effectively.