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Introduction:: Prostate cancer is the second-leading cause of cancer death in men. Sinularin is a soft coralsderived natural compound that has anticancer activity in many cancer cells. However, the pharmacological action of sinularin in prostate cancer is unclear. Aim: The aim of the study is to examine the anticancer effects of sinularin in prostate cancer cells. Methods: We explored the anticancer effects of sinularin on the prostate cancer cell lines, PC3, DU145, and LNCaP, by MTT, Transwell assay, wound healing, flow cytometry, and western blotting. Results: Sinularin inhibited the cell viability and colony formation of these cancer cells. Furthermore, sinularin inhibited testosterone-induced cell growth in LNCaP cells by downregulating the protein expression levels of androgen receptor (AR), type Ⅱ 5α-reductase, and prostate-specific antigen (PSA). Sinularin significantly attenuated the invasion and migration ability of PC3 and DU145 cells, with or without TGF-β1 treatment. Sinularin inhibited epithelialmesenchymal transition (EMT) in DU145 cells after 48 h of treatment by regulating the protein expression levels of Ecadherin, N-cadherin, and vimentin. Sinularin induced apoptosis, autophagy, and ferroptosis by regulating the protein expression levels of Beclin-1, LC3B, NRF2, GPX4, PARP, caspase-3, caspase-7, caspase-9, cleaved-PARP, Bcl-2, and Bax. Moreover, intracellular reactive oxygen species (ROS) were increased but glutathione was decreased after sinularin treatment in PC3, DU145 and LNCaP cells. Conclusion: Sinularin regulated the androgen receptor signaling pathway and triggered apoptosis, autophagy, and ferroptosis in prostate cancer cells. In conclusion, the results indicated that sinularin may be a candidate agent for human prostate cancer and need further study for being applied to human.

Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brain Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we found corresponding changes in subsynaptic regions in the hippocampus. Specifically, we detected significant reductions in the concentrations of Arc in the presynaptic terminal of Schaffer collateral glutamatergic synapses in the stratum radiatum of the CA1 area in TLE, as well as in their adjacent postsynaptic spines. In CA3, there was a significant reduction of Arc only in the presynaptic terminal cytoplasm. Conversely, in CA3, there was a significant increase in the expression of BDNF in the presynaptic terminal, but not in the postsynaptic spine. Significant increase in BDNF concentration in the CA1 postsynaptic density was also obtained. We hypothesize that the observed changes in Arc and BDNF may contribute to both cognitive impairment and increased excitotoxic vulnerability in chronic epilepsy.

Introduction. Assessment of clinical competence is a significant part of the training for young occupational therapists (OTs). Objective and systematic assessment allows both supervisors and trainees to be aware of the training objectives and monitor the progress. The direct observation of procedural skills (DOPS) is a work-based assessment to evaluate professional knowledge, skills, and attitude in clinical training. This study investigated the perspectives of OT educators and trainees on using DOPS and their discrepancy for OT postgraduate year (PGY) training. Methods. This study used a quantitative online survey. Eighty-six supervisors and 41 trainees of OT PGY training programs from 95 hospitals returned the questionnaire (a 90.5% return rate), and 64 supervisors and 30 trainees who used DOPS were analyzed. Outcomes included the practicality in using the DOPS in clinical settings, the ease of rating the DOPS, and advantages and the disadvantages of the DOPS. Results. Most respondents reported that completing one DOPS required at least 11 minutes for direct observation (11-40 minutes: teacher 92.2%; trainee 80.6%). Most respondents (teacher 96.9%, trainee 96.8%) had feedback after direct observation of DOPS, and about half of the feedback assessments took 5 to 10 minutes (teacher 53.1%, trainee 48.4%). Most OT educators and trainees agreed that clinical resources were sufficient and that DOPS matched with OT training goals, benefited OT competence training, and had a fair, objective, and consistent scoring system. Significantly higher percentages of OT trainees felt stressed in and satisfied with the DOPS assessment than trainers. Differences between teachers and trainees regarding easiness of rating DOPS items were not significant. Conclusion. Most OT educators and trainees agreed that DOPS was a practical and appropriate assessment for OT PGY training.

Modern electronic design automation flows depend on both implementation and signoff tools to perform timing-constrained power optimization through Engineering Change Orders (ECOs), which involve gate sizing and threshold-voltage ( V th )-assignment of standard cells. However, the signoff ECO optimization is highly time-consuming, and the power improvement is hard to predict in advance. Ever since the industrial benchmarks released by the ISPD-2012 gate-sizing contest, active research has been conducted extensively to improve the optimization process. Nonetheless, previous works were mostly based on heuristics or analytical methods whose timing models were oversimplified and lacked of formal validations from commercial signoff tools. In this article, we propose ECO-graph neural networks (GNN), a transferable graph-learning-based framework, which harnesses GNNs to perform commercial-quality signoff power optimization through discrete ( V th -assignment. One of the highlights of our framework is that it generates tool-accurate optimization results instantly on unseen netlists that are not utilized in the training process. Furthermore, we propose a subgraph approximation technique to improve training and inferencing time of the proposed GNN model. We show that design instances with non-overlapping subgraphs can be optimized in parallel so as to improve the inference time of the learning-based model. Finally, we implement a GNN-based explanation method to interpret the optimization results achieved by our framework. Experimental results on 14 industrial designs, including a RISC-V-based multi-core system and the renowned ISPD-2012 benchmarks, demonstrate that our framework achieves up to 14× runtime improvement with similar signoff power optimization quality compared with Synopsys PrimeTime , an industry-leading signoff tool.

Practice ESG information disclosure is of great significance to promote green development of China's banking industry and achieve our country's double carbon goal. Firstly, based on the realistic background of the steady progress of ESG information disclosure and the green development of China's banking industry, the paper systematically combs the mechanism of the influence of ESG information disclosure on the green development of China's banking industry. Then, through correlation analysis, multiple linear regression analysis, structural equation model and other data analysis methods, explore the influence factors of ESG information disclosure on the green development of the four banks and their influence strength. Finally, it puts forward some feasible suggestions based on the research results and the actual situation to help our country achieve the Carbon peaking and carbon neutrality goals.

As a hot topic in the world, the promotion of green finance in underdeveloped regions has many obstacles with complex levels and different attributes. This paper combined relevant surveys and expert opinions to determine the barriers to the promotion of green finance in underdeveloped areas, used the ISM (Interpretative Structural Modeling) to sort out the hierarchical structure and action paths of the factors, and applied MICMAC (Matriced Impacts Corises-multiplcation Appliance Classement) to determine the key focus objects. The research results show that: the system of obstacles to the promotion of green finance in underdeveloped areas consists of 15 factors, which can be divided into three levels: the surface layer, the intermediate layer and the bottom layer. Among them, low policy effectiveness, low utilization rate of advantageous resources, single green financial products and services, lack of professional talents, and frail resultant force of ecological poverty have strong dependence and low driving force. The solutions to these factors depend on other factors’ solution. Insufficient government guidance, incomplete construction of information sharing platform, and unbalanced development of productivity have relatively high driving forces, which are the most fundamental hindering factors and should be focused on.

Under the joint action of dynamic and static loads, the connecting bolts of the top cover of the pump turbine are prone to cumulative damage in local areas such as threads, resulting in cracks or development, and fatigue fracture may occur in severe cases, which will cause serious safety accidents. Therefore, it is necessary to carry out accurate fatigue life estimation analysis for connecting bolts, which has always been a hot spot and difficulty in the industry. This paper introduces several commonly used fatigue life analysis methods of parts, combined with the force characteristics and structural characteristics of the connecting bolts of the top cover, and analyzes and discusses the fatigue life analysis methods suitable for the top cover bolts. Finally, it is believed that the application of stress-strain field strength method can better describe the actual state of the bolt danger area, and the current damage state has an influence on the amount of damage generated by further loading, and the fatigue life analysis of connecting bolts can be combined with the stress-strain field strength method and variable damage linear cumulative damage theory, and the fatigue life and residual fatigue life can be estimated in the design stage or after the phased service of the bolt.

Background. Both low skeletal muscle mass and delirium are prevalent in older hospitalized patients, while their associations are unclear. This systematic review and meta-analysis aim to investigate the associations between low skeletal muscle mass and the incidence of delirium in hospitalized patients. Methods. The PubMed, Web of Science, and Embase were searched for relevant studies published before May 2022, and we conducted this systematic review and meta-analysis according to the PRISMA and MOOSE guidelines. The summary odds ratios (OR) and 95% confidence intervals (CI) were estimated, and subgroup analyses were also conducted according to the age and major surgeries. Results. Finally, nine studies with 3 828 patients were included. The pooled result showed no significant association between low skeletal muscle mass and the incidence of delirium (OR 1.69, 95% CI 0.85 to 2.52). However, sensitivity analysis suggested that one study caused a significant alteration of the summary result, and the meta-analysis of the remaining 8 studies showed that low skeletal muscle mass was significantly associated with an 88% increased incidence of delirium (OR 1.88, 95% CI 1.43 to 2.33). Furthermore, subgroup analyses indicated that low skeletal muscle mass was associated with a higher incidence of delirium in patients ≥75 years old or undergoing major surgeries instead of those

Study of Air Quality Objectives (AQOs) and long-term changes of air pollution plays a decisive role in formulating and refining pollution control strategies. In this study, 10-year variations of six major air pollutants were analyzed at seven monitoring sites in Hong Kong. The continuous decrease of annual averaged concentrations of NO

As a tissue conductivity imaging method, magneto-acousto-electric tomography (MAET) has the advantage of high axial spatial resolution compared with traditional electrical impedance imaging methods. However, it has the problems of difficulty in imaging targets with irregular conductivity distribution and poor lateral spatial resolution. Although the rotation-based MAET method can partly solve the irregular target problem, there is still a poor imaging signal-to-noise ratio (SNR) problem. Our previous study established a framework of an innovative MAET method, which has a very similar imaging theory and reconstruction algorithm to those of computed tomography (CT). Therefore, we name the method magneto-acoustic-electric computed tomography (MAE-CT). This paper proposes an improved implementation of MAE-CT based on multi-angle plane wave excitation. This method combines the electronic steering of the linear array transducer with the mechanical rotation to increase the number of projection angles while keeping the imaging complexity. In this study, we first established a finite element simulation model to verify the method's feasibility. Then phantom experiments were conducted to systematically investigate the performance of the proposed method. Finally, in vitro liver tissue experiment was conducted to further explore the feasibility of the method. The experimental results show that our method improves both the SNR and spatial resolution of the reconstructed image. For the phantom results, this method can detect conductivity of 0.67 S/m in an area with a size of 2 mm. To the best of our knowledge, this is the best result of spatial resolution available for MAET.

Lei Guo,1,&ast; Xiangzhao Xu,2,&ast; Rui Qin,1 Yongqiang Shi,1 Wei Xue,3 Ling He,3 Shuqin Ma,3 Yi Chen1 1Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Nanchuan, Chongqing, People’s Republic of China; 3Department of Obstetrics, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Chen, Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, 804S Shengli Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86-951-6743252, Email czzyxgp@163.comBackground: Norepinephrine and phenylephrine are widely used for obstetric anesthesia. Our central objective was to determine the ED (effective dose) 90 and potency ratio of prophylactic norepinephrine and phenylephrine boluses for preventing postspinal anesthesia hypotension during cesarean section.Methods: Patients scheduled for elective cesarean section (n = 80) were randomly allocated to receive prophylactic norepinephrine (NE) or phenylephrine (PE) boluses immediately after induction of spinal anesthesia. An initial dose of NE (3 μg) and PE (37.5 μg) was given to the first patient, and an up-and-down sequential allocation method was used to determine the next dose level according to the responses (the effectiveness for preventing postspinal anesthesia hypotension [defined as SBP < 80% of baseline value]). Primary outcomes were ED90 and the potency ratio of prophylactic norepinephrine and phenylephrine boluses. Secondary outcomes were the incidence of postspinal anesthesia hypotension, severe postspinal anesthesia hypotension, nausea, vomiting, bradycardia, hypertension, umbilical artery blood gas values, and Apgar scores.Results: The ED90 values for prophylactic norepinephrine and phenylephrine boluses were 8.0 μg (95% CI 7.1– 11.0 μg) and 90.9 μg (95% CI 82.0– 123.9 μg), respectively. The estimated relative potency ratio was 11.4:1. The incidence of bradycardia was lower in the NE group (2.5% vs 20%, P = 0.034). Other outcomes were comparable between the two groups.Conclusion: An 8-μg prophylactic bolus of norepinephrine and a 90-μg prophylactic bolus of phenylephrine can effectively prevent postspinal anesthesia hypotension in patients during cesarean section.Keywords: cesarean section, norepinephrine, phenylephrine, postspinal anesthesia hypotension

Background: The high heterogeneity of ovarian cancer (OC) brings great difficulties to its early diagnosis and prognostic forecast. It is an urgent need to establish a prognostic model of OC based on clinicopathological features and genomics. Methods: We identified hypoxia-related differentially expressed genes (DEGs) between OC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression (GTEx). LASSO Cox regression analysis was applied for building a prognostic model in the TCGA-GTEx cohorts, and its predictive value was validated in the GEO-OC cohort. Functional enrichment analysis was performed to investigate the underlying mechanisms. By constructing a hypoxia model of SKOV3 cell line and applying qRT-PCR, we investigated the relationship between hypoxia with two novel genes in the prognostic model (ISG20 and ANGPTL4). Results: Twelve prognostic hypoxia-related DEGs were identified and nine of them were selected to establish a prognostic model. OC patients were stratified into two risk groups, and the high-risk group showed reduced survival time compared to the low-risk group upon survival analysis. Univariate and multivariate Cox regression analysis demonstrated that the risk score acted as an independent risk factor for overall survival. The biological function of the identified prognostic hypoxia-related gene signature was involved in immune cells infiltration. Low expression of ISG20 was observed in the CoCl2-mimicked hypoxic SKOV3 cell line and negatively correlated with HIF-1α. Conclusion: Our findings showed that this hypoxia-related gene signature can serve as a satisfactory prognostic classifier for OC and will be beneficial to the research and development of targeted therapeutic strategies.

Hinge joint performance during the operation of prefabricated prestressed concrete (PC) hollow slab bridges is critical to ensure their lateral collaborative working condition and safe serviceability. Traditional performance identification of hinge joints mainly relies on manual inspection, which is inefficient and inaccurate. At the same time, existing indexes (such as acceleration and strain) can only qualitatively detect the damage to hinge joints. This study proposes a novelty detection method based on impact vibration testing to rapidly perform the quantitative assessment of the working condition of the hinge joints. The relationship between hinge joint performance and lateral load distribution (LLD) is first derived in detail by theoretical analysis. And then, the quantitative analysis of collaborative performance is converted to the identification of the LLD influence line, which is innovatively established by the lateral flexibility of the hollow slab bridge. The effectiveness of the proposed method is verified through a multibeam model using ABAQUS software, and the lateral collaborative working relationship between slabs is simulated using the connector elements. Furthermore, the LLD influence lines and hinge joints performance of a PC hollow slab Yanhu Bridge are evaluated based on the impact vibration testing with sensor lateral arrangement strategy. The detection results show that the proposed method can quickly and accurately identify the damage location and the stiffness loss of hinge joints.

Background: The relationship between cataracts and Alzheimer’s disease (AD) has been reported in recent observational studies. However, it is still unclear whether a causal effect of cataracts on AD or reverse causation exists. Objective: To explore the association between cataracts and AD genetically, we performed a bidirectional two-sample Mendelian randomization study. Methods: We obtained genetic instrumental variables related to cataracts and AD from recently published genome-wide association studies (GWASs). SNP-outcome associations for AD were obtained from a GWAS with 111,326 cases and 677,663 controls. SNP-outcome associations for cataracts were drawn from two sources: a GWAS with 67,844 cases and 517,399 controls and the FinnGen consortium (42,843 cases and 262,698 controls). Inverse variance weighted (IVW) was used as the primary method for Mendelian randomization (MR) analyses. Results: No genetic evidence suggested that cataracts were associated with the risk of AD (IVW odds ratio =1.04, 95% confidence interval: 0.98-1.10, p=0.199). In contrast, an effect of genetically determined AD on a decreased risk of cataract was observed with suggestive evidence (IVW odds ratio =0.96, 95% confidence interval: 0.93-0.99, p=0.004). However, this result might be distorted by survival bias. Conclusion: Genetically determined cataracts were not related to AD, as demonstrated by our study. In contrast, there was suggestive evidence that AD might prevent cataract development, but there might be potential survival bias. To define the exact association between the two diseases, more prospective research and studies on the pathogenesis are needed.