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Summary: Genomics studies have detected numerous genetic alterations in esophageal squamous cell carcinoma (ESCC). However, the functions of these mutations largely remain elusive, partially due to a lack of feasible animal models. Here, we report a convenient platform with CRISPR-Cas9-mediated introduction of genetic alterations and orthotopic transplantation to generate a series of primary ESCC models in mice. With this platform, we validate multiple frequently mutated genes, including EP300, FAT1/2/4, KMT2D, NOTCH2, and TGFBR2, as tumor-suppressor genes in ESCC. Among them, TGFBR2 loss dramatically promotes tumorigenesis and multi-organ metastasis. Paradoxically, TGFBR2 deficiency leads to Smad3 activation, and disruption of Smad3 partially restrains the progression of Tgfbr2-mutated tumors. Drug screening with tumor organoids identifies that pinaverium bromide represses Smad3 activity and restrains Tgfbr2-deficient ESCC. Our studies provide a highly efficient platform to investigate the in vivo functions of ESCC-associated mutations and develop potential treatments for this miserable malignancy.

In clinical practice, the limited efficacy of standard comprehensive therapy for advanced bladder cancer and the lack of targeted treatment options are well recognized. Targeting abnormal epigenetic modifications in tumors has shown considerable potential in cancer therapy. Through drug screening in tumor organoids, we identified that ML324, a histone lysine demethylase 4A (KDM4A) inhibitor, exhibits potent antitumor effects in both in vitro and in vivo cancer models. Mechanistically, Kdm4a demethylates H3K9me3, leading to chromatin opening and increased accessibility of Gabpa to the squalene epoxidase (Sqle) gene promoter, resulting in transcriptional activation. Inhibition of Kdm4a downregulates Sqle transcription, blocking cholesterol synthesis and causing squalene (SQA) accumulation. This process induces reactive oxygen species (ROS) clearance and suppresses JNK/c-Jun phosphorylation, ultimately inducing apoptosis. Furthermore, ML324 treatment significantly inhibited tumor growth in bladder cancer patient-derived xenograft (PDX) models. Our findings reveal the presence of a Kdm4a-Sqle-ROS-JNK/c-Jun signaling axis that regulates oxidative stress balance, offering a novel strategy for targeted therapy in bladder cancer.

The rising prevalence of viral-induced diseases, particularly those caused by certain strains, poses a substantial risk to the genetic diversity of Solanaceae crops and the overall safety of horticultural produce. According to the “gene-for-gene” hypothesis, resistance proteins are capable of selectively identifying nontoxic effectors produced by pathogens, as they are under purview of the host’s immune defenses. The sensitivity and responsiveness of Solanaceae plants to viral attacks play a crucial role in shaping the outcomes of their interactions with viruses. Pathogenic organisms, devise an array of infection tactics aimed at circumventing or neutralizing the host’s immune defenses to facilitate effective invasion. The invasion often accomplishes by suppressing or disrupting the host’s defensive mechanisms or immune signals, which are integral to the infection strategies of such invading pathogens. This comprehensive review delves into the myriad approaches that pathogenic viruses employ to infiltrate and overcome the sophisticated immune system of tomatoes. Furthermore, the review explores the possibility of utilizing these viral strategies to bolster the resilience of horticultural crops, presenting a hopeful direction for forthcoming progress in plant health and agricultural stability.

Abstract Objective To investigate the prognostic significance of body composition and nutritional indicators in patients undergoing radical cystectomy with muscle‐invasive bladder cancer (MIBC) and to develop a novel nomogram that accurately predicts overall survival (OS). Methods From December 2010 to December 2020, we retrospectively collected clinical and pathological data from 373 MIBC patients who underwent radical cystectomy at our hospital. Preoperative computed tomography (CT) images were used to measure the skeletal muscle index (SMI), subcutaneous adipose index (SAI), visceral adipose index (VAI), skeletal muscle density (SMD), subcutaneous adipose density (SAD), visceral adipose density (VAD), and visceral adipose to subcutaneous adipose area ratio (VSR). The clinicopathological characteristics were evaluated using LASSO regression and multivariate Cox regression, and a nomogram was constructed to predict 1‐, 3‐, and 5‐year overall survival. The concordance index (C‐index), time‐dependent receiver operating characteristic curves (t‐ROC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminative ability, calibration, and clinical practicality of the nomogram. Results Multivariate analyses demonstrated that pT stage, lymph node status, LVI, SMD, and prognostic nutritional index (PNI) are independent prognostic factors for OS. Additionally, a nomogram was created. The nomogram's C‐index was 0.714 (95% CI: 0.695–0.733). The area under the t‐ROC curve of 1‐, 3‐, and 5‐year survival corresponding to the model was 0.726, 0.788, and 0.785, respectively. The calibration curve demonstrated excellent agreement between the predicted and observed outcomes. The DCA revealed that patients with MIBC could benefit from the nomogram. Conclusion Based on body composition and nutritional indicators, we developed a novel nomogram with excellent predictive accuracy and reliability for predicting the prognosis of MIBC patients undergoing RC.

Abstract Background Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. Methods The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. Results ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. Conclusions In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

Abstract There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1‐year local control rate (1‐yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%–95%, I2 = 67%) and 52% (95% CI: 37%–67%, I2 = 90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1‐yr LCR (p

IntroductionDespite extensive research on contextual factors will relieve college students’ depressive symptoms, significant gaps remain in understanding the underlying mechanisms of this relationship, particularly through individual strength factors such as mindfulness and self-esteem. Based on self-determination theory, we explore the association between parental autonomy support and depressive symptoms among Chinese college students and whether mindfulness and self-esteem serve as mediators.MethodsA total of 1,182 Chinese college students aged 16 to 27 years (Mage = 20.33, SD = 1.63; female = 55.7%) participated in this research. Questionnaires pertaining to parental autonomy support, mindfulness, self-esteem, and depressive symptoms were administered.ResultsThe results revealed that depressive symptoms were negatively correlated with both paternal and maternal autonomy support, with mindfulness and self-esteem acting as chain-mediators. Specifically, mindfulness and self-esteem were positively impacted by parental autonomy support, whereas depressive symptoms were negatively impacted by mindfulness and self-esteem. Furthermore, paternal and maternal autonomy support significantly impacted depressive symptoms via both direct and indirect pathways. Indirect effects included three paths: mediation through mindfulness, mediation through self-esteem, and mediation through the mindfulness and self-esteem chain.DiscussionThe study highlights the fundamental mechanisms that account for the association between Chinese college students’ parental autonomy support and depressive symptoms, these insights can be used to prevent and manage mental health problems among Chinese college students. For example, parents’ autonomy support can directly reduce depressive symptoms, but we can also indirectly promote college students’ mental health by emphasizing the mediation role of students’ mindfulness and self-esteem.

BackgroundRhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children.MethodsFour FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3.ResultsWe found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P

Abstract. Background:. Studies have classified muscle-invasive bladder cancer (MIBC) into primary (initially muscle-invasive, PMIBC) and secondary subtypes (initially non-muscle-invasive but progresses, SMIBC), for which controversial survival outcomes were demonstrated. This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China. Methods:. Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included. Kruskal–Wallis and Fisher tests were employed to compare clinicopathological characteristics. Kaplan–Meier curves and Cox competing proportional risk model were used to compare survival outcomes. Propensity score matching (PSM) was employed to reduce the bias and subgroup analysis was used to confirm the outcomes. Results:. A total of 405 MIBC patients were enrolled, including 286 PMIBC and 119 SMIBC, with a mean follow-up of 27.54 and 53.30 months, respectively. The SMIBC group had a higher proportion of older patients (17.65% [21/119] vs. 9.09% [26/286]), chronic disease (32.77% [39/119] vs. 22.38% [64/286]), and neoadjuvant chemotherapy (19.33% [23/119] vs. 8.04% [23/286]). Before matching, SMIBC had a lower risk of overall mortality (OM) (hazard ratios [HR] 0.60, 95% confidence interval [CI] 0.41–0.85, P = 0.005) and cancer-specific mortality (CSM) (HR 0.64, 95% CI 0.44–0.94, P = 0.022) after the initial diagnosis. However, higher risks of OM (HR 1.47, 95% CI 1.02–2.10, P = 0.038) and CSM (HR 1.58, 95% CI 1.09–2.29, P = 0.016) were observed for SMIBC once it became muscle-invasive. After PSM, the baseline characteristics of 146 patients (73 for each group) were well matched, and SMIBC was confirmed to have an increased CSM risk (HR 1.83, 95% CI 1.09–3.06, P = 0.021) than PMIBC after muscle invasion. Conclusions:. Compared with PMIBC, SMIBC had worse survival outcomes once it became muscle-invasive. Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.

Abstract Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Combined tumors displayed rampant lung metastases, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT, and motility of neighboring VHL+ cells. Periostin (POSTN), a soluble protein overexpressed and secreted by VHL non-expressing (VHL−) cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

Wilderness plays a crucial role in biodiversity conservation, and its preservation represents a pivotal objective emphasized in the Post-2020 Global Biodiversity Framework (GBF). Nonetheless, wilderness frequently faces threats from the escalating impact of human activities, leading to significant repercussions on diverse ecological processes. Despite the abundance of previous studies on wilderness, there has been a limited focus on the temporal dynamics at the local scale, as well as on identifying the conservation priorities in terms of their ecosystem services. In this study, taking the Lhasa River Basin in the Qinghai-Tibet Plateau of China as an example, the spatio-temporal variations of wilderness were analyzed, and conservation priorities of them were further identified based on ecosystem services. The results revealed a persistent decline in the wilderness from 1990 to 2020, particularly in terms of bare land and grassland. Furthermore, we identified that 33.56% of the remaining wilderness necessitated special attention. These findings offer valuable insights into potential future threats to wilderness and hold critical importance for formulating regional conservation strategies at the local scale.

Ceramics and ceramic composites are often utilised for armour applications, where light weight and ballistic protection are essential. Recently, bio-inspired materials and composites for future armour applications are attracting increasing attention from researchers and engineers. In order to choose the suitable methods and techniques to fabricate ceramic and bioinspired ceramic composite armours cost-effectively, it is necessary to understand current techniques for manufacturing ceramic and ceramic composite products. In this paper, we provide a state-of-the-art review of advanced/potential manufacturing techniques available to fabricate ceramic and bioinspired ceramic composites. These methods encompass powder-based techniques (e.g., Selective Laser Melting/Sintering, Binder Jetting) used for prototyping porous ceramic structures, as well as vat polymerisation (e.g., Stereolithography, Digital Light Processing) and Slurry-Based Deposition (e.g., Direct Ink Writing, Fused Deposition Modelling), which are employed for fabricating dense ceramic parts.

Abstract Perturbations of the circadian clock are linked to multiple diseases, including cancers. Pharmacological activation of REV-ERB nuclear receptors, the core components of the circadian clock, has antitumor effects on various malignancies, while the impact of SR9009 on prostate cancer (PCa) remains unknown. Here, we found that SR9009 was specifically lethal to PCa cell lines but had no cytotoxic effect on prostate cells. SR9009 significantly inhibited colony formation, the cell cycle, and cell migration and promoted apoptosis in PCa cells. SR9009 treatment markedly inhibited prostate cancer subtype 1 (PCS1), the most lethal and aggressive PCa subtype, through FOXM1 pathway blockade, while it had no impacts on PCS2 and PCS3. Seven representative genes, including FOXM1, CENPA, CENPF, CDK1, CCNB1, CCNB2, and BIRC5, were identified as the shared genes involved in the FOXM1 pathway and PCS1. All of these genes were upregulated in PCa tissues, associated with worse clinicopathological outcomes and downregulated after SR9009 treatment. Nevertheless, knockdown or knockout of REV-ERB could not rescue the anticancer effect of SR9009 in PCa. Further analysis confirmed that it was LXRα rather than REV-ERBs which has been activated by SR9009. The expression levels of these seven genes were changed correspondingly after LXRα knockdown and SR9009 treatment. An in vivo study validated that SR9009 restrained tumor growth in 22RV1 xenograft models and inhibited FOXM1 and its targeted gene expression. In summary, SR9009 can serve as an effective treatment option for highly aggressive and lethal PCS1 tumors through mediating the LXRα/FOXM1 pathway independently of REV-ERBs.

Abstract Asynchronous advantage actor‐critic (A3C) algorithm is a commonly used policy optimization algorithm in reinforcement learning, in which asynchronous is parallel interactive sampling and training, and advantage is a sampling multi‐step reward estimation method for computing weights. In order to address the problem of low efficiency and insufficient convergence caused by the traditional heuristic exploration of A3C algorithm in reinforcement learning, an improved A3C algorithm is proposed in this paper. In this algorithm, a noise network function, which updates the noise tensor in an explicit way is constructed to train the agent. Generalised advantage estimation (GAE) is also adopted to describe the dominance function. Finally, a new mean gradient parallelisation method is designed to update the parameters in both the primary and secondary networks by summing and averaging the gradients passed from all the sub‐processes to the main process. Simulation experiments were conducted in a gym environment using the PyTorch Agent Net (PTAN) advanced reinforcement learning library, and the results show that the method enables the agent to complete the learning training faster and its convergence during the training process is better. The improved A3C algorithm has a better performance than the original algorithm, which can provide new ideas for subsequent research on reinforcement learning algorithms.

Abstract The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tropomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway. Thus, our study suggests an unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference.

Gene expression programming (GEP) is one of the most prominent algorithms in function mining. In order to obtain a more accurate function model in configuration parameters-execution efficiency (CP-EE) of map-reduce job in the high-speed railway catenary monitoring system, this paper proposes a novel algorithm, called GEP based on multi-strategy (MS-GEP). Compared to traditional GEP, the proposed algorithm can escape premature convergence and jump out of local optimum. First, an adaptive mutation rate is designed according to the evolutionary generations, population diversity, and individual fitness values. A manual intervention strategy is then proposed to determine whether the algorithm enters the dilemma of local optimum based on the generations of population evolutionary stagnation. Finally, the average quality of the population is changed by randomly replacing individuals, and the ancestral population is traced to change the evolutionary direction. The experimental results on the benchmarks of function mining show that the proposed MS-GEP has better solution quality and higher population diversity than other GEP algorithms. Furthermore, the proposed MS-GEP has higher accuracy on the function model of CP-EE of high-speed railway catenary monitoring system than other commonly used algorithms in the field of function mining.

BackgroundBiomarkers acquired from blood samples are easy to obtain and cost-effective, have attracted considerable interest, and have been widely investigated. Inflammation plays a crucial role in cancer cell initiation, proliferation, and metastasis. We aimed to evaluate the association of the preoperative systemic immune-inflammation index (SII) with the clinical outcomes of patients diagnosed with bladder cancer and who underwent radical cystectomy (RC).Materials and methodsData from patients diagnosed with bladder cancer and who underwent RC from December 2010 to May 2020 in West China Hospital were retrospectively collected according to the inclusion and exclusion criteria. Patients were divided into a low-SII group and a high-SII group according to the SII level. Survival outcomes were obtained during follow-up. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazard models were performed to estimate the effect of SII on OS and RFS and control for potential confoundings. Subgroup analyses were conducted, and the log likelihood ratio test was used to inspect the interaction.ResultsA total of 725 patients who underwent RC were ultimately involved in this study. Of these patients, 621 (85.66%) were men and 104 (14.34%) were women. The median age was 65 years. The median follow-up was 36 months for OS and 33.6 months for RFS. The optimal cutoff value was identified as 554.23 × 109/l. A total of 467 (64.41%) patients were divided into the low-SII group (SII

This paper provides a numerical investigation on the ballistic performance of ceramic composite armour panels with porous architectures inspired by nacre from mollusc shells. The development of such armour panels can lead to reduced weight and improve ballistic performance through projectile rotation induced by non-uniform contact stresses. The porous tablets of nacre have the potential to reduce the mass of armour panels without compromising their ballistic performance. Preliminary simulations were conducted to assess the performance of several porous bio-inspired structures that have the potential to survive projectile impact with less mass. Several bio-inspired panels composed of various porous designs were generated based on the different void architectures of nacre's tablets. Their performances were benchmarked against a monolithic panel under the same projectile impact condition and having the same 4.5 mm overall panel thickness but higher mass. It was found that for the cases considered, the biomimetic panels with porous architectures possess better ballistic performance compared to the corresponding monolithic panel by arresting the projectile having an initial impact velocity of 500 m/s, whilst reducing its mass by up to 18%. A further study was conducted on bio-inspired panels with a higher thickness but the same mass as the solid monolithic panel under the same projectile impact condition. It was found that the bio-inspired panel exhibits significantly improved ballistic performance when subjected to a fragment simulating projectile having an initial velocity chosen to be the ballistic limit velocity of the corresponding monolithic panel.

Biological structures possess excellent damage tolerance, which makes them attractive for ballistic protection applications. This paper develops a finite element modelling framework to investigate the performance of several biological structures that are most relevant for ballistic protection, including nacre, conch, fish scales, and crustacean exoskeleton. Finite element simulations were conducted to determine the geometric parameters of the bio-inspired structures that can survive projectile impact. The performances of the bio-inspired panels were benchmarked against a monolithic panel with the same 4.5 mm overall thickness and projectile impact condition. It was found that the biomimetic panels that were considered possessed better multi-hit resistant capabilities compared to the selected monolithic panel. Certain configurations arrested a fragment simulating projectile with an initial impact velocity of 500 m/s, which was similar to the performance of the monolithic panel.

Introduction: Microbiome research based on high-throughput sequencing has grown exponentially in recent years, but methodological variations can easily undermine the reproducibility across studies. Objectives: To systematically evaluate the comparability of sequencing results of 16S rRNA gene sequencing (16Ss)- and shotgun metagenomic sequencing (SMs)-based microbial community profiling in laboratories under routine conditions. Methods: We designed a multicenter study across 35 participating laboratories in China using designed mock communities and homogenized fecal samples. Results: A wide range of practices and approaches was reported by the participating laboratories. The observed microbial compositions of the mock communities in 46.2% (12/26) of the 16Ss and 82.6% (19/23) of the SMs laboratories had significant correlations with the expected result (Spearman r>0.59, P

Objective Nephrotoxicity is the main side effect of cyclosporine A and finding an effective combating method is urgent. The present study investigates the improving effect of erythropoietin (EPO) on cyclosporine A induce renal injury in rats and further explores its possible mechanism. Methods Recombinant adenovirus for expression of EPO was constructed and injected into kidney with multipoint. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by kits. HE staining and Masson’s trichrome staining were used to evaluate pathological changes. ELISA was performed to detect the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, and IL-6 in serum. Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney were detected according to manufacturer’s instruction. Western blotting was performed to observe the protein expression levels of peroxisome proliferator-activated receptor γ (PPAR γ), Toll-like receptor (TLR) 4, and TGF-β1. Results Results showed that EPO overexpression in rat kidney could significantly improve renal injury and fibrosis, suppress the release of inflammatory factors and reduce oxidative stress induced by cyclosporine A. Western blotting results showed that EPO overexpression could up-regulate the expression of PPARγ and down-regulate the expression of TLR4 and TGF-β1. Interestingly, when PPARγ activity was inhibited by T0070907, an effective and specific PPARγ inhibitor, the therapeutic effect of EPO was significantly attenuated. Conclusion Taken together, above results shown the protective effect of EPO on cyclosporine A-induced renal injury and confirmed that EPO’s anti-inflammation and antioxidative stress involving the PPAR γ/TLR4/TGFβ1 axis.

With the rapid development and wide application of Internet technology, the use of the concept of “smart city” has been concerned and promoted. It is an inevitable way to strengthen the breadth and depth of urban services, and to move forward from digital to intelligent application. The purpose of this study is to further promote the small and medium-sized cities in China to improve the “smart city” management mode and promote the harmonious development of society, which has important reference and practical significance. In this paper, in-depth analysis of the background of smart city, different image target detection algorithms are studied. The infrared target detection algorithm suppresses the background by means of a high-pass filter, and the coefficient of correlation between the characteristics is used as the fusion weight, while the weighted grey synthesis is performed, area and seroid offset. The ultra-spectral target detection algorithm extracts some content indicators from the initial data, and finally realizes the optimization of the algorithm. The mean filtering algorithm can reduce the effect of noise by pre-processing the image. The algorithm a hog-target detection describes the features of the object’s surface edges in areas such as graphics and image processing; and calculates the distribution of characteristics in the direction of inclination of the particular part of the image. These algorithms have their own advantages and characteristics. The results of the experiment show that the accuracy and rate of recall of the infrared target detection algorithm after aggregation of characteristics are higher than other algorithms, the accuracy is higher than 6.3% of the original infrared image algorithm, and the recall rate is 5.4% higher than the infrared image anide algorithm. The change in the value m of the main vector dimension will affect the accuracy of target detection.

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l−1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan–Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1–168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.

As an important equipment for high-speed railway (HSR) to obtain electric power from outside, the state of the pantograph will directly affect the operation safety of HSR. In order to solve the problems that the current pantograph detection method is easily affected by the environment, cannot effectively deal with the interference of external scenes, has a low accuracy rate and can hardly meet the actual operation requirements of HSR, this study proposes a pantograph detection algorithm. The algorithm mainly includes three parts: the first is to use you only look once (YOLO) V4 to detect and locate the pantograph region in real-time; the second is the blur and dirt detection algorithm for the external interference directly affecting the high-speed camera (HSC), which leads to the pantograph not being detected; the last is the complex background detection algorithm for the external complex scene “overlapping” with the pantograph when imaging, which leads to the pantograph not being recognized effectively. The dirt and blur detection algorithm combined with blob detection and improved Brenner method can accurately evaluate the dirt or blur of HSC, and the complex background detection algorithm based on grayscale and vertical projection can greatly reduce the external scene interference during HSR operation. The algorithm proposed in this study was analyzed and studied on a large number of video samples of HSR operation, and the precision on three different test samples reached 99.92%, 99.90% and 99.98%, respectively. Experimental results show that the algorithm proposed in this study has strong environmental adaptability and can effectively overcome the effects of complex background and external interference on pantograph detection, and has high practical application value.

This article presents a brief survey to visual simultaneous localization and mapping (SLAM) systems applied to multiple independently moving agents, such as a team of ground or aerial vehicles, a group of users holding augmented or virtual reality devices. Such visual SLAM system, name as collaborative visual SLAM, is different from a typical visual SLAM deployed on a single agent in that information is exchanged or shared among different agents to achieve better robustness, efficiency, and accuracy. We review the representative works on this topic proposed in the past ten years and describe the key components involved in designing such a system including collaborative pose estimation and mapping tasks, as well as the emerging topic of decentralized architecture. We believe this brief survey could be helpful to someone who are working on this topic or developing multi-agent applications, particularly micro-aerial vehicle swarm or collaborative augmented/virtual reality. Keywords: Visual SLAM, Multiple agent, UAV swarm, Collaborative AR/VR

The East China Continental Margin (ECCM) is an exemplified natural laboratory not only for studying the origin and evolution of trench-arc-basin system, but also for investigating the deformation mechanism within continent and its margins. For a better understanding on the structure and evolution of the ECCM, a NW–SE trending onshore-offshore seismic profile was recently carried out there using controlled source wide-angle and passive broadband seismic experiments in combination. This 1050-km-long seismic profile transects the East China Sea Continental Shelf Basin (CSB), Zhemin Volcanic Belt, Lower Yangtze Block, and southern North China Craton from East China Sea to continental East China. Preliminary results, such as crustal reflected and refracted phases and P-wave receiver functions, show a good quality of the seismic data and tentatively delineate some first-order characteristics of the crustal structure of the ECCM. Expectably, more detailed crustal seismic velocity and geometric structures along the profile can be constructed by a further processing of the seismic data, and enable continuous and detailed comparisons of the crustal structure and inherent nature among different blocks, combined with other existing seismic profiles in the study region. And these further studies will provide reliable constraints on some controversial geologic issues, such as the origin of CSB, the contacting boundaries and collisional processes among Cathaysian Block, Yangtze and North China cratons. Keywords: Onshore-offshore seismic survey, Controlled source wide-angle seismic experiment, Passive broadband seismic experiment, Crustal structure, East China continental margin

Abstract Purposes To investigate the value of prognostic nutritional index (PNI) in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). Patients and methods A total of 717 patients were included in our study from 2003 to 2016. PNI was calculated as 10 × serum albumin level (g/dL) + 0.005 × total lymphocyte count (per mm3). Kaplan‐Meier analysis and Cox regression models were adapted to analyze the value of PNI on survival outcomes. Results The cutoff value of PNI was set as 46.91 and 298 patients (47.6%) had PNI

Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were downregulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were involved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.

RFID localization methods have been widely used in indoor positioning systems (IPS). Most localization techniques involve the use of multiple antennas and the placement of antennas and readers in order to ensure accurate positioning results. However, most localization techniques are complex and require high overhead costs in terms of needing multiple antennas and RFID readers. In this paper, we proposed a method to use a single antenna to perform all the reads and rely rather on the antenna beams to acquire multiple positioning data. A single array of antennas is configured to have multiple angles of operation and rely on different power levels as compared to regular antennas. By manipulating the beam pattern, direction and power, multiple sub-antennas can be conceived and the method utilizes antenna beams and relies mainly on one antenna to realize two-dimensional localization.

Background: Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. VPS13B was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis.Methods: Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector.Results: A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247.Conclusions: The homozygous VPS13B splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.

Due to the accessibility and economy of human speech, speaker verification has become the research hotspot in the field of biometric authentication. A novel normalization sequence kernel based on Bhattacharyya distance clustering and within class covariance normalization was proposed in this paper. In this kernel, the high computation complexity and channel interference susceptibility that commonly exist in speaker verification could be restrained. In our method, we calculated the Bhattacharyya distance between pairs of Gaussian mixture models first. And then, a clustering algorithm was designed according to Gaussian mixture model’s Bhattacharyya distance to obtain clustering center models. Maximum a posteriori was applied on these clustering center models to generate super-vectors immediately following. The sequence kernel was generated based on Bhattacharyya distance transformation and super-vectors. Finally, within class covariance normalization was utilized to restrain the channel distortion in kernel space. We adopted support vector machine as classifier to decide the target speaker. The experiment results on TIMIT corpus and NIST 2008 SRE showed that our proposed kernel has superior recognition accuracy and better robustness.

In this study, in a novel buckling-restrained steel plate shear wall (BRSPSW) with out-of-plane deformation spaces, angle steel stiffeners have been installed so as to create gaps between the steel plate and the covering concrete slabs. A finite element model has been developed to analyse the effect of the gap. According to the finite element results, seismic performance of this novel BRSPSW has been tested under cyclic loading at the scale ratio of 1/3. The failure pattern, hysteretic characteristics, skeleton curve, equivalent stiffness, ductility, and energy dissipation have all been systematically analysed. A stiffened steel plate shear wall (SPSW) has also been tested in order to determine the differences between these two steel shear walls in load-carrying capability and the function and significance of the gap. The test results show that the novel BRSPSW does not only significantly enhance the ultimate bearing capacity, stiffness, ductility, and accumulated energy dissipation of the SPSW but also keep the steel plate basically intact at the end of the test. This can be attributed to the existence of the gaps between the infilled steel plate and the covering concrete slabs. The hysteretic characteristics and the strength and deformation characteristics of this novel BRSPSW have been simulated by using the finite element model, and the test results are in good agreement with the finite element results. Hence, the BRSPSW is an excellent steel plate shear wall to be used in high rise structure to resist horizontal loadings.

Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. Materials and methods: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. Findings: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. Interpretation: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.

ObjectiveIdentifying biomarkers of prostatic inflammation has been a question of great interest in the development of anti-inflammatory pharmacotherapy for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Systemic inflammation and serum prostate-specific antigen (PSA) have been linked with prostatic inflammation. This study set out to develop a diagnostic model for prostatic inflammation using clinical and laboratory parameters.MethodsWe included LUTS/BPH patients undergoing transurethral resection of the prostate. The severity of prostatic inflammation was determined by pathological review. Clinical manifestations and preoperative laboratory test results were recorded. We used LASSO regression with 10-fold cross-validation to select variables with the most diagnostic value of prostatic inflammation. Furthermore, we used multivariable logistic regression analysis to develop the diagnostic model, presented in a nomogram. The discrimination, calibration of the post-LASSO diagnostic model, and the model supplemented with clinical parameters were assessed. Decision curve analysis was performed.ResultsA total of 164 patients were included. Of all patients, 97 (59.1%) had no or mild prostatic inflammation, and 67 (40.9%) had moderate to severe prostatic inflammation. A higher peripheral white blood cell count, higher peripheral lymphocyte count, lower free/total (f/t) PSA ratio, and acute urinary retention history were associated with a higher risk of moderate to severe prostatic inflammation. Peripheral lymphocyte count and f/t PSA ratio were selected by the LASSO method and entered into the nomogram. The post-LASSO diagnostic model had an AUC of 0.756 (95% CI: 0.684–0.829) and good calibration. The addition of clinical parameters failed to show incremental diagnostic value. The decision curve analysis demonstrated that the post-LASSO laboratory nomogram was clinically useful.ConclusionOur findings demonstrated that peripheral lymphocyte count and f/t PSA ratio appear to be reliable diagnostic markers, based on which we build a clinically useful nomogram for prostatic inflammation. This diagnostic model could facilitate the development of anti-inflammatory pharmacotherapy for LUTS/BPH. Before this model is adopted in clinical practice, future validation is needed to determine its clinical utility.

Abstract A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

The compositive passive control (CPC) method of “interlayer seismic isolation “plus “shock absorption between adjacent towers” was applied to a multi-tower building (MTB) with a large podium. The interaction between adjacent towers was used to reduce the structural response under seismic action. Based on the Clough–Penzien spectral seismic model, the extended state equation of random response of MTB was derived with the minimum total energy of structural vibration as the optimization control objective. By comparing the seismic scheme and interlayer seismic isolation scheme, the relationship between the control parameters of the connecting control device and the random response of the structure was discussed and analyzed, and the control effect of the composite passive control system under different control schemes was also studied from the perspective of seismic response time history and vibration cumulative energy time history. Through numerical analysis, it was proved that the damping coefficient of the Kelvin-Voigt model has a great influence on the mean square error of total vibration energy while the stiffness coefficient has a poor sensitivity to it. Under the optimization control objective, the connection control device was better arranged at the top of the structure. The control effect can reach 84.64% under the condition of random ground motion as input. The CPC method maintains the advantages of the interlayer seismic isolation scheme and reduces the defect of the response amplification caused by the interlayer isolation, which provides a reference for the follow-up study of the CPC method of MTB.

This study investigated the effects of labels on preschool teachers' attitudes (i.e. openness) towards the strengths and difficulties of autistic preschool students in the mainstream setting. It also examined the differential effect of disclosure of a specific or a generic label, and the teacher-related factors influencing their attitude. Sample consisted of 106 mainstream preschool teachers (mean age = 30.37 years, "SD" = 8.85) from Singapore randomly assigned to one of three groups: "Autism Spectrum Disorder Label", "Special Needs Label", or the "No Label" group. Participants read a total of 15 vignettes depicting characteristics of autistic preschool students as strengths, difficulties, and neutral behaviours. They then rated their openness towards the featured student and complete a measure of their autism knowledge. Results indicated that the disclosure of a student's special needs label improved teachers' attitudes towards the difficulties faced by autistic students compared to when no label was disclosed. Teachers' knowledge of autism and whether teachers had experience teaching autistic students predicted the openness rating. This study has implications for parents regarding diagnosis disclosure, for the whole educational system when designing diagnosis and information transfer and the importance of professional training among early childhood educators.

The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed (1984.1-2015.3), MEDLINE (1984.1-2015.3), and EMBASE (1990.1-2015.3). Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CI). Statistic heterogeneity scores were assessed with the standard Cochran′s Q-test and I2 statistic. Publication bias was detected using the Begg′s and Egger′s tests. All statistical analyses were conducted by STATA version 10. Finally, fourteen studies were included in the meta-analysis. Both hydrophilic and hydrophobic statins showed no association with incidence of prostate cancer (RR = 1.00, 95% CI: 0.82-1.17; RR = 0.90, 95% CI: 0.73-1.08, respectively). Meanwhile, the risk of prostate cancer was not reduced in simvastatin (RR = 0.89, 95% CI: 0.72-1.05), pravastatin (RR = 1.02, 95% CI: 0.94-1.11), atorvastatin (RR = 0.89, 95% CI: 0.76-1.02), fluvastatin (RR = 0.99, 95% CI: 0.97-1.01), or lovastatin users (RR = 0.94, 95% CI: 0.79-1.08). The funnel plot showed that there was no publication bias. The results showed that statins had a neutral effect on prostate cancer risk; hydrophilic and hydrophobic statins as well as any subtype of statins did not affect the risk of prostate cancer.

Combining immune checkpoint inhibitors has shown its efficacy compared to monotherapy in advanced malignancies. We conducted this meta-analysis to provide latest evidence on the objective response rate (ORR) and incidence of treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab combination treatment and further explore from different drug dose level. PubMed and the 2019 American Society of Clinical Oncology (ASCO) annual meeting abstracts were searched for qualified clinical trials up to June 2019. Of the 23 clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 and 2,674 patients were eligible for efficacy and safety analysis, respectively. Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% confidence interval (CI), 29.1–40.4%] of patients. There was no significant difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39–1.30; P = 0.275]. Grade 3–4 AEs related to combination therapy occurred in 39.9% (95% CI, 33.5–46.7%) of patients; the most commonly reported grade 3–4 treatment-related AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase (3.51%). Incidence of grade 3–4 AEs were significant lower in N3I1-Q3W arm than in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32–0.87; P = 0.012). Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5–2.7%) of patients. Our comprehensive study provides more precise data on the incidence of treatment-related high-grade AEs and ORR among patients receiving nivolumab and ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR and significantly occurred less grade 3–4 AEs than patients on the N1I3-Q3W arm. Our finding is of great importance in assisting clinical trial design and clinical medication choice.

The pathogenesis of contrast-induced acute kidney injury (CI-AKI) is incompletely understood. MicroRNAs (miRNAs) are important mediators that normally function via post-transcriptional degradation of target mRNAs. Emerging evidence indicates the appearance of differentially expressed (DE) miRNAs in CI-AKI following the injection of intravenous contrast medium. However, there are differences in the pathological mechanism and incidence of CI-AKI between intravenous and intra-arterial contrast administration. The present study aimed to investigate the critical roles of dysregulated miRNAs and their associated mRNAs in kidney injury following intra-arterial contrast medium exposure. Based on a reliable CI-AKI rat model, we conducted genome-wide miRNA and mRNA expression profiling analysis using deep sequencing. In the study, 36 DE mature miRNAs were identified (fold change > 1.5 and p value < 0.05) in the kidneys of CI-AKI rats (n = 3) compared with that in the controls (n = 3), consisting of 23 up-regulated and 13 down-regulated DE miRNAs. Bioinformatic analysis revealed that wingnut (Wnt), transforming growth factor beta (TGF-β), and 5'-AMP-activated protein kinase (AMPK) signaling pathways were most likely to be modulated by these dysregulated miRNAs. Around 453 dysregulated genes (fold change > 2.0 and p value < 0.05) were identified. Integrated analysis revealed 2037 putative miRNA-mRNA pairs with negative correlations. Among them, 6 DE miRNAs and 13 genes were selected for further quantitative real-time reverse transcription polymerase chain reaction validation (n = 6 for each group), and a good correspondence between the two techniques was observed. In conclusion, the present study provided evidence of miRNA-mRNA interactions in the development of kidney injury following an intra-arterial contrast injection. These findings provide insights into the underlying mechanisms of CI-AKI.

A novel cost-effective isolator reinforced by engineering plastics has been designed and manufactured for seismic protection for low-rise buildings in less developed areas. The reinforcement is flexible in tension, which is similar to fiber-reinforced isolators. However, available solutions for fiber-reinforced isolators are not applicable, because the Poisson effect of engineering plastics cannot be neglected, which is done for fiber reinforcement. In this paper, analytical solutions for compression and bending stiffness for rectangular isolators reinforced by engineering plastics are proposed, with both the Poisson effect of the reinforcement and the effect of rubber compressibility taken into consideration. Then, the simplified solutions are also derived, which can greatly improve calculation efficiency. To validate the solutions, finite element analysis is conducted on a set of isolators with different reinforcement stiffnesses. The results show the superiority of the proposed solutions to the previous solutions for fiber-reinforced isolators. A series of experimental tests of the isolators are also carried out to verify the solutions. Both the analytical and the simplified solutions match well with the experimental results.

A mosaic of color filter arrays (CFAs) is commonly used in digital cameras as a spectrally selective filter to capture color images. The captured raw image is then processed by a demosaicing algorithm to recover the full-color image. In this paper, we formulate demosaicing as a restoration problem and solve it by minimizing the difference between the input raw image and the sampled full-color result. This under-constrained minimization is then solved with a novel convolutional neural network that estimates a linear subspace for the result at local image patches. In this way, the result in an image patch is determined by a few combination coefficients of the subspace bases, which makes the minimization problem tractable. This approach further allows joint learning of the CFA and demosaicing network. We demonstrate the superior performance of the proposed method by comparing it with state-of-the-art methods in both settings of noise-free and noisy data.

Plant-derived natural products are an important source of potential medicines and continue to have a major impact on the drug discovery process. Natural product discovery assignments provide an opportunity to present various experimental techniques to undergraduate students in introductory medicinal chemistry. This assignment was developed to serve as a meaningful hands-on exercise to introduce undergraduate Chemistry students to the common procedure in the early phase of drug discovery using inexpensive corn silk, in which the final year undergraduate student used Recycling Preparative High-Performance Liquid Chromatography to separate and purify steroids from corn silk. The student used advanced spectroscopic methods such as UV, IR, and one- and two-dimensional NMR to elucidate the structures of these steroids. The cytotoxic activity of these steroids was also evaluated and found to be non-cytotoxic to normal human MRC-5 cells at 60 µg/mL via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. With this assignment, students gain meaningful multidisciplinary hands-on exercises with the common procedure in the early stages of drug discovery and understand the process of isolating natural compounds that may lead to the development of new drugs.

The purpose of this study was to investigate the incidence and clinical significance of alterations in EGFR, IGF1R and the cell signaling pathway activities induced by them, as well as EGR1 expression in resected non-small cell lung cancer (NSCLC). The protein expressions of biomarker were evaluated by Western blotting in tissues from 19 surgically resected NSCLCs. High expressions of EGR1, EGFR and IGF1R were detected in more than 30% tumor tissues. High expressions of pErk and pAkt were detected in more than 50% paracancer tissues. There were significant correlations between the NSCLC target factors detected (p

Predictions of fiducial cross sections, differential cross sections, and lepton charge asymmetry are presented for the production of W± bosons with leptonic decay up to next-to-next-to-leading order (NNLO) in perturbative QCD. Differential cross sections of W± bosons and W boson lepton charge asymmetry are computed as a function of lepton pseudorapidity for a defined fiducial region in pp collisions at s=13 TeV. Numerical results of fiducial W± cross section predictions are presented with the latest modern PDF models at next-to-leading order (NLO) and NNLO. It is found that the CT14 and NNPDF 3.0 predictions with NNLO QCD corrections are about 4% higher than the NLO CT14 and NNPDF 3.0 predictions while MMHT 2014 predictions with NLO QCD corrections are smaller than its NNLO QCD predictions by approximately 6%. In addition, the NNLO QCD corrections reduce the scale variation uncertainty on the cross section by a factor of 3.5. The prediction of central values and considered uncertainties are obtained using FEWZ 3.1 program.

The equation of motion of mega-sub-isolation system is established. The working mechanism of the mega-sub-isolation system is obtained by systematically investigating its dynamic characteristics corresponding to various structural parameters. Considering the number and location of the isolated substructures, a procedure to optimally design the isolator parameters of the mega-sub-isolation system is put forward based on the genetic algorithm with base shear as the optimization objective. The influence of the number and locations of isolated substructures on the control performance of mega-sub-isolation system has also been investigated from the perspective of energy. Results show that, with increase in substructure mass, the working mechanism of the mega-sub-isolation system is changed from tuned vibration absorber and energy dissipation to seismic isolation. The locations of the isolated substructures have little influence on the optimal frequency ratio but have great influence on the optimal damping ratio, while the number of isolated substructures shows great impact on both the optimal frequency ratio and damping ratio. When the number of the isolated substructures is determined, the higher the isolated substructures, the more the energy that will be consumed by the isolation devices, and with the increase of the number of isolated substructures, the better control performance can be achieved.