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Abstract Accurately assigning standardized diagnosis and procedure codes from clinical text is crucial for healthcare applications. However, this remains challenging due to the complexity of medical language. This paper proposes a novel model that incorporates extreme multi-label classification tasks to enhance International Classification of Diseases (ICD) coding. The model utilizes deformable convolutional neural networks to fuse representations from hidden layer outputs of pre-trained language models and external medical knowledge embeddings fused using a multimodal approach to provide rich semantic encodings for each code. A probabilistic label tree is constructed based on the hierarchical structure existing in ICD labels to incorporate ontological relationships between ICD codes and enable structured output prediction. Experiments on medical code prediction on the MIMIC-III database demonstrate competitive performance, highlighting the benefits of this technique for robust clinical code assignment.

This study was aimed to retrospectively analyze the potential of non-invasive serum biomarkers in clinically predicting the detrusor underactivity (DU) in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS) and low prostate volume (PV). The study enrolled 196 patients with BPH and LUTS at our hospital in the period from January 2018 to October 2023. The patients were divided into two groups based on the projected isovolumetric pressure (PIP): the DU and the control groups. The patients included in the study had PV of less than 50 mL. A total of 93 and 103 cases were placed in the DU and control groups, respectively. Univariate analysis exhibited that the age was associated with DU occurrence (p = 0.004), and the serum prostate specific antigen (PSA) might act as DU protective factor (p = 0.001). However, there was no statistically significant relation between pre-selected serum hematological parameters and the DU diagnosis accuracy. Multivariate analysis suggested that only the age (OR (odds ratio) 1.07, 95% CI (confidence interval) 1.03–1.12, p = 0.001) and PSA (OR 0.79, 95% CI 0.69–0.90, p < 0.001) were the independent predictors of DU. In this study, it was observed that the pre-selected serum hematological parameters had no relevance in diagnosing DU in low PV male patients. Nonetheless, it was found that the age and PSA could be the independent non-invasive predictors of male patients with LUTS and low PV, who were unable to undergo urodynamic examinations.

Abstract Chemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD). A domain-specific inhibitory approach to multidomain-containing proteins may identify exceptional-responding tumor types, thereby expanding a therapeutic index. Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types. Group 3 medulloblastoma (G3MB) cells are especially sensitive to BRD, compared with HAT inhibition. Structurally, these effects are mediated by the difluorophenyl group in the catalytic core of CCS1477. Mechanistically, bromodomain inhibition causes rapid disruption of genetic dependency networks that are required for G3MB growth. These studies provide a domain-specific structural foundation for drug discovery efforts targeting EP300/CBP and identify a selective role for the EP300/CBP bromodomain in maintaining genetic dependency networks in G3MB.

Abstract Purpose Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. Methods We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. Results Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. Conclusion In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. Chinese clinical trial registry ChiCTR2000033814, Registered 13/ June/2020.

Abstract Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominate SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency and required for in vivo growth of human CRC models. These studies highlight the utility of biologically designed endogenous reporter platforms to uncover regulators with therapeutic potential.

Introduction: Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF.Methods: Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes. A visualized lncRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, while key genes in the network were identified using the cytoNCA plugin.Results: Seventy-four differentially expressed lncRNAs and 118 differentially expressed mRNAs were identified. Gene Ontology analysis revealed that the target genes were mainly enriched in the cell membrane and in response to organic substances, while Kyoto Encyclopedia of Genes and Genomes analysis showed that the target genes were mainly enriched in the AMPK, PPAR, and cAMP signaling pathways. We elucidated a ceRNA axis, namely, Plcd3-OT1/rno-miR-150-3p/Fkbp5, with potential implications in PF. Key genes, such as AABR07051308.1-201, F2rl2-OT1, and LINC3337, may be important targets for the treatment of PF, while the AMPK, PPAR, and cAMP signaling pathways are potential key targets and important pathways through which SRL-4 mitigates PF.Conclusion: Our findings suggest that SRL-4 improves PF by regulating the lncRNA-miRNA-mRNA network.

Abstract Combination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-risk patients do not survive. Our screen examines all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest existing drug combination screens. Using dense drug-drug rescreening, we find that the top CRISPR-nominated drug combinations are more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discover that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicin in vitro and in vivo using patient-derived xenograft (PDX) models. Our findings provide a valuable resource and demonstrate the feasibility of using targeted CRISPR knockout to discover combinations with common chemotherapeutics, a methodology with application across all cancers.

Abstract Hydrogen peroxide (H2O2) electrosynthesis through oxygen reduction reaction (ORR) is drawing worldwide attention, whereas suffering seriously from the sluggish oxygen evolution reaction (OER) and the difficult extraction of thermodynamically unstable H2O2. Herein, we present an electrosynthesis protocol involving coupling ORR-to-H2O2 with waste polyethylene terephthalate (PET) upcycling and the first H2O2 conversion strategy. Ni-Mn bimetal- and onion carbon-based catalysts are designed to catalyze ORR-to-H2O2 and ethylene glycol electrooxidation with the Faradaic efficiency of 97.5% (H2O2) and 93.0% (formate). This electrolysis system runs successfully at only 0.927 V to achieve an industrial-scale current density of 400 mA cm−2, surpassing all reported H2O2 electrosynthesis systems. H2O2 product is upgraded through two downstream routes of converting H2O2 into sodium perborate and dibenzoyl peroxide. Techno-economic evolution highlights the high gross profit of the ORR || PET upcycling protocol over HER || PET upcycling and ORR || OER. This work provides an energy-saving methodology for the electrosynthesis of H2O2 and other chemicals.

Objective: In this study, we studied whether minocycline hydrochloride improved neuropathic pain induced by spinal cord injury (SCI) in rats through PI3K/Akt pathway. Methods: The SCI was induced by compressed at level of T9-T11 of spinal cord in Sprague Dawley male rats. Animals were given different concentrations of minocycline (3 mg/kg, 30 mg/kg, 90 mg/kg) at the first and 24 h after SCI, then subsequently every 7, 12, 16, 20, 25 days via peroral route. The locomotor function was assessed by Basso Mouse Scale (BMS). The changes of spinal cord tissues were observed by HE. The inflammatory cytokines in spinal cord, IL-6, IL-1β and TNF-α, were measured by ELISA. The LC3B levels of spinal cord were observed by immunofluorescence. The autophagy related proteins and PI3K/AKT pathway related proteins were analysed by Western blot. Furthermore, the PI3K/AKT pathway inhibitor LY294002, and activator IGF-1 were used to confirm the mechanism of minocycline. Results: Contrasted to sham group, the inflammatory response in spinal cord was enhanced after SCI. Compared with the SCI rats, minocycline treatment significantly improved the locomotor activity, pathological injury of spinal cord, suppressed the levels of inflammatory factors. In addition, minocycline treatment upregulated autophagy response in damaged spinal cord through increasing LC3B, Beclin-1 and decreasing P62. The results of mechanism study showed that minocycline treatment clearly suppressed phosphorylation of PI3K, Akt and mTOR proteins expression. Conclusion: Minocycline could improve neuropathic pain induced by SCI through activating autophagy and inhibiting PI3K/AKT/mTOR pathway.

Objective: Motivated by Health Care 4.0, this study aims to reducing the dimensionality of traditional EEG features based on manual extracted features, including statistical features in the time and frequency domains. Methods: A total of 22 multi-scale features were extracted from the UNM and Iowa datasets using a 4th order Butterworth filter and wavelet packet transform. Based on single-channel validation, 29 channels with the highest R2 scores were selected from a pool of 59 common channels. The proposed channel selection scheme was validated on the UNM dataset and tested on the Iowa dataset to compare its generalizability against models trained without channel selection. Results: The experimental results demonstrate that the proposed model achieves an optimal classification accuracy of 100%. Additionally, the generalization capability of the channel selection method is validated through out-of-sample testing based on the Iowa dataset Conclusions: Using single-channel validation, we proposed a channel selection scheme based on traditional statistical features, resulting in a selection of 29 channels. This scheme significantly reduced the dimensionality of EEG feature vectors related to Parkinson’s disease by 50%. Remarkably, this approach demonstrated considerable classification performance on both the UNM and Iowa datasets. For the closed-eye state, the highest classification accuracy achieved was 100%, while for the open-eye state, the highest accuracy reached 93.75%.

The increasing integration of various energy sources and the adoption of smart grid technologies have revolutionized the way we generate, distribute, and consume energy. While these advancements offer numerous benefits, they also introduce vulnerabilities to cyber–physical attacks. To this aim, this paper investigates a resilient energy management strategy for integrated energy systems. By adopting a switched control approach and incorporating a local estimation mechanism, we have developed a resilient distributed energy management strategy to tackle the energy management problem (EMP) in integrated energy systems (IESs). This methodology demonstrates strong robustness and resilience, successfully detecting data integrity attacks and denial-of-service (DoS) attacks. Finally, we provide a case study to demonstrate the effectiveness of our proposed strategy in a real-world scenario.

Urinary tract cells respond to bladder distension by releasing adenosine triphosphate (ATP). Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) exhibit elevated urinary ATP levels compared to asymptomatic controls. This study aimed to evaluate the potential of urinary ATP as a non-invasive biomarker for IC/BPS and its correlation with symptom severity. We included 56 patients diagnosed with IC/BPS and 50 asymptomatic controls. Urine samples were collected from both groups. Urinary ATP levels were quantified using the luciferin-luciferase bioluminescence method. The severity of IC/BPS symptoms was assessed using the visual analogue score (VAS), Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI) from the O'Leary-Sant score. We specifically examined the correlation between symptom scores and urinary ATP levels in IC/BPS patients. Urinary ATP levels were significantly higher in IC/BPS patients compared to the control group (P < 0.0001). There was a significant positive correlation between urinary ATP concentrations and VAS, ICPI, and ICSI scores among IC/BPS patients (P < 0.0001). The threshold value for ATP concentration was set at 56.6 nM, with an area under the receiver operating characteristic (ROC) curve of 0.811 (95% CI 0.730 - 0.892). Our findings indicate that IC/BPS patients excrete elevated amounts of ATP in their urine. This suggests that urinary ATP might serve as a non-invasive biomarker for IC/BPS, with a predictive potential in terms of symptom severity.

AbstractExisting deep learning-based change detection networks encounter challenges related to the temporal dependency inherent in dual-temporal images. In this study, a weight-shared dual-difference change detection network(DDCDNet) model is proposed based on feature extraction networks. The model employs feature discrimination modules fused with spatial and channel attention mechanisms at different hierarchical levels of the backbone network. In the encoding phase, the tiny version of the Swin Transformer is utilized as the backbone network, with a weight-sharing strategy applied to extract feature information from bi-temporal remote sensing images. The proposed model in this paper is experimented on the LEVIR-CD + and DSIFN datasets, achieving F1-scores (F1) of 87.71% and 85.79%,recalls of 83.87% and 81.17%, and IoU (Intersection over Union) scores of 78.11% and 75.12%, respectively. These results indicate that the proposed model significantly outperforms other comparative models, demonstrating a better capability of identifying temporal changes in buildings, excellent generalization capability.

Objective To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. Methods The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. Results Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P

Urban blue–green spaces (UBGSs) are a significant avenue for addressing the worldwide mental health crisis. To effectively optimise landscape design and management for the promotion of health benefits from UBGS, it is crucial to objectively understand public preferences. This paper proposes a method to evaluate public landscape preference from the perspective of seeing and thinking, takes the examples of seven parks around the Dianchi Lake in Kunming, China, and analyses the social media data by using natural language processing technology and image semantic segmentation technology. The conclusions are as follows: (1) The public exhibits significantly high positive sentiments towards various UBGSs, with over 93% of comments expressed positive sentiments. (2) Differences exist in the frequency and perception of landscape features between image and text modalities. Landscape elements related to stability are perceived more in images than in text, while dynamic and experiential elements are perceived more in text than in images. (3) In both modalities, the distinctive landscape features of parks are more frequently perceived and preferred by the public. In the end, the intrinsic links between landscape elements and public sentiment and preferences are discussed, and suggestions for design and management improvements are made to consolidate their health benefits to the public.

ABSTRACT Jingmen tick virus (JMTV), belonging to the Flaviviridae family, is a novel segmented RNA virus identified in 2014 in the Jingmen region of Hubei Province, China. Up to now, JMTV has been detected in a variety of countries or regions in Asia, Europe, Africa, and the Americas, involving a wide range of arthropods and mammals, and even humans. The JMTV genome is composed of four linear RNA segments, two of which are derived from flaviviruses, while the other two segments are unique to JMTV and has no matching virus. Currently, JMTV has been shown to have a pathogenic effect on humans. Humans who had been infected would develop viremia and variable degrees of clinical symptoms. However, the pathogenic mechanism of JMTV has not been elucidated yet. Therefore, it is crucial to strengthen the epidemiological surveillance and laboratory studies of JMTV.

The present study investigated the mechanical characteristics, hydrophobicity, antioxidant and antibacterial properties, FTIR, SEM and XRD of films fabricated with corn starch and pullulan (CS/PUL) by adding different concentrations of Gallic acid (GA) (0%, 0.5%, 1.0%, 1.5% w/v). The mechanical strength and opacity of CS/PUL films were enhanced by the addition of 1.0% GA. The water vapor permeability (WVP) of CS/PUL films was significantly lower in films with GA compared to those without (P

Objective To investigate the relationship between the neutrophil-to-lymphocyte ratio and chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD + PH). Methods We retrospectively analyzed clinical data from 242 COPD patients at our hospital from July 2018 to July 2019. Patients underwent examinations including blood analysis, C-reactive protein, N-terminal brain natriuretic peptide (BNP), pulmonary function, and cardiac color ultrasound. Results Patients were divided into the COPD and COPD + PH groups using pulmonary arterial pressure (

Abstract The noisy intermediate-scale quantum devices enable the implementation of the variational quantum circuit (VQC) for quantum neural networks (QNN). Although the VQC-based QNN has succeeded in many machine learning tasks, the representation and generalization powers of VQC still require further investigation, particularly when the dimensionality of classical inputs is concerned. In this work, we first put forth an end-to-end QNN, TTN-VQC, which consists of a quantum tensor network based on a tensor-train network (TTN) for dimensionality reduction and a VQC for functional regression. Then, we aim at the error performance analysis for the TTN-VQC in terms of representation and generalization powers. We also characterize the optimization properties of TTN-VQC by leveraging the Polyak-Lojasiewicz condition. Moreover, we conduct the experiments of functional regression on a handwritten digit classification dataset to justify our theoretical analysis.

This paper presents a novel visual-admittance-based model predictive control scheme to cope with the problem of vision/force control and several constraints of a nuclear collaborative robotic visual servoing system. A visual-admittance model considering the desired image feature and force command in the image feature space is proposed. Moreover, a novel constraint scheme of the model predictive control (MPC) is proposed to cancel the overshoot in the interaction force control for most cases by taking the desired force command as the constraint of the proposed MPC. Via applying the robotic dynamic image-based visual servoing (IBVS) model, some other constraints, such as the actuator saturation, joint angle, and visual limits, can be satisfied simultaneously. The simulation results for the two-degrees-of-freedom (DOF) robot manipulator with an eye-to-hand camera are present to demonstrate the effectiveness of the proposed controller.

Abstract Epigenetic dysregulation is reported in multiple cancers including Ewing sarcoma (EwS). However, the epigenetic networks underlying the maintenance of oncogenic signaling and therapeutic response remain unclear. Using a series of epigenetics‐ and complex‐focused CRISPR screens, RUVBL1, the ATPase component of NuA4 histone acetyltransferase complex, is identified to be essential for EwS tumor progression. Suppression of RUVBL1 leads to attenuated tumor growth, loss of histone H4 acetylation, and ablated MYC signaling. Mechanistically, RUVBL1 controls MYC chromatin binding and modulates the MYC‐driven EEF1A1 expression and thus protein synthesis. High‐density CRISPR gene body scan pinpoints the critical MYC interacting residue in RUVBL1. Finally, this study reveals the synergism between RUVBL1 suppression and pharmacological inhibition of MYC in EwS xenografts and patient‐derived samples. These results indicate that the dynamic interplay between chromatin remodelers, oncogenic transcription factors, and protein translation machinery can provide novel opportunities for combination cancer therapy.

Objective To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. Methods A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. Results The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. Conclusion The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.

Abstract Background Occult hepatitis B virus (HBV) infection (OBI) is primarily characterized by the persistence of HBV‐DNA in the liver tissues and/or in the serum without detectable HBsAg. Human leukocyte antigen (HLA) polymorphisms have been found to be strongly associated with HBV in different ethnic backgrounds. The association of HLA‐DRB1‐DQB1 haplotypes with OBI has not been previously reported in China. The aim of this study was to identify the potential association of HLA‐DRB1‐DQB1 haplotypes that may be involved in OBI genetic susceptibility. Methods A case–control study was conducted between 107 OBI subjects and 280 healthy controls from the blood donors in the Shaanxi Province Blood Center. The HLA‐DRB1, DQB1 loci were genotyped using polymerase chain reaction‐sequence based typing (PCR‐SBT). Based on the genotype data of the two loci, haplotype estimation was performed. Results HLA‐DRB1*07:01‐DQB1*02:02 (pc = 0.344 × 10−3, OR = 3.489, 95%CI = 2.000–6.088) and HLA‐DRB1*09:01‐DQB1*03:03 (pc = 0.02, OR = 2.370, 95%CI = 1.450–3.873) serve as the possible risk and susceptibility haplotypes for OBI in Xi'an Han after Bonferroni correction. Conclusions This study demonstrated that HLA II haplotypes were significantly associated with OBI in the Xi'an Han population. To the best of our knowledge, this is the first study to associate HLA‐DRB1‐DQB1 haplotypes with OBI, which can provide valuable insights into the relationship between the various genetic factors and immune responses in the Xi'an population. The findings can also form the basis for future studies about the role of HLA in OBI.

A solitary functioning kidney (SFK) with renal cell carcinoma (RCC) is an imperative indication for nephron-sparing surgery (NSS). Nevertheless, a giant pT3 RCC mass (maximum diameter >20 cm) on the functioning side of a patient with SFK is extremely rare. However, whether NSS is more beneficial than radical nephrectomy (RN) in such patients is controversial. Here, we present the case of a 71-year-old female patient with a 20 cm*16 cm RCC mass in the SFK, who initially presented with hematuria and acute urinary tract obstructive anuria caused by renal calculi. The patient underwent NSS treatment after our evaluation, and the 26-month follow-up revealed that her renal function recovered to the state before the tumor formation. In addition, no relapse or metastasis was detected.

Abstract Aim To investigate the association of human leukocyte antigen (HLA)-DRB1 alleles and the variations of polymorphic amino acid changes in DRβ1 chain in Shaanxi Han population with Occult hepatitis B infection (OBI). Methods High-resolution HLA-DRB1 genotyping was performed in 107 OBI carriers and 280 normal controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Three-dimensional modeling was performed to explore the effect of the key residues on the HLA-DRB1 molecule. Results Strong susceptible association for allele DRB1*07:01 was observed in OBI carriers. The amino acid variation at HLA-DRβ1 molecule revealed susceptible associations for residues Gln4β, Val57β(P9), Ser60β(P9) and Val78β(P4), the amino acids Arg4β, Asp57β(P9), Tyr60β(P9) and Tyr78β(P4) showed protective associations. Conclusion Alleles DRB1*07:01 showed strong susceptible associations in OBI carriers. The amino acid variations in DRβ molecules revealed significant molecular markers for susceptibility and protection from OBI in Shaanxi Han population.

Abstract Background Mechanical loading has been widely considered to be essential for growth plate to maintain metabolism and development. Cyclic mechanical strain has been demonstrated to induce autophagy, whereas the relationship between cyclic tensile strain (CTS) and autophagy in growth plate chondrocytes (GPCs) is not clear. The objective of this study was to investigate whether CTS can regulate autophagy in GPCs in vitro and explore the potential mechanisms of this regulation. Methods The 2-week-old Sprague–Dawley rat GPCs were subjected to CTS of varying magnitude and duration at a frequency of 2.0 Hz. The mRNA levels of autophagy-related genes were measured by RT-qPCR. The autophagy in GPCs was verified by transmission electron microscopy (TME), immunofluorescence and Western blotting. The fluorescence-activated cell sorting (FACS) was employed to detect the percentage of apoptotic and necrotic cells. Results In GPCs, CTS significantly increased the mRNA and protein levels of autophagy-related genes, such as LC3, ULK1, ATG5 and BECN1 in a magnitude- and time-dependent manner. There was no significant difference in the proportion of apoptotic and necrotic cells between control group and CTS group. The autophagy inhibitors, 3-methyladenine (3MA) and chloroquine (CQ) reversed the CTS-induced autophagy via promoting the formation of autophagosomes. Cytochalasin D (cytoD), an inhibitor of G-actin polymerization into F-actin, could effectively block the CTS-induced autophagy in GPCs. Conclusion Cyclic mechanical strain with high-tensile triggers autophagy in GPCs, which can be suppressed by 3MA and CQ, and cytoskeletal F-actin microfilaments organization plays a key role in chondrocytes’ response to mechanical loading.

With the continuous improvement of the penetration rate of renewable energy and the continuous integration of advanced network control technology and measurement equipment, the traditional distribution network is developing into an active distribution network (ADN) with the characteristics of flexible scheduling control, high user interaction, and high energy utilization. This article fully considers the economy of the overall operation of the distribution network, and proposes a hierarchical optimization economic dispatch method for active distribution networks based on the alternating direction multiplier method (ADMM). Firstly, a hierarchical optimization scheduling model of active distribution network is established with the goal of minimizing the overall operating cost of the distribution network. The alternating direction multiplier method algorithm is decomposed into upper and lower layers to solve. The upper layer is optimized with the goal of minimizing the overall operating cost of the distribution network, and the lower layer considers the distribution network. The distributed photovoltaic and energy storage units connected to the internal nodes of the network are optimized with the goal of minimizing the local energy storage operation cost and power purchase cost. The upper and lower layers, through the exchange of limited boundary information, iterate each other until the convergence conditions are met, and the optimal solution is obtained. Finally, a design example is tested to verify the effectiveness and feasibility of the proposed scheduling method.

In this paper, a topology optimization method combining Bi-directional Evolutionary Structural Optimization (BESO) and Fast Non-dominated Sorting Genetic Algorithm II (NSGA-II) is proposed, which is called BESO-NSGA-II. To effectively fuse the two algorithms, a semi-random double-penalized crossover and mutation operator is developed. The proposed algorithm extends the traditional single-objective optimization to a double objective optimization problem, and investigates the influence of the stress norm parameters on the optimization results. To verify the effectiveness of the new method, several examples of 2D structural stiffness and stress optimization are given. At the same time, the optimization design of each model was repeated six times to demonstrate the ability of the new method to converge to a solution. Compared with BESO, BESO-NSGA-II can effectively realize the double objective optimization of stiffness and stress, and eliminate the stress concentration phenomenon on the premise of ensuring that the structure has greater stiffness.

Purpose: Radiation therapy (RT) is one of the main treatments for cancer. The response to radiotherapy varies widely between individuals and some patients have poor response to RT treatment due to tumor radioresistance. Stratifying patients according to molecular signatures of individual tumor characteristics can improve clinical treatment. In here, we aimed to use clinical and genomic databases to develop miRNA signatures that can predict response to radiotherapy in various cancer types.Methods: We analyzed the miRNAs profiles using tumor samples treated with RT across eight types of human cancers from TCGA database. These samples were divided into response group (S, n = 224) and progressive disease group (R, n = 134) based on RT response of tumors. To enhance the discrimination for S and R samples, the predictive models based on binary logistic regression were developed to identify the best combinations of multiple miRNAs.Results: The miRNAs differentially expressed between the groups S and R in each caner type were identified. Total 47 miRNAs were identified in eight cancer types (p values

Abstract Frizzled (Fzd) proteins are Wnt receptors and play essential roles in development, homeostasis, and oncogenesis. How Wnt/Fzd signaling is coupled to physiological regulation remains unknown. Cholesterol is reported as a signaling molecule regulating morphogen such as Hedgehog signaling. Despite the elusiveness of the in‐depth mechanism, it is well‐established that pancreatic cancer specially requires abnormal cholesterol metabolism levels for growth. In this study, it is unexpectedly found that among ten Fzds, Fzd5 has a unique capacity to bind cholesterol specifically through its conserved extracellular linker region. Cholesterol‐binding enables Fzd5 palmitoylation, which is indispensable for receptor maturation and trafficking to the plasma membrane. In Wnt‐addicted pancreatic ductal adenocarcinoma (PDAC), cholesterol stimulates tumor growth via Fzd5‐mediated Wnt/β‐catenin signaling. A natural oxysterol, 25‐hydroxylsterol competes with cholesterol and inhibits Fzd5 maturation and Wnt signaling, thereby alleviating PDAC growth. This cholesterol‐receptor interaction and ensuing receptor lipidation uncover a novel mechanism by which Fzd5 acts as a cholesterol sensor and pivotal connection coupling lipid metabolism to morphogen signaling. These findings further suggest that cholesterol‐targeting may provide new therapeutic opportunities for treating Wnt‐dependent cancers.

Summary: Transcriptional dysregulation is a prominent feature in leukemia. Here, we systematically surveyed transcription factor (TF) vulnerabilities in leukemia and uncovered TF clusters that exhibit context-specific vulnerabilities within and between different subtypes of leukemia. Among these TF clusters, we demonstrated that acute myeloid leukemia (AML) with high IRF8 expression was addicted to MEF2D. MEF2D and IRF8 form an autoregulatory loop via direct binding to mutual enhancer elements. One important function of this circuit in AML is to sustain PU.1/MEIS1 co-regulated transcriptional outputs via stabilizing PU.1’s chromatin occupancy. We illustrated that AML could acquire dependency on this circuit through various oncogenic mechanisms that results in the activation of their enhancers. In addition to forming a circuit, MEF2D and IRF8 can also separately regulate gene expression, and dual perturbation of these two TFs leads to a more robust inhibition of AML proliferation. Collectively, our results revealed a TF circuit essential for AML survival.

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared to single agents, these combinations cooperated to decrease levels of N-myc. We treated both TP53-wild type and mutant, MYCN-amplified cell lines with the BETi JQ1 and the AURKAi Alisertib. The combination had improved efficacy in the TP53-WT context, notably driving apoptosis in both genetic backgrounds. JQ1+Alisertib combination treatment of a MYCN-amplified, TP53-null or TP53-restored genetically engineered mouse model of NBL prolonged survival better than either single agent. This was most profound with TP53 restored, with marked tumor shrinkage and apoptosis induction in response to combination JQ1+Alisertib. BETi+AURKAi in MYCN-amplified NBL, particularly in the context of functional TP53, provided anti-tumor benefits in preclinical models. This combination should be studied more closely in a pediatric clinical trial.

The androgen receptor (AR) signaling is a key contributor to tumorigenesis and the progression of prostate cancer. A subset of patients may develop neuroendocrine (NE) features, resulting in resistance to androgen deprivation therapy and poor prognosis. In this study, we combined immunostaining and bulk and single-cell transcriptome analyses to better characterize the status of AR in prostate cancer with neuroendocrine differentiation. The exploration of online datasets indicated the existence of ARHIGH/NEHIGH prostate cancer and revealed that these double-high cases are majorly present in castration-resistant prostate cancer with a less neuroendocrine-transdifferentiated state. We then reviewed 8,194 prostate cancer cases with available immunohistochemistry reports and found 2.3% cases (n = 189) that showed at least one of the NE markers (chromogranin A, synaptophysin, and neural cell adhesion molecule 1) being positive in at least 5% of epithelial cells. Within these 189 cases, we observed that 81.0% cases (n = 153) showed AR positive and 19.0% (n = 36) showed AR negative. Patients with AR loss tumors demonstrated a correlation with adverse clinical stages, indicating a trade-off between AR and advanced disease in neuroendocrine differentiation. Using multiplex immunofluorescence staining, we observed the co-localization of AR and NE markers in prostate cancer cells. In addition, data mining of single-cell transcriptome further confirmed the existence of ARHIGH/NEHIGH prostate cancer cells in castration-resistant samples and suggested that AR still exerts its androgen response and anti-apoptotic effect in these double-high cells. Thus, our study provides a better understanding of AR signaling in the cellular plasticity of prostate cancer with neuroendocrine differentiation and allows new insights into the therapeutic development.

ObjectiveTo investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active ankylosing spondylitis (AS) patients with etanercept and celecoxib alone/combined treatment.MethodsA randomized controlled trial was conducted in three medical centers in China. Adult AS patients with BASDAI ≥4 or ASDAS ≥2.1, CRP >6 mg/L, or ESR 28 mm/1st hour were randomly assigned (1:1:1 ratio) to celecoxib 200 mg bid or etanercept 50 mg qw or combined therapy for 52 weeks. The primary outcomes were SPARCC change of the sacroiliac joint (SIJ) and spine and the proportion of patients achieving ASAS20 response at 52 weeks.ResultsBetween September 2014 and January 2016, we randomly assigned 150 patients (mean age, 32.4 years; mean disease duration, 109 months), and 133 (88.6%) completed the study. SPARCC inflammation scores of the SIJ and spine decreased in the three groups, and significant differences were found between the combined group and the celecoxib group [between-group difference: −6.33, 95% CI (−10.56, −2.10) for SIJ; −9.53, 95% CI (−13.73, −5.33) for spine] and between the etanercept group and the celecoxib group [between-group difference: −5.02, 95% CI (−9.29, −0.76) for SIJ; −5.80, 95% CI (−10.04, −1.57) for spine]. The ASAS20 response rates were 44%, 58%, and 84% in the celecoxib, etanercept, and combined groups, respectively, and a significant difference was only found between the combined and the celecoxib groups.ConclusionEtanercept with or without celecoxib decreases inflammation detected by MRI at 1 year compared to celecoxib alone in active AS patients. The combination of etanercept and celecoxib was superior to celecoxib alone for the primary clinical response.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01934933.

The class I histone deacetylases are essential regulators of cell fate decisions in health and disease. While pan- and class-specific HDAC inhibitors are available, these drugs do not allow a comprehensive understanding of individual HDAC function, or the therapeutic potential of isoform-specific targeting. To systematically compare the impact of individual catalytic functions of HDAC1, HDAC2 and HDAC3, we generated human HAP1 cell lines expressing catalytically inactive HDAC enzymes. Using this genetic toolbox we compare the effect of individual HDAC inhibition with the effects of class I specific inhibitors on cell viability, protein acetylation and gene expression. Individual inactivation of HDAC1 or HDAC2 has only mild effects on cell viability, while HDAC3 inactivation or loss results in DNA damage and apoptosis. Inactivation of HDAC1/HDAC2 led to increased acetylation of components of the COREST co-repressor complex, reduced deacetylase activity associated with this complex and derepression of neuronal genes. HDAC3 controls the acetylation of nuclear hormone receptor associated proteins and the expression of nuclear hormone receptor regulated genes. Acetylation of specific histone acetyltransferases and HDACs is sensitive to inactivation of HDAC1/HDAC2. Over a wide range of assays, we determined that in particular HDAC1 or HDAC2 catalytic inactivation mimics class I specific HDAC inhibitors. Importantly, we further demonstrate that catalytic inactivation of HDAC1 or HDAC2 sensitizes cells to specific cancer drugs. In summary, our systematic study revealed isoform-specific roles of HDAC1/2/3 catalytic functions. We suggest that targeted genetic inactivation of particular isoforms effectively mimics pharmacological HDAC inhibition allowing the identification of relevant HDACs as targets for therapeutic intervention.

Raising the water pollution control countermeasures on the basis of rational pollution load estimation is significant for improving water quality. Zhangze Reservoir, the largest water body in Changzhi city, China, was selected for this study. Considering the information constraints of the reservoir basin, the pollution load estimation method system covering point sources, non-point sources, and internal sources is systematically constructed using an export coefficient model, an sediment pore water diffusion model, and other methods, with the aim of estimating the discharge of pollutants into the Zhangze Reservoir from domestic sources, industrial sources, agricultural sources, sediment release, and urban runoff. The findings indicate the following: 1) the pollution loads of COD, NH3-N, TN, and TP are 3,157.82t, 177.62t, 760.72t, and 42.29t, respectively; 2) in terms of the distribution of pollution sources, urban domestic sources top the rest, accounting for 65.47% of COD, 82.83% of NH3-N, 79.00% of TN, and 60.65% of TP, followed by the agricultural source; 3) the total discharge of the main water pollutants exceeds the water environmental capacity, characterized as the dominating existence of domestic point source, the coexistence of point sources and non-point sources, and the coexistence of exogenous sources and endogenous sources. Finally, control countermeasures are raised to minimize the total discharge of pollutants for improving the water quality.

Path planning in complex environments remains a challenging task for unmanned vehicles. In this paper, we propose a decoupled path-planning algorithm with the help of a deep reinforcement learning algorithm that separates the evaluation of paths from the planning algorithm to facilitate unmanned vehicles in real-time consideration of environmental factors. We use a 3D surface map to represent the path cost, where the elevation information represents the integrated cost. The peaks function simulates the path cost, which is processed and used as the algorithm’s input. Furthermore, we improved the double deep Q-learning algorithm (DDQL), called retrospective-double DDQL (R-DDQL), to improve the algorithm’s performance. R-DDQL utilizes global information and incorporates a retrospective mechanism that employs fuzzy logic to evaluate the quality of selected actions and identify better states for inclusion in the memory. Our simulation studies show that the proposed R-DDQL algorithm has better training speed and stability compared to the deep Q-learning algorithm and double deep Q-learning algorithm. We demonstrate the effectiveness of the R-DDQL algorithm under both static and dynamic tasks.

The objective of this study was to examine the effect of pulling angle on time-zero mechanical properties of intact infraspinatus tendon or infraspinatus tendon repaired with the modified Mason-Allen technique in a canine model in vitro. Thirty-six canine shoulder samples were used. Twenty intact samples were randomly allocated into functional pull (135°) and anatomic pull (70°) groups (n = 10 per group). The remaining sixteen infraspinatus tendons were transected from the insertion and repaired using the modified Mason-Allen technique before being randomly allocated into functional pull or anatomic pull groups (n = 8 per group). Load to failure testing was performed on all specimens. The ultimate failure load and ultimate stress of the functional pulled intact tendons were significantly lower compared with anatomic pulled tendons (1310.2 ± 167.6 N vs. 1687.4 ± 228.2 N, p = 0.0005: 55.6 ± 8.4 MPa vs. 67.1 ± 13.3 MPa, p = 0.0334). For the tendons repaired with the modified Mason-Allen technique, no significant differences were observed in ultimate failure load, ultimate stress or stiffness between functional pull and anatomic pull groups. The variance of pulling angle had a significant influence on the biomechanical properties of the rotator cuff tendon in a canine shoulder model in vitro. Load to failure of the intact infraspinatus tendon was lower at the functional pulling position compared to the anatomic pulling position. This result indicates that uneven load distribution across tendon fibers under functional pull may predispose the tendon to tear. However, this mechanical character is not presented after rotator cuff repair using the modified Mason-Allen technique.

Objective: Decellularized adipose-derived matrix (DAM) can promote adipogenic differentiation and adipose tissue remodeling, but the biological impact of tissue origin on DAM remains unknown. The present study aimed to investigate the effects of tissue origins on the adipogenic capacity of the decellularized matrix by comparing the cellular and tissue responses of DAM versus acellular dermal matrix (ADM).Methods: The in vitro response of adipose-derived stem/stromal cells (ADSCs) to DAM and ADM was characterized by proliferation and differentiation. The in vivo remodeling response was evaluated in the subcutaneous injection model of immunocompromised mice, using histology, protein expression, and transcriptome analysis.Results: Both DAM and ADM exhibited excellent decellularization effects and cytocompatibility. In the absence of exogenous stimuli, DAM could induce adipogenic differentiation of ADSCs compared with ADM. In the animal model, the levels of PDGF, VEGF, and ACRP30 were higher in the DAM groups than in the ADM group, and more neovascularization and extensive adipose tissue remodeling were observed. The mRNA-seq analysis indicated that the DAM implant regulated tissue remodeling by modulating Lat1/2 expression along with Hippo Signaling pathway in the early stage.Conclusion: Tissue origin can influence the biological response of the decellularized matrix. DAM can retain favorable tissue-specific characteristics after the decellularization process and have unique adipogenic effects in vitro and vivo, which can be fully utilized for soft tissue repair and regeneration.

Understanding how external water affects the water quality of target water bodies is an important prerequisite for predicting water quality changes and formulating pollutant reduction plans. Using the EFDC modeling system platform, this study constructed the hydrodynamic and pollutant dispersion and diffusion models of Zhangze Reservoir, and by using the hydrology and water quality data from 2013 to 2018, this study examines the different water quality responses of Zhangze Reservoir under different inflow water control scenarios. The results show that the simulated value of the hydrological station is basically consistent with the measured value of the hydrological station. Under the current Class III water quality requirements for Zhangze Reservoir, direct inflow of effluent from the wastewater treatment plant of the main urban area into the reservoir will have a significant impact on the water quality. When the effluent is purified through constructed wetlands, it significantly improves the water quality of the reservoir, but the concentration of TN and TP still cannot reach the Class III standard in the short term,. When all rivers entering the reservoir meet the standard and the effluent from the wastewater treatment plant in the main urban area does not enter the reservoir, the content of COD, ammonia nitrogen and TP in water will reach the Class III standard, but reducing the TN content to meet the standard requirement will be difficult within 3 years.

Background: Osteoarthritis (OA) is a common degenerative joint disease. The aims of this study are to explore the effects of mechanical stress on whole transcriptome landscape and to identify a non-coding transcriptome signature of mechanical stress.Methods: Next-generation RNA sequencing (RNA-seq) was performed on IL-1β-induced OA-like chondrocytes stimulated by mechanical stress. Integrated bioinformatics analysis was performed and further verified by experimental validations.Results: A total of 5,022 differentially expressed mRNAs (DEMs), 88 differentially expressed miRNAs (DEMIs), 1,259 differentially expressed lncRNAs (DELs), and 393 differentially expressed circRNAs (DECs) were identified as the transcriptome response to mechanical stress. The functional annotation of the DEMs revealed the effects of mechanical stress on chondrocyte biology, ranging from cell fate, metabolism, and motility to endocrine, immune response, and signaling transduction. Among the DELs, ∼92.6% were identified as the novel lncRNAs. According to the co-expressing DEMs potentially regulated by the responsive DELs, we found that these DELs were involved in the modification of immune and metabolism. Moreover, immune- and metabolism-relevant DELs exhibited a notable involvement in the competing endogenous RNA (ceRNA) regulation networks. Silencing lncRNA TCONS_00029778 attenuated cellular senescence induced by mechanical stress. Moreover, the expression of Cd80 was elevated by mechanical stress, which was rescued by silencing TCONS_00029778.Conclusion: The transcriptome landscape of IL-1β-induced OA-like chondrocytes was remarkably remodeled by mechanical stress. This study identified an immune- and metabolism-related ncRNA transcriptome signature responsive to mechanical stress and provides an insight of ncRNAs into chondrocyte biology and OA.

Abstract This present study was designed to evaluate the immunomodulatory activity of Konjac glucomannan (KGM) on immunosuppressed mice induced by cyclophosphamide (CTX) treatment. The mice immunodeficiency model was established by CTX. KGM was used to modulate the activities of immunosuppressive mice. It was proved that KGM could promote the proliferation of lymphocyte, thymus, and spleen indices, and alleviate the atrophy of immune organs and weight loss. Besides, in mice serum, the levels of cytokines including TNF‐α, IgG, IL‐2, and the contents of hemolysin were also increased after treatment with KGM. Furtherly, in nonspecific immunity, KGM could enhance natural killer (NK) cell lethality and pinocytic activity of mouse peritoneal macrophages. Therefore, all of these results revealed that KGM could improve the reduced immunity of CTX‐induced mice via modulation innate immunity and adaptive immunity.

Abstract For controlling recent COVID-19 outbreaks around the world, many countries have implemented suppression and mitigation interventions. This work aims to conduct a feasibility study for accessing the effect of multiple interventions to control the COVID-19 breakouts in the UK and other European countries, accounting for balance of healthcare demand. The model is to infer the impact of mitigation, suppression and multiple rolling interventions for controlling COVID-19 outbreaks in the UK, with two features considered: direct link between exposed and recovered population, and practical healthcare demand by separation of infections. We combined the calibrated model with COVID-19 data in London and non-London regions in the UK during February and April 2020. Our finding suggests that rolling intervention is an optimal strategy to effectively control COVID-19 outbreaks in the UK for balancing healthcare demand and morality ratio. It is better to implement regional based interventions with varied intensities and maintenance periods. We suggest an intervention strategy named as “Besieged and rolling interventions” to the UK that take a consistent suppression in London for 100 days and 3 weeks rolling intervention in other regions. This strategy would reduce the overall infections and deaths of COVID-19 outbreaks, and balance healthcare demand in the UK.

This paper is concerned with the $H_{\infty }$ filtering for Lipschitz nonlinear systems under aperiodically sampled measurements. The developed filter is a hybrid system, whose states undergo a change or reset at sampling instants. The resulting filtering error system is then modelled as a kind of nonlinear impulsive systems. By introducing a time-varying Lyapunov functional candidate, a sufficient condition for the existence of desired filter is derived to ensure the filtering error system asymptotic stability and guarantee an $H_{\infty }$ performance. The optimal $H_{\infty }$ performance and corresponding filter gain matrix can be obtained by solving a convex problem with linear matrix inequalities (LMIs) constrains. Two examples are given to show the effectiveness of the theoretical results, and our results are less conservative than existing ones through comparisons.

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2–q13.43 and 16q22.2–q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.

This study was intended to characterize six types of commercial smoked chicken products in China by using gas chromatography-mass spectrometry (GC-MS), odor-activity values (OAVs), and sensory evaluation. Results demonstrated that a total of 89 components were identified in all samples, and 34 were considered as odor-active compounds because their OAVs were greater than one. Liaocheng Chicken that smoked with fruit tree sawdust had more phenols, which contributed to the smoky aroma. Jinshan and Goubangzi Chicken that smoked with sugar had more furans which contributed the overall odor with sweety and caramel aroma. Zhuozishan and Laoting Chicken that smoked with sugar and wood chips had similar flavor and volatile compounds. Tengqiao Chicken that smoked with sugar, tea and rice had significant difference with other chicken in smoky, bittern and caramel aroma (P< .05). The diversity of these smoked chicken flavors was mainly due to the cooking culture differences.

The differences of emulsion properties between normal colour chicken livers (NCCLs) and discolouration chicken livers (DCCLs) were evaluated. Compared with NCCLs, the L* and b*-value of DCCLs were extremely higher (p