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The wake behind an aircraft carrier under heavy wind condition is a key concern in ship design. The Chinese Liaoning ship’s upturned bow and the island on the deck could cause serious flow separation in the landing and take-off area. The flow separation induces strong velocity gradients and intense pulsations in the flow field. In addition, the sway of the aircraft carrier caused by waves could also intensify the flow separation. The complex flow field poses a significant risk to the shipboard aircraft take-off and landing operation. Therefore, accurately predicting the wake of an aircraft carrier during wave action motion is of great interest for design optimization and recovery aircraft control. In this research, the aerodynamic around an aircraft carrier (i.e., Liaoning) was analyzed using the computational fluid dynamics technique. The validity of two turbulence models was verified through comparison with the existing data from the literature. The upturned bow take-off deck and the right-hand island were the main areas where flow separation occurred. Delayed detached eddy simulation (DDES), which combines the advantages of LES and RANS, was adopted to capture the full-scale spatial and temporal flow information. The DDES was also coupled with the overset grid to calculate the flow field characteristics under the effect of hull sway. The downwash area at 15° starboard wind became shorter when the hull was stationary, while the upwash area and turbulence intensity increased. The respective characteristics of the wake flow field in the stationary and swaying state of the ship were investigated, and the flow separation showed a clear periodic when the ship was swaying. Comprehensive analysis of the time-dependent flow characteristic of the approach line for fixed-wing naval aircraft is also presented.

This research delves into the complex impact of High Involvement Work Practices (HIWPs) on various facets of employee well-being and service outcomes within the framework of the trichromatic service conception. Utilizing the Job Demands-Resources (JD-R) model, the study uncovers the dual, both beneficial and detrimental, effects of HIWPs on service performance, work–family conflict, subjective well-being, and work-family enrichment. Examining the conflicting paths of job demands (workload) and job resources (customer orientation), the analysis incorporates the moderating influence of a strategic contextual factor—supervisor support. Data was collected through self-administered questionnaires from 475 respondents in Pakistani banks, and the analysis employed moderated mediation analysis using SPSS, AMOS, and the PROCESS Macro. All proposed hypotheses received support. The results indicate that HIWPs enhance service performance by promoting customer orientation but concurrently escalate workload, leading to adverse consequences for subjective well-being and work–family conflict. The study underscores the importance of implementing HIWPs under supportive leadership to maximize positive outcomes and mitigate negative consequences. Ultimately, this approach enables employees to effectively serve customers, maintain a healthy work-family balance, and contribute to the long-term growth and sustainability of organizations.

As a new technology in the field of food science, three-dimensional (3D) printing technology has tremendous development potential due to its rapid prototyping capabilities, suitability for complex structures, and customization. Proteins, lipids, and other edible substances are generally used as materials in 3D food printing, but not all ingredients can be printed or processed well. 3D food printing technology, the properties of 3D printing materials, common food additives and their effects on rheological properties, processing properties, and nutritional properties of print materials are reviewed in this paper. This study would provide a scientific basis for the application of 3D food printing technology in the food field and theoretical references.

Abstract Aims and objectives To summarize the use of machine learning (ML) for hospital‐acquired pressure injury (HAPI) prediction and to systematically assess the performance and construction process of ML models to provide references for establishing high‐quality ML predictive models. Background As an adverse event, HAPI seriously affects patient prognosis and quality of life, and causes unnecessary medical investment. At present, the performance of various scales used to predict HAPIs is still unsatisfactory. As a new statistical tool, ML has been applied to predict HAPIs. However, its performance has varied in different studies; moreover, some deficiencies in the model construction process were observed in each study. Design Systematic review. Methods Relevant articles published between 2010–2021 were identified in the PubMed, Web of Science, Scopus, Embase and CINHAL databases. Study selection was performed in accordance with the preferred reporting items for systematic reviews and meta‐analysis guidelines. The quality of the included articles was assessed using the prediction model risk of bias assessment tool. Results Twenty‐three studies out of 1793 articles were considered in this systematic review. The sample size of each study ranged from 149–75353; the prevalence of pressure injuries ranged from 0.5%–49.8%. ML showed good performance for HAPI prediction. However, some deficiencies were observed in terms of data management, data pre‐processing and model validation. Conclusions ML, as a powerful decision‐making assistance tool, is helpful for the prediction of HAPIs. However, existing studies have been insufficient in terms of data management, data pre‐processing and model validation. Future studies should address these issues to establish ML models for HAPI prediction that can be widely used in clinical practice. Relevance to Clinical Practice This review highlights that ML is helpful in predicting HAPI; however, in the process of data management, data pre‐processing and model validation, some deficiencies still need to be addressed. The ultimate goal of integrating ML into HAPI prediction is to develop a practical clinical decision‐making tool. A complete and rigorous model construction process should be followed in future studies to develop high‐quality ML models that can be applied in clinical practice.

Abstract Background Dislocation is a common complication after total hip arthroplasty (THA). This study aimed to compare the outcomes of mesh reconstruction versus conventional capsular repair in maintaining capsular integrity and preventing dislocation after THA. Methods This was a prospective, randomized controlled study of consecutive patients. A total of 124 high-dislocation-risk THAs were identified and randomized into two groups, one using mesh reconstruction and the other using the conventional capsular repair method. Perioperative data and radiological data were collected. Patients were followed up regularly. The main indices were the capsular integrity assessed by magnetic resonance imaging (MRI) and hip dislocation rate. The secondary indices included the Harris hip score (HHS), complications, and satisfaction. Results A total of 106 patients completed the follow-up and the average follow-up times were 19 ± 3.1 and 18 ± 3.3 months. The operation time of the mesh group was longer than that of the conventional group (P

Established taxonomy system based on disease symptom and tissue characteristics have provided an important basis for physicians to correctly identify diseases and treat them successfully. However, these classifications tend to be based on phenotypic observations, lacking a molecular biological foundation. Therefore, there is an urgent to integrate multi-dimensional molecular biological information or multi-omics data to redefine disease classification in order to provide a powerful perspective for understanding the molecular structure of diseases. Therefore, we offer a flexible disease classification that integrates the biological process, gene expression, and symptom phenotype of diseases, and propose a disease-disease association network based on multi-view fusion. We applied the fusion approach to 223 diseases and divided them into 24 disease clusters. The contribution of internal and external edges of disease clusters were analyzed. The results of the fusion model were compared with Medical Subject Headings, a traditional and commonly used disease taxonomy. Then, experimental results of model performance comparison show that our approach performs better than other integration methods. As it was observed, the obtained clusters provided more interesting and novel disease-disease associations. This multi-view human disease association network describes relationships between diseases based on multiple molecular levels, thus breaking through the limitation of the disease classification system based on tissues and organs. This approach which motivates clinicians and researchers to reposition the understanding of diseases and explore diagnosis and therapy strategies, extends the existing disease taxonomy. Availability of data and materials: The preprocessed dataset and source code supporting the conclusions of this article are available at GitHub repository https://github.com/yangxiaoxi89/mvHDN.

Introduction: Fear of progression (FoP) is associated with the quality of life and behavioral change in acute pancreatitis (AP) patients, but lack of assessment tools. Aim: This study aimed to develop and evaluate the psychometric properties of the Fear of Progression Questionnaire-Short Form in AP patients (AP-FoP-Q-SF). Methods: Internal consistency, factorial structure, convergent validity, and criterion validity of AP-FoP-Q-SF were assessed. A receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value for high FoP. Associations between patient variables and FoP were evaluated using multiple logistic regression. Wilcox rank sum test was used to analyses the costs and length of hospital stay of the patients with high FoP. Results: The two-factor structure showed a good fit. Internal consistency was acceptable (Cronbach's α = 0.771). The cutoff of 26 identified 35.3% of patients with high FoP. High FoP scores were associated with age (OR = 0.96, 95%CI: 0.94–0.98), recurrence times (OR = 1.22, 95%CI: 1.02–1.45) and anxiety (OR = 1.27, 95%CI: 1.16–1.40). Patients with high FoP spent more cost and time in the hospital. Conclusions: The AP-FoP-Q-SF is a good FoP tool for AP patients in China. Implications for practice: Clinicians can use the AP-FoP-Q-SF to assess FoP and take promotion programs to avoid worse effects.

The widespread usage of 3-tert-butyl-4-hydroxyanisole (3-BHA) as an anthropogenic antioxidant has caused considerable environmental contamination and frequent detection in diverse human-derived samples. 3-BHA can promote adipogenesis and impair hepatic lipid metabolism, while its effects on renal lipid homeostasis remain to be uncertain. Herein, using the human kidney 2 (HK-2) cell experiments, 3-BHA was found to cause a significant reduction in lipid accumulation of the HK-2 cells in both exposure concentration- and duration-dependent manners. Exposure to 3-BHA lowered the transcriptional expressions of sterol regulatory element-binding protein 1 (SREBP1) and acetyl-CoA carboxylase (ACC), as well as ACC activity, indicating the inhibition in the process of de novo lipogenesis in HK-2 cells. On this basis, the mechanism study suggested that the reduced glucose absorption and accelerated glycolysis were concomitantly involved. The antagonism of 3-BHA on the transactivation of androgen receptor (AR) contributed to the lowered de novo lipogenesis and the consequent intracellular lipid reduction. The metabolomics data further confirmed the imbalance of lipid homeostasis and dysregulation of de novo lipogenesis. The new findings on the impaired renal lipid metabolism induced by 3-BHA warranted proper care about the usage of this chemical as a food additive.

Abstract Aim This study aimed to investigate the role of lncRNA MCM3AP-AS1 in diabetic retinopathy (DR). Methods Plasma MCM3AP-AS1 levels in DR patients (n = 80), T2DM patients (n = 80), and Controls (n = 80) were measured by qPCR and compared using ANOVA (one-way) and Tukey test. The expressions of lncRNA MCM3AP-AS1 and miR-211 in Human retinal pigment epithelial cells (hRPE) line ARPE-19 were detected by RT-qPCR. Western blot and annexin V-FITC staining were performed to investigate the role of MCM3AP-AS1/SIRT1 in ARPE-19 cell proliferation and apoptosis in vitro. Results We observed that MCM3AP-AS1 was downregulated in DR patients 25 comparing to T2D patients without significantly complications. Bioinformatics analysis showed that MCM3AP-AS1 might bind miR-211. However, no significant correlation between these two factors was observed in DR patients. Consistently, overexpression of MCM3AP-AS1 and miR-211 failed to affect the expression of each other in hRPE. Interestingly, MCM3AP-AS1 overexpression upregulated SIRT1, a target of miR-211. Moreover, MCM3AP-AS1 was downregulated in DR patients compared to type 2 diabetic mellitus patients without significant complications. In RPEs, high glucose treatment downregulated MCM3AP-AS1. Cell apoptosis analysis showed that MCM3AP-AS1 and SIRT1 overexpression decreased the apoptotic rate of RPEs, and miR-211 overexpression reduced the effect of MCM3AP-AS1 and SIRT1 overexpression. Conclusion MCM3AP-AS1 is downregulated in DR and promotes cell apoptosis by regulating miR-211/SIRT1.

To date, Alzheimer’s disease (AD) has grown to be a predominant health challenge that disturbs the elderly population. Studies have shown that mitochondrial dysfunction is one of the most significant features of AD. Transplantation therapy of healthy mitochondria (mitotherapy), as a novel therapeutic strategy to restore mitochondrial function, is proposed to treat the mitochondria−associated disease. Also, the molecular mechanism of mitotherapy remains unclear. Here, we applied the mitotherapy in AD model mice induced by amyloid−β (Aβ) plaque deposition and suggested that autophagy would be an important mechanism of the mitotherapy. After the healthy mitochondria entered the defective neuronal cells damaged by the misfolded Aβ protein, autophagy was activated through the NAD+−dependent deacetylase sirtuin 1 (SIRT1) signal. The damaged mitochondria and Aβ protein were eliminated by autophagy, which could also decrease the content of radical oxygen species (ROS). Moreover, the levels of brain−derived neurotrophic factor (BDNF) and extracellular−regulated protein kinases (ERK) phosphorylation increased after mitotherapy, which would be beneficial to repair neuronal function. As a result, the cognitive ability of AD animals was ameliorated in a water maze test after the healthy mitochondria were administrated to the mice. The study indicated that mitotherapy would be an effective approach to AD treatment through the mechanism of autophagy activation.

Abstract Growth‐differentiation factor (GDF)‐15 is a member of transforming growth factor‐β‐related cytokine and may respond to right ventricular overload. The objective of this article was to assess the diagnosis and prognostic value of GDF‐15 in systemic lupus erythematosus‐associated pulmonary arterial hypertension (SLE‐PAH). Serum samples were obtained from 65 patients with SLE‐PAH, 51 sex and age matched patients of SLE without PAH (SLE‐non‐PAH), and 32 healthy controls. Serum GDF‐15 level was detected by enzyme‐linked immunosorbent assay and the optimal cut‐off point was determined by receiver operating characteristic curve. The primary end‐point was death from any cause and the secondary end‐point was target goal achievement (TGA). Cox regression analyses and Kaplan−Meier method were performed to identify the prognostic value of GDF‐15. Serum GDF‐15 levels were significantly higher in SLE‐PAH patients (1112.14 ± 781.80 pg/mL) than SLE‐non‐PAH patients (810 ± 408 pg/mL) and healthy controls (442 ± 139 pg/mL) at baseline. The optimal cut‐off value of GDF‐15 in the diagnosis of SLE‐PAH was 733 pg/mL (AUC = 0.84). In patients with SLE‐PAH, GDF‐15 level was associated with 6 min walking distance (ρ = −0.385, p = 0.017) and higher serum N terminal‐pro brain natriuretic peptide (NT‐proBNP) (ρ = 0.605, p 733 pg/mL were more likely to death (adjusted hazard ratio [HR] = 4.01, 95% confidence intervals [CI]: 1.23−6.27, p = 0.041) and less likely to achieve treatment goal (adjusted HR = 0.57, 95% CI: 0.23−0.79, p = 0.028). In addition, patients with simultaneous elevation of GDF‐15 and NT‐proBNP showed lower proportion of TGA (p = 0.046). In conclusion, GDF‐15 is a new and promising biomarker of development and prognosis in SLE‐PAH. The combination of GDF‐15 and NT‐proBNP may provide more accurate prognostic information.

Abstract Background The effect of comorbid hypertriglyceridemia (HTG) and abdominal obesity (AO) on acute pancreatitis (AP) remains unclear. The aim of this study was to explore the effect of comorbid HTG and AO and discuss which is the dominant disorder. Methods In this study, 1219 AP patients who presented with HTG or AO were stratified into four groups: non-HTG + non-AO, HTG + non-AO, non-HTG + AO, and HTG + AO. Results The 328 patients with comorbid HTG + AO were much younger (42.29 ± 11.77), mainly male (79.57%), and had higher TG levels, larger waist circumferences, and more past medical histories than the patients in the other three non-comorbid groups (P 60 years (OR = 1.326, 95% CI = 1.047–1.679), AO (OR = 1.701, 95% CI = 1.308–2.212), diabetes mellitus (OR = 1.551, 95% CI = 1.063–2.261), mild HTG (OR = 1.549, 95% CI = 1.137–2.112), and moderate to very severe HTG (OR = 2.810, 95% CI = 1.926–4.100) were independent risk factors associated with local complications (P

The study tested the water purification mechanism of the combination of microorganisms and purification materials via characteristic, enzymatic, and metagenomics methods. At 48 h, the removal rates of total nitrogen, total phosphorous, and Mn chemical oxygen demand in the combination group were 46.91, 50.93, and 65.08%, respectively. The alkaline phosphatase (AKP) activity increased during all times tested in the volcanic rock, Al@TCAP, and exogenous microorganism groups, while the organophosphorus hydrolase (OPH), dehydrogenase (DHO), and microbial nitrite reductase (NAR) activities increased at 36-48, 6-24, and 36-48 h, respectively. However, the tested activities only increased in the combination groups at 48 h. Al@TCAP exhibits a weak microbial loading capacity, and the Al@TCAP removal is primarily attributed to adsorption. The volcanic rock has a sufficient ability to load microorganisms, and the organisms primarily perform the removal for improved water quality. The predominant genera Pirellulaceae and Polynucleobacter served as the sensitive biomarkers for the treatment at 24, 36-48 h. Al@TCAP increased the expression of Planctomycetes and Actinobacteria, while volcanic rock increased and decreased the expression of Planctomycetes and Proteobacteria. The growth of Planctomycetes and the denitrification reaction were promoted by Al@TCAP and the exogenous microorganisms. The purification material addition group decreased the expression of Hyaloraphidium, Chytridiomycetes (especially Hyaloraphidium), and Monoblepharidomycetes and increased at 36-48 h, respectively. Ascomycota, Basidiomycota, and Kickxellomycota increased in group E, which enhanced the nitrogen cycle through microbial enzyme activities, and the growth of the genus Aspergillus enhanced the phosphorous purification effect.

The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo. The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.

Human uptake abundance of microplastics via various pathways, and they accumulate in human liver, kidney, gut and even placenta (especially with a diameter of 1 μm or less). Recent scientific studies have found that exposure to microplastics causes intestinal inflammation and liver metabolic disorder, but it remains largely unknown that whether the damage and inflammation may cause further development of severe diseases. In this study, we discovered one of such potential diseases that may be induced by the exposure to small-sized microplastics (with a diameter of 1 μm) performing a multi-organ and multi-omics study comprising metabolomics and microbiome approaches. Unlike other animal experiments, the dosing strategy was applied in mice according to the daily exposure of the highly exposed population, which was more environmentally relevant and reflective of real-world human exposure. Our studies on the gut-liver axis metabolism have shown that the crosstalk between the gut and liver ultimately leaded to insulin resistance and even diabetes. We proactively verified this hypothesis by measuring the levels of fasting blood glucose and fasting insulin, which were found significantly elevated in the mice with microplastics exposure. These results indicate the urgent need of large-scale cohort evaluation on epidemiology and prognosis of insulin resistance after microplastics exposure in future.

Abstract Background The accumulation of various multi-omics data and computational approaches for data integration can accelerate the development of precision medicine. However, the algorithm development for multi-omics data integration remains a pressing challenge. Results Here, we propose a multi-omics data integration algorithm based on random walk with restart (RWR) on multiplex network. We call the resulting methodology Random Walk with Restart for multi-dimensional data Fusion (RWRF). RWRF uses similarity network of samples as the basis for integration. It constructs the similarity network for each data type and then connects corresponding samples of multiple similarity networks to create a multiplex sample network. By applying RWR on the multiplex network, RWRF uses stationary probability distribution to fuse similarity networks. We applied RWRF to The Cancer Genome Atlas (TCGA) data to identify subtypes in different cancer data sets. Three types of data (mRNA expression, DNA methylation, and microRNA expression data) are integrated and network clustering is conducted. Experiment results show that RWRF performs better than single data type analysis and previous integrative methods. Conclusions RWRF provides powerful support to users to decipher the cancer molecular subtypes, thus may benefit precision treatment of specific patients in clinical practice.

Abstract Background Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case-control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients. Methods SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements, and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia. Results We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p

BackgroundOssification of ligamentum flavum (OLF) is an insidious and debilitating heterotopic ossifying disease with etiological heterogeneity and undefined pathogenesis. Obese individuals predispose to OLF, whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood. Therefore, this study aims to explore distinct obesity-related genes and their functional signatures in OLF.MethodsThe transcriptome sequencing data related to OLF were downloaded from the GSE106253 in the Gene Expression Omnibus (GEO) database. The obesity-related differentially expressed genes (ORDEGs) in OLF were screened, and functional and pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI), module analysis, transcription factor enrichment analysis (TFEA), and experiment validation were used to identify hub ORDEGs. The immune infiltration landscape in OLF was depicted, and correlation analysis between core gene SOCS3 and OLF-related infiltrating immune cells (OIICs) as well as 5mC/m6A modifiers in OLF was constructed.ResultsNinety-nine ORDEGs were preliminarily identified, and functional annotations showed these genes were mainly involved in metabolism, inflammation, and immune-related biological functions and pathways. Integrative bioinformatic algorithms determined a crucial gene cluster associated with inflammatory/immune responses, such as TNF signaling pathway, JAK-STAT signaling pathway, and regulation of interferon-gamma-mediated signaling. Eight hub ORDEGs were validated, including 6 down-regulated genes (SOCS3, PPARG, ICAM-1, CCL2, MYC, and NT5E) and 2 up-regulated genes (PTGS2 and VEGFA). Furthermore, 14 differential OIICs were identified by ssGSEA and xCell, and SOCS3 was overlapped to be the core gene, which was associated with multiple immune infiltrates (dendritic cells, macrophage, and T cells) and six m6A modifiers as well as four 5mC regulators in OLF. Reduced SOCS3 and FTO expression and up-regulated DNMT1 level in OLF were validated by Western blotting.ConclusionThis study deciphered immune/inflammatory signatures of obesity-related gene clusters for the first time, and defined SOCS3 as one core gene. The crosstalk between 5mC/m6A methylation may be a key mediator of SOCS3 expression and immune infiltration. These findings will provide more insights into molecular mechanisms and therapeutic targets of obesity-related OLF.

This paper compares the performance of unified power flow controllers (UPFCs), static var compensators (SVCs), and static compensators (STATCOMs) in commutation failure immunity (CFI) improvement of line-commutated converter-based high-voltage direct-current transmission (LCC-HVDC) systems. Theoretical analysis is presented to investigate the capacity requirements of SVCs, STATCOMs, and UPFCs to maintain the inverter-side ac voltage in the cases where three-phase faults occur on the receiving-end ac grids with different short-circuit ratio (SCR). Simulation studies were undertaken to validate the CFI improving performance achieved by UPFCs in comparison to SVCs and STATCOMs. Results of three-phase and single-phase fault tests manifest the superior CFI of LCC-HVDC systems having UPFCs installed.

Synergistic drug combinations have demonstrated effective therapeutic effects in cancer treatment. Deep learning methods accelerate identification of novel drug combinations by reducing the search space. However, potential adverse drug–drug interactions (DDIs), which may increase the risks for combination therapy, cannot be detected by existing computational synergy prediction methods. We propose DEML, an ensemble-based multi-task neural network, for the simultaneous optimization of five synergy regression prediction tasks, synergy classification, and DDI classification tasks. DEML uses chemical and transcriptomics information as inputs. DEML adapts the novel hybrid ensemble layer structure to construct higher order representation using different perspectives. The task-specific fusion layer of DEML joins representations for each task using a gating mechanism. For the Loewe synergy prediction task, DEML overperforms the state-of-the-art synergy prediction method with an improvement of 7.8% and 13.2% for the root mean squared error and the R2 correlation coefficient. Owing to soft parameter sharing and ensemble learning, DEML alleviates the multi-task learning ‘seesaw effect’ problem and shows no performance loss on other tasks. DEML has a superior ability to predict drug pairs with high confidence and less adverse DDIs. DEML provides a promising way to guideline novel combination therapy strategies for cancer treatment.

Abstract Background Pedicle subtraction osteotomy (PSO) and vertebral column decancellation (VCD) are frequently used methods for correction of thoracolumbar kyphosis resulting from ankylosing spondylitis (AS). However, there are limited reports performed to evaluate the difference of loss of correction and the effectiveness of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. Objective To retrospectively estimate the effectiveness of correction and loss of correction of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. Methods We performed a retrospective review of 61 consecutive AS kyphosis patients undergoing PSO or VCD surgery from March 2012 to April 2015. The patients were divided into PSO group (n = 25) and VCD group (n = 36) according to the types of osteotomies. Measurement of the radiographic parameters was performed and the change was analyzed. Results Mean loss of correction in the global kyphosis was 2.31° in the PSO group and 2.29° in VCD group at the last follow-up, respectively, with no significant difference. Progressive junctional kyphosis occurred in both groups. VCD obtained a significantly larger correction than PSO while sharing a similar incidence of complications. No serious complications were observed in the two groups. Conclusion The PSO osteotomy and VCD osteotomy are both safe and effective methods in treating thoracolumbar kyphosis secondary to AS. Mild loss of correction mainly occurred in the global kyphosis in both techniques with no significant difference.

In order to study the characteristics and causes of ozone (O3) pollution in 16 cities of Yunnan Plateau, the methods of COD, backward trajectory and potential source contribution function (PSCF) were used to analyze the O3 concentrations from 2015 to 2020 of all state-controlled environmental monitoring stations in 16 cities of Yunnan. The results show that the O3 concentrations in Yunnan gradually increased from 2015 to 2019, and the concentration in 2020 was the lowest due to the COVID-19 pandemic. The peak O3 concentration appears in spring. The daily change trend is a typical single peak shape, the lowest value appears around 8: 00, and the highest value is between 15:00 and 16:00. High concentrations of O3 are from the cities of Zhaotong and Kunming in northeastern Yunnan, while low concentrations of O3 mainly occur in the southwest and northwest border areas. Temperature and relative humidity are two meteorological parameters that have significant effect on O3 concentration. Temperature has the best correlation with O3 in winter, and relative humidity has a better correlation with O3 in autumn and winter than in spring and summer. Finally, source analysis of O3 showed that local ozone precursor emission sources and long-distance transmission from South and Southeast Asia constituted the major contributions of O3 in Yunnan.

Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan–Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child–Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65–0.78), and the adjusted C-index was 0.72 (95% CI, 0.66–0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease–Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69–0.79), and the adjusted C-index was 0.74 (95% CI, 0.68–0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment.

Pathological changes in the ligamentum flavum (LF) can be defined as a process of chronic progressive aberrations in the nature and structure of ligamentous tissues characterized by increased thickness, reduced elasticity, local calcification, or aggravated ossification, which may cause severe myelopathy, radiculopathy, or both. Hypertrophy of ligamentum flavum (HLF) and ossification of ligamentum flavum (OLF) are clinically common entities. Though accumulated evidence has indicated both genetic and environmental factors could contribute to the initiation and progression of HLF/OLF, the definite pathogenesis remains fully unclear. MicroRNAs (miRNAs), one of the important epigenetic modifications, are short single-stranded RNA molecules that regulate protein-coding gene expression at posttranscriptional level, which can disclose the mechanism underlying diseases, identify valuable biomarkers, and explore potential therapeutic targets. Considering that miRNAs play a central role in regulating gene expression, we summarized current studies from the point of view of miRNA-related molecular regulation networks in HLF/OLF. Exploratory studies revealed a variety of miRNA expression profiles and identified a battery of upregulated and downregulated miRNAs in OLF/HLF patients through microarray datasets or transcriptome sequencing. Experimental studies validated the roles of specific miRNAs (e.g., miR-132-3p, miR-199b-5p in OLF, miR-155, and miR-21 in HLF) in regulating fibrosis or osteogenesis differentiation of LF cells and related target genes or molecular signaling pathways. Finally, we discussed the perspectives and challenges of miRNA-based molecular mechanism, diagnostic biomarkers, and therapeutic targets of HLF/OLF.

Extensive amounts of multi-omics data and multiple cancer subtyping methods have been developed rapidly, and generate discrepant clustering results, which poses challenges for cancer molecular subtype research. Thus, the development of methods for the identification of cancer consensus molecular subtypes is essential. The lack of intuitive and easy-to-use analytical tools has posed a barrier. Here, we report on the development of the COnsensus Molecular SUbtype of Cancer (COMSUC) web server. With COMSUC, users can explore consensus molecular subtypes of more than 30 cancers based on eight clustering methods, five types of omics data from public reference datasets or users' private data, and three consensus clustering methods. The web server provides interactive and modifiable visualization, and publishable output of analysis results. Researchers can also exchange consensus subtype results with collaborators via project IDs. COMSUC is now publicly and freely available with no login requirement at http://comsuc.bioinforai.tech/ (IP address: http://59.110.25.27/). For a video summary of this web server, see S1 Video and S1 File.

Background Cancer classification is of great importance to understanding its pathogenesis, making diagnosis and developing treatment. The accumulation of extensive omics data of abundant cancer cell line provide basis for large scale classification of cancer with low cost. However, the reliability of cell lines as in vitro models of cancer has been controversial. Methods In this study, we explore the classification on pan-cancer cell line with single and integrated multiple omics data from the Cancer Cell Line Encyclopedia (CCLE) database. The representative omics data of cancer, mRNA data, miRNA data, copy number variation data, DNA methylation data and reverse-phase protein array data were taken into the analysis. TumorMap web tool was used to illustrate the landscape of molecular classification.The molecular classification of patient samples was compared with cancer cell lines. Results Eighteen molecular clusters were identified using integrated multiple omics clustering. Three pan-cancer clusters were found in integrated multiple omics clustering. By comparing with single omics clustering, we found that integrated clustering could capture both shared and complementary information from each omics data. Omics contribution analysis for clustering indicated that, although all the five omics data were of value, mRNA and proteomics data were particular important. While the classifications were generally consistent, samples from cancer patients were more diverse than cancer cell lines. Conclusions The clustering analysis based on integrated omics data provides a novel multi-dimensional map of cancer cell lines that can reflect the extent to pan-cancer cell lines represent primary tumors, and an approach to evaluate the importance of omic features in cancer classification.

Background: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats. Methods: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Results: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Conclusion: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis.

Abstract Background The protein kinase C (PKC) family comprises central regulators of multiple signal transduction processes and is involved in the progression of many cancers. Nuclear factor Kappa-B (NF-κB) is constitutively expressed in cancer tissues and stimulates the transcription of various tumor-related genes. The present study aims to investigate the clinical significance of PKCα and NF-κB p65 in bladder cancer tissues and the mechanism underlying PKCα induction of bladder cancer cell apoptotic resistance through stimulation of p65 nuclear translocation. Methods Expression of PKCα and NF-κB subunit p65 was detected in seven bladder cancer cell lines by western blot and in 30 bladder cancer tissue specimens by immunostaining. Immunofluorescence was performed to evaluate p65 nuclear translocation induced by Phorbol 12-myristate 13-acetate (PMA). PKCα/β selective inhibitor Gö6976, PKC pan-inhibitor sotrastaurin, and the PKC siRNA were employed to conduct PKC inhibition/knockdown in bladder cancer cells. Luciferase reporter assays were performed to measure the activity of NF-κB. Flow cytometry and TUNEL analysis were used to assess cell apoptosis. Results Expression of PKCα and NF-κB was found to positively correlate with tumor progression in 30 tumor tissue specimens. Furthermore, a Pearson’s correlation coefficient analysis revealed a positive correlation between PKCα and NF-κB expression. Among the PKC inhibitors, the PKCα/β selective inhibitor Gö6976 yielded the most significant block of PKCα and NF-κB activation by PMA. Knockdown of NF-κB p65 remarkably induced cell apoptosis, but PMA restored p65 expression and significantly suppressed cell apoptosis that was otherwise induced by the p65 knockdown alone. Conclusion Our study showed that PKCα modulated cell resistance to apoptosis by stimulating NF-κB activation and thus promoted the tumorigenesis of bladder cancer.

In the last decade, the use of magnesium and its alloys as biodegradable implant materials has become increasingly accepted. However, surface modification of these materials to control the degradation rate in the early stages of healing and improve their biocompatibility is crucial to the successful implementation of magnesium alloy implants in medicine. Cell adhesion and proliferation at the implant surface is a vital factor for successful integration of a biomaterial within the body. Cells accomplish this task by binding to ligands such as the arginine-glycine-aspartic acid peptide sequence (RGD) commonly found on adhesive proteins present in the extracellular matrix. In this paper, we report a biomimetic surface modification strategy involving deposition of a mixed organosilane layer on Mg AZ31 followed by covalent immobilization of RGD peptides through a heterobifunctional cross-linker molecule. Our results indicate that with optimized deposition conditions uniform organosilane coatings were successfully deposited on the Mg AZ31 substrate. Furthermore, we have demonstrated that the surface density of immobilized RGD can be varied by depositing organosilane layers from solutions containing two different organosilanes in specified ratios. Increases in cell adhesion and cell proliferation were observed on the surface modified substrates.

Background: Genome-wide association studies (GWAS) have identified numerous loci associated with diseases and traits. However, the elucidation of disease mechanisms followed by drug development has remained a challenge owing to complex gene interactions. We performed pathway analysis with MAGENTA (Meta-Analysis Geneset Enrichment of variaNT Associations) to clarify the pathways in genetic background of AF. Methods: The existing GWAS data were analyzed using MAGENTA. A microarray analysis was then performed for the identified pathways with human atrial tissues, followed by Gene-Set Enrichment Analysis (GSEA). Results: MAGENTA identified two novel candidate pathways for AF pathogenesis, the CTCF (CCCTC-binding factor, p = 1.00 × 10−4, FDR q = 1.64 × 10−2) and mTOR pathways (mammalian target of rapamycin, p = 3.00 × 10−4, FDR q = 3.13 × 10−2). The microarray analysis with human atrial tissue using the GSEA indicated that the mTOR pathway was suppressed in AF cases compared with non-AF cases, validating the MAGENTA results, but not CTCF pathway. Conclusions: MAGENTA identified a novel pathway, mTOR, followed by GSEA with human atrial tissue samples. mTOR pathway is a key interface that adapts the change of environments by pressure overload and metabolic perturbation. Our results indicate that the MTOR pathway is involved in the pathogenesis of AF, although the details of the basic mechanism remain unknown and further analysis for causal-relationship of mTOR pathway to AF is required. CTCF pathway is essential for construction of chromatin structure and transcriptional process. The gene-set components of CTCF overlap with those of mTOR in Biocarta. Keywords: Atrial fibrillation, Pathway analysis, mTOR, MAGENTA, Transcriptome analysis

This data article provides complementary data for the article entitled “DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding” Li et al. (2016) [1]. The experimental methods for the preparation and characterization of DNA-conjugated nanoparticle networks on cell membranes were described. Confocal fluorescence images, agarose gel electrophoresis images and hydrodynamic diameter of DNA-conjugated gold nanoparticle (DNA-AuNP) networks were presented. In addition, we have prepared QDs-labeled RSV (QDs-RSV) to real-time monitor the RSV infection on HEp-2 cells in the absence and presence of DNA-AuNP networks. Finally, the cell viability of HEp-2 cells coated by six types of DNA-nanoparticle networks was determined after RSV infection. Keywords: DNA-AuNP networks, Cell membrane, Viral infection, Inhibition

Thoracic ossification of the ligamentum flavum (TOLF) is heterotopic ossification of spinal ligaments, which may cause serious thoracic spinal canal stenosis and myelopathy. However, the underlying etiology remains inadequately understood. In this study, the ossification patterns of TOLF were analyzed by micro-computer tomography (micro-CT). The expression profile of genes associated with angiogenesis was analyzed in thoracic ligamentum flavum cells at sites of different patterns of ossification using RNA sequencing. Significant differences in the expression profile of several genes were identified from Gene Ontology (GO) analysis. Angiopoietin-2 (ANGPT2) was significantly up-regulated in primary thoracic ligamentum flavum cells during osteogenic differentiation. To address the effect of ANGPT2 on Notch signaling and osteogenesis, ANGPT2 stimulation increased the expression of Notch2 and osteogenic markers of primary thoracic ligamentum flavum cells of immature ossification, while inhibition of ANGPT2 exhibited opposite effect on Notch pathway and osteogenesis of cells of mature ossification. These findings provide the first evidence for positive regulation of ANGPT2 on osteogenic differentiation in human thoracic ligamentum flavum cells via modulating the Notch signaling pathway.

The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age.In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials.Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings.

Radiotherapy is one of the major therapeutic strategies in cancer treatment. The telomere-binding protein TPP1 is an important component of the shelterin complex at mammalian telomeres. Our previous reports showed that TPP1 expression was elevated in radioresistant cells, but the exact effects and mechanisms of TPP1 on radiosensitivity is unclear.In this study, we found that elevated TPP1 expression significantly correlated with radioresistance and longer telomere length in human colorectal cancer cell lines. Moreover, TPP1 overexpression showed lengthened telomere length and a significant decrease of radiosensitivity to X-rays. TPP1 mediated radioresistance was correlated with a decreased apoptosis rate after IR exposure. Furthermore, TPP1 overexpression showed prolonged G2/M arrest mediated by ATM/ATR-Chk1 signal pathway after IR exposure. Moreover, TPP1 overexpression accelerated the repair kinetics of total DNA damage and telomere dysfunction induced by ionizing radiation.We demonstrated that elevated expressions of TPP1 in human colorectal cancer cells could protect telomere from DNA damage and confer radioresistance. These results suggested that TPP1 may be a potential target in the radiotherapy of colorectal cancer.