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Abstract Traffic information is crucial for managing transportation and city planning, but obtaining national-scale data is difficult due to privacy concerns. Consequently, most current traffic datasets have limitations in terms of time and location coverage, leading to a lack of comprehensive public access to national traffic data. To address this issue, a multi-source highway traffic dataset has been created, featuring 2042 sensors in New Zealand over a 9-year period with 15-minute intervals and accompanying metadata. The dataset includes data of both light-duty and heavy-duty vehicles, as well as weather information like temperature and precipitation. This dataset has diverse potential research applications such as traffic flow prediction and congestion management.

Abstract Aims We aim to integrate the parameters of two‐dimensional (2D) echocardiography and identify the high‐risk population for all‐cause mortality in patients with acute ST‐segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods The study involved a retrospective cohort population with STEMI who were admitted to Yongchuan Hospital of Chongqing Medical University between January 2016 and January 2019. Baseline data were collected, including 2D echocardiography parameters and left ventricular ejection fraction (LVEF). The parameters of 2D echocardiography were subjected to cluster analysis. Logistic regression models were employed to assess univariate and multivariate adjusted odds ratios (ORs) of cluster information in relation to all‐cause mortality. Four logistic regression models were generated, utilizing cluster information, clinical variables, clinical variables in conjunction with LVEF, and clinical variables in conjunction with LVEF and cluster information as predictive variables, respectively. The area under the curve (AUC) were utilized to evaluate the incremental risk stratification value of cluster information. Results The study included 633 participants with 28.8% female, a mean age of 65.68 ± 11.98 years. Over the course of a 3‐year follow‐up period, 108 (17.1%) patients experienced all‐cause mortality. Utilizing cluster analysis of 2D echocardiography parameters, the patients were categorized into two distinct clusters, with statistically significant differences observed in most clinical variables, echocardiography, and survival outcomes between the clusters. Multivariate regression analysis revealed that cluster information was independently associated with the risk of all‐cause mortality with adjusted OR 7.33 (95% confidence interval [CI] 3.99–14.06, P

Abstract Background Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC. Methods We obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups. Results There was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively. Conclusions We constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.

Abstract Background Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Results 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (β:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. Conclusion Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

IntroductionCardiac hypertrophy is a compensatory stress response produced by a variety of factors, and pathologic hypertrophy can lead to irreversible, severe cardiac disease. Glycosphingolipids (GSLs) are vital constituents of cells, and changes in their content and composition are important factors causing mitochondrial dysfunction in diabetic cardiomyopathy; however, the relationship between GSLs expression and cardiac hypertrophy and specific mechanisms associated with it are not clear.MethodsHere, using male C57BL/6 mice, we performed aortic arch reduction surgery to establish an animal model of pressure overload cardiac hypertrophy. In addition, phenylephrine was used in vitro to induce H9c2 cells and neonatal rat left ventricular myocytes (NRVMs) to establish a cellular hypertrophy model.ResultsMass spectrometry revealed that the composition of GSLs was altered in pressure overload-induced hypertrophied mouse hearts and in stimulated hypertrophied cardiomyocyte cell lines. Specifically, in both cases, the proportion of endogenous lactosylceramide (LacCer) was significantly higher than in controls. Inhibition of GSL synthesis with Genz-123346 in NRVMs reduced cell hypertrophy, as well as fibrosis and apoptosis. By Western blotting, we detected decreased intracellular expression of Sirt3 and elevated phosphorylation of JNK after phenylephrine stimulation, but this was reversed in cells pretreated with Genz-123346. Additionally, increased protein expression of FoxO3a and Parkin, along with a decreased LC3-II/I protein ratio in phenylephrine-stimulated cells (compared with unstimulated cells), indicated that the mitochondrial autophagy process was disrupted; again, pretreatment with Genz-123346 reversed that.DiscussionOur results revealed that changes in GSLs in cardiomyocytes, especially an increase of LacCer, may be a factor causing cellular hypertrophy, which can be alleviated by inhibition of GSLs synthesis. A possible mechanism is that GSLs inhibition increases the expression of Sirt3 protein, scavenges intracellular reactive oxygen species, and restores mitochondrial autophagy homeostasis, thereby lessening cardiomyocyte hypertrophy. In all, these results provide a new perspective for developing drugs for cardiac hypertrophy.

Background: Atopic dermatitis is a common chronic inflammatory skin disease characterized by relapsing eczema and intense itch. DGT is a novel synthetic heterocyclic diterpenoid derived from plants. Its therapeutic potential and mechanism(s) of action are poorly understood. Objectives: We investigated the potent therapeutic effect of DGT on atopic dermatitis, exploring the underlying mechanisms and determining whether DGT is a safe and well-tolerated topical treatment. Methods: We observed anti-inflammatory effects of DGT on tumor necrosis factor-α/interferon-γ–treated human keratinocytes, and anti-allergic effects on immunoglobulin E–sensitized bone marrow–derived mast cells. In vivo, DGT was topically applied to two experimental mouse models of atopic dermatitis: oxazolone-induced sensitization and topically applied calcipotriol. Then the therapeutic effects of DGT were evaluated physiologically and morphologically. Moreover, we performed nonclinical toxicology and safety pharmacology research, including general toxicity, pharmacokinetics, and safety pharmacology on the cardiovascular, respiratory, and central nervous systems. Results: In keratinocytes, DGT reduced the expression of inflammatory factors, promoting the expression of barrier functional proteins and tight junctions and maintaining the steady state of barrier function. DGT also inhibited the activation and degranulation of mast cells induced by immunoglobulin E. Moreover, we found that interleukin-4 receptor-α was the possible target of DGT. Meanwhile, DGT had therapeutic effects on oxazolone/calcipotriol-treated mice. Notably, our pharmacology results demonstrated that DGT was safe and nontoxic in our studies. Conclusion: DGT’s potent anti-inflammatory effects and good safety profile suggest that it is a potential candidate for the treatment of atopic dermatitis.

Vanadium dioxide (VO2) has become a reliable phase change material (PCM) and is increasingly utilized in multifunctional metasurface design. This study introduces designs of bilayer anisotropic VO2 meta-atoms in simulation for multifunctional wavefront modulation in the terahertz band. By leveraging the phase change property of VO2 and incident wave polarization, a reconfigurable metasurface composing anisotropic meta-atoms is proposed with four distinct functions. When VO2 is in its insulating state, the metasurface serves as a hologram generator for the x-polarized wave and a focusing reflector for the y-polarized wave. Upon the transition of VO2 into the metallic state, the metasurface functions as a generator of vortex beam for the x-polarized wave, while as an anomalous reflector for the y-polarized wave. The proposed metasurface showcases an outstanding broadband performance, delivering impressive four-channel wavefront modulation within a frequency range of 2.2–3.0 THz. Depending on the compact structure and integrated multi-functionalities, our design may have immense potential across a wide range of terahertz applications, including communication exchange and multiplexing utilization.

Abstract A foundational assumption of quantum error correction theory is that quantum gates can be scaled to large processors without exceeding the error-threshold for fault tolerance. Two major challenges that could become fundamental roadblocks are manufacturing high-performance quantum hardware and engineering a control system that can reach its performance limits. The control challenge of scaling quantum gates from small to large processors without degrading performance often maps to non-convex, high-constraint, and time-dynamic control optimization over an exponentially expanding configuration space. Here we report on a control optimization strategy that can scalably overcome the complexity of such problems. We demonstrate it by choreographing the frequency trajectories of 68 frequency-tunable superconducting qubits to execute single- and two-qubit gates while mitigating computational errors. When combined with a comprehensive model of physical errors across our processor, the strategy suppresses physical error rates by ~3.7× compared with the case of no optimization. Furthermore, it is projected to achieve a similar performance advantage on a distance-23 surface code logical qubit with 1057 physical qubits. Our control optimization strategy solves a generic scaling challenge in a way that can be adapted to a variety of quantum operations, algorithms, and computing architectures.

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs.Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran’s Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach.Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007–1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019–1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859–0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918–0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008–1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02–1.098, p = 0.002).Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF.

Objective To assess the association between the serum triglyceride-glucose product index (TyG index) and the risk for all-cause mortality in patients with ST-segment elevated myocardial infarction (STEMI).Design Retrospective.Setting and participants This retrospective study included 896 patients with STEMI who underwent percutaneous coronary intervention (PCI) at a comprehensive university-affiliated hospital between January 2016 and January 2019.Methods Patients were equally divided into quartiles (Q1, Q2, Q3 and Q4 group) according to TyG index values.Primary endpoint All-cause mortality.Results After a median follow-up of 3 years, 108 (17.1%) patients died. TyG index was independently associated with increased all-cause mortality (OR, 1.39; 95% CI, 1.22 to 1.58) after adjusting for age, sex, low-density lipoprotein cholesterol (LDL-c), cardiac troponin I, B-type natriuretic peptide, delayed PCI, post-PCI complications, medication and left ventricular ejection fraction. The adjusted OR was 1.31 (95% CI, 0.62 to 2.77) for Q2, 2.12 (95% CI, 1.01 to 4.53) for Q3 and 4.02 (95% CI, 1.90 to 8.78) for Q4 compared with the lowest quartile (Q1) (p for trend

In recent years, vanadium dioxide (VO2) has drawn enormous attention in dynamic electromagnetic (EM) manipulation, owing to its mild phase change condition and prominent diversity of optical characteristics. In this paper, anisotropic meta-atoms integrating VO2 are proposed to obtain four polarization-multiplexing channels. The meta-atom is composed of two stacking metal–insulator–metal (MIM) structures. For the modulation of EM wavefront in desired manners, a meta-atom database composed of 256 meta-atoms is elaborately designed. Applying the meta-atom database and the degree of freedom in interfacial phase distribution, two metasurfaces are demonstrated in the verification of four-channel polarization-multiplexed vortex beams. The firstly proposed metasurface realizes the generation of four vortex beams with different topological charges. Each channel is dependent on the polarization of the incident wave and VO2 state. The further investigated metasurface achieves simultaneous control over the reflection direction, quantity, and mode of vortex beams under different VO2 states and polarization states of incident wave. In addition, designed metasurfaces exhibit wideband effect for over 100 GHz. The proposed design method enables four-channel generation of vortex beams using a single metasurface, and may have potential applications in dynamic and integrated terahertz communication.

Abstract Background RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5–methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. Methods In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. Results A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10–5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. Conclusion In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.

Abstract Background Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known. Results In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway. Conclusions This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants. Graphical Abstract

Background: The low osteogenic differentiation potential and attenuated anti-inflammatory effect of adipose-derived stem cells (ADSCs) from animals with type 2 diabetes mellitus (T2DM) limits osseointegration of the implant. However, the underlying mechanisms are not fully understood.Methods: Western blotting and qRT-PCR analyses were performed to investigate the effects of PTEN on the osteogenic capacity of ADSCs of T2DM rats (TADSCs). We conducted animal experiments in T2DM-Sprague Dawley (SD) rats to evaluate the osteogenic capacity of modified TADSC sheets in vivo. New bone formation was assessed by micro-CT and histological analyses.Results: In this study, adipose-derived stem cells of T2DM rats exhibited an impaired osteogenic capacity. RNA-seq analysis showed that PTEN mRNA expression was upregulated in TADSCs, which attenuated the osteogenic capacity of TADSCs by inhibiting the AKT/mTOR/HIF-1α signaling pathway. miR-140-3p, which inhibits PTEN, was suppressed in TADSCs. Overexpression or inhibition of PTEN could correspondingly reduce or enhance the osteogenic ability of TADSCs by regulating the AKT/mTOR/HIF-1α signaling pathway. TADSCs transfected with PTEN siRNA resulted in higher and lower expressions of genes encoded in M2 macrophages (Arg1) and M1 macrophages (iNOS), respectively. In the T2DM rat model, PTEN inhibition in TADSC sheets promoted macrophage polarization toward the M2 phenotype, attenuated inflammation, and enhanced osseointegration around implants.Conclusion: Upregulation of PTEN, which was partially due to the inhibition of miR-140-3p, is important for the attenuated osteogenesis by TADSCs owing to the inhibition of the AKT/mTOR/HIF-1α signaling pathway. Inhibition of PTEN significantly improves the anti-inflammatory effect and osteogenic capacity of TADSCs, thus promoting peri-implant bone formation in T2DM rats. Our findings offer a potential therapeutic approach for modifying stem cells derived from patients with T2DM to enhance osseointegration.

Abstract The development of fifth‐generation technology has resulted in increased demand for materials with low dielectric losses and superior thermal and mechanical properties. However, ensuring the widespread use of such materials by investigating their aging mechanisms and operating lifetimes remains challenging. In this study, a glass‐fiber (GF)‐reinforced acrylate‐styrene‐acrylonitrile/polycarbonate (ASA/GF/PC) composite is designed and comprehensively investigated its aging behavior, mechanism, and service lifetime under long‐term hygrothermal conditions. Based on the general Peck model, the composite maintains a high level of quality for over 10 years, including under harsh conditions of 40 °C and 80% relative humidity. The aging mechanism is primarily ascribed to cracking between the GF fibers and matrix, the breaking of chemical bonds, the generation of new cross‐linked domains, and physical aging. These findings provide valuable insights into the long‐term utilization of ASA/GF/PC composites in harsh environments.

Abstract Leucocyte immunoglobulin‐like receptors (LILRs) are closely related to tumourigenesis, but their clinical value in early‐stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy remains unknown. Kaplan–Meier and Cox proportional hazards regression models is used to investigate the association between LILR expression and prognosis in tumour biopsies and peripheral blood mononuclear cells. Risk score was calculated for each patient based on the prognostic model. DAVID, STRING, GeneMANIA, and GSEA were used to conduct pathway and functional analyses. The CIBERSORT algorithm is used to analyse tumour‐infiltrating immune cells. Survival analysis showed that high levels of LILRA4 (p = 0.006) and LILRB4 (p = 0.04) were significantly associated with better overall survival. High levels of LILRA2 (p = 0.008) and LILRB4 (p = 0.038) were significantly associated with better relapse‐free survival. JAK‐STAT signalling pathway, regulation of T cell activation, regulation of the immune effector process, and tumour necrosis factor superfamily cytokine production were involved in molecular mechanisms that affected poor prognoses in the high‐risk group in GSEA. CIBERSORT demonstrated that the high‐risk group had significantly higher infiltrating fraction of memory‐activated CD4 T cells and activated NK cells and lower fraction of resting dendritic cells and neutrophils. LILRB4 plays crucial roles in affecting the clinical outcomes of early‐stage PDAC.

Spatialization and analysis of the gross domestic product of second and tertiary industries (GDP23) can effectively depict the socioeconomic status of regional development. However, existing studies mainly conduct GDP spatialization using nighttime light data; few studies specifically concentrated on the spatialization and analysis of GDP23 in a built-up area by combining multi-source remote sensing images. In this study, the NPP-VIIRS-like dataset and Sentinel-2 multi-spectral remote sensing images in six years were combined to precisely spatialize and analyze the variation patterns of the GDP23 in the built-up area of Zibo city, China. Sentinel-2 images and the random forest (RF) classification method based on PIE-Engine cloud platform were employed to extract built-up areas, in which the NPP-VIIRS-like dataset and comprehensive nighttime light index were used to indicate the nighttime light magnitudes to construct models to spatialize GDP23 and analyze their change patterns during the study period. The results found that (1) the RF classification method can accurately extract the built-up area with an overall accuracy higher than 0.90; the change patterns of built-up areas varied among districts and counties, with Yiyuan county being the only administrative region with an annual expansion rate of more than 1%. (2) The comprehensive nighttime light index is a viable indicator of GDP23 in the built-up area; the fitted model exhibited an R2 value of 0.82, and the overall relative errors of simulated GDP23 and statistical GDP23 were below 1%. (3) The year 2018 marked a significant turning point in the trajectory of GDP23 development in the study area; in 2018, Zhoucun district had the largest decrease in GDP23 at −52.36%. (4) GDP23 gradation results found that Zhangdian district exhibited the highest proportion of high GDP23 (>9%), while the proportions of low GDP23 regions in the remaining seven districts and counties all exceeded 60%. The innovation of this study is that the GDP23 in built-up areas were first precisely spatialized and analyzed using the NPP-VIIRS-like dataset and Sentinel-2 images. The findings of this study can serve as references for formulating improved city planning strategies and sustainable development policies.

The interfacial bonding capacity between cement emulsified asphalt composite binder (CEACB) and reclaimed asphalt pavement (RAP) plays a critical role in improving the pavement performance of cold recycled asphalt emulsion mixtures (CRAEMs). This study aims to investigate the formation and development of the interfacial bonding capacity between CEACB and RAP. First, the dynamic wettability and the spreading behaviors of CEACB on RAP surfaces were explored according to the surface free energy theory. Second, digital image processing (DIP) technology was employed to recognize interfacial failure patterns. Lastly, the influence of internal and external factors on the interfacial bonding capacity between CEACB and RAP during the curing process was analyzed via grey relational analysis (GRA). The results indicate that a moderate cement content with a mass ratio of asphalt to cement equivalent to 1.0 can significantly enhance the wettability of CEACB on RAP surfaces. By appropriately prolonging the curing time and controlling the curing temperature, it is possible to increase the bonding strength between CEACB and RAP. Additionally, a strong correlation exists between initial wettability and ultimate bonding capacity during the bonding strength curing process. The good wettability that developed in the initial stage of interfacial strength formation relates to the decreased spalling rate of CEACB on the RAP surface. This study is not only devoted to understanding the mechanisms that can enhance CRAEM performance but also provides important guidance for practical engineering applications of cold recycled asphalt pavements.

Background: Volatile organic compounds (VOCs) contain hundreds of chemicals and human exposure to VOCs is pervasive. However, most studies have considered only a single chemical or a class of similar chemicals. Objective: We aimed to investigate the association between urinary volatile organic compound metabolites (mVOCs) and the risk of cardiovascular disease (CVD) in the general population. Methods: The data in this study were collected from the National Health and Nutrition Examination Survey in 2011–2018. Eligible patients were aged ≥20 years for whom complete data for 20 types of urinary mVOCs and CVD outcomes were available. Multivariate logistic regression models were used to elucidate the association between mVOCs and CVD. Generalized additive models were used to examine the nonlinear relationships between mVOCs and CVD. Results: 6814 indiviuals were included in the final analysis, of whom 508 had CVD. Higher urinary concentrations of N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) and N-Acetyl-S-(2-cyanoethyl)-l-cysteine (CYMA) and a lower urinary concentration of 2-aminothiazoline-4-carboxylic acid (ATCA) were associated with CVD outcomes after the adjustment for potential confounding factors. A nonlinear relationship and a threshold effect were only observed between N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) and CVD among 20 types of mVOCs. There was a significantly positive correlation between AMCC and CVD when AMCC concentration was >2.32 g/mL. Conclusion: The findings of this study suggested a significant correlation between urinary VOC metabolites and CVD. Urinary mVOCs may indicate hazardous exposure or distinct metabolic traits in patients with CVD.

Salient object detection (SOD) is to segment significant regions of images. Noticing that the saliency maps in existing SOD methods suffer from blurring boundaries owing to insufficient extraction of boundary features and inadequate fusion between boundary features and salient region features, a dual-branch network of information mutual optimization (DIMONet) is proposed. The DIMONet has a region detection branch and a boundary detection branch to extract the corresponding features simultaneously and is mainly composed of two components. One is the mutual optimization module (MOM) that refines salient region features and boundary features based on their internal relationship. The other is the fusion module of multi-receptive fields (FMMF) that integrates multi-layer features with the refined features to distinguish salient objects better and sharpen their boundaries. With the help of MOMs and FMMFs, noises from the background in the boundary features are gradually reduced and hence the boundaries of the salient regions get sharpened. Experiments on five benchmark datasets show that our method is superior to the 18 state-of-the-art methods.

Background A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients.Methods We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings.Results Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p

Abstract Purpose Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [18F]olaparib and the injected mass of [TotalF]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models. Methods [18F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [TotalF]olaparib (varying injected mass: 0.04–8.0 µg, and molar activity: 1–320 GBq/μmol). Results Selective uptake of [18F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [TotalF]olaparib (µg) but not the molar activity. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [TotalF]olaparib resulted in lower relative tumour uptake (%ID/g; P 0.5 µg). Conclusion Our findings show that the injected mass of [TotalF]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy.

We present context-aware fidelity estimation (CAFE), a framework for benchmarking quantum operations that offers several practical advantages over existing methods such as randomized benchmarking (RB) and cross-entropy benchmarking. In CAFE, a gate or a subcircuit from some target experiment is repeated n times before being measured. By using a subcircuit, we account for effects from the spatial and temporal circuit context. Since coherent errors accumulate quadratically while incoherent errors grow linearly, we can separate them by fitting the measured fidelity as a function of n. One can additionally interleave the subcircuit with dynamical decoupling sequences to remove certain coherent error sources from the characterization when desired. We have used CAFE to experimentally validate our single- and two-qubit unitary characterizations by measuring fidelity against estimated unitaries. In numerical simulations, we find that CAFE produces fidelity estimates at least as accurate as interleaved RB while using significantly fewer resources. We also introduce a compact formulation for preparing an arbitrary two-qubit state with a single entangling operation and use it to present a concrete example using CAFE to study controlled-Z gates in parallel on a Sycamore processor.

Abstract Aims This study aims to analyse the factors associated with prognosis in hospitalized patients with heart failure, particularly the role of depressive symptoms, and to develop a prediction model for depressive symptoms based on clinical characteristics in hospitalized patients with heart failure. Methods and results Baseline information was collected at admission, and patients were followed up after discharge. The endpoint events were being hospitalized for heart failure or all‐cause death. Depressive symptoms were evaluated and defined via the Patient Health Questionnaire (PHQ)‐2 and PHQ‐9. The bidirectional elimination was used to screen independent predictors of heart failure with depression symptoms. The least absolute shrinkage and selection operator (LASSO) optimized the predictor variables, and the prediction model was constructed. The model was internally validated by the bootstrap sampling method (Bootstrap), and its performance was assessed by discrimination and calibration. The mean age of patients with heart failure was 69.43 ± 12.15 years, and the proportion of males was 66.67%. The prevalence of depressive symptoms in hospitalized patients with heart failure was 46.83%, and the prevalence of moderate/severe depressive symptoms was 11.62%. Eighty cases (30.30%) were readmitted for heart failure, and 13 cases (4.92%) were all‐cause deaths. Depressive symptoms (HR = 2.43, 95% CI: 1.55–3.80) and the PHQ‐9 score (HR = 1.11, 95% CI: 1.06–1.16) were both independent risk factors for endpoint events (P

ObjectiveRisk stratification of patients with congestive heart failure (HF) is vital in clinical practice. The aim of this study was to construct a machine learning model to predict the in-hospital all-cause mortality for intensive care unit (ICU) patients with HF.MethodseXtreme Gradient Boosting algorithm (XGBoost) was used to construct a new prediction model (XGBoost model) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV) (training set). The eICU Collaborative Research Database dataset (eICU-CRD) was used for the external validation (test set). The XGBoost model performance was compared with a logistic regression model and an existing model (Get with the guideline-Heart Failure model) for mortality in the test set. Area under the receiver operating characteristic cure and Brier score were employed to evaluate the discrimination and the calibration of the three models. The SHapley Additive exPlanations (SHAP) value was applied to explain XGBoost model and calculate the importance of its features.ResultsThe total of 11,156 and 9,837 patients with congestive HF from the training set and test set, respectively, were included in the study. In-hospital all-cause mortality occurred in 13.3% (1,484/11,156) and 13.4% (1,319/9,837) of patients, respectively. In the training set, of 17 features with the highest predictive value were selected into the models with LASSO regression. Acute Physiology Score III (APS III), age and Sequential Organ Failure Assessment (SOFA) were strongest predictors in SHAP. In the external validation, the XGBoost model performance was superior to that of conventional risk predictive methods, with an area under the curve of 0.771 (95% confidence interval, 0.757–0.784) and a Brier score of 0.100. In the evaluation of clinical effectiveness, the machine learning model brought a positive net benefit in the threshold probability of 0%–90%, prompting evident competitiveness compare to the other two models. This model has been translated into an online calculator which is accessible freely to the public (https://nkuwangkai-app-for-mortality-prediction-app-a8mhkf.streamlit.app).ConclusionThis study developed a valuable machine learning risk stratification tool to accurately assess and stratify the risk of in-hospital all-cause mortality in ICU patients with congestive HF. This model was translated into a web-based calculator which access freely.

Abstract Background Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation (RFCA) as a hybrid procedure is commonly performed to treat atrial fibrillation (AF). Although this treatment carries a low risk of coronary artery spasm (CAS), and has never been observed in LAAC procedure, caution still needed to be taken. We presented a case of CAS that occurred in an AF patient during the hybrid procedure. Case presentation The patient was a 65-year-old man with paroxysmal AF who developed CAS during RFCA and LAAC. In this case, LAAC was performed ahead of RFCA. After atrial septal puncture, the occluder was advanced into left atrium through delivery sheath, and successfully deployed in the LAA. After verifying the assessment of “PASS” criteria, we decided to release the device. However, before releasing the occluder in LAAC, the patient’s blood pressure (BP) fell to 70/45 mmHg with heart rate (HR) drop and ST-segment elevation in II, III, and aVF and reciprocal ST-segment depression in I and aVL. Isotonic sodium chloride load was administered. After 3 min, the BP and HR raised, and ST-segment returned to normal. The occluder was successfully released after the stable condition of the patient. Then, RFCA was sequentially performed. When isolating the right pulmonary veins, the patient’s BP and HR fell again with ST-segment elevation in inferior leads. Spontaneous ventricular tachycardia and fibrillation developed rapidly and defibrillation was performed immediately with success. Coronary angiography revealed the obstruction of the right coronary artery which disappeared completely after intracoronary nitroglycerin injection (1 mg). Under systemic diltiazem infusion, the RFCA procedure was accomplished. After the procedure, the patient recovered without any neurologic deficit, and CAS has never recurred with isosorbide mononitrate treatment during follow-up. Conclusions CAS is a rare complication associated with AF hybrid procedure. Attention should be paid to this rare but potentially life-threatening complication.

Owing to label-free modeling of complex heterogeneity, self-supervised heterogeneous graph representation learning (SS-HGRL) has been widely studied in recent years. The goal of SS-HGRL is to design an unsupervised learning framework to represent complicated heterogeneous graph structures. However, based on contrastive learning, most existing methods of SS-HGRL require a large number of negative samples, which significantly increases the computation and memory costs. Furthermore, many methods cannot fully extract knowledge from a heterogeneous graph. To learn global and local information simultaneously at low time and space costs, we propose a novel Siamese Network based Multi-scale bootstrapping contrastive learning approach for Heterogeneous graphs (SNMH). Specifically, we first obtain views under the meta-path schema and the 1-hop relation type schema through dual-schema view generation. Then, we propose cross-schema and cross-view bootstrapping contrastive objectives to maximize the similarity of node representations between different schemas and views. By integrating and optimizing the above objectives, we can extract local and global information and eventually obtain the node representations for downstream tasks. To demonstrate the effectiveness of our model, we conduct experiments on several public datasets. Experimental results show that our model is superior to the state-of-the-art methods on the premise of lower time and space complexity. The source code and datasets are publicly available at https://github.com/lorisky1214/SNMH.

Abstract Background Compared with singleton pregnancy, twin gestation is featured by a greater increase in cardiac output. Therefore, norepinephrine might be more suitable than phenylephrine for maintaining blood pressure during cesarean section for twins, as phenylephrine causes reflex bradycardia and a resultant decrease in cardiac output. This study was to determine whether norepinephrine was superior to phenylephrine in maintaining maternal hemodynamics during cesarean section for twins. Methods Informed consent was obtained from all the patients before enrollment. In this double-blinded, randomized clinical trial, 100 parturients with twin gestation undergoing cesarean section with spinal anesthesia were randomized to receive prophylactic norepinephrine (3.2 μg/min) or phenylephrine infusion (40 μg/min). The primary outcome was the change of heart rate and blood pressure during the study period. The secondary outcomes were to compare maternal complications, neonatal outcomes, Apgar scores and umbilical blood acid-base status between the two vasopressors. Results There was no significant difference observed for the change of heart rate between two vasopressors. The mean standardized area under the curve of heart rate was 78 ± 12 with norepinephrine vs. 74 ± 11 beats/min with phenylephrine (mean difference 4.4, 95%CI − 0.1 to 9.0; P = .0567). The mean standardized area under the curve of systolic blood pressure (SBP) was significantly lower in parturients with norepinephrine, as the mean of differences in standardized AUC of SBP was 6 mmHg, with a 95% CI from 2 to 9 mmHg (P = .0013). However, requirements of physician interventions for correcting maternal hemodynamical abnormalities (temporary cessation of vasopressor infusion for reactive hypertension, rescuing vasopressor bolus for hypotension and atropine for heart rate less

ObjectiveTo investigate the diagnostic role of heart rate variability in breast cancer and its relationship with Carcinoembryonic antigen (CEA) in peripheral serum.MethodsWe reviewed the electronic medical records of patients who attended Zhujiang Hospital of Southern Medical University between October 2016 and May 2019. The patients were grouped based on breast cancer history and were divided into two groups: breast cancer group(n = 19) and control group(n = 18). All women were invited for risk factor screening, including 24-hour ambulatory ECG monitoring and blood biochemistry after admission. The difference and correlation between the breast cancer group and control group were performed by comparing the heart rate variability and serum CEA levels. Additionally, diagnostic efficacy analysis of breast cancer was calculated by combining heart rate variability and serum CEA.ResultsIn total, 37 patients were eligible for analysis, with 19 and 18 patients in the breast cancer group and control groups, respectively. Women with breast cancer had a significantly lower level of total LF, awake TP, and awake LF, and a significantly higher level of serum CEA compared with women with no breast cancer. Total LF, awake TP, and awake LF were negatively correlated with the CEA index (P < 0.05). The receiver operating characteristic (ROC) curves indicated the highest area under the curve (AUC) scores and specificity of the combination of awake TP, awake LF, and serum CEA (P < 0.05), while sensitivity was highest for total LF, awake TP, and awake LF (P < 0.05).ConclusionsWomen with history of breast cancer had abnormalities in autonomic function. The combined analysis of heart rate variability and serum CEA analysis may have a predictive effect on the development of breast cancer and provide more basis for clinical diagnosis and treatment.

An innovative explosive welding method for the fabrication of multiple plates (EWMP) was proposed to further improve the energy efficiency of explosive welding explosive charges and reduce the impact on the surrounding environment. In this method, six metal plates were placed in parallel and three composite plates were obtained through one explosion in this paper. The microstructure of the joint was analyzed by optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron backscattering diffraction (EBSD). Compared to traditional explosive welding (TEW), the EWMP dramatically reduced the noise and vibration and increased the energy efficiency of explosives. The results showed the vibration data of EWMP were reduced by 16.7, 16.4, 2.8, and 1.5%, respectively, and at places of 3, 4, 5, and 6 m away from the explosion center, and explosive consumption of EWMP was reduced by at least half, compared to the traditional method when obtaining the same amount of welded plates. Through numerical simulation, the collision speeds of the composite plate are 610, 516, and 471 m/s, respectively, and the waveform of the composite plate is basically in coincidence with the result of the experiment.

In recent years, inert gases such as helium, argon, and xenon have gained considerable attention for their medical value. Noble gases present an intriguing scientific paradox: although extremely chemically inert, they display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge about their mechanisms of action, some noble gases have been used successfully in clinical practice. The neuroprotection elicited by these noble gases has been investigated in experimental animal models of various types of brain injuries, such as traumatic brain injury, stroke, subarachnoid hemorrhage, cerebral ischemic/reperfusion injury, and neurodegenerative diseases. Collectively, these central nervous system injuries are a leading cause of morbidity and mortality every year worldwide. Treatment options are presently limited to thrombolytic drugs and clot removal for ischemic stroke, or therapeutic cooling for other brain injuries before the application of noble gas. Currently, there is increasing interest in noble gases as novel treatments for various brain injuries. In recent years, neuroprotection elicited by particular noble gases, xenon, for example, has been reported under different conditions. In this article, we have reviewed the latest in vitro and in vivo experimental and clinical studies of the actions of xenon, argon, and helium, and discuss their potential use as neuroprotective agents.

BackgroundCardiac sympathetic nerve system (SNS) might play an important role in arrhythmogenesis of arrhythmogenic cardiomyopathy (ACM). This study aims to assess the activity of cardiac SNS in ACM patients by heart rate variability (HRV), and to investigate its predictive value for sustained ventricular tachycardia (sVT).MethodsA total of 88 ACM patients and 65 sex- and age- matched healthy participants were enrolled. The time domain measures were used to evaluate the activity of cardiac SNS. An independent cohort with 48 ACM patients was as the validation cohort.ResultsACM patients had lower levels of standard deviation of all NN intervals (SDNN) [118.0 (90.3, 136.8) vs. 152.0 (132.5, 174.5) ms, p < 0.001] compared with healthy participants. Further analysis showed ACM patients with sVT had lower levels of SDNN than those without sVT (105.0 ± 28.1 vs. 131.8 ± 33.1 ms, p < 0.001). Multivariate logistic regression analysis showed SDNN was independently associated with sVT in ACM patients [odds ratio (OR) 0.59, 95% confidence interval (CI) (0.45–0.78), p < 0.001]. Receiver operating characteristics curve demonstrated SDNN had clinical values in predicting sVT in ACM patients [area under the curve (AUC) = 0.73, 95% CI (0.63–0.84), p < 0.001], which was verified in the validation cohort.ConclusionThe present study suggests that HRV is impaired in patients with ACM, and the SDNN level has a moderate value in risk stratification for sVT in ACM patients. In addition, the finding might provide new target for the further management of ACM with integrated traditional Chinese and western medicine.

Summary: RNA helicase DDX21 plays vital roles in ribosomal RNA processing and the regulation of host innate immunity during virus infection. Here, we describe the optimized protocols for nucleic acid-free protein purification and crystallization of DDX21 in its different unwinding states. Rational design of the flexible region within the helicase core, and biophysical approach to characterize interactions between DDX21 and RNA, leads to successful crystallization of DDX21. This protocol can be applied to the crystallography of other DExD/H-box RNA helicases.For complete details on the use and execution of this protocol, please refer to Chen et al. (2020). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The excessive accumulation of bile acids (BA) in hepatocytes can trigger inflammatory response and recruit macrophages, thereby accelerating cholestatic liver injury. The crosstalk between hepatocytes and macrophages has been recently implicated in the pathogenesis of cholestasis; however, the underlying mechanisms remain unclear. Here, we demonstrated that BA initiate NLRP3 inflammasome activation in hepatocytes to release proinflammatory cytokines and promote the communication between hepatocytes and macrophages, thus enhancing liver inflammation in an NLRP3-dependent manner. NLRP3-inhibition by geniposidic acid (GPA), a novel NLRP3-specific covalent inhibitor that directly interacts with NLRP3, in hepatocytes and macrophages abated BA-induced inflammation. Moreover, NLRP3-deletion or its inhibition mitigated ANIT-induced cholestatic inflammation, whereas disrupting the crosstalk between hepatic macrophages and hepatocytes attenuated the hepatoprotective effect of GPA against ANIT-induced cholestatic inflammation. Therefore, blocking this crosstalk by suppressing NLRP3 inflammasome activation may represent a novel therapeutic strategy for cholestasis.

The incidence of stroke or transient ischemic attacks (TIA) in atrial fibrillation (AF) catheter ablation procedures is around 1% and may be unnoted under anesthesia. The artery of Percheron (AOP) infarction is a rare kind of stroke with heterogeneity in manifestation, which further makes the perioperative early detection and diagnosis a challenge. Herein, we present one patient who underwent AF ablation and presented mental status alteration after withdrawing anesthetics. An emergency head CT was obtained, which revealed no apparent pathological changes. A late MRI test confirmed the diagnosis of AOP infarction. With oral anticoagulants and rehabilitation therapies, the patient’s awareness improved and fully recovered on the sixth-month follow-up. Variability in manifestation, no positive radiological finding on initial CT, and a low incidence has made few clinicians to gain much experience with this type of infarct, which delays the diagnosis and initiation of appropriate treatment.

MXene materials have shown numerous useful mechanical and electronic properties, and have been found to possess nice potential in the field of optical modulation. Here, we fabricated a MXene Cr2C saturable absorber by the liquid-phase exfoliation method, and systemically analyzed the surface morphology and nonlinear properties of the Cr2C sample. Applying the Cr2C saturable absorber as a Q-switch in a thulium-doped yttrium aluminum perovskite (Tm: YAP) laser, the shortest single pulse was obtained with a width of 602 ns under an absorbed pump power of 3.3 W at a repetition rate of 55 kHz with a T = 1% output coupler. The maximum output power was obtained with a T = 5% output coupler at a repetition rate of 58 kHz. The obtained maximum pulse energy and peak power were 3.96 μJ and 4.36 W, separately, which reveal that the MXene Cr2C can be applied as a promising modulation material in the near-infrared pulsed lasers.

Goal-oriented movement is a fundamental animal behaviour. Here, the authors show that neurons in the superior colliculus project to the substantia nigra pars compacta, regulating dopaminergic signaling and specifically appetitive locomotion in mice.

Background: The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)− 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) is a novel diarylheptane compound, which is designed to treat IBD. Hence, we investigated the potent therapeutic activity of SDH against IBD and explored the underlying mechanisms, and determined if SDH is a safe and well-tolerated oral therapeutic for IBD treatment. Methods: We characterized its therapeutic properties in vitro and in vivo using Caco-2 cell monolayer and dextran sodium sulfate (DSS)- or 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced colitis models. We conducted nonclinical toxicology and safety pharmacology research, including general toxicity, toxicokinetics, pharmacokinetics, metabolism and plasma protein binding, cardiovascular safety pharmacology, central nervous system safety pharmacology, respiratory safety pharmacology, fertility and early embryonic development toxicity, reverse mutation assay, chromosomal aberration assay and micronucleus test. Results: The results showed that SDH promoted expression of tight junction proteins, and protected the integrity and permeability of the epithelial barrier in both cell and animal models. Moreover, lower doses of SDH showed the similar or better efficacy than cyclosporine A (CsA) and mesalazine in DSS- or TNBS-induced colitis animals. Furthermore, our results identified that SDH has satisfactory safety in these studies we tested. In summary, SDH restored the epithelial barrier through tight junction proteins and was expected to be a novel therapeutic agent for the treatment of IBD.

Abstract Background The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. Methods A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. Results A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. Conclusions We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

Two aplysiatoxin derivatives, neo-debromoaplysiatoxin I (1) and neo-debromoaplysiatoxin J (2), were isolated from marine cyanobacterium Lyngbya sp. collected from the South China Sea. Their structures including absolute configurations were assigned by spectroscopic analysis, in combination with GIAO NMR shift calculation and DP4+ analysis. Structures of neo-debromoaplysiatoxin I and neo-debromoaplysiatoxin J contained a decahydro-5H-pyrano [2,3,4-de] chromen-5-one 6/6/6 ring skeleton and an intriguing peroxide bridge group, respectively, which are unprecedented structure scaffold and motif in aplysiatoxins. Two compounds displayed comparable inhibitory activities against Kv1.5 K+ channel with IC50 values of 2.59 ± 0.37 μM (1) and 1.64 ± 0.15 μM (2); however, they presented differential cytotoxic effects. It is worth noting that neo-debromoaplysiatoxin J, containing a peroxide bridge, showed remarkable cytotoxicity against four cancer cell lines including SW480, SGC7901, LoVo and PC-9 compared to the human normal cell line.

Introduction and objectives: Whether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy. Patients and methods: This retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence. Results: Male patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084–2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093–2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215–2.936], P = 0.006), but not for late recurrence. Conclusions: There is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.

Graft versus host disease after solid organ transplantation is very rare. This article reports a case of graft versus host disease after liver transplantation following targeted therapy and radiotherapy for the treatment of hepatocellular carcinoma. The patient developed a symptomatic skin rash and pancytopenia 13 days after surgery, which was confirmed as graft versus host disease after liver transplantation by histopathology and fluorescence in situ hybridization. Early diagnosis of graft versus host disease after solid organ transplantation is difficult and often delayed due to nonspecific manifestations that overlap with other diseases. Currently, the treatment of graft versus host disease after liver transplantation occurs by either strengthening the immune suppression or weakening the immune suppression; however, there is no unified standard treatment strategy. We found that in addition to age, gender, and human leukocyte antigen type, preoperative radiotherapy is a likely risk factor for graft versus host disease after liver transplantation.

A new brain circuit that contributes to aversive states, such as fear or anxiety, has been characterized in mice.

In order to obtain high-quality CuCrZr/316L clad plates prepared by explosive welding (EW), theoretical analysis and numerical simulation were introduced to optimize welding parameters. The bonding properties of the achieved joints were systematically studied through multiscale interface analyses, mechanical performance tests, and evaluation of sealing properties. It was concluded that the theoretical analysis in collaboration with numerical calculations is an effective way to design parameters, because its predicted result was in good agreement with the ultrasonic test (UT) one. In both microstructure observations and mechanical tests, an excellent bonding quality of the CuCrZr/316L bimetallic plate was confirmed, where a uniform wavy morphology without defects such as voids and cracks was found at the bonding interface. The bonding strength was higher than the CuCrZr alloy. Moreover, a self-designed hydraulically pressed mold method was developed to manufacture a U-shaped CuCrZr/316L component, and the resulting sample matches well with the designed dimensions. Finally, the helium-leak test results demonstrate that the sealing property of the CuCrZr/316L bimetallic plate meets the practical requirements, indicating that the welded specimens were sound.

Abstract Background Esterases and lipases hydrolyze short-chain esters and long-chain triglycerides, respectively, and therefore play essential roles in the synthesis and decomposition of ester bonds in the pharmaceutical and food industries. Many SGNH family esterases share high similarity in sequences. However, they have distinct enzymatic activities toward the same substrates. Due to a lack of structural information, the detailed catalytic mechanisms of these esterases remain barely investigated. Results In this study, we identified two SGNH family esterases, CrmE10 and AlinE4, from marine bacteria with significantly different preferences for pH, temperature, metal ion, and organic solvent tolerance despite high sequence similarity. The crystal structures of these two esterases, including wild type and mutants, were determined to high resolutions ranging from 1.18 Å to 2.24 Å. Both CrmE10 and AlinE4 were composed of five β-strands and nine α-helices, which formed one compact N-terminal α/β globular domain and one extended C-terminal domain. The aspartic residues (D178 in CrmE10/D162 in AlinE4) destabilized the conformations of the catalytic triad (Ser-Asp-His) in both esterases, and the metal ion Cd2+ might reduce enzymatic activity by blocking proton transfer or substrate binding. CrmE10 and AlinE4 showed distinctly different electrostatic surface potentials, despite the similar atomic architectures and a similar swap catalytic mechanism. When five negatively charged residues (Asp or Glu) were mutated to residue Lys, CrmE10 obtained elevated alkaline adaptability and significantly increased the enzymatic activity from 0 to 20% at pH 10.5. Also, CrmE10 mutants exhibited dramatic change for enzymatic properties when compared with the wide-type enzyme. Conclusions These findings offer a perspective for understanding the catalytic mechanism of different esterases and might facilitate the industrial biocatalytic applications.

Abstract The purpose of this investigation was to explore the prognostic value of phospholipase C delta (PLCD) genes in early stage pancreatic ductal adenocarcinoma (PDAC) and its potential molecular mechanisms. The prognostic value of PLCD genes in early stage PDAC was assessed using the Kaplan‐Meier method and multivariate Cox proportional hazards regression model. Genome‐wide correlation analysis was performed on PLCD3 to identify the highly correlated genes in the transcriptome. Then, PLCD3 and these correlated genes together underwent a bioinformatics analysis to elucidate the potential molecular biological functions of PLCD3 in PDAC. PLCD1 and PLCD3 are significantly overexpressed in PDAC. In PDAC patients, PLCD3 is overexpressed in certain groups of people with a history of alcoholism (P = .032). High expression of PLCD3 was found to be associated with lower overall survival (OS) of patients with early stage PDAC (P = .020; adjusted P = .016). A combination of PLCD3 and clinical variables was able to better predict the outcome of patients with early stage PDAC. These clinical variables are histological grade (P = .001; adjusted P = .001), targeted molecular therapy (P

Advances in cancer therapy have resulted in more cancer therapy-related cardiac dysfunction (CTRCD), which is the main cause of death in older female survivors of breast cancer. Traditionally, guideline-recommended medications for heart failure, such as beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), are commonly used to prevent or attenuate CTRCD. However, sometimes their effectiveness is not satisfactory. Recently, the drug combination of sacubitril plus valsartan has been proven to be more beneficial for heart failure with reduced ejection fraction in the long term compared with an ACEI/ARB alone. However, there is a lack of evidence of the efficacy and safety of this drug combination in CTRCD. We report a case of worsening CTRCD, despite treatment with traditional medications, in which the patient improved after changing perindopril to sacubitril/valsartan. The patient’s heart function greatly improved after changing this ACEI to sacubitril/valsartan. Changing an ACEI/ARB to sacubitril/valsartan in patients with worsening chemotherapy-induced heart failure is appropriate. Further studies with a high level of evidence are required to assess the efficacy and safety of sacubitril/valsartan for CTRCD.

The rapid, stable, and undamaged picking of small-sized spherical fruits are one of the key technologies to improve the level of intelligent picking robots and reduce grading operations. Cherry tomatoes were selected as the research object in this work. Picking strategies of two-stage “Holding-Rotating” and finger-end grasping were determined. The end-effector was designed to separate the fruit from the stalk based on the linear motion of the constraint part and the rotating gripper. This work first studied the human hand-grasping of cherry tomatoes and designed the fingers with sinusoidal characteristics. The mathematical model of a single finger of the gripper was established. The structural parameters of the gripper were determined to meet the requirements of the grabbing range from 0 to 61.6 mm. Based on the simulation model, the constraint part was set to 6 speeds, and the fruit sizes were set to 20 mm, 30 mm, and 40 mm, respectively. When the speed was 0.08m/s, the results showed that the grabbing time was 0.5381 s, 0.387 s, and 0.2761 s, respectively, and the maximum grabbing force was 0.9717 N, 3.5077 N, and 4.0003 N now of clamping, respectively. It met the picking requirements of high speed and low loss. The criterions of two-index stability and undamaged were proposed, including the grasping index of the fixed value and the slip detection of variance to mean ratio. Therefore, the control strategy and algorithm based on two-stage and two-index for rapid, stable, and non-destructive harvesting of small fruit were proposed. The results of the picking experiment for seventy-two cherry tomatoes showed that the picking success rate was 95.82%, the average picking time was 4.86 s, the picking damage rate was 2.90%, the browning rate was 2.90% in 72 h, and the wrinkling rate was 1.49% in 72 h, which can meet the actual small spherical fruit picking requirements. The research will provide an idea for the flexible end-effectors with humanoid grasp function and provides a theoretical reference for small spherical fruit picking.

Tungstate and molybdate phosphors have received great attention for their excellent photoluminescent properties and thermal stabilities. In the article, Tb3+-activated tungstate and molybdate green phosphors were prepared by a solid-state reaction method at different caline temperatures and were compared and studied. The crystal structures and the morphologies of samples were characterized by X-ray diffraction (XRD) patterns and field emission scanning electron microscopy (FE-SEM) images. The energy-dispersive spectra (EDS) proved the compositions of the prepared samples. The photoluminescence (PL) spectra showed that the PL excitation spectra of Tb3+-doped Lu2W3O12 and Lu2Mo3O12 green phosphors consisted of a broad and strong charge transfer band (CTB) and 4f–5d transitions of Tb3+ in the ultraviolet (UV) wavelength range and some narrowed excitation peaks from the 4f–4f transition of Tb3+ in the near ultraviolet (NUV) wavelength region. The PL emission spectra of the phosphors exhibited the characteristic green emissions owing to the 5D4→7F5 transition of Tb3+ located at about 547 nm. The values of energy gap Eg were calculated based on the diffuse reflection spectra (DRS). The measuring temperature-dependent PL spectra illustrated the thermal stabilities of phosphors. The Tb3+-doped Lu2Mo3O12 phosphor presented normal thermal quenching phenomena and the values of the thermal activation energy Ea were calculated based on the measuring temperature dependent PL emission spectra. The Tb3+-doped Lu2W3O12 phosphor exhibited abnormal thermal enhancing CTB excitation intensity at about 170 °C. Furthermore, the PL decay curves suggested that the lifetime corresponding to the 5D4 level of Tb3+ in the Lu2W3O12 host lattice was longer than that in the Lu2Mo3O12 host lattice. Compared the Tb3+-doped Lu2Mo3O12 phosphor, the Tb3+-doped Lu2W3O12 phosphor has shown potential as an application in temperature sensors.