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Red flesh apple (Malus pumila var. medzwetzkyana Dieck), purple leaf plum (Prunus cerasifera Ehrhar f), and purple leaf peach (Prunus persica 'Atropurpurea') are significant ornamental plants within the Rosaceae family. The coloration of their fruits and leaves is crucial in their appearance and nutritional quality. However, qualitative and quantitative studies on flavonoids in the succulent fruits and leaves of multicolored Rosaceae plants are lacking. To unveil the diversity and variety-specificity of flavonoids in these three varieties, we conducted a comparative analysis of flavonoid metabolic components using ultra-high-performance liquid phase mass spectrometry (UPLC-MS/MS). The results revealed the detection of 311 metabolites, including 47 flavonoids, 105 flavonols, 16 chalcones, 37 dihydroflavonoids, 8 dihydroflavonols, 30 anthocyanins, 14 flavonoid carbon glycosides, 23 flavanols, 8 isoflavones, 11 tannins, and 12 proanthocyanidins. Notably, although the purple plum and peach leaves exhibited distinct anthocyanin compounds, paeoniflorin and corythrin glycosides were common but displayed varying glycosylation levels. While the green purple leaf peach fruit (PEF) and red flesh apple leaf (AL) possessed the lowest anthocyanin content, they exhibited the highest total flavonoid content. Conversely, the red flesh apple fruit (AF) displayed the highest anthocyanin content and a diverse range of anthocyanin glycosylation modifications, indicating that anthocyanins predominantly influenced the fruit's color. Purple PLF, PLL, and PEL showcased varying concentrations of anthocyanins, suggesting that their colors result from the co-color interaction between specific types of anthocyanins and secondary metabolites, such as flavonols, flavonoids, and dihydroflavonoids. This study provides novel insights into the variations in tissue metabolites among Rosaceae plants with distinct fruit and leaf colors. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prognostic significance of anoikis related genes (ARGs) in ovarian cancer (OC) and to develop a prognostic signature based on ARG expression. We analyzed cohorts of OC patients and used nonnegative matrix factorization (NMF) for clustering. Single-sample gene-set enrichment analysis (ssGSEA) was employed to quantify immune infiltration. Survival analyses were performed using the Kaplan–Meier method, and differences in survival were determined using the log-rank test. The extent of anoikis modification was quantified using a risk score generated from ARG expression. The analysis of single-cell sequencing data was performed by the Tumor Immune Single Cell Hub (TISCH). Our analyses revealed two distinct patterns of anoikis modification. The risk score was used to evaluate the anoikis modification patterns in individual tumors. Three hub-genes were screened using the LASSO (Least Absolute Shrinkage and Selection Operator) method and patients were classified into different risk groups based on their individual score and the median score. The low-risk subtype was characterized by decreased expression of hub-genes and better overall survival. The risk score, along with patient age and gender, were considered to identify the prognostic signature, which was visualized using a nomogram. Our findings suggest that ARGs may play a novel role in the prognosis of OC. Based on ARG expression, we have developed a prognostic signature for OC that can aid in patient stratification and treatment decision-making. Further studies are needed to validate these results and to explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

This study explores the hot deformation behavior of Al–Zn–Mg–Cu alloy through uniaxial hot compression (200 °C–450°C) using the Gleeble-1500. True stress–strain curves were corrected, and three models were established: the Arrhenius model, strain compensated (SC) Arrhenius model, and strain compensated recrystallization temperature (RT) segmentation-based (TS-SC) Arrhenius model. Comparative analysis revealed the limited predictive accuracy of the SC Arrhenius model, with a 25.12% average absolute relative error (AARE), while the TS-SC Arrhenius model exhibited a significantly improved to 9.901% AARE. Material parameter calculations displayed variations across the temperature range. The SC Arrhenius model, utilizing an average slope method for parameter computation, failed to consider temperature-induced disparities, limiting its predictive capability. Hot processing map, utilizing the Murty improved Dynamic Materials Model (DMM), indicated optimal conditions for stable forming of the Al–Zn–Mg–Cu alloy. Microstructural analysis revealed MgZn2 precipitation induced by hot deformation, with crystallographic defects enhancing nucleation rates and precipitate refinement. [ABSTRACT FROM AUTHOR]

We developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan's National Health Insurance Research Database 2003–2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54–0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings. [ABSTRACT FROM AUTHOR]

The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs. 14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with all other subtypes at a 10% false discovery rate. The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses. Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype. Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis. These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD. [ABSTRACT FROM AUTHOR]

Metallothionein (MT) is a protein with function of heavy metal detoxification. However, studies about how single nucleotide polymorphisms (SNPs) of MT genes influence lead nephropathy are relatively scarce. Therefore, our aim is to investigate the association between blood lead levels and renal biomarkers and to study whether this association is influenced by the combination of MT1A and MT2A SNPs. Blood lead, urinary uric acid (UA), and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were analyzed from 485 participants. Genotyping were performed on MT1A SNPs (rs11640851 and rs8052394) and MT2A SNPs (rs10636 and rs28366003). The combined MT1A 2A SNPs were divided into 16 groups. Among renal biomarkers, urinary UA was negatively significant associated with the time-weighted index of cumulative blood lead (TWICL), while urinary NAG was positively significant with TWICL. Furthermore, the association between urinary UA and TWICL was significantly modified by group 6 of combined SNPs (MT1A 2 A SNPs combination were AAAGGGAA, ACAGGGAA, and ACGGGGAA). In conclusion, the negative association of urinary UA and TWICL is modified by group 6, which means participants of group 6 are more susceptible to lead nephrotoxicity. [ABSTRACT FROM AUTHOR]

In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020–2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortality P-score metrics were also compared with the neighboring countries. In summary, there were three "waves" of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new "wave" of the all-cause mortality was higher than the previous one and the mortality "peaks" corresponded in time to three "waves" of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic. [ABSTRACT FROM AUTHOR]

In this paper, a novel composite is constructed as a non-enzymatic hydrogen peroxide (H2O2) sensor by liquid-phase exfoliation method, which is composed of copper oxide, cuprous oxide and silver nanoparticles doped few-layer-graphene (CuxO/Ag@FLG). Its surface morphology and composition were characterized by scanning electron microscopy (SEM) and X-ray photo spectroscopy (XPS), and its H2O2 sensing performances include catalytic reduction and quantitative detection were studied with electrochemical methods. Our sensor had a high sensitivity of 174.5 μA mM−1 cm−2 (R2 = 0.9978) in an extremely wide range of concentrations from 10 μM to 100 mM, a fast response (about 5 s) and a low limit of detection (S/N = 3) of 2.13 μM. The sensor exhibits outstanding selectivity in the presence of various biological interference, such as dopamine, ascorbic acid, uric acid, citric acid, etc. In addition, the constructed sensor continued 95% current responsiveness after 1 month of storage further points to its long-term stability. Last but not least, it has a good recovery rate (90.12–102.00%) in milk sold on the open market, indicating that it has broad application possibilities in the food industry and biological medicine. [ABSTRACT FROM AUTHOR]

Polyps are well-known cancer precursors identified by colonoscopy. However, variability in their size, appearance, and location makes the detection of polyps challenging. Moreover, colonoscopy surveillance and removal of polyps are highly operator-dependent procedures and occur in a highly complex organ topology. There exists a high missed detection rate and incomplete removal of colonic polyps. To assist in clinical procedures and reduce missed rates, automated methods for detecting and segmenting polyps using machine learning have been achieved in past years. However, the major drawback in most of these methods is their ability to generalise to out-of-sample unseen datasets from different centres, populations, modalities, and acquisition systems. To test this hypothesis rigorously, we, together with expert gastroenterologists, curated a multi-centre and multi-population dataset acquired from six different colonoscopy systems and challenged the computational expert teams to develop robust automated detection and segmentation methods in a crowd-sourcing Endoscopic computer vision challenge. This work put forward rigorous generalisability tests and assesses the usability of devised deep learning methods in dynamic and actual clinical colonoscopy procedures. We analyse the results of four top performing teams for the detection task and five top performing teams for the segmentation task. Our analyses demonstrate that the top-ranking teams concentrated mainly on accuracy over the real-time performance required for clinical applicability. We further dissect the devised methods and provide an experiment-based hypothesis that reveals the need for improved generalisability to tackle diversity present in multi-centre datasets and routine clinical procedures. [ABSTRACT FROM AUTHOR]

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC–MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI. [ABSTRACT FROM AUTHOR]

This study was to develop a computer vision evaluation method to automatically measure the degree of scoliosis based on the machine learning algorithm. For the X-ray images of 204 patients with idiopathic scoliosis who underwent full-spine radiography, histogram equalization of original image was performed before a flipping method was used to magnify asymmetric elements, search for the global maximum pixel value in each line, and scan local maximal pixel value, with the intersection set of two point sets being regarded as candidate anchor points. All fine anchors were fitted with cubic spline algorithm to obtain the approximate curve of the spine, and the degree of scoliosis was measured by the standardized integral area. All measured data were analyzed. In manual measurement, the Cobb angle was 11.70–25.00 (20.15 ± 3.60), 25.20–44.70 (33.89 ± 5.41), and 45.10–49.40 (46.98 ± 1.25) in the mild, moderate and severe scoliosis group, respectively, whereas the value for the standardized integral area algorithm was 0.072–0.298 (0.185 ± 0.040), 0.100–0.399 (0.245 ± 0.050), and 0.246–0.901 (0.349 ± 0.181) in the mild, moderate and severe scoliosis group, respectively. Correlation analysis between the manual measurement of the Cobb angle and the evaluation of the standardized integral area algorithm demonstrated the Spearman correlation coefficient r = 0.643 (P < 0.001). There was a positive correlation between the manual measurement of the Cobb angle and the measurement of the standardized integral area value. Two methods had good consistency in evaluating the degree of scoliosis. ROC curve analysis of the standardized integral area algorithm to measure the degree of scoliosis showed he cutoff value of the standardized integral area algorithm was 0.20 for the moderate scoliosis with an AUC of 0.865, sensitivity 0.907, specificity 0.635, accuracy 0.779, positive prediction value 0.737 and negative prediction value 0.859, and the cutoff value of the standardized integral area algorithm was 0.40 for the severe scoliosis with an AUC of 0.873, sensitivity 0.188, specificity 1.00, accuracy 0.936, positive prediction value 1 and a negative prediction value 0.935. Using the standardized integral area as an independent variable and the Cobb angle as a dependent variable, a linear regression equation was established as Cobb angle = 13.36 + 70.54 × Standardized area, the model has statistical significance. In conclusion, the integrated area algorithm method of machine learning can quickly and efficiently assess the degree of scoliosis and is suitable for screening the degree of scoliosis in a large dataset as a useful supplement to the fine measurement of scoliosis Cobb angle. [ABSTRACT FROM AUTHOR]

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC–MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI. [ABSTRACT FROM AUTHOR]

With the rapid growth and increasing use of brain MRI, there is an interest in automated image classification to aid human interpretation and improve workflow. We aimed to train a deep convolutional neural network and assess its performance in identifying abnormal brain MRIs and critical intracranial findings including acute infarction, acute hemorrhage and mass effect. A total of 13,215 clinical brain MRI studies were categorized to training (74%), validation (9%), internal testing (8%) and external testing (8%) datasets. Up to eight contrasts were included from each brain MRI and each image volume was reformatted to common resolution to accommodate for differences between scanners. Following reviewing the radiology reports, three neuroradiologists assigned each study to abnormal vs normal, and identified three critical findings including acute infarction, acute hemorrhage, and mass effect. A deep convolutional neural network was constructed by a combination of localization feature extraction (LFE) modules and global classifiers to identify the presence of 4 variables in brain MRIs including abnormal, acute infarction, acute hemorrhage and mass effect. Training, validation and testing sets were randomly defined on a patient basis. Training was performed on 9845 studies using balanced sampling to address class imbalance. Receiver operating characteristic (ROC) analysis was performed. The ROC analysis of our models for 1050 studies within our internal test data showed AUC/sensitivity/specificity of 0.91/83%/86% for normal versus abnormal brain MRI, 0.95/92%/88% for acute infarction, 0.90/89%/81% for acute hemorrhage, and 0.93/93%/85% for mass effect. For 1072 studies within our external test data, it showed AUC/sensitivity/specificity of 0.88/80%/80% for normal versus abnormal brain MRI, 0.97/90%/97% for acute infarction, 0.83/72%/88% for acute hemorrhage, and 0.87/79%/81% for mass effect. Our proposed deep convolutional network can accurately identify abnormal and critical intracranial findings on individual brain MRIs, while addressing the fact that some MR contrasts might not be available in individual studies. [ABSTRACT FROM AUTHOR]

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan's National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population. [ABSTRACT FROM AUTHOR]

Immediate postoperative intensive care unit (ICU) admission can increase the survival rate in patients undergoing high-risk surgeries. Nevertheless, less than 15% of such patients are immediately admitted to the ICU due to no reliable criteria for admission. The surgical Apgar score (SAS) (0–10) can be used to predict postoperative complications, mortality rates, and ICU admission after high-risk intra-abdominal surgery. Our study was performed to determine the relationship between the SAS and postoperative ICU transfer after all surgeries. All patients undergoing operative anesthesia were retrospectively enrolled. Among 13,139 patients, 68.4% and < 9% of whom had a SASs of 7–10 and 0–4. Patients transferred to the ICU immediately after surgery was 7.8%. Age, sex, American Society of Anesthesiologists (ASA) class, emergency surgery, and the SAS were associated with ICU admission. The odds ratios for ICU admission in patients with SASs of 0–2, 3–4, and 5–6 were 5.2, 2.26, and 1.73, respectively (P < 0.001). In general, a higher ASA classification and a lower SAS were associated with higher rates of postoperative ICU admission after all surgeries. Although the SAS is calculated intraoperatively, it is a powerful tool for clinical decision-making regarding the immediate postoperative ICU transfer. [ABSTRACT FROM AUTHOR]

Outer membrane proteins (OMPs) are essential to gram-negative bacteria, and molecular chaperones prevent the OMPs from aggregation in the periplasm during the OMPs biogenesis. Skp is one of the molecular chaperones for this purpose. Here, we combined single-molecule fluorescence resonance energy transfer and fluorescence correlation spectroscopy to study the affinity and stoichiometric ratio of Skp in its binding with OmpC at the single-molecule level. The half concentration of the Skp self-trimerization (C1/2) was measured to be (2.5 ± 0.7) × 102 nM. Under an Skp concentration far below the C1/2, OmpC could recruit Skp monomers to form OmpC·Skp3. The affinity to form the OmpC·Skp3 complex was determined to be (5.5 ± 0.4) × 102 pM with a Hill coefficient of 1.6 ± 0.2. Under the micromolar concentrations of Skp, the formation of OmpC·(Skp3)2 was confirmed, and the dissociation constant of OmpC·(Skp3)2 was determined to be 1.2 ± 0.4 μM. The precise information will help us to quantitatively depict the role of Skp in the biogenesis of OMPs. [ABSTRACT FROM AUTHOR]

Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR < 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process 'receptor-mediated endocytosis', and 52 TMPRSS2-correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a common pathogen in chronic rhinosinusitis (CRS) patients, the pathogenesis of which involves the ability to form biofilms and produce various virulence factors. Tobacco smoke, another risk factor of CRS, facilitates S. aureus biofilm formation; however, the mechanisms involved are unclear. Here, we studied the effect of nicotine on S. aureus biofilm formation and the expression of virulence-related genes. S. aureus strains isolated from CRS patients and a USA300 strain were treated with nicotine or were untreated (control). Nicotine-treated S. aureus strains showed dose-dependent increases in biofilm formation, lower virulence, enhanced initial attachment, increased extracellular DNA release, and a higher autolysis rate, involving dysregulation of the accessory gene regulator (Agr) quorum-sensing system. Consequently, the expression of autolysis-related genes lytN and atlA, and the percentage of dead cells in biofilms was increased. However, the expression of virulence-related genes, including hla, hlb, pvl, nuc, ssp, spa, sigB, coa, and crtN was downregulated and there was reduced bacterial invasion of A549 human alveolar epithelial cells. The results of this study indicate that nicotine treatment enhances S. aureus biofilm formation by promoting initial attachment and extracellular DNA release but inhibits the virulence of this bacterium. [ABSTRACT FROM AUTHOR]

A new, precast concrete frame beam-column connection is designed in this research. The connection adopts the assembly mode of the precast column and seam area jointly to maintain the integrity of the joint area and increase the assembly efficiency. Based on the conventional grouting sleeve connection, a disc spring device is constructed on the beam end to improve the ductility of the joint. Ten connecting specimens were tested under low cyclic loads, including two monolithic connections, four ordinary precast connections, and four new precast connections. The test parameters included the joint type and axial pressure ratio, and the difference in the seismic performance was determined by evaluating the failure mode, hysteresis characteristics, stiffness degradation, energy dissipation, and shear deformation of the joint area. Compared to monolithic connections, conventional precast connections display similar hysteresis characteristics. Although their ductility is slightly lower, their bearing capacity is higher. Compared with the previous two connections, the new connection with the built-in disc spring device has superior seismic performance. The axial pressure ratio is a significant aspect in determining the failure mode of the precast connection, and the specimen exhibits less shear damage at a larger axial pressure ratio. [ABSTRACT FROM AUTHOR]

The hetero-chitooligosaccharide (HTCOS) is a naturally occurring biopolymer in the exoskeleton of crustaceans and insects. Although some studies have been carried out on HTCOS in inducing plant resistance and promoting growth, the molecular mechanism of HTCOS in plants is not clear. In this study, an integrated analysis of metabolomics and transcriptomics was performed to analyze the response of Brassica napus to hetero-chitooligosaccharides treatment. The levels of 26 metabolites in B. napus were significantly changed under the HTCOS treatment. Amongst these metabolites, 9 metabolites were significantly up-regulated, including pentonic acid, indole-3-acetate, and γ-aminobutyric acid. Transcriptome data showed that there were 817 significantly up-regulated genes and 1064 significantly down-regulated genes in B. napus under the HTCOS treatment. Interestingly, the indole-3-acetate (IAA) content under the HTCOS treatment was about five times higher than that under the control condition. Moreover, four genes related to plant hormone signal transduction, three AUX/IAA genes, and one ARF gene, were significantly up-regulated under the HTCOS treatment. Furthermore, the plant height, branching number, and biomass of B. napus under the HTCOS treatment were significantly increased compared to that in the control condition. This evidence indicated that the HTCOS treatment contributed to accumulating the content of plant hormone IAA in the B. napus, up-regulating the expression of key genes in the signaling pathway of plant growth and improving the agronomic traits of B. napus. [ABSTRACT FROM AUTHOR]

The emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles from ccRCC cohorts were explored for integrative analysis. A credible method was developed to identify synthetic lethality (SL) pairs and a list of 72 candidate pairs was determined, which might be utilized to selectively eliminate tumors with genetic aberrations using SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medical targets for patients with BAP1 mutations. After mapping these target genes to the comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potentials in the BAP1 mutant tumors. Overall, our findings provided insight into the overview of ccRCC mutation patterns and offered novel opportunities for improving individualized cancer treatment. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan's National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients. [ABSTRACT FROM AUTHOR]

Surface enhanced Raman scattering (SERS) substrate based on fabricated Ag@Au core-shell dendrite was achieved. Ag dendrites were grown on Si wafer by the hydrothermal corrosion method and Au nanofilm on the surface of Ag dendritic nanostructure was then fabricated by chemical reduction. With the help of sodium borohydride in water, Au surface absorbates such as thiophene, adenine, rhodamine, small anions (Br- and I-), and a polymer (PVP, poly(N-vinylpyrrolidone)) can be completely and rapidly removed. After four repeatable experiments, the substrate SERS function did not decrease at all, indicating that the Ag@Au dendrite should be of great significance to SERS application because it can save much resource. Six-month-duration stability tests showed that the Ag@Au core-shell dendrite substrate is much more stable than the Ag dendrite substrates. We have also experimented on fast detection of Cd2+ at 10−8 M concentration by decorating single-stranded DNA containing adenine and guanine bases on the surface of this Ag@Au dendrite. Finite-difference time-domain simulations were carried out to investigate the influence of Au nanolayer on Ag dendrites, which showed that the local electric fields and enhancement factor are hardly affected when a 4 nm Au nanolayer is coated on Ag dendrite surface. [ABSTRACT FROM AUTHOR]

The optimal method of tumor burden evaluation in newly diagnosed multiple myeloma (NDMM) is yet to be determined. This study aimed to compare the value of 11C-acetate positron-emission tomography (PET)/computed tomography (CT) (AC-PET and 18F-fluorodeoxyglucose PET/CT (FDG-PET) in the assessment of tumor burden in NDMM. This study evaluated 64 NDMM patients between February 2015 and July 2018. AC-PET and FDG-PET were used to assess myeloma lesions. The clinical data, imaging results, and their correlations were analyzed. Diffuse bone marrow uptake in AC-PET was significantly correlated with biomarkers for tumor burden, including serum hemoglobin (P = 0.020), M protein (P = 0.054), the percentage of bone marrow plasma cells (P < 0.001), and the Durie–Salmon stage of the disease (P = 0.007). The maximum standard uptake value (SUVmax) of focal lesions and high diffuse bone marrow uptake in AC-PET showed stronger correlations with high-risk disease (P = 0.017, P = 0.013) than those in FDG-PET. Moreover, the presence of diffuse bone marrow uptake, more than ten focal lesions, and an SUVmax of focal lesions of > 6.0 in AC-PET, but not in FDG-PET, predicted a higher probability of disease progression and shorter progression-free survival (P < 0.05). AC-PET outperformed FDG-PET in tumor burden evaluation and disease progression prediction in NDMM. [ABSTRACT FROM AUTHOR]

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in "volume reduction" and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD. [ABSTRACT FROM AUTHOR]

To assess real-world effectiveness of hyperbaric oxygen therapy (HBOT) on delayed neuropsychiatric sequelae (DNS) after carbon monoxide (CO) poisoning we conducted a retrospective review of patients with CO poisoning admitted to Linkou Chang-Gung Memorial Hospital, Taiwan's largest medical center, during 2009–2015. We included patients developing DNS after CO poisoning and compared improvements in neuropsychiatric function, with and without HBOT, after 12 months post-DNS to understand differences in recovery rates. DNS improvement-associated factors were also evaluated. We used receiver operating characteristic (ROC) curve analysis to assess the role of time elapsed between DNS diagnosis and HBOT initiation in predicting DNS improvement. A total of 62 patients developed DNS, of whom 11 recovered while the rest did not. Possible factors predicting DNS improvement included receiving HBOT post-DNS (72.7% vs 25.5%; P = 0.006), and treatment with more than three HBOT sessions during acute stage CO poisoning (81.8% vs 27.5%; P = 0.003). The relevant area under the ROC curve was 0.789 (95% CI 0.603–0.974), and the best cut-off point was 3 days post-DNS diagnosis, with 87.5% sensitivity and 61.5% specificity. Early HBOT in patients who developed DNS after CO poisoning significantly improved their DNS symptoms, with treatment effects sustained for 1 year after DNS diagnosis. [ABSTRACT FROM AUTHOR]

Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring. [ABSTRACT FROM AUTHOR]

Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09–3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19–7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65–2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable. [ABSTRACT FROM AUTHOR]

Fabric-based personal heating patches have small geometric profiles and can be attached to selected areas of garments for personal thermal management to enable significant energy savings in built environments. Scalable fabrication of such patches with high thermal performance at low applied voltage, high durability and low materials cost is critical to the widespread implementation of these energy savings. This work investigates a scalable Intense Pulsed Light (IPL) sintering process for fabricating silver nanowire on woven polyester heating patches. Just 300 microseconds of IPL sintering results in 30% lesser electrical resistance, 70% higher thermal performance, greater durability (under bending up to 2 mm radius of curvature, washing, humidity and high temperature), with only 50% the added nanowire mass compared to state-of-the-art. Computational modeling combining electromagnetic and thermal simulations is performed to uncover the nanoscale temperature gradients during IPL sintering, and the underlying reason for greater durability of the nanowire-fabric after sintering. This large-area, high speed, and ambient-condition IPL sintering process represents an attractive strategy for scalably fabricating personal heating fabric-patches with greater thermal performance, higher durability and reduced costs. [ABSTRACT FROM AUTHOR]

The lateral movement of soil carbon has a profound effect on the carbon budget of terrestrial ecosystems; however, it has never been quantified in China, which is one of the strongest soil erosion areas in the world. In this study, we estimated that the overall soil erosion in China varies from 11.27 to 18.17 Pg yr21 from 1982 to 2011, accounting for 7–21% of total soil erosion globally. Soil erosion induces a substantial lateral redistribution of soil organic carbon ranging from 0.64 to 1.04 Pg C yr21. The erosion-induced carbon flux ranges from a 0.19 Pg C yr21 carbon source to a 0.24 Pg C yr21 carbon sink in the terrestrial ecosystem, which is potentially comparable in magnitude to previously estimated total carbon budget of China (0.19 to 0.26 Pg yr21). Our results showed that the lateral movement of soil carbon strongly alters the carbon budget in China, and highlighted the urgent need to integrate the processes of soil erosion into the regional or global carbon cycle estimates. [ABSTRACT FROM AUTHOR]

We demonstrate an effective approach to realize excitation and outcoupling of the SPP modes associated with both cathode/organic and anode/organic interfaces in OLEDs by integrating dual-periodic corrugation. The dual-periodic corrugation consists of two set gratings with different periods. The light trapped in the SPP modes associated with both top and bottom electrode/organic interfaces are efficiently extracted from the OLEDs by adjusting appropriate periods of two set corrugations, and a 29% enhancement in the current efficiency has been obtained. [ABSTRACT FROM AUTHOR]

Yinma River is a typical river in the major Phaeozems zone of Northeast China. It has been suffering an increasing environmental pressure from heavy metal contamination due to the rapid development of population, social-economy and urbanization as well as long term over cultivation. This study investigated the spatial distribution, chemical fraction of heavy metals (Cu, Pb, Zn, Cr, Cd, Ni, As, and Hg) in sediments of Yinma River based on BCR procedure, assessed the contamination level, and identified their sources via multivariate statistical analysis. The chemical fraction results indicated that Cd, Pb, Ni, and Zn exhibited higher mobility susceptibility and bioavailability with a significant and late anthropogenic origin. Hg and Cd might exert a potential hazardous influence on aquatic biota according to the geo-accumulation index (Igeo). The pollution load index (PLI) assessment suggested that all of the sediment samples have been contaminated. Multivariate statistical analysis revealed that Zn, Cu, Hg, Cd, and Pb reflected the anthropogenic sources with a close correlation with TOC and socio-economic development; Ni, As and Cr tended to represent the geochemical background. Furthermore, Changchun City and Shitoukoumen Reservoir as the major drinking water source may be hotspots of the heavy metal contamination in the watershed. [ABSTRACT FROM AUTHOR]

Early diagnosis of primary central nervous system lymphoma (PCNSL) represents a challenge, and cerebrospinal fluid (CSF) cytokines may be diagnostic biomarkers for PCNSL. We used an electrochemiluminescence immunoassay to measure interleukin (IL)-10, IL-6, IL-8 and tumor necrosis factor α (TNF-α) in the CSF of 22 B cell PCNSL patients and 80 patients with other CNS diseases. CSF IL-10 was significantly higher in PCNSL patients than in the control group (median 74.7 pg/ml vs < 5.0 pg/ml, P < 0.000). Using a CSF IL-10 cutoff value of 8.2 pg/ml, the diagnostic sensitivity and specificity were 95.5% and 96.1%, respectively (AUC, 0.957; 95% CI, 0.901-1.000). For a CSF IL-10/IL-6 cutoff value of 0.72, the sensitivity was 95.5%, and the specificity was 100.0% (AUC, 0.976; 95% CI, 0.929-1.000). An increased CSF IL-10 level at diagnosis and post-treatment was associated with poor Progression free survival (PFS) for patients with PCNSL (P = 0.0181 and P = 0.0002, respectively). A low diagnostic value for PCNSL was found with CSF IL-8 or TNF-α. In conclusion, increased CSF IL-10 was a reliable diagnostic biomarker for large B cell PCNSL, and an IL-10/IL-6 ratio facilitates differentiation from other conditions, especially a CNS infection. [ABSTRACT FROM AUTHOR]

Calcium-activated potassium ion channel-3.1 (KCa3.1) plays a pivotal role in the potassium-calcium exchange involved in atopy. This study aimed to explore the impact of lentiviral-mediated shRNA silencing KCa3.1 on allergic response in a murine allergic rhinitis (AR) model. The BALB/c mice were divided into four groups: untreated AR group, negative control AR group, lentiviral KCa3.1-shRNA treated AR group and normal control group. Concentrations of ovalbumin (OVA)-specific IgE, histamine and leukotrienes C4 (LTC4) in serum, and IL-4, IL-9 and IL-17 in nasal lavage fluid (NLF) were analyzed. Goblet cells and mast cells were counted. KCa3.1 positive cells were counted after immunolabelling by immunofluorescence method. KCa3.1, Mucin 5AC (MUC5AC), and tryptase mRNA levels were determined using real-time polymerase chain reaction. Furthermore, P815 cell line was used to explore the role and mechanism of lentiviral KCa3.1-shRNA on mast cells. The results showed that LV-KCa3.1-shRNA intervention effectively attenuated allergic responses in LV-KCa3.1-shRNA treated mice. LV-KCa3.1-shRNA intervention effectively suppressed KCa3.1 levels and phosphorylation of AKT in P815 cells, leading to the downregulation of tryptase, IL-6 and IL-8 levels. LV-KCa3.1-shRNA intervention effectively attenuated the allergic responses in AR and suppressed mast cell activity by inhibiting PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

We report a transient absorption (TA) imaging method for fast visualization and quantitative layer analysis of graphene and GO. Forward and backward imaging of graphene on various substrates under ambient condition was imaged with a speed of 2 μs per pixel. The TA intensity linearly increased with the layer number of graphene. Real-time TA imaging of GO in vitro with capability of quantitative analysis of intracellular concentration and ex vivo in circulating blood were demonstrated. These results suggest that TA microscopy is a valid tool for the study of graphene based materials. [ABSTRACT FROM AUTHOR]