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A recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations. This study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies. In this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. Of 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies. In cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men. [Display omitted] [ABSTRACT FROM AUTHOR]

The widespread use of chlorine-based disinfectants in drinking water treatment has led to the proliferation of chlorine-resistant bacteria and the risk of disinfection byproducts (DBPs), posing a serious threat to public health. This study aims to explore the effectiveness and potential applications of epigallocatechin gallate (EGCG) against chlorine-resistant Bacillus and its spores in water, providing new insights for the control of chlorine-resistant bacteria and improving the biological stability of distribution systems. The inactivation effects of EGCG on Bacillus subtilis (B. subtilis) and its spores were investigated using transmission electron microscopy, ATP measurement, and transcriptome sequencing analysis to determine changes in surface structure, energy metabolism, and gene expression levels, thereby elucidating the inactivation mechanism. The results demonstrate the potential application of EGCG in continuously inhibiting chlorine-resistant B. subtilis in water, effectively improving the biological stability of the distribution system. However, EGCG is not suitable for treating raw water with high spore content and is more suitable as a supplementary disinfectant for processes with strong spore removal capabilities, such as ozone, ultraviolet, or ultrafiltration. EGCG exhibits a disruptive effect on the morphological structure and energy metabolism of B. subtilis and suppresses the synthesis of substances, energy metabolism, and normal operation of the antioxidant system by inhibiting the expression of multiple genes, thereby achieving the inactivation of B. subtilis. [Display omitted] • EGCG counters chlorine-resistant Bacillus subtilis , enhancing water stability. • EGCG disrupts Bacillus subtilis structure and metabolism, leading to inactivation. • EGCG inhibits gene expression, suppressing synthesis and antioxidant properties. • EGCG is a suitable auxiliary disinfectant for processes with strong spore removal. [ABSTRACT FROM AUTHOR]

To investigate the association of VitD with GDM, and examine the potential modifying effect of prepregnancy BMI in Chinese pregnant women. 3318 pregnant women underwent oral glucose tolerance test (OGTT) were selected from Zhoushan Pregnant Women Cohort. Plasma VitD levels were measured in the first (T1) and/or second trimester (T2). Multiple linear and logistic regression models were used for evaluating the association of VitD with GDM. Prepregnancy BMI was positively associated with all three time-point glucose of OGTT. 25(OH)D level in T1 (β = −0.003) and T2 (β = −0.004), and its change from T1 to T2 (β = −0.004) were significantly and inversely associated with fasting blood glucose (FBG) of OGTT, but not 1-h and 2-h postload blood glucose of OGTT, respectively. The negative associations of VitD and FBG were stronger among overweight/obese women. VitD deficiency (25(OH)D < 20 ng/ml) in T2 was associated with an increased risk of GDM with increased FBG, GDM subtype 1 (OR: 2.10) and subtype 3 (OR: 2.19). Moreover, prepregnancy BMI modified this effect on GDM subtype 1 (BMI < 24: OR = 1.42; BMI ≥ 24: OR = 9.61, P for interaction = 0.002). Lower VitD increment from T1 to T2 was associated with a higher risk for GDM among overweight/obese women. Additionally, GDM prevalence fluctuated with the season, i.e. lower in summer/fall and higher in winter/spring. Maternal VitD deficiency was associated with a higher risk of GDM subtype with increased FBG, and the risk is much greater among overweight/obesity women. The lower the VitD increment during pregnancy, the greater the risk of GDM, especially in overweight/obesity women. Furthermore, seasonal variation of GDM may be exhibited as a critical confounder in the association of VitD and GDM. [ABSTRACT FROM AUTHOR]

Little is known about variation of vitamin D (VD) status during pregnancy among Chinese women. This study is to assess the change of VD status during pregnancy and its influencing factors among Chinese women. A running cohort study has being conducted in southeast China. The pregnant women were interviewed and the peripheral blood samples were collected at the first (T1), second (T2) and third trimester (T3), respectively. 25(OH)D 2 and 25(OH)D 3 were measured by liquid chromatography tandem-mass spectrometry. Multiple linear and logistic regression models were applied to explore the associations of VD supplement with 25(OH)D concentration and VD deficiency, respectively. There were 4368 pregnant women enrolled in the current study. The 25(OH)D concentration increased notably with gestational week. The average plasma 25(OH)D concentration in T1, T2 and T3 was 18.94 ± 8.74, 23.05 ± 11.15, and 24.65 ± 11.59 ng/mL, respectively. Correspondingly, VD deficiency (25(OH)D < 20 ng/mL) rate was 65.26%, 33.56% and 32.12%. In T1 phase, higher pre-pregnancy BMI, more parity, sampling in summer/autumn were related to higher 25(OH)D level, and similar patterns were observed in T2 and T3 phase. There was positive dose–response effect between VD supplement frequency and 25(OH)D concentration during pregnancy, adjusting for potential confounders (T1: β(SE) = 3.907 (0.319), P < 0.001; T2: β(SE) = 2.780 (0.805), P < 0.001; T3: β(SE) = 3.640 (1.057), P = 0.006). Not surprisingly, supplementing VD > 3 times/week reduced the risk of VD deficiency during pregnancy significantly, compared to without VD supplement (T1: OR = 0.30, 95% CI: 0.24–0.37; T2: 0.56, 0.38–0.82; T3: 0.67, 0.44–0.96). VD level increased with gestational week among Chinese pregnant women. High frequency of VD supplement during pregnancy is an effective way to reduce risk of VD deficiency, especially among the pregnant women with younger age, low prepregnancy BMI and primipara, and during winter and spring season. [ABSTRACT FROM AUTHOR]

Anatomic skeletal features of the shoulder play important roles in anterior shoulder dislocation. However, studies on the effect of the humeral structure are few. This case-control study aimed to analyze the risk factors of anterior shoulder instability, including glenoid and humeral factors. Anterior shoulder instability was found in 64 of 10,035 individuals who underwent magnetic resonance imaging. Propensity score matching was used to select controls matched for age, sex, height, and weight. We analyzed the glenoid and humeral structural data using conditional logistic regression analysis and identified cutoff points using receiver operating characteristic curve analysis. Significant differences were found between the control and dislocation groups in the depth-to-width ratio (0.119 ± 0.034 vs. 0.105 ± 0.037, P =.021), height-to-width ratio (1.51 ± 0.13 vs. 1.67 ± 0.16, P <.001), humeral head diameter-to-glenoid fossa diameter ratio (1.56 ± 0.11 vs. 1.64 ± 0.20, P <.001), and humeral containing angle (67.3° ± 5.9° vs. 60.4° ± 5.9°, P <.001). The humeral containing angle (odds ratio, 0.95; P =.024) and the glenoid height-to-width ratio (odds ratio, 7.88; P =.002), adjusted for the depth-to-width ratio and diameter ratio, were associated with anterior shoulder instability. The cutoff point for the humeral containing angle was 64° and for the height-to-width ratio was 1.60. This study revealed significant risk factors for shoulder instability in the Chinese Han population. The humeral containing angle and the glenoid height-to-width ratio were risk factors for anterior shoulder instability. [ABSTRACT FROM AUTHOR]

Abstract The trans -sialidase protein expressed by Trypanosoma cruzi is an important enzyme in the life cycle of this human pathogenic parasite and is considered a promising target for the development of new drug treatments against Chagas' disease. Here we describe α-amino phosphonates as a novel class of inhibitor of T. cruzi trans -sialidase. Molecular modelling studies were initially used to predict the active-site binding affinities for a series of amino phosphonates, which were subsequently synthesised and their IC 50 s determined in vitro. The measured inhibitory activities show some correlation with the predictions from molecular modelling, with 1-napthyl derivatives found to be the most potent inhibitors having IC 50 s in the low micromolar range. Interestingly, kinetic analysis of the mode of inhibition demonstrated that the α-aminophosphonates tested here operate in a non-competitive manner. Graphical abstract Image 1 Highlights • Aryl α-aminophosphonates are effective inhibitors of T. cruzi trans -sialidase. • Inhibition of trans -sialidase is improved using substituted aryl α-aminophosphonates. • Aryl α-aminophosphonates inhibit trans -sialidase in a non-competitive manner. [ABSTRACT FROM AUTHOR]

The PairwiseIHA is an open-source toolkit written in Python that enables the user to quickly obtain the Indicators of Hydrologic Alteration (IHA) from inflow and outflow time series for headwater reservoirs. Specifically, the IHA metrics obtained from inflows (outflows) are considered as natural (regulated) and the differences are used to indicate how the magnitude, frequency, duration, timing and rate of change are altered by reservoir operation. It extends the functionality of the popular IHA software for analyzing concurrent inflows and outflows. The results of three case study reservoirs in California highlight that reservoir operation leads to considerable alterations in the five components of the flow regime. The findings on flow regime alteration are consistent across wet, normal and dry years. Overall, the PairwiseIHA can serve as an effective tool to investigate alterations in flow regime induced by human activities for water managers, scientists, natural resource agencies and water users. • The PairwiseIHA toolkit was developed to investigate the hydrological regime. • The toolkit illustrated the flow regime alterations subject to reservoir operation. • The toolkit was shown to be effective for three case study reservoirs in California. [ABSTRACT FROM AUTHOR]

Background Survivin plays an important role in cancer pathogenesis, which has been suggested to be related to poor prognosis in renal cell carcinoma (RCC). We performed a meta-analysis to quantify the prognostic value of survivin in renal cell carcinoma (RCC) patients. Patients and methods Relevant articles exploring the relationship between survivin expression and survival of RCC patients published up to 10 November 2015 were retrieved in PubMed, Web of science and Cochrane databases. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated by a random-effects model. Results A total of 1583 patients from 10 studies were included. The high expression of survivin was associated with poor Overall Survival (OS) in two studies (Pooled HRs = 2.77, 95%CI: 1.46–5.26, I 2 = 0.0%, P = 0.329). Further, meta-analysis of seven studies showed that elevated survivin expression predicted shorter cancer-specific survival (CSS) of RCC (HR = 2.85, 95% CI: 2.25–3.61, I 2 = 17.6%, P = 0.295). Additionally, subgroup analysis showed that survivin over-expression was associated significantly with worse CSS regardless of different source of survivin, sample size, follow-up duration, race and detection method. Conclusions A higher survivin expression seems to represent an unfavorable and robust prognostic factor for clinical outcomes in RCC patients. [ABSTRACT FROM AUTHOR]

Organoids have great potential as ex vivo disease models for drug discovery and personalized drug screening. Accurate segmentation of individual organoids can provide fundamental indicators of drug response, such as morphology, number, and size. However, for organoids microscopic images data, existing methods cannot automatically and accurately segment organoids due to its problems such as strong adhesion, high background noise, and blurred boundaries. In bridging the gap, we propose a novel unified scheme (PTMBNet) driven by positionable texture and multi-level boundary for achieving accurate organoid segmentation. In particular, we introduce a Texture Positioning Module (TPM) and a Texture Feature Extraction Module (TFM) based on a learnable texture quantification method to capture enhanced texture quantification information and localize segmentation targets under high background noise, respectively. Subsequently, we design a Multi-level Boundary Feature Extraction Module (MBFM) to extract multi-dimensional semantics associated with organoids boundaries. Then, a specially crafted Boundary Restraint Module (BRM) is leveraged to seamlessly extend the positional boundary features to the global context and refine the organoids boundary. Furthermore, we present a Boundary-Texture Consistency loss (BTC) that aims to jointly supervise boundary prediction and texture segmentation outcomes. As part of this study, we manually annotate a substantial and high-quality dataset of lung cancer organoids (LCOs) microscopic images. In comparison to the state-of-the-art methods, the proposed PTMBNet achieves superior segmentation results on the LCOs dataset, with an improvement of 3.4% on Dice and 4.9% on Iou. • PTMBNet: A Novel unified scheme for high-throughput organoid segmentation. • Proposed TFM and TPM for detailed organoid texture feature amid elevated noise. • MBFM and BRM extract multi-level boundaries, ensuring consistency with BTC. • Introducing a large-scale LCOs dataset. PTMBNet surpasses state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Algal polysaccharide activates macrophages to alter physiologic biomarkers to drive the immunomodulatory phenotype, but it lacks specific biomarkers involved in the biochemical underpinning process. Here, we undertook an extensive analysis of the RAW 264.7 macrophages induced by an immunostimulating sulfated polysaccharide from Caulerpa racemosa var. peltata (CRVP-1) employing combined transcriptomic, proteomic, and metabolomic analyses to reveal the molecular details occurring in the CRVP-1-induced immunomodulatory process. The omics profiling of CRVP-1-activated macrophage demonstrated a total of 8844 genes (4354 downregulated and 4490 upregulated), 1243 proteins (620 downregulated and 623 upregulated), and 68 metabolites (52 downregulated and16 upregulated). Further, the co-mapped correlation network of omics combined with Western blot and immunofluorescence staining indicated that the cluster of differentiation 14 (CD14) might assist Toll-like receptor 4 (TLR4) involved in nuclear factor kappa-B (NF-κB) signaling pathway to drive the immunomodulatory phenotype. Together, our results discover novel physiologic biomarkers in the immunomodulatory activities of algal polysaccharides. • Transcriptomic, proteomic, and metabolomic correlation networks were used for analysis. • CRVP-1 could activate the immunomodulatory of RAW264.7 macrophages. • RAW264.7 cells were activated through CD14 assist TLR4 receptor involved in NF-kappa B signaling pathway. [ABSTRACT FROM AUTHOR]

Background: An increasing number of bicuspid aortic valve (BAV) patients are undergoing transcatheter aortic valve replacement (TAVR), but the risk of brain injury in diffusion-weighted magnetic resonance imaging (DW-MRI) is currently unknown.Objectives: This study sought to evaluate the risk of brain injury in BAV patients following TAVR.Methods: A total of 204 consecutive severe aortic stenosis patients who underwent TAVR were enrolled. A total of 83 (40.7%) patients were BAV patients, and the other 121 patients were tricuspid aortic valve (TAV) patients. All patients received DW-MRI at baseline, and after TAVR.Results: Median ages (76 years [interquartile range (IQR): 71 to 81 years] vs. 79 years [IQR: 74 to 83 years]; p = 0.004) and Society of Thoracic Surgeons scores (4.87 [IQR: 3.72 to 8.54] vs. 6.38 [IQR: 3.96 to 9.50]; p = 0.044) of the BAV and TAV patients were significantly different, while the overt stroke rates (2.4% vs. 1.7%; p = 0.704) were comparable between the 2 groups. BAV patients were associated with higher number of new lesions (4.0 [IQR: 1.0 to 8.0] vs. 2.0 [IQR: 1.0 to 5.0]; p = 0.008), total lesion volume (290 mm3 [IQR: 70 to 930 mm3] vs. 140 mm3 [IQR: 35 to 480 mm3]; p = 0.008), and the volume per lesion (70.0 mm3 [IQR: 45.0 to 115.0 mm3] vs. 57.5 mm3 [IQR: 24.5 to 93.0 mm3]; p = 0.037) in DW-MRI. Moreover, the proportion of patients with lesions larger than 1 cm3 (28.6% vs. 10.9%; p = 0.005) was higher in BAV patients than in TAV patients.Conclusions: BAV patients may encounter more severe brain injuries not only due to greater number of lesions, but also due to larger lesion size in the early phase after TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294). [ABSTRACT FROM AUTHOR]

The soils in mining lands with cadmium (Cd) contamination usually are deficient in nutrients. Disclosing how P nutrition and N:P stoichiometric ratio influences Cd accumulation and stress tolerance in stems of Populus spp. will facilitate the phytoremediation of mining sites polluted by Cd. In this study, investigations at the anatomical and physiological levels were conducted using a clone of Populus × euramericana. Both phosphorus deficiency and cadmium exposure inhibited xylem development via reducing cell layers in the xylem. Under P-sufficient condition, appropriate P status and balanced N:P ratio in stem promoted xylem development under Cd exposure via stimulating cell division, which enhanced Cd accumulation in stems. Cd accumulation in cell walls of collenchyma tissues of the stem was enhanced by P application due to increased polysaccharide production and cell wall affinity for Cd. The low P concentrations (0.3–0.4 mg g−1) and imbalanced N:P ratio under P deficiency inhibited the production of APX and ascorbate–GSH cycle, which increased oxidative stress and lipid peroxidation as indicated by high MDA concentration in stem. Under P-sufficient condition, the interactions between phytohormones and antioxidants play crucial roles in the process of antioxidant defense under Cd exposure. In conclusions, appropriate P addition and balanced N:P ratio enhanced secondary xylem development and promoted cadmium accumulation and stress tolerance in Populus stems, which can benefit the phytoextraction of Cd from Cd-contaminated soil. Image 1 • Sufficient tissue P concentration and balanced N:P ratio enhanced cell division in stem. • Low tissue P concentration and imbalanced N:P ratio inhibited xylem development. • Phosphorus increased cell wall affinity for Cd and Cd accumulation in cell wall in stem. • P deficiency decreased phytohormone levels and increased oxidative stress in stem. • Phosphorus enhanced Cd phytoextraction via promoting xylem development and antioxidant defense. [ABSTRACT FROM AUTHOR]

The prognostic impact of diabetes mellitus (DM) with or without coronary microvascular dysfunction (CMD) in patients undergoing fractional flow reserve (FFR)-guided revascularization has not been clarified. We sought to investigate the clinical outcomes of patients undergoing FFR-guided revascularization according to the existence of DM and CMD. A total of 283 patients with available FFR data as well as index of microcirculatory resistance (IMR) were selected from the 3 V FFR-FRIENDS study. CMD was defined as an IMR ≥25U. Patients were grouped according to the presence of DM and CMD into group A (DM-, CMD-), group B (DM-, CMD+), group C (DM+, CMD-), and group D (DM+, CMD+). The primary outcome was a major adverse cardiac event (MACE, a composite of myocardial infarction, ischemia-driven revascularization, and cardiac death) at 2 years. DM patients displayed a notably higher risk of MACEs in comparison with non-DM patients (HR 4.88, 95% CI 1.54–15.48, p = 0.003). MACEs at 2 years among the four groups were 2.2%, 2.0%, 7.0%, and 18.5%, respectively. Group D exhibited a significantly higher risk of MACEs as compared to group A (HR 8.98, 95% CI 2.15–37.41, p = 0.003). Multivariable regression analysis showed that the presence of DM and CMD was an independent predictor of a 2-year MACE (HR 11.24, 95% CI 2.53–49.88, p = 0.002), and integrating CMD into a model with DM increased discriminant ability (C-index 0.683 vs. 0.710, p = 0.010, integrated discrimination improvement 0.015, p = 0.040). Among the patients undergoing FFR-guided revascularization, those with DM and CMD were correlated with an augmented risk of MACEs. Integration of CMD improved risk stratification in predicting the occurrence of a MACE. • Patients with DM showed higher risk of MACE than non-DM population after FFR-guided treatment strategy. • Patients with both DM and CMD were at increased risk among patients undergoing FFR-guided revascularization. • Integration of CMD into a prediction model with DM significantly improved discriminant function and reclassification ability for 2-year MACE. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the most common cause to dementia and predicted to influence about 35 million people by the end of 2050. In this study, we discover alterations of myelin morphology in hippocampus tissues of 2-month-old APP/PS1 mouse. Myelin sheath is thicker and internodal distance is shorter in APP/PS1 mouse. Oligodendrocytes, differentiated from oligodendrocytes progenitor cells (OPCs), are responsible for formation and maintenance of myelin sheath in central nervous system (CNS). Our current results demonstrate that the oligodendrocytes development is disordered in 2-month-old APP/PS1 mouse. Neuregulin-1 type III, which is critical for both oligodendrocytes development and CNS myelination, is found up-regulated in hippocampus tissues of APP/PS1 mouse by western blots. Furthermore, we find active-caspase-6 can cleave neuregulin-1 type III at the cytoplasmic region. Given together, this study indicates the alterations of myelin morphology and oligodendrocytes development in 2-month-old APP/PS1 mouse, and the alterations might be highly associated with neuregulin-1 type III and active-caspase-6. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether social relationships were associated with sleep status in Chinese undergraduate students. A cross-sectional questionnaire survey was conducted in November 2012 at Huzhou Teachers College, China. The questionnaire involved demographic characteristics, personal lifestyle habits, social relationships and Pittsburgh Sleep Quality Index (PSQI). The associations between social relationships and sleep status were analyzed by using regression models after adjustment for potential factors. Poor sleep quality was prevalent among Chinese undergraduate students. Men tended to have better sleep than women. Lower social stress, better management of stress and good social support were correlated with better sleep status, and stress or support from friends, family and classmates were all related with sleep variables. While only weak associations between number of friends and sleep were detected. The results were consistent in men and women. Educators and instructors should be aware of the importance of social relationships as well as healthy sleep in undergraduates. [ABSTRACT FROM AUTHOR]