Residue Degradation and Risk Assessment of Difenoconazole and Its Metabolite during Tea Growing, Processing and Brewing by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Determination.

Residue dissipation and risk assessment of difenoconazole and its metabolite difenoconazole-alcohol during tea growing, processing, and brewing was first investigated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The limits of quantification for both difenoconazole and difenoconazole-alcohol were 0.001 mg/kg in fresh tea leaves and tea, and 0.0002 mg/L in tea infusion. In field trials, the dissipation half-lives of difenoconazole in fresh tea leaves was 1.77 days. After spraying, the residues of difenoconazole-alcohol increased and then gradually dissipated like difenoconazole. After 14 days, the dissipation rates of difenoconazole and difenoconazole-alcohol reached 99%. When fresh tea leaves were harvested on different days, the total processing factors (PFs) of difenoconazole and difenoconazole-alcohol for green tea were 0.86-1.05 and 0.78-0.85, respectively, while the total PFs for black tea were 0.83-1.13 and 0.82-1.66, respectively. Metabolism of difenoconazole was accelerated during tea processing. When brewing black tea, the leaching rates (LRs) of difenoconazole and difenoconazole-alcohol were 8.4-17.9% and 31.8-38.9%, respectively, while when brewing green tea, the LRs were 15.4-23.5% and 30.4-50.6%, respectively. The LRs of difenoconazole and difenoconazole-alcohol in black tea were higher than those in green tea. The potential threat to human health for dietary intake of difenoconazole and difenoconazole-alcohol residues from tea consumption is negligible. However, the dietary risk of difenoconazole in fruits and vegetables that are essential for daily diets is concerning, with a risk probability of 158%.

Assessment of the association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: A systematic review and meta-analysis.

According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34-1.59; p < 0.001). We also performed subgroup analyses based on sample size, d -dimer threshold, follow-up time, and HR source to further validate the prognostic value of pretreatment d -dimer levels in PC. In addition, according to the analysis, high pretreatment d -dimer levels in PC patients were associated with late tumor stage (OR = 4.78, 95% CI 1.73-13.20, p < 0. 005), larger tumor size (OR = 1.72, 95% CI 1.25-2.35, p < 0.005), and distant metastasis of tumor (OR = 5.06, 95% CI 2.45-10.43, p < 0.005) were significantly associated. In contrast, other clinicopathological factors, including age, gender and lymph node metastasis, were not associated with d-dimer levels. In conclusion, we found that high pre-treatment d-dimer levels were associated with a poor prognosis in PC patients, in relation to later tumor stage, larger tumor size and the development of distant metastases. Plasma d-dimer levels can be used as a biomarker of prognosis in PC patients.

Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia/reperfusion injury.

OBJECTIVES: Multi-parametric magnetic resonance imaging (MRI) can provide comprehensive and valuable information for precise diagnosis and treatment evaluation of a number of diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microenvironment. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into three groups: the Sham, CIRI and CIRI + Mel groups. At multiple time points after ischemia, MRI scanning was performed on a 7.0 Tesla MRI scanner. Multi-parametric MRI includes T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and chemical exchange saturation transfer (CEST)-MRI. CEST effects were calculated by the Lorentzian difference method, 3.5 ppm indicates amide protons of mobile proteins/peptide (Amide-CEST) and 2.0 ppm indicates amine protons (Guan-CEST). Multiple histopathological techniques were used to examine the histopathological changes and explore the therapeutic effects of Mel. RESULTS: T2WI and DWI-MRI could localize the infarct foci and areas in CIRI rats, which was further validated by staining, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining. After Mel treatment, T2WI and DWI-MRI showed smaller infarct volume, and neurons displayed improved morphology with less apoptosis rates. Notably, Amide-CEST and Guan-CEST signal decreased as early as 2 h after CIRI (all P <0.001), reflecting the change of pH after ischemia. After Mel treatment, both Amide-CEST and Guan-CEST signal increased in ischemic cortex and striatum compared with control group (all P < 0.001). The immunofluorescence staining and western blotting analysis suggested the expression of M2 microglia increased after Mel treatment; While，after Mel treatment the inflammatory factor interleukin-1ß (IL-1ß) decreased compared with control CIRI rats. CONCLUSIONS: Multi-parametric MRI was shown to be an effective method to monitor the brain damage in a rat model of CIRI and assess the therapeutic effects of Mel treatment. Amide-CEST and Guan-CEST were especially sensitive to the changes in brain microenvironment during the early stage after CIRI. Furthermore, the neuroprotective effect of Mel treatment is associated with its promotion of the microglia polarized to M2 type in CIRI rats.

A low-cost efficient online derivatization system for the determination of saccharides by high-performance liquid chromatograph-ultraviolet detector.

In this study, a low-cost efficient online derivatization system was developed which allows for the detection of various types of mono- and oligo-saccharides only utilizing high-performance liquid chromatography (HPLC)-ultraviolet detector (UV) system. In the proposed method, phenylhydrazine was used as the derivatization reagent and directly spiked in the mobile phase, allowing for the separation and detection of mono- and oligosaccharides in an accessible instrument system (HPLC-UV). And the online derivatization design of the proposed method has significantly reduced the potential harm of derivatization reagents to the analysts. Furthermore, critical chromatographic parameters were optimized via the Box-Behnken design strategy, culminating in the ideal response for saccharides. Finally, the methodology validation of the proposed method was conducted. The proposed method showed satisfactory linear ranges with acceptable correlation coefficients (R2  > 0.99), outstanding accuracy (Recovery: 95.3%-105.6%), high intra-day precision (relative standard deviation [RSD]: 1.4%-7.1%) and inter-day precision (RSD: 2.0%-7.4%). The robustness and ruggedness of the proposed method were proved as the recovery values in the range of 95.0%-104.6% and 95.1%-104.8% for robustness and ruggedness, respectively. These satisfactory validation results confirm the applicability and reliability of the proposed method for the analysis of saccharides in various complex real-world samples.

Development of a solubility parameter calculation-based method as a complementary tool to traditional techniques for indoor dust microplastic determination and risk assessment.

Herein, a method based on solubility parameter calculation was first used to analyze microplastics in indoor dust. The limit of quantification (LOQ) reached 0.2 mg/g, and the result of reference material SRM 2585 (n = 3) was 14.8 mg/g ± 1.8 %, suggesting satisfying sensitivity and precision. Recoveries of spiking experiments were > 80 % with no obvious matrix interferences observed, except ethylene propylene diene monomer (EPDM) MPs. Further, 69 indoor dust samples were analyzed to verify the method and to assess exposure scenarios for graduate students in Tianjin, China. EPDM was identified in an indoor environment for the first time as the second most widely detected type after PET in this work. The mass-based result is complementary to the outcomes from thermogravimetric analysis-gas chromatography-mass spectrometry and laser direct infrared imaging. Significant correlations were found between total organic carbon (TOC), microplastics, and BDE-209 concentrations, indicating microplastics important contaminant vectors in indoor dust. Dormitory stays and PET contributed the most to health risks among the three exposure scenarios and detected four polymers, respectively. This work provides an approach with the potential for the standardized determination of microplastics in complex environmental matrices and reveals exposure characteristics of indoor dust microplastics.

Burden of early-onset colorectal cancer along with attributable risk factors from 1990 to 2019: a comparative study between China and other G20 countries.

PURPOSE: The credible data about the burden of early-onset colorectal cancer (EOCRC) in China when compared to other countries in the group of twenty (G20) remained unavailable. We aimed to assess the burden and trends of EOCRC and attributable risk factors in China. Meanwhile, the comparison in the burden and attributable risk factors between China and other G20 countries was also evaluated. METHODS: Data on the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and attributable risk factors of EOCRC in China were obtained from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and compared with other G20countries. Temporal trends of age-standardized rates for incidence, prevalence, mortality, and DALYs were evaluated by estimated annual percentage change (EAPC). The autoregressive integrated moving average (ARIMA) model was used to forecast the incidence, mortality, and DALY rates of EOCRC in China from 2020 to 2029. RESULTS: From 1990 to 2019, the age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) of EOCRC in China increased with the EAPCs of 4.61 [95% confidence interval (CI): 4.45-4.77] and 5.82 (95% CI: 5.60-6.05). When compared to G20 countries, China was ranked 13th in the ASIR in 1990 and then increased to 2nd in 2019, second only to Japan. The ASPRs increased in all G20 countries, being highest in Saudi Arabia, followed by China and Mexico. Moreover, China had the highest age-standardized mortality rate and highest age-standardized DALY rate in 2019. In China, the five leading risk factors, for both sexes, were diet low in milk [18.54% (95% UI: 12.71-24.07)], diet low in calcium [15.06% (95% UI: 10.70-20.03)], alcohol use [12.16% (95% UI: 8.87-15.64)], smoking [9.08% (95% UI: 3.39-14.11)], and diet high in red meat [9.08% (95% UI: 3.39-14.11)] in 2019. Over the next 10 years, ASIR, ASMR, and age-standardized DALY rate of EOCRC will increase continuously in males and females. CONCLUSION: The burden of EOCRC in China and other G20 countries is worrisome, indicating that coordinated efforts are needed to conduct high-quality researches, allocate medical resources, adjust screening guidelines, and develop effective treatment and prevention strategies in the G20 countries.

Biotransformation of Organophosphate Esters by Rice and Rhizosphere Microbiome: Multiple Metabolic Pathways, Mechanism, and Toxicity Assessment.

The biotransformation behavior and toxicity of organophosphate esters (OPEs) in rice and rhizosphere microbiomes were comprehensively studied by hydroponic experiments. OPEs with lower hydrophobicity were liable to be translocated acropetally, and rhizosphere microbiome could reduce the uptake and translocation of OPEs in rice tissues. New metabolites were successfully identified in rice and rhizosphere microbiome, including hydrolysis, hydroxylated, methylated, and glutathione-, glucuronide-, and sulfate-conjugated products. Rhizobacteria and plants could cooperate to form a complex ecological interaction web for OPE elimination. Furthermore, active members of the rhizosphere microbiome during OPE degradation were revealed and the metagenomic analysis indicated that most of these active populations contained OPE-degrading genes. The results of metabolomics analyses for phytotoxicity assessment implied that several key function metabolic pathways of the rice plant were found perturbed by metabolites, such as diphenyl phosphate and monophenyl phosphate. In addition, the involved metabolism mechanisms, such as the carbohydrate metabolism, amino acid metabolism and synthesis, and nucleotide metabolism in Escherichia coli, were significantly altered after exposure to the products mixture of OPEs generated by rhizosphere microbiome. This work for the first time gives a comprehensive understanding of the entire metabolism of OPEs in plants and associated microbiome, and provides support for the ongoing risk assessment of emerging contaminants and, most critically, their transformation products.

Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. RESULTS: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. CONCLUSIONS: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

A Monte Carlo method for Rayleigh scattering in liquid detectors.

A new Monte Carlo method has been implemented to describe the angular and polarization distributions of anisotropic liquids, such as water and linear alkylbenzene (LAB), by considering orientational fluctuations of polarizability tensors. The scattered light of anisotropic liquids is depolarized with an angular distribution of 1 + (1 - ρv)/(1 + 3ρv) cos2 θ, which is modified by the depolarization ratio ρv. A standalone experiment has validated the simulation results of LAB. The new method can provide more accurate knowledge on light propagation in large liquid detectors, which is beneficial to the development of reconstruction for detectors.

Fat mass index as a screening tool for the assessment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is replacing hepatitis B as the leading cause of chronic liver disease in China. The purpose of this study is to select good tools to identify NAFLD from the body composition, anthropometry and related routine clinical parameters. A total of 5076 steelworkers, aged 22-60 years, was included in this study. Body fat mass was measured via bioelectrical impedance analysis (BIA) and fat mass index (FMI) was derived. Ultrasonography method was used to detect hepatic steatosis. Random forest classifier and best subset regression were used to select useful parameters or models that can accurately identify NAFLD. Receiver operating characteristic (ROC) curves were used to describe and compare the performance of different diagnostic indicators and algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) in NAFLD screening. ROC analysis indicated that FMI can be used with high accuracy to identify heavy steatosis as determined by ultrasonography in male workers [area under the curve (AUC) 0.95, 95% CI 0.93-0.98, sensitivity 89.0%, specificity 91.4%]. The ability of single FMI to identify NAFLD is no less than that of combination panels, even better than the combination panel of HSI. The best subset regression model that including FMI, waist circumference, and serum levels of triglyceride and alanine aminotransferase has moderate accuracy in diagnosing overall NAFLD (AUC 0.83). FMI and the NAFLD best subset (BIC) score seem to be good tools to identify NAFLD in Chinese steelworkers.

Both family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are cost-effective for gastric cancer prevention.

BACKGROUND: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family-based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost-effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost-effectiveness of FBCM, screen-and-treat, and no-screen strategies in Chinese population. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model. RESULTS: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen-and-treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer-related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no-screen strategy. Cost-effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen-and-treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no-screen strategy. One-way sensitivity analysis revealed that screening from younger age by both strategies are more cost-effective. When compared with FBCM strategy, screen-and-treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results. CONCLUSIONS: Both FBCM and screen-and-treat strategies are cost-effective for gastric cancer prevention compared with no-screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost-effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas.

De novo Creation and Assessment of a Prognostic Fat-Age-Inflammation Index "FAIN" in Patients With Cancer: A Multicenter Cohort Study.

Background and Aims: Malnutrition is highly prevalent and is related to multiple impaired clinical outcomes in cancer patients. This study aimed to de novo create an objective, nutrition-related index specially for prognostic purposes in oncology populations. Methods: We performed a multicenter cohort study including 14,134 cancer patients. The prognostic impact for each baseline characteristic was estimated by calculating Harrell's C-index. The optimal parameters reflecting the nutritional and inflammatory impact on patients' overall survival were selected to develop the fat-age-inflammation (FAIN) index. The associations of the FAIN with the nutritional status, physical performance, quality of life, short-term outcomes and mortality of patients were comprehensively evaluated. Independent external validation was performed to further assess the prognostic value of the FAIN. Results: The study enrolled 7,468 men and 6,666 women with a median age of 57 years and a median follow-up of 42 months. The FAIN index was defined as: (triceps skinfold thickness + albumin) / [age + 5 × (neutrophil count/lymphocyte count)]. There were significant associations of the FAIN with the nutritional status, physical performance, quality of life and short-term outcomes. The FAIN also showed better discrimination performance than the Nutritional Risk Index, the Prognostic Nutritional Index and the Controlling Nutritional Status index (all P < 0.05). In multivariable-adjusted models, the FAIN was independently associated with a reduced death hazard both as a continuous variable (HR = 0.57, 95%CI = 0.47-0.68) and per one standard deviation (HR = 0.83, 95%CI = 0.78-0.88). External validation in a multicenter lung cancer cohort (n = 227) further confirmed the prognostic value of the FAIN. Conclusions: This study created and assessed the prognostic FAIN index, which might act as a feasible option to monitor the nutritional status and help develop intervention strategies to optimize the survival outcomes of cancer patients.

Multi-Scenario Landscape Ecological Risk Simulation for Sustainable Development Goals: A Case Study on the Central Mountainous Area of Hainan Island.

The sustainable development goals (SDGs) of the United Nations are focused on regional development and ecological security. Based on these SDGs, quantitative regional landscape ecological risk assessment is significant to realize regional sustainable development. This study took the central mountainous area (CMA) of Hainan Island as the research area, and combined SDGs and a patch-generating land-use simulation (PLUS) model to analyze multi-scenario land-use change and landscape ecological risk simulation. The study results show that the low ecological risk areas are located in the central hinterland of the CMA, and the high ecological risk areas are located on the northern and southern edges, with strong disturbances from human activities. The construction land in the CMA expanded drastically from 2010 to 2018, mainly invading forestland and grassland, leading to landscape fragmentation, which was the main cause of the increased ecological risk in the CMA landscape. The future multi-scenario simulations for SDGs show that under the scenario of natural development and economic development, the construction land and water area will significantly expand and the forest land will be dramatically reduced. Under the ecological protection scenario, the expansion of construction land will be restrained, and the area of forest land will increase. The results showed that the landscape ecological risks in the three simulated scenarios would be higher than in 2018, but the increase in the landscape ecological risks under the ecological protection scenario would be relatively slight. Forest land plays an essential role in maintaining the ecological security of the CMA. The expanding construction land in the CMA has led to landscape fragmentation and increased ecological risk. Therefore, it is necessary to protect the forest land in the CMA. In addition, construction and development should be limited in high-risk areas. Although the adoption of the ecological conservation scenario favors regional sustainability, it is still necessary to improve ecological protection policies such as ecological compensation to ensure the realization of other SDGs.

Trans-Ethnic Meta-Analysis of Interactions Between Genetics and Early-Life Socioeconomic Context on Memory Performance and Decline in Older Americans.

BACKGROUND: Later-life cognitive function is influenced by genetics as well as early- and later-life socioeconomic context. However, few studies have examined the interaction between genetics and early childhood factors. METHODS: Using gene-based tests (interaction sequence kernel association test [iSKAT]/iSKAT optimal unified test), we examined whether common and/or rare exonic variants in 39 gene regions previously associated with cognitive performance, dementia, and related traits had an interaction with childhood socioeconomic context (parental education and financial strain) on memory performance or decline in European ancestry (EA, N = 10 468) and African ancestry (AA, N = 2 252) participants from the Health and Retirement Study. RESULTS: Of the 39 genes, 22 in EA and 19 in AA had nominally significant interactions with at least one childhood socioeconomic measure on memory performance and/or decline; however, all but one (father's education by solute carrier family 24 member 4 [SLC24A4] in AA) were not significant after multiple testing correction (false discovery rate [FDR] < .05). In trans-ethnic meta-analysis, 2 genes interacted with childhood socioeconomic context (FDR < .05): mother's education by membrane-spanning 4-domains A4A (MS4A4A) on memory performance, and father's education by SLC24A4 on memory decline. Both interactions remained significant (p < .05) after adjusting for respondent's own educational attainment, apolipoprotein-ε4 allele (APOE ε4) status, lifestyle factors, body mass index, and comorbidities. For both interactions in EA and AA, the genetic effect was stronger in participants with low parental education. CONCLUSIONS: Examination of common and rare variants in genes discovered through genome-wide association studies shows that childhood context may interact with key gene regions to jointly impact later-life memory function and decline. Genetic effects may be more salient for those with lower childhood socioeconomic status.

Establishment of an in vitro safety assessment model for lipid-lowering drugs using same-origin human pluripotent stem cell-derived cardiomyocytes and endothelial cells.

Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 µM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 µM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.

Root phosphatase activity aligns with the collaboration gradient of the root economics space.

The adoption of diverse resource acquisition strategies is critical for plant growth and species coexistence. Root phosphatase is of particular importance in the acquisition of soil phosphorus (P), yet it is often overlooked in studies of root trait syndromes. Here, we evaluated the role of root phosphatase activity (RPA) within the root economics space and the order-based variation of RPA, as well as the correlations between RPA and a suite of leaf traits and soil properties over a range of evergreen tree species in a subtropical forest. Root phosphatase activity exhibited a high degree of inter-specific variation. We found that there were two leading dimensions of the multidimensional root economics space, the root diameter-specific root length axis (collaboration trait gradient) and the root tissue density-root nitrogen concentration axis (classical trait gradient), and RPA aligned with the former. Root phosphatase activity is used as a 'do it yourself' strategy of soil P acquisition, and was found to be inversely correlated with mycorrhizal colonization, which suggests a trade-off in plant P acquisition strategies. Compared with soil and foliar nutrient status, root traits mattered most for the large inter-specific changes in RPA. Furthermore, RPA generally decreased from first- to third-order roots. Taken together, such diverse P-acquisition strategies are conducive to plant coexistence within local forest communities. The use of easily measurable root traits and their tight correlations with RPA could be a feasible and promising approach to estimating species-specific RPA values, which would be helpful for better understanding plant P acquisition and soil P cycling.

Association between breakfast consumption frequency and the risk of irritable bowel syndrome among Chinese female college students: A cross-sectional study.

ABSTRACT: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects specific groups of people. The relationship between breakfast consumption frequency and the risk of IBS is unclear. This study aimed to investigate the association between breakfast consumption frequency and the risk of IBS among Chinese female college students.In this cross-sectional study (n = 706) conducted in October 2018, the frequency of breakfast consumption was categorized as 0 to 3 times/week, 4 to 6 times/week, or daily. IBS was diagnosed according to the Rome III criteria and was based on the presence of abdominal pain or discomfort for at least 3 months during the previous 6 months, with at least 2 or more of the following conditions: changes in frequency or form of stool and/or decrease in pain after defecation. We adjusted for confounding factors, including age, only child (yes or no), parents' educational levels (senior high school or below, college, or postgraduate), parents' marital status (married, widowed, or divorced), smoking status (smoker or nonsmoker), drinking status (drinker or nondrinker), body mass index, and depressive symptoms. A multiple logistic regression analysis was performed to determine the relationship between breakfast frequency and the risk of IBS.Among 706 participants, 23.7% were the only child in their family, and the proportion of parents divorced or widowed was 18.5%. The proportion of fathers and mothers with high school education or above was 93.3% and 96.3%, respectively. The prevalence of IBS among the participants was 17.3% (122/706). Multivariate logistic regressions analysis showed that breakfast consumption frequency is negatively associated with the risk of IBS after adjusting for confounding factors. The odds ratios (95% confidence intervals) for IBS in the breakfast frequency category of 0 to 3 times/week, 4 to 6 times/week, and daily were 1.00 (reference), 0.96 (0.58, 1.60), and 0.45 (0.26, 0.78), respectively (P = .002).Our data revealed that regular breakfast consumption is associated with a lower risk of IBS among Chinese college students. Future cohort and/or interventional studies should be conducted to further explore the association between breakfast consumption frequency and IBS.

Whole family-based Helicobacter pylori eradication is a superior strategy to single-infected patient treatment approach: A systematic review and meta-analysis.

BACKGROUND: Two critical concerns during Helicobacter pylori (H. pylori) eradication are the successful eradication and recurrence. It is debatable whether whole family-based H. pylori treatment regimen might have any advantage over single-infected patient treatment approach in increasing eradication rate and reducing recurrence rate. We conduct systematic review and meta-analysis to compare the efficacy of these two treatment regimens in order to provide clinical practice a better option for H. pylori eradication. METHODS: Randomized controlled trials evaluating H. pylori eradication and recurrence in whole family-based treatment group (WFTG) versus single-infected patient treatment group (SPTG) were collected from published literature up to July 2020 from common databases. Pooled results were analyzed using either fixed-effect or random-effect model. Results were expressed as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 1751 relevant articles were identified, and 12 studies were eligible for analysis. Among them: (a) Eight articles including 1198 patients were selected to analyze H. pylori eradication rate, pooled result showed that eradication rate of WFTG was higher than that of SPTG (OR=2.93; 95% CI 1.68-5.13). Stratified analysis showed that H. pylori eradication rate in WFTG were higher over SPTG in children subgroup, but had no difference in spouse subgroup. (b) Six studies including 881 patients were analyzed for recurrence rate between the two groups, pooled analysis showed that the overall recurrence rate of WFTG was lower than that of SPTG (OR=0.3; 95% CI 0.19-0.48). Stratified analysis showed that the recurrence rate in WFTG was lower over SPTG at 6, 12, 18, and more than 24 months post-treatment subgroups. CONCLUSION: Whole family-based H. pylori treatment can partially increase eradication rate and reduce recurrence rate over single-infected patient treatment approach, the results provide clinical practice a novel notion for H. pylori eradication and infection prevention.

Quantifying financial market dynamics: Scaling law in rank mobility of Chinese stock prices.

Rank mobility, which was designed to measure the average variation of relative rank positions with respect to any absolute variable over a given time period, can be used to explore how the memory of stock price ranking orders fades over time. We investigate the variation in rank order of the closing prices of stocks registered at the Shanghai A-share market over a long period of 16 years. And we find that rank mobility increases as a power law with increasing time scale, and eventually converges to a constant level. This power-law relationship can be observed not only over a long period of 16 years but also for each consecutive year, especially their power law exponents are very close. The empirical evidence indicates a fundamental dynamics of Chinese stock price movements.

The GLIM criteria as an effective tool for nutrition assessment and survival prediction in older adult cancer patients.

BACKGROUND & AIMS: Elderly cancer patients are at particularly high risk for malnutrition because both the disease and the old age threaten their nutritional status. The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing and grading malnutrition, but the validation of these criteria in elderly cancer population is not well documented. Our objective was to investigate the application of the GLIM criteria in nutrition assessment and survival prediction in elderly cancer patients. METHODS: This retrospective cohort analysis was conducted on a primary cohort of 1192 cancer patients aged 65 years or older enrolled from a multi-institutional registry, and a validation cohort of 300 elderly cancer patients treated at the First Affiliated Hospital of Sun Yat-sen University. Patients considered at-risk for malnutrition based on the NRS-2002 were assessed using the GLIM criteria. The association between the nutritional status and patients' overall survival (OS) was then analyzed by the Kaplan-Meier method and a Cox model. A nomogram was also established that included additional independent clinical prognostic variables. To determine the predictive accuracy and discriminatory capacity of the nomogram, the C-index, receiver operating characteristic (ROC) curve and calibration curve were evaluated. RESULTS: The percentage of patients considered "at-risk" for malnutrition was 64.8% and 67.3% for the primary and validation cohorts, respectively. GLIM-defined malnutrition was diagnosed in 48.4% of patients in the primary cohort and 46.0% in the validation cohort. In the primary cohort, patients at risk of malnutrition (NRS-2002 ≥ 3) showed a worse OS than those with a NRS-2002 < 3 (HR 1.34, 1.10-1.64; p = 0.003). Additionally, patients with GLIM-defined severe malnutrition (HR1.71, 1.37-2.14; p < 0.001) or moderate malnutrition (HR1.35, 1.09-1.66; p = 0.006) showed a significantly shorter OS compared to those without malnutrition. The nomogram incorporating the domains of the GLIM with other variables was accurate, especially for predicting the 1- and 2-year overall survival rates. CONCLUSIONS: The GLIM criteria can be used in elderly cancer patients not only to assess malnutrition, but also to predict survival outcome. The nomogram developed based on the GLIM domains can provide a more accurate prediction of the prognosis than existing systems.