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Abstract The precise extraction of winter wheat planting structure holds significant importance for food security risk assessment, agricultural resource management, and governmental decision-making. This study proposed a method for extracting the winter wheat planting structure by taking into account the growth phenology of winter wheat. Utilizing the fitting effect index, the optimal Savitzky–Golay (S–G) filtering parameter combination was determined automatically to achieve automated filtering and reconstruction of NDVI time series data. The phenological phases of winter wheat growth was identified automatically using a threshold method, and subsequently, a model for extracting the winter wheat planting structure was constructed based on three key phenological stages, including seeding, heading, and harvesting, with the combination of hierarchical classification principles. A priori sample library was constructed using historical data on winter wheat distribution to verify the accuracy of the extracted results. The validation of fitting effect on different surfaces demonstrated that the optimal filtering parameters for S–G filtering could be obtained automatically by using the fitting effect index. The extracted winter wheat phenological phases showed good consistency with ground-based observational results and MOD12Q2 phenological products. Validation against statistical yearbook data and the proposed priori knowledge base exhibited high statistical accuracy and spatial precision, with an extracting accuracy of 94.92%, a spatial positioning accuracy of 93.26%, and a kappa coefficient of 0.9228. The results indicated that the proposed method for winter wheat planting structure extracting can identify winter wheat areas rapidly and significantly. Furthermore, this method does not require training samples or manual experience, and exhibits strong transferability.

Abstract Background Temperature extremes are anticipated to become more frequent and more intense under the context of climate change. While current evidence on health effects of compound extreme temperature event is scarce. Methods This nationwide cross-sectional study collected daily data on weather and mortality for 161 Chinese districts/counties during 2007-2013. A quasi-Poisson generalized linear model was first applied to assess effects of daytime-only, nighttime-only and compound daytime-nighttime heat wave (and cold spell) on cause-specific mortality. Then a random-effect meta-analysis was used to produce pooled estimates at national level. Stratification analyses were performed by relative humidity, individual and regional characteristics. Results Here we show that mortality risks of compound daytime-nighttime temperature extremes are much higher than those occurring only in the daytime or nighttime. Humid weather further exaggerates the mortality risk during heat waves, while dry air enhances the risk during cold weather. People who are elderly, illiterate, and those with ischemic heart disease and respiratory disease are particularly vulnerable to extreme temperature. At the community-level, population size, urbanization rate, proportion of elderly and PM2.5 are positively associated with increased risks associated with heat waves. Temperature, humidity and normalized difference vegetation index are positively associated with the effects of cold weather, with an opposite trend for latitude and diurnal temperature range. Conclusions This nationwide study highlights the importance of incorporating compound daytime-nighttime extreme temperature events and humid conditions into early warning systems and urban design/planning.

Background The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear.Objectives The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS).Methods Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies.Results A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk.Conclusions The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

Abstract Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

Groupitizing is a well-established strategy in numerosity perception that enhances speed and sensory precision. Building on the ATOM theory, Anobile proposed the sensorimotor numerosity system, which posits a strong link between number and action. Previous studies using motor adaptation technology have shown that high-frequency motor adaptation leads to underestimation of numerosity perception, while low-frequency adaptation leads to overestimation. However, the impact of motor adaptation on groupitizing, and whether visual motion adaptation produces similar effects, remain unclear. In this study, we investigate the persistence of the advantage of groupitizing after motor adaptation and explore the effects of visual motion adaptation. Surprisingly, our findings reveal that proprioceptive motor adaptation weakens the advantage of groupitizing, indicating a robust effect of motor adaptation even when groupitizing is employed. Moreover, we observe a bidirectional relationship, as groupitizing also weakens the adaptation effect. These results highlight the complex interplay between motor adaptation and groupitizing in numerosity perception. Furthermore, our study provides evidence that visual motion adaptation also has an adaptation effect, but does not fully replicate the effects of proprioceptive motor adaptation on groupitizing. In conclusion, our research underscores the importance of groupitizing as a valuable strategy in numerosity perception, and sheds light on the influence of motion adaptation on this strategy.

ObjectiveThe purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted.ResultsThe RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, PConclusionThe findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

Abstract Background Capecitabine maintenance therapy is safe and efficacious for early-stage triple-negative breast cancer (TNBC) patients, but the cost-effectiveness of its long-term use has not been investigated. Here, we evaluated the cost-effectiveness of capecitabine maintenance therapy, compared with routine follow-up, in early-stage TNBC patients after standard treatment from a perspective of Chinese society. Methods A three-state Markov model based on the data from the SYSUCC-001 trial was constructed to estimate the cost-effectiveness of capecitabine maintenance therapy in a month cycle over a period of 30-year time horizon. A 5% annual discount rate was set for all costs and benefits. One-way and probabilistic sensitivity analyses were performed to explore the model uncertainties. The main outcomes include quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and the number needed to treat (NNT) to prevent one additional event. Results Compared with routine follow-up, 1-year capecitabine maintenance therapy yielded an additional 1.29 quality-adjusted life years (QALYs) at an additional cost of $3391.70, with an ICER of $2630.53 (95% CI: $1159.81–$5090.12) per QALY gained. The ICER was considerably lower than the recommended willingness-to-pay (WTP) threshold (i.e., $28,130.00 per QALY). The results were sensitive to the discount rate, drug cost, and treatment cost after relapse. Further, the NNT to prevent one additional relapse case was 29.2 (95% CI: 13.2–196.6), 16.7 (95% CI: 8.4–111.6), and 12.0 (95% CI: 5.7–82.6) at 1, 2, and 5 years, respectively. Conclusions One-year capecitabine maintenance therapy for early-stage TNBC after standard treatment, compared with routine follow-up, was found to be highly cost-effective with promising clinical benefits and acceptable increased costs. Real-world studies are warranted to validate our findings in the future.

Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) have been used for thousands of years as traditional Chinese medicine (TCM) with sedative effects. Modern studies have shown that Citrus plants also have protective effects on the nervous system. However, the effective substances and mechanisms of action in Citrus TCMs still remain unclear. In order to explore the pharmacodynamic profiles of identified substances and the action mechanism of these herbs, a comprehensive approach combining ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) analysis and network pharmacology was employed. Firstly, UNIFI 2.1.1 software was used to identify the chemical characteristics of AF and AFI. Secondly, the SwissTargetPrediction database was used to predict the targets of chemical components in AF and AFI. Targets for neuroprotection were also collected from GeneCards: The Human Gene Database (GeneCards-Human Genes|Gene Database|Gene Search). The networks between targets and compounds or diseases were then constructed using Cytoscape 3.9.1. Finally, the Annotation, Visualization and Integrated Discovery Database (DAVID) (DAVID Functional Annotation Bioinformatics Microarray Analysis) was used for GO and pathway enrichment analysis. The results showed that 50 of 188 compounds in AF and AFI may have neuroprotective biological activities. These activities are associated with the regulatory effects of related components on 146 important signaling pathways, derived from the KEGG (KEGG: Kyoto Encyclopedia of Genes and Genomes), such as neurodegeneration (hsa05022), the Alzheimer’s disease pathway (hsa05010), the NF-kappa B signaling pathway (hsa04064), the hypoxia-inducible factor (HIF)-1 signaling pathway (hsa04066), apoptosis (hsa04210), the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance signaling pathway (hsa01521), and others, by targeting 108 proteins, including xanthine dehydrogenase (XDH), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), and glucose-6-phosphate dehydrogenase (G6PD), among others. These targets are thought to be related to inflammation, neural function and cell growth.

Background Despite increasing public concerns about the widespread health effects of climate change, the impacts of ambient temperature on atopic dermatitis (AD) remain poorly understood. Objectives We aimed to explore the effect of ambient temperature on AD and to estimate the burdens of AD attributed to extreme temperature. Methods Data on outpatients with AD and climate conditions in Chengdu, China were collected. A distributed lag nonlinear model (DLNM) was adopted to explore the association between daily mean temperature and AD outpatient visits. Subgroup analysis was used to identify vulnerable populations. Attributable burden was estimated by the epidemiological attributable method. Results We analyzed 10,747 outpatient visits from AD patients at West China Hospital in Chengdu between January 1, 2015, and December 31, 2020. Both low (25.3 °C) were associated with increased AD outpatient visits, with the increase being more pronounced at low temperature, as evidenced by a 160% increase in visits when the temperature dropped below zero from the minimum mortality temperature (22.8 °C). Children and males were the most susceptible populations. Approximately 25.4% of AD outpatient visits were associated with temperatures, causing an excessive 137161.5 US dollars of health care expenditures during this 6-year period. Conclusions Both high and low temperatures, particularly low temperatures, were significantly associated with an increased risk of AD, with children and males showing the strongest associations. Extreme environmental temperature has been identified as one of the major factors promoting the development of AD. However, individual patient-level exposures still needed to be investigated in future studies to confirm the causality between temperature and AD.

In this article, we propose a highly sensitive vertically plug-in source drain contacts high Schottky barrier based bilateral gate and assistant gate controlled bidirectional tunnel field Effect transistor (VPISDC-HSB-BTFET). It can achieve much more sensitive forward current driving ability than the previously proposed High Schottky barrier source/drain contacts based bilateral gate and assistant Gate controlled bidirectional tunnel field Effect transistor (HSB-BTFET). Silicon body of the proposed VPISDC-HSB-BTFET is etched into a U-shaped structure. By etching both sides of the silicon body to form vertically plug-in source drain contacts, the source and drain electrodes are plugged into a certain height of the vertical parts of both sides of the U-shaped silicon body. Thereafter, the efficient area of the band-to-band tunneling generation region near the source drain contacts is significantly increased, so as to achieve sensitive ON-state current driving ability. Comparing to the mainstream FinFET technology, lower subthreshold swing, lower static power consumption and Higher Ion-Ioff ratio can be achieved.

Summary: Background: Evidence concerning effects of air pollution on influenza-like illness (ILI) from multi-center is limited and little is known about how regional factors might modify this relationship. Methods: In this ecological study, ILI cases defined as outpatients with temperature ≥38 °C, accompanied by cough or sore throat, were collected from National Influenza Surveillance Network in China. We adopted generalized additive model with quasi-Poisson to estimate province-specific association between air pollution and ILI in 30 Chinese provinces during 2015–2019, after adjusting for time trend and meteorological factors. We then pooled province-specific association by using random-effect meta-analysis. Potential effect modifications of season and regional characteristics were explored. Findings: A total of 26, 004, 853 ILI cases and 777, 223, 877 hospital outpatients were collected. In general, effects of air pollutants were acute. An inter-quartile range increase of PM2.5, SO2, PM10, NO2 and CO at lag0, and O3 at lag0-2 was associated with 3.08% (95% CI: 1.91%, 4.27%), 3.00% (1.86%, 4.16%), 6.46% (4.71%, 8.25%), 7.21% (5.73%, 8.71%), 4.37% (3.05%, 5.70%), and −9.26% (−11.32%, −7.14%) change of ILI at national level, respectively. Associations between air pollutants and ILI varied by season and regions, with higher effect estimates in cold season, eastern and central regions and provinces with more humid condition and larger population. Interpretation: This study indicated that most air pollutants increased the risk of ILI in China. Our findings might provide implications for the development of policies to protect public health from air pollution and influenza. Funding: National Natural Science Foundation of China and Chongqing Health Commission Program.

Abstract The number of items in an array can be quickly and accurately estimated by dividing the array into subgroups, in a strategy termed “groupitizing.” For example, when memorizing a telephone number, it is better to do so by divide the number into several segments. Different forms of visual grouping can affect the precision of the enumeration of a large set of items. Previous studies have found that when groupitizing, enumeration precision is improved by grouping arrays using visual proximity and color similarity. Based on Gestalt theory, Palmer (Cognit Psychol 24:436, 1992) divided perceptual grouping into intrinsic (e.g., proximity, similarity) and extrinsic (e.g., connectedness, common region) principles. Studies have investigated groupitizing effects on intrinsic grouping. However, to the best of our knowledge, no study has explored groupitizing effects for extrinsic grouping cues. Therefore, this study explored whether extrinsic grouping cues differed from intrinsic grouping cues for groupitizing effects in numerosity perception. The results showed that both extrinsic and intrinsic grouping cues improved enumeration precision. However, extrinsic grouping was more accurate in terms of the sensory precision of the numerosity perception.

Objective The aim of this study was to assess the reliability and validity of the Chinese version of the Family Resilience (FaRE) Questionnaire among patients with breast cancer in China.Design It was a cross-sectional study, which involved translation, back-translation, cultural adjustment and psychometric testing of a 24-item FaRE Questionnaire.Setting Three tertiary hospitals in Zhengzhou, China: respectively are the First Affiliated Hospital of Zhengzhou University, Second Hospital Affiliated to Zhengzhou University and Henan Provincial People’s hospital.Participants A total of 559 patients with breast cancer volunteered to participate in the studyPrimary outcome measures Data analysis was performed using the IBM SPSS software V.21.0 and AMOS software V.21.0. Cronbach’s α coefficient was used to examine the internal consistency. The test–retest reliability was calculated using the intraclass correlation coefficient on 30 participants. The content validity index was calculated based on the values obtained from six expert opinions. Construct validity test was performed using factor analysis including exploratory factor analysis and confirmatory factor analysis.Results For the Chinese version of FaRE Questionnaire, the Cronbach’s α coefficient of the total questionnaire was 0.909, and Cronbach’s α coefficients of four factors were 0.902, 0.932, 0.905 and 0.963, respectively. The test–retest reliability index of the total questionnaire was 0.905. The Scale-Content Validity Index was 0.97, and Item-Content Validity Index ranged from 0.83 to 1.00. The questionnaire included 24 items, exploratory factor analysis extracted four factors with loading >0.4, which could explain 72.146% of the total variance. Confirmatory factor analysis showed the Chinese version of FaRE Questionnaire had an excellent four-factor model consistent with the original questionnaire.Conclusion The Chinese version of FaRE Questionnaire has acceptable reliability and validity among patients with breast cancer in China. It can effectively assess family resilience and provide basis for personalised family resilience interventions for patients with breast cancer.

Abstract. Rationale:. Anaplastic lymphoma kinase (ALK) fusion, an important oncogenic mutation, occurs in 3% to 7% of non-small cell lung cancer (NSCLC) cases, and EML4 is the most common partner gene. With the widespread application of next-generation sequencing (NGS), more gene breakpoint fusions have been discovered and functional fusion transcripts can provide targeted clinical benefits. Patient concerns and diagnosis:. A 40-year-old woman was diagnosed with lung adenocarcinoma with brain metastases. A novel CLHC1/RNT4 intergenic region, ALK (Exon20-29) (abundance 39.97%), was identified using lung puncture tissue by NGS analysis (Simceredx), and results of immunohistochemistry and fluorescence in situ hybridization confirmed ALK fusion. Interventions and outcomes:. The patient was administered oral crizotinib (250 mg bid) combined with endostar (30 mg d1-7) for 12 cycles from June 18, 2020. The patient's condition was controlled, and the curative effect was evaluated as stable disease (SD). Unfortunately, brain magnetic resonance images showed multiple nodules in the left cerebellar hemisphere, and chest computed tomography showed no significant changes in the progression of the disease. Subsequently, alectinib (600 mg bid) was administered on April 1, 2021. Brain lesions were significantly reduced and partial remission (PR) was achieved. No significant changes were observed in the lung lesions. Lessons:. ALK fusion is a risk factor for brain metastasis (BM) in patients with advanced non-small NSCLC patients. In our case, a novel CLHC1/RNT4 intergenic region, ALK fusion, was identified for the first time in a lung adenocarcinoma patient with BM, who benefited from crizotinib and endostar sequential alectinib. Our case highlights the advantages of NGS for fusion detection and provides promising treatment options for NSCLC patients with BM harboring ALK fusions.

The degradation of aflatoxin B1 (AFB1) and zearalenone (ZEA) is investigated using power ultrasound to identify suitable methods to reduce the mycotoxin content of corn. AFB1 and ZEA in corn are simultaneously degraded via power ultrasound; thus, this method has a significant effect on corn quality. The power intensity, solid-liquid ratio, and ultrasonic treatment modes significantly affect the degradation rates of AFB1 and ZEA. The dissolution of AFB1 and ZEA in water also facilitates their degradation. At the initial stage of ultrasonic treatment, power ultrasound promotes the dissolution of mycotoxins in water, whereupon they are partially oxidized by free radicals. With a treatment time of 10 min, the reduction rates decreased owing to the dissolution of combined-state mycotoxins. After ultrasonic treatment, the contents of the essential amino acids, the total number of amino acids, and the fatty acids in corn decreased; however, ΔH values decreased during starch gelatinization. In contrast, the amylose content and viscosity of corn significantly increased during gelatinization. Therefore, this method is potentially suitable for the reduction of AFB1 and ZEA contents in corn.

Abstract Background In recent years, copper complexes have gradually become the focus of potential anticancer drugs due to their available redox properties and low toxicity. In this study, a novel mitochondrion-targeting copper (II) complex, [Cu (ttpy-tpp)Br2] Br (simplified as CTB), is first synthesized by our group. CTB with tri-phenyl-phosphine (TPP), a targeting and lipophilic group, can cross the cytoplasmic and mitochondrial membranes of tumor cells. The present study aims to investigate how CTB affects mitochondrial functions and exerts its anti-tumor activity in hepatoma cells. Methods Multiple molecular experiments including Flow cytometry, Western blot, Immunofluorescence, Tracker staining, Transmission Electron Microscopy and Molecular docking simulation were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo. Results CTB induced apoptosis via collapse of mitochondrial membrane potential (MMP), ROS production, Bax mitochondrial aggregation as well as cytochrome c release, indicating that CTB-induced apoptosis was associated with mitochondrial pathway in human hepatoma cells. Mechanistic study revealed that ROS-related mitochondrial translocation of p53 was involved in CTB-mediated apoptosis. Simultaneously, elevated mitochondrial Drp1 levels were also observed, and interruption of Drp1 activation played critical role in p53-dependent apoptosis. CTB also strongly suppressed the growth of liver cancer xenografts in vivo. Conclusion In human hepatoma cells, CTB primarily induces mitochondrial dysfunction and promotes accumulation of ROS, leading to activation of Drp1. These stimulation signals accelerate mitochondrial accumulation of p53 and lead to the eventual apoptosis. Our research shows that CTB merits further evaluation as a chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).

Abstract Background Contraction of hepatic stellate cells (HSCs) plays an important role in the pathogenesis of liver fibrosis by regulating sinusoidal blood flow and extracellular matrix remodeling. Here, we investigated how HSC contraction was affected by the natural compound oroxylin A, and elucidated the underlying mechanism. Methods Cell contraction and glycolysis were examined in cultured human HSCs and mouse liver fibrosis model upon oroxylin A intervention using diversified cellular and molecular assays, as well as genetic approaches. Results Oroxylin A limited HSC contraction associated with inhibiting myosin light chain 2 phosphorylation. Oroxylin A blocked aerobic glycolysis in HSCs evidenced by reduction in glucose uptake and consumption and lactate production. Oroxylin A also decreased extracellular acidification rate and inhibited the expression and activity of glycolysis rate-limiting enzymes (hexose kinase 2, phosphofructokinase 1 and pyruvate kinas type M2) in HSCs. Then, we identified that oroxylin A blockade of aerobic glycolysis contributed to inhibition of HSC contraction. Furthermore, oroxylin A inhibited the expression and activity of lactate dehydrogenase-A (LDH-A) in HSCs, which was required for oroxylin A blockade of glycolysis and suppression of contraction. Oral administration of oroxylin A at 40 mg/kg reduced liver injury and fibrosis, and inhibited HSC glycolysis and contraction in mice with carbon tetrachloride-induced hepatic fibrosis. However, adenovirus-mediated overexpression of LDH-A significantly counteracted the oroxylin A’s effects in fibrotic mice. Conclusions Blockade of aerobic glycolysis by oroxylin A via inhibition of LDH-A reduced HSC contraction and attenuated liver fibrosis, suggesting LDH-A as a promising target for intervention of hepatic fibrosis.

ObjectiveTo screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH).MethodThe iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats.ResultsTwenty-three DEPs (fold change ≥1.2 or ≤0.833, p3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4, pConclusionAPOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications.

The turning points of housing prices play a significant role in the real estate market and economy. However, because multiple factors impact the market, the prediction of the turning points of housing prices faces significant challenges. To solve this problem, in this study, a historical data-based model that incorporates a multi-population genetic algorithm with elitism into the log-periodic power law model is proposed. This model overcomes the weaknesses of multivariate and univariate methods that it does not require any external factors while achieving excellent interpretations. We applied the model to the case study collected from housing prices in Wuhan, China, from December 2016 to October 2018. To verify its reliability, we compared the results of the proposed model to those of the log-periodic power law model optimized by the standard genetic algorithm and simulated annealing, the results of which indicate that the proposed model performs best in terms of prediction. Efficiently predicting and analyzing the housing prices will help the government promulgate effective policies for regulating the real estate market and protect home buyers.

The new type of pneumonia caused by the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has been declared as a global public health concern by WHO. As of April 3, 2020, more than 1,000,000 human infections have been diagnosed around the world, which exhibited apparent person-to-person transmission characteristics of this virus. The capacity of vertical transmission in SARS-CoV-2 remains controversial recently. Angiotensin-converting enzyme 2 (ACE2) is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. In present study, we collected the online available single-cell RNA sequencing (scRNA-seq) data to evaluate the cell specific expression of ACE2 in maternal-fetal interface as well as in multiple fetal organs. Our results revealed that ACE2 was highly expressed in maternal-fetal interface cells including stromal cells and perivascular cells of decidua, and cytotrophoblast and syncytiotrophoblast in placenta. Meanwhile, ACE2 was also expressed in specific cell types of human fetal heart, liver and lung, but not in kidney. And in a study containing series fetal and post-natal mouse lung, we observed ACE2 was dynamically changed over the time, and ACE2 was extremely high in neonatal mice at post-natal day 1~3. In summary, this study revealed that the SARS-CoV-2 receptor was widely spread in specific cell types of maternal-fetal interface and fetal organs. And thus, both the vertical transmission and the placenta dysfunction/abortion caused by SARS-CoV-2 need to be further carefully investigated in clinical practice.

Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart failure. However, they have different clinical and pathophysiological phenotype and the expressional spectrum of miRNAs in left ventricles of HCM and DCM has never been compared before. Methods This study selected 30 human left ventricular heart samples belonged to three diagnostic groups (Control, HCM, DCM). Each group has ten samples. Based on previous findings, the expression of 13 different microRNAs involving heart failure and hypertrophy (miR-1-3p, miR-10b, miR-21, miR-23a, miR-27a, miR-29a, miR-133a-3p, miR-142-3p, miR-155, miR-199a-3p, miR-199a-5p, miR-214, miR-497) was measured. 17 HCM patients were included as second group to validate the associations. Results We found miR-155, miR-10b and miR-23a were highly expressed in both HCM and DCM compared with control. MiR-214 was downregulated and miR-21 was upregulated in DCM but not in HCM. We also identified miR-1-3p and miR-27a expressed significantly different between HCM and DCM and both miRNAs downregulated in HCM. And only miR-1-3p correlated with left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) that reflected the cardiac function in HCM. A second HCM group also confirmed this correlation. We then predicted Chloride voltage-gated channel 3 (Clcn3) as a direct target gene of miR-1-3p using bioinformatics tools and confirmed it by Luciferase reporter assay. Conclusion Our data demonstrated that different cardiomyopathies had unique miRNA expression pattern. And the expression levels of miR-1-3p and miR-27a had disease-specificity and sensitivity in HCM, whereas only miR-1-3p was significantly associated with left ventricular function in HCM identifying it as a potential target to improve the cardiac function in end-stage HCM. We also provide Clcn3 as a direct target of miR-1-3p which sheds light on the mechanism of HCM.

Abstract Esophageal and gastric cancers share some risk factors. This study aimed to compare the long-term trends in mortality rates of esophageal and gastric cancers in China to provide evidence for cancer prevention and control. Mortality data were derived from 103 continuous points of the Disease Surveillance Points system during 1991–2009, stratified by gender and urban-rural locations. Age-period-cohort models were used to disentangle the time trends of esophageal and gastric cancer mortality. The downward slope of the period effect for esophageal cancer was steeper than that for gastric cancer in rural areas. Cohort effect patterns were similar between esophageal and gastric cancers, with an inverse U-shape peaking around the late 1920s and early 1930s. A second peak, appearing around the 1950s, was weaker than the first but apparent in males, especially for esophageal cancer. The more marked changes in period effect for esophageal cancer in rural areas suggest esophageal cancer screening practices are effective in reducing mortality, and similar programs targeting gastric cancer should be implemented. The similarities of the cohort effects in these two cancers support the implication of nutrition deficiency in early childhood in the development of upper gastrointestinal cancer.

This paper reports the development and baseline data of a vignettes-based measure of gender equality. METHODS:Vignettes were developed through 3-day long focus groups. After piloting in 13 sites and repiloting a revised version in 6 countries, responses were categorized by the construct tapped and a scoring system developed. Finalized vignettes were then tested in DR Congo, Ecuador and China. RESULTS:Young adolescents can successfully respond to vignettes; and can differentiate self from hypothetical protagonists of same and opposite sex. Response differences by sex of respondent and protagonist were statistically significant across a range of scenarios and settings. CONCLUSION:This is the first vignettes-based measure for young adolescents assessing young adolescent perceptions of relationships differentiated by sex of the protagonist.

Aflatoxin B1 (AFB1) is one of the most commonly found mycotoxin in corn, which is highly toxic, carcinogenic, teratogenic, and mutagenic for the health of humans and animals. In order to reduce the AFB1 in corn, corn kernels were processed with Water-assisted Microwaves Treatment (WMT) and the feasibility of WMT processing on AFB1 reduction and its effects on corn quality were analyzed. Increasing the treatment time and microwave power could increase the reduction of AFB1, and the maximum reduction rate could reach 58.6% and 56.8%, respectively. There was no significant correlation between the initial concentration of AFB1 and the reduction rate of AFB1. During WMT, the main toxigenic molds were sterilized completely, and the moisture content of corn climbed up and then declined to the initial level. WMT could obviously increase the fatty acid value and pasting temperature of corn and reduce the all paste viscosity of corn. However, it had little effect on the color of corn. The results indicated that WMT could reduce AFB1 effectively and avoid the vast appearance of heat-damaged kernels simultaneously. Undoubtedly, water played an important role in WMT. This result provides a new idea for the reduction of AFB1 by microwave.

Aflatoxin B1, a type of highly toxic mycotoxin produced by some species belonging to the Aspergillus genus, such as Aspergillus flavus and Aspergillus parasiticus, is widely distributed in feed matrices. Here, coumarin was used as the sole carbon source to screen microorganism strains that were isolated from types of feed ingredients. Only one isolate (ND-1) was able to degrade aflatoxin B1 after screening. ND-1 isolate, identified as a strain of Aspergillus niger using phylogenetic analysis on the basis of 18S rDNA, could remove 26.3% of aflatoxin B1 after 48 h of fermentation in nutrient broth (NB). Optimization of fermentation conditions for aflatoxin B1 degradation by selected Aspergillus niger was also performed. These results showed that 58.2% of aflatoxin B1 was degraded after 24 h of culture under the optimal fermentation conditions. The aflatoxin B1 degradation activity of Aspergillus niger supernatant was significantly stronger than cells and cell extracts. Furthermore, effects of temperature, heat treatment, pH, and metal ions on aflatoxin B1 degradation by the supernatant were examined. Results indicated that aflatoxin B1 degradation of Aspergillus niger is enzymatic and this process occurs in the extracellular environment.

Ultrasound is an emerging decontamination technology with potential use in the global food processing industry. In the present study, we explored power ultrasound for processing aqueous aflatoxin B1 (AFB1). AFB1 was degraded by 85.1% after 80 min of ultrasound exposure. The reaction products of AFB1 were identified and their molecular formulae elucidated by ultra-high-performance liquid chromatography Q-Orbitrap mass spectrometry. Eight main reaction products were found, and their structures were clarified by parental ion fragmentation. Two degradation pathways were proposed according to the degradation product structures: One involved the addition of H• and OH• radicals, whereas the other involved H2O2 epoxidation and H•, OH•, and H2O2 oxidation of AFB1. Ultrasound treatment significantly reduced AFB1 bioactivity and toxicity by disrupting the C8=C9 double bond in the furan ring and modifying the lactone ring and methoxy group.

Fusarium Head Blight (FHB) or scab is a fungal disease of cereal grains. Wheat scab affects the yield and quality of wheat and produces mycotoxins such as deoxynivalenol (DON), which can seriously threaten human and animal health. In this study, gaseous ozone was used to degrade DON in wheat scab and the degradation products of ozonolysis were analyzed by ultra-performance liquid chromatography quadrupole-orbitrap mass spectrometry (UHPLC Q-Orbitrap). Toxicology analyses of the degradation products were also studied using structure-activity relationships. Ozone (8 mg L−1 concentration) was applied to 2 μg mL−1 of DON in ultrapure water, resulted in 95.68% degradation within 15 s. Ten ozonized products of DON in ultrapure water were analyzed and six main products (C15H18O7, C15H18O9, C15H22O9, C15H20O10, C15H18O8, and C15H20O9) were analyzed at varying concentrations of ozone and DON. Structural formulae were assigned to fragmentation products generated by MS2 and Mass Frontier® software. According to structure-activity relationship studies, the toxicities of the ozonized products were significantly decreased due to de-epoxidation and the attack of ozone at the C9-10 double bond in DON. Based on the results of the study above, we can find that gaseous ozone is an efficient and safe technology to degrade DON, and these results may provide a theoretical basis for the practical research of detoxifying DON in scabby wheat and other grains.

Deoxynivalenol (DON) is the most commonly found mycotoxin in scabbed wheat. In order to reduce the DON concentration in scabbed wheat with superheated steam (SS) and explore the feasibility to use the processed wheat as crisp biscuit materials, wheat kernels were treated with SS to study the effects of SS processing on DON concentration and the quality of wheat. Furthermore, the wheat treated with SS were used to make crisp biscuits and the texture qualities of biscuits were measured. The results showed that DON in wheat kernels could be reduced by SS effectively. Besides, the reduction rate raised significantly with the increase of steam temperature and processing time and it was also affected significantly by steam velocity. The reduction rate in wheat kernels and wheat flour could reach 77.4% and 60.5% respectively. In addition, SS processing might lead to partial denaturation of protein and partial gelatinization of starch, thus affecting the rheological properties of dough and pasting properties of wheat flour. Furthermore, the qualities of crisp biscuits were improved at certain conditions of SS processing.

The growth and development of plants under drought stress depends mainly on the expression levels of various genes and modification of proteins. To clarify the molecular mechanism of drought-tolerance of plants, suppression subtractive hybridisation cDNA libraries were screened to identify drought-stress-responsive unigenes in Grimmia pilifera, and a novel E3 ubiquitin ligase gene, GpDSR7, was identified among the 240 responsive unigenes. GpDSR7 expression was induced by various abiotic stresses, particularly by drought. GpDSR7 displayed E3 ubiquitin ligase activity in vitro and was exclusively localised on the ER membrane in Arabidopsis mesophyll protoplasts. GpDSR7-overexpressing transgenic Arabidopsis plants showed a high water content and survival ratio under drought stress. Moreover, the expression levels of some marker genes involved in drought stress were higher in the transgenic plants than in wild-type plants. These results suggest that GpDSR7, an E3 ubiquitin ligase, is involved in tolerance to drought stress at the protein modification level.

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.

To explore the effect of miR-20b on apoptosis, differentiation, the BMP signaling pathway and mitochondrial function in the P19 cell model of cardiac differentiation in vitro.A miR-20b over-expression vector, a miR-20b silencing vector and their corresponding empty vectors were constructed and transfected into P19 cells, separately. Stably miR-20b overexpressing and silenced P19 cell lines were successfully selected by blasticidin and puromycin, separately. The cells were induced to undergo apoptosis in FBS-free-α-MEM. The induced cells were examined by flow cytometry and measurement of their caspase-3 activities. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the relative expression of marker genes of cardiomyocytes during differentiation, such as cTnT, GATA4 and ANP. QRT-PCR was also used to detect the mitochondrial DNA (mtDNA) copy number. We investigated the cellular ATP production using a luciferase-based luminescence assay. The reactive oxygen species (ROS) was determined by DCFDA (2', 7'-Dichlorofluorescein diacetate) and the mitochondrial membrane potential (MMP) was elucidated by a JC-1 fluorescent probe, both using fluorescence microscopy and flow cytometer. The expression of BMP signaling pathway-related proteins were analyzed by Western blotting.Stably miR-20b overexpressing and silenced P19 cell lines were successfully obtained. MiR-20b overexpression increased apoptosis and promoted differentiation in P19 cells by promoting the activation of the BMP signaling pathway. In addition, miR-20b overexpression induced mitochondrial impairment in P19 cells during differentiation, which was characterized by lower MMP, raised ATP synthesis and increased ROS levels. The effects of miR-20b silencing were the exact opposite to those of overexpression.Collectively, these results suggested that miR-20b was very important in apoptosis, differentiation and mitochondrial function of P19 cells. MiR-20b may represent a new therapeutic target for congenital heart diseases and provide new insights into the mechanisms of cardiac diseases.

Leaf epidermal micromorphology and mesophyll structure during the development of Populus euphratica heteromorphic leaves, including linear, lanceolate, ovate, dentate ovate, dentate rhombic, dentate broad-ovate and dentate fan-shaped leaves, were studied by using electron and light microscopy. During development of heteromorphic leaves, epidermal appendages (wax crystals and trichomes) and special cells (mucilage cells and crystal idioblasts) increased in all leaf types while chloroplast ultrastructure and stomatal characters show maximum photosynthetic activity in dentate ovate and rhombic leaves. Also, functional analysis by subordinate function values shows that the maximum adaptability to adverse stress was exhibited in the broad type of mature leaves. The 12 heteromorphic leaf types are classified into three major groups by hierarchical cluster analysis: young, developing and mature leaves. Mature leaves can effectively obtain the highest stress resistance by combining the protection of xerophytic anatomy from drought stress, regulation of water uptake in micro-environment by mucilage and crystal idioblasts, and assistant defense of transpiration reduction through leaf epidermal appendages, which improves photosynthetic activity under arid desert conditions. Our data confirms that the main leaf function is differentiated during the developing process of heteromorphic leaves.

Caffeine (1, 3, 7-trimethylxanthine) and theobromine (3, 7-dimethylxanthine) are the major purine alkaloids in plants, e.g., tea (Camellia sinensis) and coffee (Coffea arabica). Caffeine is a major component of coffee and is used widely in food and beverage industries. Most of the enzymes involved in the caffeine biosynthetic pathway have been reported previously. Here, we demonstrated the biosynthesis of caffeine (0.38 mg/L) by co-expression of Coffea arabica xanthosine methyltransferase (CaXMT) and Camellia sinensis caffeine synthase (TCS) in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this production platform for making other purine-based alkaloids. To increase the catalytic activity of TCS in an effort to increase theobromine production, we identified four amino acid residues based on structural analyses of 3D-model of TCS. Two TCS1 mutants (Val317Met and Phe217Trp) slightly increased in theobromine accumulation and simultaneously decreased in caffeine production. The application and further optimization of this biosynthetic platform are discussed.

Protein trans-splicing by split inteins has many uses in protein production and research. Splicing proteins with synthetic peptides, which employs atypical split inteins, is particularly useful for site-specific protein modifications and labeling, because the synthetic peptide can be made to contain a variety of unnatural amino acids and chemical modifications. For this purpose, atypical split inteins need to be engineered to have a small N-intein or C-intein fragment that can be more easily included in a synthetic peptide that also contains a small extein to be trans-spliced onto target proteins. Here we have successfully engineered multiple atypical split inteins capable of protein trans-splicing, by modifying and testing more than a dozen natural inteins. These included both S1 split inteins having a very small (11-12 aa) N-intein fragment and S11 split inteins having a very small (6 aa) C-intein fragment. Four of the new S1 and S11 split inteins showed high efficiencies (85-100%) of protein trans-splicing both in E. coli cells and in vitro. Under in vitro conditions, they exhibited reaction rate constants ranging from ~1.7 × 10(-4) s(-1) to ~3.8 × 10(-4) s(-1), which are comparable to or higher than those of previously reported atypical split inteins. These findings should facilitate a more general use of trans-splicing between proteins and synthetic peptides, by expanding the availability of different atypical split inteins. They also have implications on understanding the structure-function relationship of atypical split inteins, particularly in terms of intein fragment complementation.

Abstract The role and detailed mechanisms of lncRNAs in idiopathic pulmonary fibrosis (IPF) are not fully understood. qPCR was conducted to verify lncRNA FEZF1-AS1 expression in the transforming growth factor-beta 1 (TGF-β1)-stimulated human lung fibroblasts (HLF) and A549. The EMT-related proteins were performed by western blotting. Cell proliferation, migration, and transition were detected by CCK-8, colony formation, wound-healing and transwell assays. A dual-luciferase reporter assay was conducted to validate the target relationship of FEZF1-AS1 and miR-200c-3p. FEZF1-AS1 is highly expressed in the fibrotic A549 and HLF. in vitro experiments revealed that FEZF1-AS1 facilitates cell proliferation, migration and invasion. Knockdown of FEZF1-AS1 attenuated TGF-b1-induced fibrogenesis both in vitro. Moreover, silencing FEZF1-AS1 inhibited fibrogenesis through modulation of miR-200c-3p. In addition, inhibition of miR-200c-3p promoted fibrogenesis by regulation of Zinc finger E-box binding homeobox 1 (ZEB1). Mechanistically, FEZF1-AS1 promoted lung fibrosis by acting as a competing endogenous RNA (ceRNA) for miR-200c-3p. FEZF1-AS1 silencing increased the expression and activity of miR-200c-3p to inhibit ZEB1 and alleviate lung fibrogenesis in A549 and HLF. In addition, our study showed that FEZF1-AS1 can regulate enhancer of zeste homolog2 (EZH2) to upregulate fibrosis-related proteins and promote lung fibrosis. In summary, the results of our study revealed the pulmonary fibrogenic effect of FEZF1-AS1 in cellular experiments, demonstrating the potential roles and mechanisms of the FEZF1-AS1/miR-200c-3p/ZEB1 and FEZF1-AS1/EZH2 pathways, which provides a novel and potential therapeutic target to lung fibrosis.

Abstract Background Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. Methods We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson’s or Spearman’s correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. Results A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (− 18 [44] U/L, P

Abstract. Background:. Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. Methods:. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. Results:. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+ DCs, IFN-responding DCs, MHCII+ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+ monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Conclusions:. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.