Lysine acetyltransferase 14 mediates TGF-ß-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.

BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-ß (TGF-ß), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-ß remain poorly understood. METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-ß-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-ß-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-ß-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-ß treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. CONCLUSION: Our results shed light on KAT14 as a key effector of TGF-ß-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.

Pyroptosis is involved in maternal nicotine exposure-induced metabolic associated fatty liver disease progression in offspring mice.

We have investigated whether inflammasomes and pyroptosis are activated in maternal nicotine exposure (MNE) offspring mice and whether they are involved in MNE-promoted metabolic associated fatty liver disease (MAFLD) in adult offspring. We injected pregnant mice subcutaneously with saline vehicle or nicotine twice a day on gestational days 11-21. Offspring mice from both groups were fed with a normal diet (ND) or a high-fat diet (HFD) for 6 months at postnatal day 21 to develop the MAFLD model. Serum biochemical indices were analyzed, and liver histology was performed. The expression levels of inflammasome and pyroptosis proteins were detected by western blot. We found MNE significantly aggravated the injury of MAFLD in adult offspring mice. MNE activated inflammasomes and pyroptosis in both infant and adult offspring mice. HFD treatment activated inflammasomes but not pyroptosis at 3 months, while it showed no effect at 6 months. However, pyroptosis was more severe in MNE-HFD mice than in MNE-ND mice at 6 months. Taken together, our data suggest MNE promotes MAFLD progression in adult offspring mice. MNE also induces NLRP3 and NLRP6 inflammasome activation and pyroptosis in both infant and adult offspring mice, which may be involved in MNE-promoted progression of MAFLD.

A digital multimeter-based portable photoelectrochemical immunoassay for the detection of cardiac troponin I with enzymatic biocatalytic precipitation.

Early diagnosis of acute myocardial infarction (AMI) can significantly reduce mortality, which can be achieved by the highly sensitive detection of AMI-specific cardiac troponin I (cTnI) biomarkers. Herein a highly sensitive and portable photoelectrochemical (PEC) immunoassay for the detection of cTnI was innovatively fabricated based on an efficient photocurrent response of Cu2O coupling with a split-type enzymatic biocatalytic precipitation reaction with a digital multimeter readout. Initially, Cu2O cubic nanomaterials with a good photocurrent response were obtained by facile green room temperature synthesis and dropped on fluorine-doped tin oxide (FTO) plates as photoactive materials (Cu2O/FTO). In the presence of target cTnI, horseradish peroxidase (HRP) on the detection antibody catalyzes the substrate 4-chloro1-naphthol (4-CN) to produce insoluble precipitates of benzo-4-chlorohexadienone (4-CD) on Cu2O/FTO with the assistance of H2O2, resulting in a decrease in the photocurrent of the Cu2O/FTO electrode. To make the whole inspection process more concise and efficient, we used a flashlight and a digital multimeter as the excitation light source and reading device for the PEC sensing system, respectively. Under the optimal conditions of immunoreaction time, pH, and loading, the photocurrent of Cu2O/FTO decreased with increasing target cTnI concentration with a limit of detection (LOD) of 4.7 pg mL-1 in the operating range of 0.01-10 ng mL-1. It is of interest that the developed portable PEC immunoassay is also capable of detecting cTnI in human serum samples with acceptable accuracy compared to the reference cTnI enzyme-linked immunosorbent assay (ELISA) method while maintaining portability and sensitivity.

Dynamic Service Function Chain Deployment and Readjustment Method Based on Deep Reinforcement Learning.

With the advent of Software Defined Network (SDN) and Network Functions Virtualization (NFV), network operators can offer Service Function Chain (SFC) flexibly to accommodate the diverse network function (NF) requirements of their users. However, deploying SFCs efficiently on the underlying network in response to dynamic SFC requests poses significant challenges and complexities. This paper proposes a dynamic SFC deployment and readjustment method based on deep Q network (DQN) and M Shortest Path Algorithm (MQDR) to address this problem. We develop a model of the dynamic deployment and readjustment of the SFC problem on the basis of the NFV/SFC network to maximize the request acceptance rate. We transform the problem into a Markov Decision Process (MDP) and further apply Reinforcement Learning (RL) to achieve this goal. In our proposed method (MQDR), we employ two agents that dynamically deploy and readjust SFCs collaboratively to enhance the service request acceptance rate. We reduce the action space for dynamic deployment by applying the M Shortest Path Algorithm (MSPA) and decrease the action space for readjustment from two dimensions to one. By reducing the action space, we decrease the training difficulty and improve the actual training effect of our proposed algorithm. The simulation experiments show that MDQR improves the request acceptance rate by approximately 25% compared with the original DQN algorithm and 9.3% compared with the Load Balancing Shortest Path (LBSP) algorithm.

Lowered expression level of INSC predicts poor prognosis in patients with colon cancer.

The aim of this study was to investigate the prognostic value of inscuteable spindle orientation adaptor protein (INSC) in colon cancer (CC). Firstly, transcriptional change of INSC was analysed using the data from public databases. Next, INSC protein expression was assessed by immunohistochemistry. Its correlation with clinicopathological features and the prognostic values of patients were also investigated. Then, an INSC-based nomogram was built to predict CC prognosis. Compared to normal tissues, INSC was significantly downregulated at the transcriptional level in CC tissues. A low INSC mRNA level not only positively correlated with TNM stage (tumour-nodus-metastases), advanced T stage, and N stage, but also with the shorter 5- and 8-year overall survival (OS) and disease-specific survival. Concerning protein level, INSC downregulation was confirmed in CC samples. In terms of the correlation with N stage and 5- and 8-year OS, it was also consistent with mRNA levels. Cox regression analysis indicated that INSC protein expression was an independent prognostic factor for OS. The nomogram showed better prognostic accuracy and clinical net benefit for 5-year OS than TNM staging. Altogether, downregulation of INSC is related to inferior clinicopathological features and patient outcomes, and it may be a novel independent prognostic biomarker in CC.

Exercise-Mediated Alteration of miR-192-5p Is Associated with Cognitive Improvement in Alzheimer's Disease.

INTRODUCTION: Physical exercise is an important component of managing Alzheimer's disease (AD). miRNAs can be modulated by exercise intervention. OBJECTIVE: The study explored the involvement and potential mechanism of miR-192-5p in the protective effect of physical exercise on AD. METHODS: Ninety AD patients were enrolled, in which 45 cases accepted cycling training for continuous 3 months. The expression changes of miR-192-5p before and after exercise were analyzed by reverse transcription-quantitative PCR. 8-month-old APP/PS1 double Tg mice were used as the AD animal model. Mice in the voluntary exercise (VE) group received VE for 4 weeks. Morris water maze (MWM) test was used to evaluate the learning and memory function. Enzyme-linked immunosorbent assay was used to calculate the level of IL-1ß, IL-6, and TNF-α. RESULTS: AD patients showed elevated MMSE scores, decreased ADAS-cog and NPI-Q scores after 3 months of exercise. miR-192-5p was downregulated in the serum of AD patients and correlated with the levels of MMSE score, ADAS-cog, and NPI-Q score. A positive association was detected between serum miR-192-5p with TNF-α, IL-6, and IL-1ß levels. MiR-192-5p is downregulated in the hippocampus tissues of mice after VE. Overexpression of miR-192-5p reversed the neuroprotective effect of exercise on AD in mice and promoted the inflammatory response of AD mice. CONCLUSION: MiR-192-5p can be modulated by the exercise intervention and involved in the protective effect of exercise on AD.

LncRNA SUMO1P3 regulates the invasion, migration and cell cycle of gastric cancer cells through Wnt/ß-catenin signaling pathway.

OBJECTIVE: To investigate the regulatory effect of long non-coding RNA (lncRNA) SUMO1P3 on invasion, migration and cell cycle of gastric cancer (GC) cells through Wnt/ß-catenin signaling pathway. METHODS: Tumor tissues and adjacent normal tissues from the GC patients were collected, and human normal gastric epithelial cells GES1 and GC cells SGC-7901, MKN45, HGC-27 and AGS were selected for study. The expression of SUMO1P3 in GC tissues and cells were detected by RT-qPCR. The effects of SUMO1P3 on the proliferation, invasion and migration of SGC-7901 and MKN45 cells were detected by CCK-8, transwell and wound healing assay respectively, and the effects of SUMO1P3 on apoptosis and cycle progression of SGC-7901 and MKN45 cells were detected by flow cytometry. The expressions of Wnt/ß-catenin pathway-related and cell cycle-related proteins were detected by Western blot. RESULTS: The expression of SUMO1P3 was significantly upregulated in GC tissues and cell lines. Downregulation of SUMO1P3 significantly inhibited the SGC-7901 and MKN45 cell proliferation, invasion, migration, and cycle progression and promoted the cell apoptosis, while overexpression of SUMO1P3 showed the opposite effect. Further study showed that downregulation of SUMO1P3 significantly reduced the expressions of Wnt1, ß-catenin, c-myc, and Cyclin D1 in SGC-7901 and MKN45 cells. CONCLUSION: SUMO1P3 may promote invasion, migration, and cycle progression of SGC-7901 and MKN45 cells by enhancing the Wnt/ß-catenin pathway.

Maternal nicotine exposure aggravates metabolic associated fatty liver disease via PI3K/Akt signaling in adult offspring mice.

AIM: The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism. METHODS: Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11-21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high-fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis-related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element-binding transcription factor 1 (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPAR-α) were detected in the liver by immunohistochemistry and Western blotting. RESULTS: MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, and insulin while decreasing serum high-density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high-fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down-regulation of SREBP1c and PPAR-α. CONCLUSION: Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.

Seeking sustainable development policies at the municipal level based on the triad of city, economy and environment: evidence from Hunan province, China.

Keeping urbanization, economy and eco-environment in harmony is a core issue for attaining Sustainable Development Goals (SDGs) in any complex geographical regions. Previous studies mainly focused on seeking the balance between urban expansion levels, eco-environment quality and socioeconomic degree. But the challenges still exist in solving the negative influence of urban expansion that affects eco-environmental and economic development. Based on the Environmental Kuznets Curve theory, we involved inclusive indexes to analyze the interlinkages of eco-environment quality, economic level, and urban expansion degree, which closely relate to urban sustainable development goals and spatial complexity, as well as using available data corresponding to waterfront cities. Cities in Hunan were taken as a study-case, and the study period of 2006-2016 covers the last 10 years of the millennium development goals agenda and the first 2 years of SDGs agenda. The key indicators of city-economy-environment relationships were different at the provincial level, urban level and urbanization grade. According to the regression models and inverted N shape curve, urban expansion resulted in high positive effects on economic development level and negative effects on ecological environment quality, partically higher at high urbanization level than that of the low ones. But the overall trends were that the environmental quality of the cities was undergoing slowly improving processes both at low and high urban expansion levels. Promoting adaptations with the eco-environmental capacity when formulating policies and taking actions is necessary for realizing sustainable cities and communities (SDG11), life on land (SDG15), decent work and economic growth (SDG8) and responsible consumption and production (SDG12) at the same time. Regulating citizens' density, urban expansion speed in area, the quantity of enterprises with heavy pollution, and the structure of industry to the suitable urbanization stages is an important way for achieving SDGs at provincial and municipal levels.

ZEB1 modulates endometrial receptivity through epithelial-mesenchymal transition in endometrial epithelial cells in vitro.

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been identified. The present study sought to verify if ZEB1 plays a role in endometrial receptivity through regulation of EMT during embryo implantation. Endometrial epithelium from sixty patients in phase of the menstrual cycle (including proliferative and secretory phases) were collected for assessment of mRNA/protein expression. In human endometrial adenocarcinoma cell line RL95-2, ZEB1 expression was suppressed by using shRNA, and the cell function and mRNA/protein expression were evaluated. RL95-2 cells and human choriocarcinoma cell line JAR were co-cultured to establish embryo implantation model in vitro. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in human endometrium during mid-secretory phase of the menstrual cycle. Knockdown of ZEB1 expression in RL95-2 cells attenuated cell growth, migration, DNA replication, and altered expression of E-cadherin and vimentin at both mRNA and protein levels. Interestingly, knockdown of ZEB1 expression in RL95-2 cells potently suppressed JAR spheroid attachment in vitro (P < 0.01). Additionally, the. Conclusively, knockdown of ZEB1 suppressed embryo implantation in vitro, paralleled with alteration of EMT markers. ZEB1 is likely to modulate endometrial receptivity through promotion of EMT, that could be crucial for embryo implantation process.

Production enhancement of the extracellular lipase LipA in Bacillus subtilis: Effects of expression system and Sec pathway components.

Lipases are among the most versatile biocatalysts, and are used in a range of industrially relevant bioconversion reactions. However, the production of LipA in recombinant Bacillus subtilis is still limited, due to unresolved issues surrounding the regulation of the expression and secretion systems. In this study, the gene encoding LipA from B. subtilis 168 was expressed in BNA under the control of the P43 and the PAE promoter. The extracellular lipase activity of the resulting strains BNACL and BNAAL was 7.8 U ml-1 and 12.6 U ml-1, respectively. To further enhance the expression of LipA, pHP13L was constructed by inserting the PAE-lip into the shuttle vector pHP13, which produced an extracellular lipase activity of 180.5 U ml-1 of BNA/pHP13L. The strain BNAY8 described in Supplement data which lacks eight extracellular proteins was constructed and the deletion a few of the much weaker secreting proteins had no significant effect on the secretion of LipA. Moreover, the four Sec pathway components, secA-prfB, secDF, secYEG, prsA, were individually overexpressed in BNA. The overexpression of secDF and prsA enhanced the production of LipA by 28% and 49%, respectively. Furthermore, the co-overexpression of secDF with prsA improved the extracellular amount of LipA by 59% over that of BNA/pHP13L, reaching 287.8 U ml-1. It can therefore be said that both regulatory elements and secretion pathway had an impact on the production of secreted LipA. Their optimization and modification is a useful strategy to improve the homologous overproduction of other extracellular proteins in B. subtilis.

A multi-center study on the risk factors of infection caused by multi-drug resistant Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii (AB) is critical for healthcare-associated infections (HAI) with significant regional differences in the resistance rate, but its risk factors and infection trends has not been well studied. We aimed to explore the risk factors, epidemiological characteristics and resistance of multidrug-resistant Acinetobacter baumannii (MDR-AB) in intensive care unit inpatients. METHODS: Data of patients with MDR-AB (195 cases), and with antibiotic-sensitive AB infection (294 cases, control) during January to December, 2015 in three medical centers in Xiamen, China were conducted and analyzed in the present retrospective study. RESULTS: Lower respiratory tract infection with AB accounted for 68.71%. MDR-AB was detected in 39.88% of all cases. Univariate analysis suggested that mechanical ventilation, indwelling catheter, cancer patients, length of hospitalization in intensive care unit (ICU) ≥15 d, Acute Physiology and Chronic Health Evaluation (APACHE) II score, combined using antibiotic before isolation of AB and use of third-lines cephalosporins were associated with the development of MDR-AB healthcare-associated infections. Dose-response relationship analysis suggested that the age and the days of mechanical ventilation were associated with increased infection with MDR-AB. Logistic regression analysis suggested that, mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter, were associated with MDR-AB infection, with odds ratios (OR) and 95% confidence intervals (CI) of 3.93 (1.52-10.14), 4.11 (1.58-10.73), and 4.15 (1.32-12.99), respectively. CONCLUSIONS: MDR-AB infection was associated with mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter. Furthermore, the age and the days of mechanical ventilation were associated with increased infection with MDR-AB.

A 21-35 kDa Mixed Protein Component from Helicobacter pylori Activates Mast Cells Effectively in Chronic Spontaneous Urticaria.

BACKGROUND: Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. METHODS: In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. RESULTS: In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD2 cells in a dose-dependent or time-dependent manner. CONCLUSIONS: A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection.

Enhanced Photoelectrocatalytic Activity of BiOI Nanoplate-Zinc Oxide Nanorod p-n Heterojunction.

The development of highly efficient and robust photocatalysts has attracted great attention for solving the global energy crisis and environmental problems. Herein, we describe the synthesis of a p-n heterostructured photocatalyst, consisting of ZnO nanorod arrays (NRAs) decorated with BiOI nanoplates (NPs), by a facile solvothermal method. The product thus obtained shows high photoelectrochemical water splitting performance and enhanced photoelectrocatalytic activity for pollutant degradation under visible light irradiation. The p-type BiOI NPs, with a narrow band gap, not only act as a sensitizer to absorb visible light and promote electron transfer to the n-type ZnO NRAs, but also increase the contact area with organic pollutants. Meanwhile, ZnO NRAs provide a fast electron-transfer channel, thus resulting in efficient separation of photoinduced electron-hole pairs. Such a p-n heterojunction nanocomposite could serve as a novel and promising catalyst in energy and environmental applications.

[Time-dependent heart rate variability in the head-up tilt test in children with postural orthostatic tachycardia syndrome].

OBJECTIVE: To study the time-dependent heart rate (HR) variability in the head-up tilt test (HUTT) in children with postural orthostatic tachycardia syndrome (POTS) and to explore the HR diagnostic criteria for POTS in children. METHODS: A retrospective analysis was performed on the clinical data of 105 children diagnosed with POTS with HR≥120 beats per minute (bpm) within the first 10 minutes of HUTT between January 2007 and December 2014. Their HR variability within the first 10 minutes of HUTT was analyzed. RESULTS: The HR of children with POTS increased gradually from the supine position to a 60° head-up tilt position, and the increase in HR was 24±12 bpm at the beginning of HUTT, 30±14 bpm at 3 minutes of HUTT, 32±13 bpm at 5 minutes of HUTT, and 38±12 bpm at 10 minutes of HUTT. The average maximal HR increase within the first 10 minutes of HUTT was 43±10 bpm. CONCLUSIONS: In children with POTS, the HR variability gradually increases with time, and therefore, it is suggested that HR increase ≥40 bpm is more suitable for diagnosis of POTS in children.

[Comparison of soil heavy metals determined by AAS/AFS and portable X-ray fluorescence analysis].

Total concentrations of Cu, Pb, As, Cr, Ni and Zn were determined for 53 soil samples using portable X-ray fluorescence (PXRF) system in in-situ and ex-situ (Lab.) conditions. PXRF metal concentrations were statistically compared with analytical results from traditional AAS/AFS analysis. The ability of PXRF instrument to produce comparable analytical results to the reference method was assessed by linear regression. To investgate the effects of soil moisture on PXRF, the in-situ moisture content of all soil samples was quantified and the metal concentrations of selected samples with known moisture contents were measured too. The results showed that the detection limits of PXRF for Cu, Pb, As, Cr, Ni and Zn were 10.6, 8.1, 5.7, 22.5, 21.6 and 10.4 mg kg(-1) respectively. A good degree of linearity was found for Pb, Cr, Ni and Zn in in-situ condition. While in ex-situ condition, quantitative level data were achieved across the entire range of samples tested for Cu, Pb, Cr, Ni and Zn. X-ray fluorescence spectrometry was shown to be an effective tool for quantification and rapid assessment of heavy metals in soils. Soil moisture content did affected the performance of PXRF, the mean percent difference for soil samples in-situ with moisture content less than 15% and higher than 25% was -17% and -31% respectively. In ex-situ condition, as the soil moisture content increased from air dried level to 30%, the mean percent difference decreased from 10% to -24%. The dilution effect of moisture in soils may cause discrepancies with conventional analytical results and induce worse data quality, and it should be controlled within 0-25% in in-situ condition.

[Evaluation of psychological fear in children undergoing head-up tilt test].

OBJECTIVE: To investigate the effects of different tilt angles of head-up tilt test (HUTT) and different responses to HUTT on the psychological fear in children undergoing the test. METHODS: HUTT was performed on children with unexplained syncope or pre-syncope (107 cases: 52 males and 55 females), aged 5.5-17.8 years (mean 12.0±2.8 years). All subjects were randomly assigned to undergo HUTT at an angle of 60°, 70° or 80°; the negative cases underwent sublingual nitroglycerin-provocation HUTT at the same tilt angle. The Wong-Baker Faces Pain Rating Scale was used for self-assessment of psychological fear in subjects during HUTT at the end point of the test. RESULTS: The positive rate, hemodynamic changes and distribution of response types showed no significant differences between children at tilt angles of 60°, 70° and 80° (P>0.05). The greater the tilt angle, the higher the degree of psychological fear in children undergoing the test, but there were no significant differences between them (P>0.05). The degree of psychological fear in children who showed a positive response to HUTT (n=76) was significantly higher than that in children who showed a negative response (n=31) (P<0.01). CONCLUSIONS: HUTT can cause psychological fear in children undergoing the test, and the degree of psychological fear increases in children tested at tilt angles from 60° to 80°, but the differences have no statistical significance. A positive response to HUTT can significantly increase the psychological fear in children.

Glycemic load, but not glycemic index, is associated with an increased risk of ovarian cancer: A systematic review and meta-analysis.

The association between glycemic index (GI),glycemic load (GL) and ovarian cancer risk remains unclear. Carbohydrate intake promotes insulin secretion, leading to cell proliferation and invasion. We hypothesized that high GI and GL intake may increase ovarian cancer risk. Therefore, we conducted a meta-analysis after systematically searching PubMed, Embase, Web of Science, and Cochrane Library from inception to December 2022. Fixed- or random-effect models calculated the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Subgroup, sensitivity, publication bias analysis, and dose-response analysis were performed. Nine original studies were included, involving 4716 cases and 119,960 controls. No significant association was observed between GI or GL and ovarian cancer risk (GI: RR = 1.02 [95% CI, 0.83-1.26]; GL: RR = 1.11 [95% CI, 0.84-1.47]). Subgroup analysis suggested the results were not significantly modified by any group. Sensitivity analysis identified the sources of heterogeneity. No publication bias was observed. A linear positive dose-response relationship was observed between dietary GL and ovarian cancer risk after removing heterogeneous sources (RR = 1.11 [95% CI, 1.05-1.17], I2 = 32.9%, P = .23 at 50 U/d; RR = 1.04 [95% CI, 1.02-1.07], I2 = 19.1%, P = .29 at 20 U/d). These outcomes suggest that high dietary GL, but not GI, is associated with significantly increased ovarian cancer risk. Thus, sufficient intake of a low dietary GL is important for reducing ovarian cancer risk.

The Gene Expression Profiles Associated with Maternal Nicotine Exposure in the Liver of Offspring Mice.

This study aims to investigate the effect of maternal nicotine exposure on the gene expression profiles in the liver of offspring mice. Pregnant mice were subcutaneously injected with either saline vehicle or nicotine twice a day on gestational days 11-21. Total RNA from the liver samples which collected from the offspring mice of postnatal day 7 and 21 was subjected to RNA sequencing. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were conducted to identify the functions of differentially expressed genes (DEGs). Four genes were selected for further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 448 DEGs and 186 DEGs were identified on postnatal day 7 and 21, respectively. GO analysis revealed that the DEGs on postnatal day 7 mainly participated in the biological functions of cell growth and proliferation, and the DEGs on postnatal day 21 mainly participated in ion transport/activity. KEGG enrichment analysis showed that the DEGs on postnatal day 7 were mainly enriched in the cell cycle, cytokine-cytokine receptor interactions, hypertrophic cardiomyopathy, and the p53 signaling pathway, while the DEGs on postnatal day 21 were mainly enriched in neuroactive ligand-receptor interactions, the calcium signaling pathway, retinol metabolism, and axon guidance. The qRT-PCR results were consistent with the RNA sequencing data. The DEGs may affect the growth of liver in early postnatal period while may affect ion transport/activity in late postnatal period.

Heat shock factor OsHsfB2b negatively regulates drought and salt tolerance in rice.

KEY MESSAGE: Expression of OsHsfB2b was strongly induced by heat, salt, ABA and PEG treatments. Drought and salt tolerances were significantly decreased by OsHsfB2b overexpression, but were enhanced by RNA interference. ABSTRACT: Plants have more than 20 heat shock factors (Hsfs) that were designated class A, B, and C. Many members of Class A Hsfs were characterized as activators of transcription, but the functional roles of class B and C Hsfs have not been fully recognized. OsHsfB2b is a member of class B Hsfs in rice (Oryza sativa). Expression of OsHsfB2b was strongly induced by heat, salt, abscisic acid (ABA) and polyethylene glycol (PEG) treatments but was almost not affected by cold stress. Drought and salt tolerances were significantly decreased in OsHsfB2b-overexpressing transgenic rice, but were enhanced in the OsHsfB2b-RNAi transgenic rice. Under drought stress, the OsHsfB2b-overexpressing transgenic rice exhibited increased relative electrical conductivity (REC) and content of malondialdehyde (MDA) and decreased proline content compared with the wild type, while the lower REC and MDA content and increased proline content were found in the OsHsfB2b-RNAi transgenic rice. These results suggest that OsHsfB2b functions as a negative regulator in response to drought and salt stresses in rice, with its existing B3 repression domain (BRD) that might be necessary for the repressive activity. The present study revealed the potential value of OsHsfB2b in genetic improvement of rice.