Search

Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Objective: To identify factors influencing the intention to quit (ItQ) among Chinese who smoke, focusing on 10th Revision of the International Classification of Diseases (ICD-10) Nicotine dependence. Additionally, to estimate the number of individuals with ItQ, supporting optimal allocation of cessation resources. Methods: This study used data from the 2018 China Health Literacy Survey, a nationally representative cross-sectional study with 20,288 participants who smoke currently aged 20–69 years. The ItQ proportions were estimated overall and by subgroup. Logistic regression was employed to estimate ORs and 95 % CIs for ItQ. The number of people who smoke with ItQ was estimated based on the census data. Results: In China, 41.34 % of individuals who smoke had ItQ, higher in females (44.89 %) than males (41.34 %). Provincial proportions ranged from 23.53 % to 63.56 %. ItQ was significantly associated with smoking characteristics, including occasional smoking (OR = 2.08, 95 % CI = 1.88–2.20), fewer pack-years (OR = 0.70, 95 % CI = 0.68–0.73), older smoking initiation age (OR = 1.22, 95 % CI = 1.18–1.27), and ICD-10 Nicotine dependence (OR = 1.12, 95 % CI = 1.06–1.19), as well as age, sex, socioeconomic factors, and health status. Withdrawal symptoms were positively associated with ItQ in individuals who smoke without ICD-10 Nicotine dependence but negatively in those with ICD-10 Nicotine dependence. An estimated 100.3 million adults aged 20–69 in China have ItQ, with 52.14 million suffering from ICD-10 Nicotine dependence. Conclusions: The intention to quit smoking among Chinese who smoke is low and varies by ICD-10 Nicotine dependence and region, underscoring the need for targeted smoking cessation interventions across diverse smoking populations.

Caffeic acid phenethyl ester (CAPE) is one of the main active components of the natural medicine propolis, which has antioxidant, anti-tumor, and immunomodulatory activities. This study aimed to analyze the effects and underlying mechanisms of CAPE added to the medium of in vitro cultures on the developmental competence, mitochondria, and endoplasmic reticulum of porcine embryos. The results demonstrated that 1 nM of CAPE significantly improved the quality of porcine embryos, increased the rate of blastocyst formation, and enhanced the proliferation ability. It also enhanced mitochondrial function by increasing the level of mitochondrial membrane potential and expression of the mitochondrial biogenesis-related protein PPARgamma coactivator 1 alpha and beta (PGC1 alpha and beta), regulating mitochondrial biogenesis, and increasing adenosine triphosphate (ATP) content. In addition, CAPE alleviated oxidative and endoplasmic reticulum (ER) stress in embryos by decreasing ROS accumulation and increasing glutathione content, as well as elevating Nrf2 and reducing GRP78 (ER stress marker) expression levels. Moreover, CAPE reduced the levels of apoptosis and autophagy in the cultivated embryos. These results indicate that CAPE improves the quality and enhances the mitochondrial function of in vitro-produced porcine embryos by alleviating oxidative and ER stress.

Dihydromyricetin (DHM), a dihydroflavonoid compound, exhibits a variety of biological activities, including antitumor activity. However, the effects of DHM on mammalian reproductive processes, especially during early embryonic development, remain unclear. In this study, we added DHM to porcine zygotic medium to explore the influence and underlying mechanisms of DHM on the developmental competence of parthenogenetically activated porcine embryos. Supplementation with 5 μM DHM during in vitro culture (IVC) significantly improved blastocyst formation rate and increased the total number of cells in porcine embryos. Further, DHM supplementation also improved glutathione levels and mitochondrial membrane potential; reduced natural reactive oxygen species levels in blastomeres and apoptosis rate; upregulated Nanog, Oct4, SOD1, SOD2, Sirt1, and Bcl2 expression; and downregulated Beclin1, ATG12, and Bax expression. Collectively, DHM supplementation regulated oxidative stress during IVC and could act as a potential antioxidant during in vitro porcine oocytes maturation.

Non-communicable diseases (NCDs) is the main cause of deaths around the world and salt reduction is considered as one of the most cost-effective priority actions to reduce the risk of NCDs. In order to reduce salt intake among residents, many countries in the world have implemented a series of salt reduction strategies and measures, such as establishing salt reduction policies, enhancing consumer health education, improving food formulations in the food industry, and implementing front-of-package labeling programs. This paper summarizes researches on source of salt, salt and health, as well as the strategies, measures and achievements of salt reduction intervention in some countries and regions, in order to provide references for carrying out relevant salt reduction actions in China.

Our previous study established that chrysoeriol (CHE) can reduce reactive oxygen species (ROS) accumulation, apoptosis, and autophagy in vitro culture (IVC) of porcine embryos. However, the role of CHE in oocyte maturation and lipid homeostasis is unclear. Herein, we aimed to elucidate the effect of CHE on porcine oocyte competence in vitro maturation (IVM) and subsequent embryo development. The study chooses parthenogenetic activated porcine oocytes as the research model. The study revealed that the cumulus expansion index and related gene expressions are significantly elevated after supplementing 1 μM CHE. Although there were no significant differences in nuclear maturation and cleavage rates, the blastocyst formation rate and total cell numbers were significantly increased in the 1 μM CHE group. In addition, CHE improved the expression of genes related to oocyte and embryo development. ROS was significantly downregulated in all CHE treatment groups, and intracellular GSH (glutathione) was significantly upregulated in 0.01, 0.1, and 1 μM CHE groups. The immunofluorescence results indicated that mitochondrial membrane potential (MMP) and lipid droplet (LD), fatty acid (FA), ATP, and functional mitochondria contents significantly increased with 1 μM CHE compared to the control. Furthermore, CHE increased the expression of genes related to lipid metabolism, mitochondrial biogenesis, and β-oxidation.

Eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) is a flavonoid derived from Artemisia plants that has beneficial biological activities, such as anti-apoptotic, anti-oxidant, and anti-inflammatory activities. However, the protective effects of eupatilin against oxidative stress and endoplasmic reticulum stress in porcine oocyte maturation are still unclear. To investigate the effect of eupatilin on the development of porcine oocytes after in vitro maturation and parthenogenetic activation, we added different concentrations of eupatilin in the process of porcine oocyte maturation in vitro, and finally selected the optimal concentration following multiple comparisons and analysis of test results using SPSS (version 17.0; IBM, Chicago, IL, USA) software. The results showed that 0.1 μM eupatilin supplementation did not affect the expansion of porcine cumulus cells, but significantly increased the extrusion rate of porcine oocyte polar bodies, the subsequent blastocyst formation rate, and the quality of parthenogenetically activated porcine embryos. Additionally, it reduced the level of reactive oxygen species in cells and increased glutathione production. Further analysis revealed that eupatilin supplementation could reduce apoptosis, DNA double-strand breaks, and endoplasmic reticulum stress. In conclusion, supplementation with 0.1 μM eupatilin during in vitro maturation improved oocyte maturation and subsequent embryo development by reducing oxidative stress and endoplasmic reticulum stress.

ObjectiveTo clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking.MethodsWe included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018–2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20–69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables.ResultsAmong ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62–1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86–2.27) were less likely to successfully quit.ConclusionsThe clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.

Imidacloprid (IMI) is an endogenous neonicotinoid insecticide widely used in agriculture and has attracted researchers’ attention because of its risks to the environment and human health. Melatonin (MT) is an antioxidant hormone produced by the pineal gland of the brain. Studies have shown that it has a variety of physiological functions and plays a crucial role in the development of animal germ cells and embryos. The potential protective effects of MT against oocyte damage caused by neonicotinoid pesticide toxicity remain unclear. In this study, we report the toxicity of IMI against, and its effects on the quality of, porcine oocytes and the protective effect of MT on IMI-exposed oocytes. The results show that IMI exposure adversely affected oocyte maturation, while MT supplementation ameliorated its toxic effects. Specifically, IMI exposure increased oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptosis, which may affect polar body expulsion rates and blastocyst formation. Also, IMI exposure reduced oocyte cleavage rates and the number of cells in blastocysts. However, all of these toxic effects can be restored after a melatonin supplementation treatment. In conclusion, these results suggest that melatonin has a protective effect on IMI-induced defects during porcine oocyte maturation.

Subsurface wastewater infiltration (SWI) is an environmentally friendly technology for the advanced treatment of domestic sewage. Clogging (including physical, chemical and biological clogging) of the porous medium not only directly reduces the hydraulic load (treatment efficiency), but also reduces the service life. Although clogging has become one of the key issues discussed in several reports, there are still several gaps in understanding, especially in its occurrence process and identification. SWI clogging causes, development process and solutions are different from those of constructed wetlands. This article quotes some reports on constructed wetlands to provide technical ideas and reference for revealing SWI clogging problems. Based on the analysis of the clogging genesis, this review gathers the main factors that affect the degree of clogging, and new methods for the identification of clogging conditions. Some preventive and unclogging measures/strategies are presented. Finally, it is suggested that to effectively alleviate the clogging phenomenon and extend the service life, priority should be given to the comprehensive analysis of wastewater quality and solid constituents accumulated in the pores. Then, the effectiveness of in-situ strategies, such as alternating operation will be the main focuses of future research. HIGHLIGHTS Up to dated methods for the identification of clogging conditions were compared.; Main factors that affect the probability and degree of clogging were gathered.; Different preventive and unclogging measures/strategies were compared.; Priority unclogging measurements are proposed.;

Summary: Background: Tobacco dependence is the key barrier to successful smoking cessation. However, little is known about its prevalence, sociodemographic characteristics and determinants. We aimed to estimate the prevalence, associated factors and burden of tobacco dependence in China. Methods: During 2018–2019, the nationally representative 2018 China Health Literacy Survey (2018 CHLS) invited 87,708 participants to participate using a multistage stratified sampling method from 31 provinces (or equivalent) in mainland China, and 84,839 participants aged 20–69 with valid data were included in the analysis. We diagnosed tobacco dependence based on international criteria (ICD-10, DSM-4) and tailored to Chinese population according to China Clinical Guideline for Tobacco Cessation (2015 version). The prevalence of tobacco dependence was estimated overall and by sociodemographic factors. The Logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tobacco dependence and success of smoking cessation (being ex-smokers), with different levels of adjustment. These were used to estimate the total number of adults who were tobacco dependent in China. Findings: In China, the estimated prevalence of current smoking was 25.1%, significantly higher in men than in women (47.6% vs 1.9%). The prevalence of current smoking varied approximately 3-fold (12.9% to 37.9%) across 31 provinces of China. Among general population aged 20–69 years, the prevalence of tobacco dependence was 13.1% (95% CI:12.2–14.1). Among current smokers, the prevalence of tobacco dependence was 49.7% (46.5–52.9%), with no difference between men and women (49.7% vs 50.8%). The prevalence of tobacco dependence was associated significantly with smoking intensity, defined by pack-years (1.62 [1.54–1.70] per 10 pack-years), cigarettes smoked per day (2.01 [1.78, 2.27] per 10 cigarettes), and smoking starting age (0.93 [0.90, 0.97] per 5 years). Given smoking intensity, the prevalence of tobacco dependence also varied by age, gender, certain socioeconomic status and regions. Compared with those without tobacco dependence, ever smokers with tobacco dependence were less likely to be ex-smokers (2.88, 2.59–3.21). In China, 183.5 (170.4–197.4) million adults (177.5 million were men) were tobacco dependent in 2018. Interpretation: In China, tobacco dependence is highly prevalent, with approximately half of current smokers being addictive, highlighting the need for coordinated effort to improve awareness, diagnosis and treatment of tobacco dependence. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), National Key R&D Program of China (grant no 2017YFC1309400), and National Natural Science Foundation of China (grant no 81720108001). Note: Chinese translation of abstract is available in appendix section.

Wedelolactone (WDL) is a coumaryl ether compound extracted from the traditional Chinese medicinal plant, Eclipta prostrata L. It is a natural polyphenol that exhibits a variety of pharmacological activities, such as anti-inflammatory, anti-free radical, and antioxidant activities in the bone, brain, and ovary. However, its effect on embryonic development remains unknown. The present study explored the influence of WDL supplementation of porcine oocytes culture in vitro on embryonic development and the underlying mechanisms and its effect on the levels of Kelch-like ECH-associated protein 1/nuclear factor-erythroid 2-related factor 2/antioxidant response element (Keap1/Nrf2/ARE). The results showed that WDL (2.5 nM) significantly increased the blastocyst formation rate, mitochondrial activity, and proliferation ability while reducing the reactive oxygen species accumulation, apoptosis, and autophagy. These findings suggested that WDL can enhance the growth and development of early porcine embryos to alleviate oxidative stress and autophagy through regulating NRF2 and microtubule-associated protein 1 light chain 3 (MAP1LC3) gene expression levels.

Background: Enterovirus 71 (EV71) is one of the major causative pathogens of hand, foot, and mouth disease (HFMD). Immune cells play a critical role in determining the outcomes of virus infection. We aimed to characterize the lymphocyte subsets and transcriptional levels of T lymphocytes-associated transcription factors in peripheral blood cells of children with EV71 infection. Methods: Peripheral blood samples from 32 children with EV71 infection and 32 control subjects were included in this study. The frequencies of T-, B-lymphocytes, and their subsets were determined by flow cytometry. The expression of transcription factors, including T-bet, Gata3, ROR γ t, Foxp3, TCF-1, and BCL-6 in the whole blood cells were evaluated by real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Results: The frequencies of T cells, helper T cells (Th), cytotoxic T cells (Tc), IFN-γ+ Th1, IFN-γ+ Tc1, and regulatory T (Treg) cells were significantly decreased (P

Abstract. Background:. The eosinophilic chronic obstructive pulmonary disease (COPD) is known to be more sensitive to corticosteroid. The sputum microbiome has been shown to affect COPD prognosis, but its role in acute exacerbations of eosinophilic COPD is unclear. This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD. Methods:. Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups. Patients with eosinophils ≥300 cells/μL in the peripheral venous blood were assigned to the eosinophilic group (Eos) and the rest to the non-eosinophilic group (Noneos). All patients received similar treatment including inhaled budesonide according to the guidelines. The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA (rRNA) method. The levels of interleukin (IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells. Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test. Categorical data were evaluated using Chi-squared test or Fisher's exact test. Results:. Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group. Prior to treatment, the alpha diversity (Shannon index) (2.65 ± 0.63 vs. 2.56 ± 0.54, t = 0.328, P = 0.747) and the structure of the sputum microbiome were similar in the Eos group and the Noneos group. After 7 days of treatment, alpha diversity increased in both groups, while the microbiome richness (Ace index) was significantly lower in the Eos group (561.87 ± 109.13 vs. 767.88 ± 148.48, t = −3.535, P = 0.002). At the same time, IL-6 (12.09 ± 2.85 pg/mL vs. 15.54 ± 2.45 pg/mL, t = −4.913, P

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants. It has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. Among common livestock embryos, porcine embryos are often considered high-quality objects for studying the antioxidant mechanisms of oocytes. Because porcine embryos contain high levels of lipids, they are more vulnerable to external stimuli, which affect development. Our study explored the influence of CHE supplementation on oxidative stress in porcine oocytes and its possible mechanisms. Different concentrations of CHE (0, 0.1, 1, and 3 µM) were supplemented in the in vitro culture medium of the porcine oocytes. The results showed that supplementation with 1 µM CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. After finding the beneficial effects of CHE, we measured reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane potential (MMP) when the oocytes reached the 4-cell stage of development and determined the levels of apoptosis, cell proliferation, and autophagy at the blastocyst stage of development. The expression levels of some related genes were preliminarily detected by qRT-PCR. The results showed that the apoptosis of blastocysts in the CHE-treated culture also decreased compared with the untreated culture. Furthermore, CHE downregulated intracellular ROS and increased GSH in the embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated. At the same time, apoptosis-related (Caspase 3) and autophagy-related (LC3B) genes showed a downward trend after supplementation with CHE. These results indicate that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

L-carnitine (LC) is well known for its antioxidant activity. In this study, we explored the potential mechanistic effects of LC supplementation on aged bovine oocytes in vitro. We showed that in-vitro maturation could enhance the subsequent developmental capacity of aging oocytes, when supplemented with LC. After in vitro fertilization, the blastocyst formation rate in the aged oocytes post-LC treatment significantly increased compared to that in untreated aged oocytes (29.23 ± 2.20% vs. 20.90 ± 3.05%). Furthermore, after LC treatment, the level of intracellular reactive oxygen species in aged oocytes significantly decreased, and glutathione levels significantly increased, compared to those in untreated aged oocytes. Mitochondrial membrane potential, the percentage of early apoptotic oocytes, and caspase-3 activity were significantly reduced in LC-treated aged oocytes compared to those in untreated aged oocytes. Furthermore, during in vitro aging, the mRNA levels of the anti-apoptotic genes, Bcl-xl and survivin in LC-treated aged oocytes were significantly higher than those in untreated aged oocytes. Overall, these results indicate that at least in in vitro conditions, LC can prevent the aging of bovine oocytes and improve the developmental capacity of bovine embryo.

Subsurface wastewater infiltration systems (SWIS) are one of the important sources of nitrous oxide (N2O) production; understanding the biological processes and contributions of N2O will help control the amount of N2O produced. To quantitatively reveal the contribution of nitrification and denitrifiaction processes, 8 g potassium nitrate with 99.99 atom % 15N (i.e. 15N accounts for 99.99% of the total N) was dissolved in the influent (concentration: 3.3 g/L). Results showed that nitrification released more N2O within 0–12 h, accounting for 79.6 ± 2.4%. The denitrification process accounted for 88.5 ± 1.3% for N2O generation after the 12th hour. Thus, in order to effectively control the release of N2O, the denitrification process should be given more attention. The maximum release rate of N2O was 8.45 ± 0.8 mg/m2·h, which occurred near the end of the first wetting-drying cycle. Since then, peaks appeared periodically, mostly in the “rest” periods.

The concentration of total nitrogen (TN) is reported to vary between 20 and 35 mg/L in domestic wastewater. In raw wastewater, ammonia nitrogen (NH4+-N) is the main nitrogen form, accounting for 70%–82% of the TN concentration. Organic nitrogen, nitrite nitrogen (NO2−-N), and nitrate nitrogen (NO3−-N) are present as well. For years, due to the lack of regulatory limits on nitrogen concentration in surface waters, nitrogen from secondary effluent has posed a significant threat to the health of aquatic ecosystems. Researchers have made substantial efforts to reduce the nitrogen concentration in secondary effluent. As a kind of advanced wastewater treatment technology, the subsurface infiltration (SI) system has been widely used, owing to its advantages, which include low operation cost, easy maintenance, and low energy consumption. This review discusses the fate of various forms of nitrogen in SI treatment, including organic nitrogen, NH4+-N, NO2−-N, and NO3−-N. Major biological processes involved in nitrogen removal and the main factors influencing its transformation are suggested. Finally, it is shown that ammonification followed by nitrification-denitrification plays a major role in nitrogen removal. Further research needs to focus on the emission characteristics of gaseous nitrogen (generated from the nitrification, denitrification, and completely autotrophic nitrogen-removal over nitrite (CANON) processes) with respect to their greenhouse effects.

Inhibition of both MEK1/2 and glycogen synthase kinase-3 (GSK3; 2i system) facilitates the maintenance of naïve stemness for embryonic stem cells in various mammalian species. However, the effect of the inhibition of the 2i system on porcine early embryogenesis is unknown. We investigated the effect of the 2i system on early embryo development, expression of pluripotency-related genes, and epigenetic modifications. Inhibition of MEK1/2 (by PD0325901) and/or GSK3 (by CHIR99021) did not alter the developmental potential of porcine parthenogenetic embryos, but improved blastocyst quality, as judged by the blastocyst cell number, diameter, and reduction in the number of apoptotic cells. The expression levels of octamer-binding transcription factor 4 and SOX2, the primary transcription factors that maintain embryonic pluripotency, were significantly increased by 2i treatments. Epigenetic modification-related gene expression was altered upon 2i treatment. The collective results indicate that the 2i system in porcine embryos improved embryo developmental potential and blastocyst quality by regulating epigenetic modifications and pluripotency-related gene expression.

Background: Cervical cancer is the second most common cancer of woman in the world, and human papillomavirus (HPV) infection plays an important role in the development of most of the cases. IκB kinase β (IKKβ) is a kinase-mediating nuclear factor kappa B (NF-κB) activation by phosphorylating the inhibitor of NF-κB (IκB) and is related by some diseases caused by virus infection. However, there is little known about the correlation between IKKβ and HPV infection in cervical cancer. This study aimed to investigate the expression of IKKβ protein in cervical cancer tissues and effects of inflammation on HPV positive or negative cervical cancer cells through detecting the expression of IKKβ, IκBα, p53, and p21 proteins after treated with lipopolysaccharide (LPS) to mimic bacterial infection. We also examined the effects of LPS on cervical cancer cells after blocking IKKβ with pharmacological inhibitor. Methods: Thirty-six matched specimens of cervical cancer and adjacent normal tissues were collected and analyzed in the study. The expression of IKKβ in the tissue specimens was determined by immunohistochemical staining. In addition, Western blot was used to detect the expression level changes of IKKβ, IκBα, p53, and p21 after LPS stimulated in the HPV16+ (SiHa) and HPV16− (C33A) cervical cancer cell lines. Furthermore, the effects of IKKβ inhibitor SC-514 on LPS-induced expression change of these proteins were investigated. Results: The expression of IKKβ was higher in cervical cancer than adjacent normal tissues, and there was no significant difference between tumor differentiation, size, and invasive depth with IKKβ expression. The LPS, which increased the expression level of IKKβ protein but decreased in the IκBα, p53 and p21 proteins, was illustrated in HPV16+ (SiHa) but not in HPV16− (C33A) cells. Moreover, IKKβ inhibitor SC-514 totally reversed the upregulation of IKKβ and downregulation of p53 and p21 by LPS in SiHa cells. Conclusions: IKKβ may mediate the downregulation of p53 and p21 by LPS in HPV16+ cervical cancer cells.

In order to enhance the hydraulic loading rate (HLR) of a subsurface wastewater infiltration system (SWIS) used in treating domestic sewage, the intermittent operation mode was employed in the SWIS. The results show that the intermittent operation mode contributes to the improvement of the HLR and the pollutant removal rate. When the wetting-drying ratio (RWD) was 1.0, the pollutant removal rate increased by (13.6 ± 0.3)% for NH3-N, (20.7 ± 1.1)% for TN, (18.6 ± 0.4)% for TP, (12.2 ± 0.5)% for BOD, (10.1 ± 0.3)% for COD, and (36.2 ± 1.2)% for SS, compared with pollutant removal rates under the continuous operation mode. The pollutant removal rate declined with the increase of the HLR. The effluent quality met The Reuse of Urban Recycling Water – Water Quality Standard for Scenic Environment Use (GB/T 18921-2002) even when the HLR was as high as 10 cm/d. Hydraulic conductivity, oxidation reduction potential (ORP), the quantity of nitrifying bacteria, and the pollutant removal rate of NH3-N increased with the decrease of the RWD. For the pollutant removal rates of TP, BOD, and COD, there were no significant difference (p

The fragmentation of shock-melted metal material is an important scientific problem in shock physics and is suitable for experimentally investigating by the laser-driven x-ray backlighting technique. This letter reports on the exploration of laser shock-melted aluminum fragmentation by means of x-ray backlighting at the SGII high energy facility in China. High-quality and high-resolution radiographs with negligible motion blur were obtained and these images enabled analysis of the mass distribution of the fragmentation product.

The dynamic fragmentation of shock-melted metal is a topic of increasing interest in shock physics. However, high-quality experimental studies of the phenomenon are limited, and data that are essential for developing predictive models of the phenomenon, such as the mass and particle sizes distributions, are quite sparse. In-line holography is an effective non-contact technique for measuring particle size distribution, but critical technical requirements, in particular, particle density limits, complicate its application to the subject phenomenon. These challenges have been reasonably overcome in the present study, allowing for successful in situ measurements of the size distribution of the fragmentation product from laser-shock-melted aluminum. In this letter, we report on our experiments and present the measured data.

Zinc is an extremely important trace element that plays important roles in several biological processes. However, the function of zinc in meiotic division of porcine oocytes is unknown. In this study, we investigated the role of zinc during meiotic resumption in in vitro matured porcine oocytes. During meiotic division, a massive release of zinc was observed. The level of free zinc in the cytoplasm significantly increased during maturation. Depletion of zinc using N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a Zn2+ chelator, blocked meiotic resumption in a dose dependent manner. The level of phosphorylated mitogen activated protein kinase (MAPK) and p34cdc2 kinase activity were reduced when zinc was depleted. Moreover, zinc depletion reduced the levels of phosphorylated protein kinase C (PKC) substrates in a dose dependent manner. Real-time PCR analysis showed that expression of the MAPK- and maturation promoting factor related genes C-mos, CyclinB1, and Cdc2 was downregulated following zinc depletion. Treatment with the PKC agonist phorbol 12-myristate 13-acetate (PMA) increased phosphorylation of PKC substrates and MAPK and increased p34cdc2 kinase activity. This rescued the meiotic arrest, even in the presence of TPEN. Activation of PKC by PMA increased the level of zinc in the cytoplasm. These data demonstrate that zinc is required for meiotic resumption in porcine oocytes, and this appears to be regulated via a PKC related pathway.

The reaction between methyl (R)-2-(2-chlorophenyl)-2-hydroxyacetate and 3-nitrobenzenesulfonyl chloride gave the title compound, C15H12ClNO7S, which is a promising intermediate for the synthesis of Clopidrogel, an antiplatelet drug used in the prevention of strokes and heart attacks. In the crystal, molecules are linked through C—H...O interactions, and there is also a short Cl...O contact present [Cl...O = 3.018 (2) Å].

Pancreatic ductal adenocarcinoma (PDAC) is amongst the deadliest of human cancers, due to its late diagnosis as well as its intense resistance to currently available therapeutics. To identify mechanisms as to why PDAC are refractory to DNA damaging cytoxic chemotherapy and radiation, we performed a global interrogation of the DNA damage response of PDAC. We find that PDAC cells generally harbor high levels of spontaneous DNA damage. Inhibition of Non-Homologous End Joining (NHEJ) repair either pharmacologically or by RNAi resulted in a further accumulation of DNA damage, inhibition of growth, and ultimately apoptosis even in the absence of exogenous DNA damaging agents. In response to radiation, PDAC cells rely on the NHEJ pathway to rapidly repair DNA double strand breaks. Mechanistically, when NHEJ is inhibited there is a compensatory increase in Homologous Recombination (HR). Despite this upregulation of HR, DNA damage persists and cells are significantly more sensitive to radiation. Together, these findings support the incorporation of NHEJ inhibition into PDAC therapeutic approaches, either alone, or in combination with DNA damaging therapies such as radiation.

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1a) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes. [ABSTRACT FROM AUTHOR]