NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

Effects of sodium arsenite exposure on behavior, ultrastructure and gene expression of brain in adult zebrafish (Danio rerio).

Arsenic, a common metal-like substance, has been demonstrated to pose potential health hazards and induce behavioral changes in humans and rodents. However, the chronic neurotoxic effects of arsenic on aquatic animals are still not fully understood. This study aimed to investigate the effects of arsenic exposure on adult zebrafish by subjecting 3-month-old zebrafish to three different sodium arsenite water concentrations: 0 µg/L (control group), 50 µg/L, and 500 µg/L, over a period of 30 days. To assess the risk associated with arsenic exposure in the aquatic environment, behavior analysis, transmission electron microscopy techniques, and quantitative real-time PCR were employed. The behavior of adult zebrafish was evaluated using six distinct tests: the mirror biting test, shoaling test, novel tank test, social preference test, social recognition test, and T maze. Following the behavioral tests, the brains of zebrafish were dissected and collected for ultrastructural examination and gene expression analysis. The results revealed that sodium arsenite exposure led to a significant reduction in aggression, cohesion, social ability, social cognition ability, learning, and memory capacity of zebrafish. Furthermore, ultrastructure and genes regulating behavior in the zebrafish brain were adversely affected by sodium arsenite exposure.

Association of meal timing of energy, macronutrients and foods with hypercholesterolaemia in the US adults.

Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003-2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.

Inverse correlations between serum carotenoids and respiratory morbidity and mortality: the Third National Health and Nutrition Examination Survey.

The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, ß-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41-0·89, ORß-cryptoxanthin = 0·67, 95% CI: 0·49-0·92), chronic bronchitis (ORß-cryptoxanthin = 0·66, 95% CI: 0·50-0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62-0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42-0·90, HRα-carotene = 0·54, 95% CI: 0·36-0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33-0·71, HRlycopene = 0·66, 95% CI: 0·45-0·96) than those in the lowest tertiles. Higher serum total carotenoids and ß-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.

Characteristics and Related Factors of High-Risk Human Papillomavirus Infection in Pregnant Women.

BACKGROUND Cervical cancer is a risk for women worldwide. The aim of this study was to examine the occurrence of high-risk human papillomavirus (HR-HPV) infection and its related factors in pregnant women and provide a scientific basis for the targeted prevention and treatment of cervical cancer in pregnant women. MATERIAL AND METHODS A total of 1774 pregnant women were included, and 1774 non-pregnant women were selected as controls. Cervical exfoliated cells were collected from all women for HR-HPV (AptimaE6, E7mRNA) and ThinPrep cytologic testing, and the vaginal discharge of all pregnant women was tested for pH level and routine pathogenic microorganisms. RESULTS The HPV-16-positive and HPV-16/18/45-positive rates in pregnant women were higher than those of non-pregnant women (P<0.05). There was a statistically significant difference in HR-HPV-positive rate, HPV-16-positive rate, and non-HPV-16/18/45-positive rate among pregnant women of different ages (P<0.05). There was a statistically significant difference in HR-HPV-positive rate and non-HPV-16/18/45-positive rate in the first, second, and third trimester (P<0.05). The HR-HPV-positive rate, HPV-16-positive rate, HPV-18/45-positive rate, and non-HPV-16/18/45-positive rate of pregnant women with concurrent infection were higher than those in women without concurrent infection (P<0.05). The HR-HPV-positive and HPV-16/18/45-positive rates in pregnant women were associated with cytologic examination results (P<0.05). CONCLUSIONS The overall infection rates of HR-HPV-16 and HR-HPV-18/45 in pregnant women were higher than those in non-pregnant women. The gestation period was found to be a susceptible period for infection with HR-HPV, and we recommend the implementation of cervical cancer screening based on HR-HPV testing in pregnant women.

Relationship of abnormal mid-term oral glucose tolerance test and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus.

To explore the correlation of mid-term oral glucose tolerance test (OGTT) and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). A total of 2611 pregnant women with GDM who were examined and delivered in Women's Hospital, Zhejiang University School of Medicine from July 1st 2017 to 30th June 2018 were enrolled in this study. According to the number of abnormal items of mid-term OGTT results or maternal gestational weight gain (GWG), patients were classified. The incidence of adverse perinatal outcomes in each group and its relation with OGTT results and GWG were analyzed. The incidence of gestational hypertension, premature delivery, macrosomia and large for gestational age infant (LGA) in three abnormal items GDM patients were significantly higher than those in one or two abnormal items GDM patients (all <0.017). The incidence of gestational hypertension and premature delivery in two abnormal items GDM patients were higher than those in one abnormal item GDM patients (all <0.017). The incidence of gestational hypertension and macrosomia in excessive GWG patients were significantly higher than those in inadequate and appropriate GWG patients (all <0.017), and the incidence of LGA were higher than that in inadequate GWG patients (all <0.017). The incidence of premature delivery and low birth weight infants in appropriate GWG patients were significantly lower than those in inadequate and excessive GWG patients, and the incidence of small for gestational age infant (SGA) were significantly lower than that in inadequate GWG patients (all <0.017). In one abnormal item GDM patients, inadequate GWG was a risk factor for premature delivery and SGA (=1.66, 95%: 1.10-2.52; =2.20, 95%: 1.07-4.53), and protective factor for LGA (=0.40, 95%: 0.27-0.59). And excessive GWG was a risk factor for gestational hypertension, premature delivery and low birth weight infants (=2.15, 95%: 1.35-3.41; =1.80, 95%: 1.20-2.72; =2.18, 95%: 1.10-4.30).In two abnormal items GDM patients, inadequate GWG was a protective factor for macrosomia and LGA (=0.24, 95%: 0.09-0.67; =0.54, 95%: 0.34-0.86), while excessive GWG was risk factor for premature delivery (=1.98, 95%: 1.23-3.18).In three abnormal items GDM patients, there was no significant relationship between GWG and adverse pregnancy outcomes. For GDM women with one or two items of elevated blood glucose in OGTT, reasonable weight management during pregnancy can reduce the occurrence of adverse pregnancy outcomes. For those with three items of elevated blood glucose in OGTT, more strict blood glucose monitoring and active intervention measures should be taken in addition to weight management during pregnancy.

Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia.

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

Control of postpartum hemorrhage in women with placenta accreta spectrum using prophylactic balloon occlusion combined with Pituitrin intra-arterial infusion.

OBJECTIVES: The aim of this study is to evaluate the efficacy of prophylactic internal iliac artery balloon occlusion combined with Pituitrin intra-arterial infusion in the control of postpartum hemorrhage in women with placenta accreta spectrum (PAS). METHODS: This is a prospective and non-randomized controlled study. The participants were assigned into three groups: without balloon catheterization (non-BC) group, balloon catheterization (BC) group, and Pituitrin combined with balloon catheterization (PBC) group. The primary outcomes were estimated blood loss (EBL) and the units of transfused packed red blood cells (PRBC). The secondary outcome was the incidence of hysterectomy. RESULTS: A total of 100 participants were recruited between August 2013 and November 2018 and assigned into the respective groups as follows: 27 in the non-BC group, 22 in the BC group, and 51 in the PBC group. No statistical differences were found in demographic characteristics among the three groups. There was a trend of lower EBL, PRBC, and hysterectomy rate in the BC group than those in the non-BC group, while all values showed no significant differences (all p > 0.05). Patients in the PBC group had significantly lower EBL, PRBC, and hysterectomy rate compared with those in the non-BC group (all p < 0.05). Linear regression analysis revealed that the PBC (vs. others) was negatively correlated with EBL and the non-BC (vs. others) independently predicted more EBL. CONCLUSIONS: Balloon occlusion combined with Pituitrin infusion is an effective treatment method which significantly reduced EBL, PRBC, and hysterectomy rate in patients with PAS. KEY POINTS: • Internal iliac artery balloon occlusion combined with Pituitrin intra-arterial infusion can significantly decrease EBL, PRBC, and hysterectomy rate during cesarean section in patients with PAS. • Cesarean section without balloon occlusion and placenta accreta depth are two independent risk factors for EBL in patients with PAS.

Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) during pregnancy is rare and seldom reported in literature. Here we report a case of pregnancy-associated HLH. A patient was admitted at 26 weeks and 2 days pregnancy complaining of cough and fever was admitted. She was found having bi-cytopenia, elevated ferritin and hypertriglyceridaemia. HLH was not confirmed because of the negative results from the first bone marrow biopsy. As the situation worsened, a timely termination of pregnancy was carried out. The second bone marrow biopsy did reveal hemophagocytosis and then pregnant-related HLH was confirmed. Prompt treatment of dexamethasone and etoposide have the puerpernat in a better situation. From this case, we learned HLH can be likely ignored and not be diagnosed promptly in a pregnant patient. In order to confirm this disease, a bone marrow biopsy should be performed promptly or repeatly for suspicious HLH. The time of termination and treatment is both essential for the foetus and the puerperant. Given the high morbidity and mortality of this disease in recent years, an expert consensus or clinical guideline should be developed.

Transferrin-Functionalized Microemulsions Coloaded with Coix Seed Oil and Tripterine Deeply Penetrate To Improve Cervical Cancer Therapy.

Tumor-targeted ligand modification and nanosized coloaded drug delivery systems are promising for cancer therapy. In this study, we showed that coix seed oil and tripterine coloaded microemulsions with a transferrin modification (Tf-CT-MEs) could improve the treatment of cervical cancer. Tf-CT-MEs exhibited good stability in serum and a notably synergistic antiproliferation effect. In the HeLa xenograft tumor-bearing mouse model, Tf-CT-MEs accumulated at tumor sites and penetrated deeply in tumor tissues. Tf-CT-MEs had superior anticancer efficacy in vivo, which greatly slowed the growth of tumors (***p < 0.001 vs saline). We also found that Tf-CT-MEs inhibited tumor cell proliferation, enhanced antiangiogenesis, and induced apoptosis by regulating bax/bcl-2 and the activating caspase-3 pathway. Tf-CT-MEs decreased by 27.7, 26.9, 61.2, and 42.5% of concentrations of TGF-ß1, CCL2, TNF-α, and IL-6 in serum, respectively. In addition, Tf-CT-MEs showed little toxicity in vital organs. These results were due to the improved drug delivery efficiency. Collectively, Tf-CT-MEs enhance tumor-targeting, facilitate deep penetration of drugs, and have promising potential as an efficient treatment for cervical cancer.

Different Infectivity of Swine Enteric Coronaviruses in Cells of Various Species.

Swine enteric coronaviruses (SECoVs), including porcine deltacoronavirus (PDCoV), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), have caused high mortality in piglets and, therefore, pose serious threats to the pork industry. Coronaviruses exhibit a trend of interspecies transmission, and understanding the host range of SECoVs is crucial for improving our ability to predict and control future epidemics. Here, the replication of PDCoV, TGEV, and PEDV in cells from different host species was compared by measuring viral genomic RNA transcription and protein synthesis. We demonstrated that PDCoV had a higher efficiency in infecting human lung adenocarcinoma cells (A549), Madin-Darby bovine kidney cells (MDBK), Madin-Darby canine kidney cells (MDCK), and chicken embryonic fibroblast cells (DF-1) than PEDV and TGEV. Moreover, trypsin can enhance the infectivity of PDCoV to MDCK cells that are nonsusceptible to TGEV. Additionally, structural analyses of the receptor ectodomain indicate that PDCoV S1 engages Aminopeptidase N (APN) via domain II, which is highly conserved among animal species of different vertebrates. Our findings provide a basis for understanding the interspecies transmission potential of these three porcine coronaviruses.

Association between dietary spermidine intake and depressive symptoms among US adults: National Health and Nutrition Examination Survey (NHANES) 2005-2014.

BACKGROUND: Spermidine (SPD) has a number of advantageous effects, including life extension and neuroprotection. However, few observational studies have investigated the association of dietary SPD intake with depression. METHODS: We used data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) and the corresponding Food Patterns Equivalents Database (FPED). SPD content of food groups from published data were merged with the appropriate FPED data to estimate the SPD intake for each subject. Patients with Patient Health Questionnaire-9 (PHQ-9) scores of 10 or above were thought to experience clinically relevant depression symptoms. Logistic regression, sensitivity analysis, and restricted cubic spline (RCS) were used. RESULTS: Among the 19,306 participants, the overall prevalence of depression was 8.72 %. After controlling for relevant confounders, individuals in the highest tertile or quartile of total SPD and SPD derived from fruits, vegetables, cereals, nuts, eggs and seafood had a significantly lower prevalence of depression (OR total SPD = 0.77, 95 % CI: 0.63-0.93); OR fruit-sourced SPD = 0.81, 95 % CI: 0.68-0.95; OR vegetable-sourced SPD = 0.72, 95 % CI: 0.61-0.85; OR cereals-sourced SPD = 0.73,95 % CI:0.60-0.88; OR nuts- sourced SPD = 0.80, 95 % CI: 0.71-0.91; OR egg-sourced = 0.72, 95 % CI: 0.62-0.84 and OR seafood-sourced SPD = 0.65, 95 % CI: 0.55-0.77) comparing those in the lowest tertile or quartile. CONCLOUSION: Our fndings reveal a negative association between dietary SPD intake and depression.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil.

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Chromosomal evolution of Escherichia coli for the efficient production of lycopene.

BACKGROUND: Plasmid-based overexpression of genes has been the principal strategy for metabolic engineering. However, for biotechnological applications, plasmid-based expression systems are not suitable because of genetic instability, and the requirement for constant selective pressure to ensure plasmid maintenance. RESULTS: To overcome these drawbacks, we constructed an Escherichia coli lycopene production strain that does not carry a plasmid or an antibiotic marker. This was achieved using triclosan-induced chromosomal evolution, a high gene copy expression system. The engineered strain demonstrated high genetic stability in the absence of the selective agent during fermentation. The replacement of native appY promoter with a T5 promoter, and the deletion of the iclR gene in E. coli CBW 12241 further improved lycopene production. The resulting strain, E. coli CBW 12241(ΔiclR, PT5-appY), produced lycopene at 33.43 mg per gram of dry cell weight. CONCLUSIONS: A lycopene hyper-producer E. coli strain that does not carry a plasmid or antibiotic marker was constructed using triclosan-induced chromosomal evolution. The methods detailed in this study can be used to engineer E. coli to produce other metabolites.

Self-emulsifying System Co-loaded with Paclitaxel and Coix Seed Oil Deeply Penetrated to Enhance Efficacy in Cervical Cancer.

BACKGROUND: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. OBJECTIVE: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. METHODS: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. RESULTS: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. CONCLUSION: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.

Distribution of picophytoplankton in the northern slope of the South China Sea under environmental variation induced by a warm eddy.

Mesoscale eddies have been reported to have a substantial impact on the distribution of phytoplankton through the regulation of environmental variables in the open ocean. However, the influence of warm eddies on phytoplankton in continental slopes remains largely unknown. To reveal the impact of mesoscale eddies within slope regions, we conducted a field investigation of picophytoplankton on the northern slope of the South China Sea during an anticyclonic warm eddy propagation. We observed different picophytoplankton distribution patterns. Synechococcus dominated the picophytoplankton community in the Kuroshio-affected eddy core rather than the previously reported Prochlorococcus, and Prochlorococcus dominated outside the eddy in the shelf. In addition, through further vertical study of typical layers, we found that the influence of warm eddy varied in different layers. Analysis of the mechanisms indicated that the distributions were attributed to warm eddy-induced nutrients and light variations and the physical processes in it.

Exploration of active sites of ethyl alcohol electro-oxidation on porous gold nanoparticles with enhanced Raman spectroscopy.

Novel porous gold nanospheres are prepared by calcination of the gold-urea complexes. The enhanced Raman spectra of ethanol catalyzed by different doses of porous gold nanospheres are measured with a 532 nm laser as the excitation source, and an enhanced charge coupled device served in spectral detection and microscopic imaging. The electrochemical experiments show that the catalytic oxidation products of ethanol with porous gold nanoparticles are acetaldehyde, acetic acid, and water, which further proved that the porous gold nanoparticles can activate the -CH2 of ethanol.

The heterogeneous associations between gestational weight gain and adverse pregnancy outcomes in gestational diabetes mellitus according to abnormal glucose metabolism.

OBJECTIVES: The gestational weight gain (GWG) and hyperglycemia are two key factors affecting adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM). We aimed to investigate the combinatorial effect of abnormal glucose metabolism and GWG on adverse outcomes in GDM. METHODS: This retrospective cohort study included 2611 pregnant women with GDM in Women's Hospital School of Medicine Zhejiang University. Bases on the OGTT glucose levels, we categorized the GDM cohort into three subgroups: impaired fasting glucose (IFG) group, impaired glucose tolerance (IGT) group, and combined impaired glucose (IFG&IGT) group. RESULTS: Among pregnant women with IGT, insufficient GWG (IGWG) was an independent protective factor for pregnancy-induced hypertension syndrome (PIH) (aOR 0.55, 95% CI 0.32-0.95), macrosomia (0.38, 0.19-0.74) and large for gestational age (0.45, 0.32-0.62), as well as an independent risk factor for low birth weight infants (2.29, 1.24-4.22) and small for gestational age (1.94, 1.17-3.19); and excessive GWG (EGWG) was related to increased risks of PIH (1.68, 1.12-2.52), preterm delivery (1.82, 1.28-2.58), postpartum hemorrhage (1.85, 1.05-3.28), cesarean delivery (1.84, 1.38-2.46) and low body weight infants (2.36, 1.33-4.20). Moreover, EGWG was positively associated with PIH (3.27, 1.09-9.80) in the IFG group. But there were no significant associations between either IGWG or EGWG and any pregnancy outcomes in women with combined IFG&IGT. CONCLUSIONS: The relationships between GWG and adverse outcomes were modified by abnormal glucose metabolism in women with GDM. Our results suggest that more specific GWG recommendations according to their metabolic state are needed for GDM.

Independent and Joint Associations of Age, Pre-pregnancy BMI, and Gestational Weight Gain with Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus.

INTRODUCTION: To explore the independent and combined effects of maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: A total of 2171 pregnant women with GDM attending the Women's Hospital of Zhejiang University were retrospectively included. We compared pregnancy outcomes in different age, BMI, and GWG groups after adjusting for confounding variables. RESULTS: Results showed that (1) advanced maternal age increased the risk of primary Cesarean section and hypertensive disorders of pregnancy (HDP) in normal weight; (2) independent of age and GWG, high BMI significantly increased the risk of HDP, primary Cesarean section, and macrosomia; (3) Women with excessive GWG had a higher risk of primary Cesarean section and HDP, even they were ≤ 29 years old or normal weight, respectively; (4) Pregnant women with inadequate GWG had a higher risk of preterm birth and a lower risk of macrosomia in both the 30-34 age group and the normal weight group; (5) BMI was a better predictor of HDP than GWG among women younger than 30. CONCLUSIONS: Among the GDM population, women over the age of 35, overweight and obese, or with an excessive GWG were more prone to adverse pregnancy outcomes, especially primary Cesarean delivery and HDP.

Dysregulation of the microbiota-brain axis during long-term exposure to polystyrene nanoplastics in rats and the protective role of dihydrocaffeic acid.

Polystyrene nano-plastics (PS-NPs) can be accumulated in the food chain and can penetrate biological barriers to affect multiple physiological functions. However, the adverse effects of nano-plastics on mammals and the underlying mechanism still remain unknown. To fill the gaps, our study administrated low-dose PS-NPs (50 and 100 µg/L) for 24 consecutive weeks in rats. Behavioral and morphological evaluations were performed to assess the neurobehavoirs. A combined analysis of multiple omics was used to evaluate the dysfunctions of the gut-microbe-brain axis. After dihydrochalcone(NHDC) treatment in the PS-NPs rat model, the inflammation response and apoptosis process were assessed and proteomics was used to explore the underlying mechanism. Our results indicated that long-term exposure to low-dose PS-NPs could induce abnormal neurobehaviors and amygdaloid nucleus impairment, and stimulate inflammatory responses and apoptosis. Metagenomics results revealed that four microbial phyla including Proteobacteria, Firmicutes, Defferibacteres, and Bacteroidetes changed significantly compared to the control. Targeted metabolomics analysis in the feces showed alteration of 122 metabolites induced by the PS-NPs exposure, among which the content of dihydrocaffeic acid was significantly associated with the different microbial genera and pivotal differential metabolites in the amygdaloid nucleus. And NHDC treatment significantly alleviated PS-NP-induced neuroinflammation and apoptosis and the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/phosphorylated cAMP-response element binding protein(p-CREB)/plasma membrane calcium-transporting ATPase 2(Atp2b2) signaling pathway was identified in the proteomics. In conclusion, long-term exposure to low-dose PS-NPs has adverse effects on emotion through the dysregulation of the gut-brain axis, and dihydrocaffeic acid can alleviate these effects via the cAMP/PKA/p-CREB/Atp2b2 signaling pathway.