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The powerful antioxidant system in tumor tissues limits the efficacy of sonodynamic therapy (SDT) by reducing the availability of the produced reactive oxygen species (ROS). To address this problem, a pH/ultrasound (US) responsive theranostic nanoplatform is elaborately constructed by self-assembly of nitrogen-doped graphene quantum dots (NGQDs), benzothiazole sulfinate (BTS), Gd3+ ions and poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG). The NGQD component with excellent sonodynamic activity wrapped in the resulting Gd-NGQDs/BTS@PLGA-PEG can efficaciously respond to ultrasonic irradiation and cause abundant ROS generation. Importantly, in response to acidic tumor microenvironment, the loaded BTS sustainably releases SO 2 , which induces the increase of intracellular •O 2 − level by inhibiting superoxide dismutase activity and further promotes the enrichment of ROS by reducing intracellular glutathione level and suppressing glutathione peroxidase 4 activity. The well-designed SO 2 gas therapy-enhanced SDT strategy leads to high oxidative stress in tumor cells and effective inhibition of the growth of bilateral tumors with only a single intravenous injection of the nanomedicine and a subsequent single US irradiation. Gd-NGQDs/BTS@PLGA-PEG can also be employed as a good T 1 -weighted magnetic resonance imaging contrast agent to guide tumor therapy. This innovative therapeutic strategy developed in our contribution may provide a new paradigm for the exploration of deep tumor therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals that are widely used in industrial and consumer products. A growing body of literature suggests that exposure to these chemicals are associated with adverse reproductive outcomes in women. However, the sources of PFAS exposure are often poorly characterized in women of child-bearing age. To examine the association of plasma PFAS concentrations with dietary intake and drinking water sources in reproductive aged women in Shanghai, one of the high PFAS polluted regions in China. Concentrations of ten PFAS in plasma samples were measured in 933 women. Information on dietary intake and type of drinking water was collected by questionnaire. We used multivariable linear regression models to assess the association of PFAS concentrations with dietary intake and drinking water. After controlling for potential confounders, a higher frequency of intake of aquatic products (freshwater fish, marine fish, shellfish, shrimp and crab) was positively and significantly associated with concentrations of PFOS, PFOA, PFNA, PFDA, PFUA and PFDoA in 900 reproductive aged women. Intake of freshwater fish showed the strongest association with PFAS. Compared with the lowest intake group of freshwater fish, the intermediate intake group had 8–32% increase in the concentrations of these pollutants; and the highest group had 11–57% increase. Conversely, intake of soy products was associated with lower levels of PFDA, PFUA, PFNA, PFOS, and PFDoA. In addition, compared with women drinking tap water, drinking bottled water was associated with significantly decreases in PFHpA, PFDA, PFOA, PFUA and PFBS blood levels by 9–13% in 905 reproductive aged women. Intake of freshwater fish, marine fish, shrimp and crab was positively associated with plasma PFAS concentrations, while intake of soy products and bottled water was associated with lower PFAS concentrations in the Chinese women of reproductive age. • The study was conducted in one of the high PFAS contaminated areas in China. • Consumption of aquatic products was positively associated with plasma PFAS levels. • Consumption of soy products was associated with lower PFAS levels. • Drinking bottled water was associated with lower PFAS levels. [ABSTRACT FROM AUTHOR]

The chitin nanocrystal is a promising nano-reinforcing agent, but the parasitic pathogens carried on crabs and shrimp shells as main sources limit its application in some fields. In this study, the ChNs which avoided possible safety risks were extracted from mushrooms via protein/mineral-purification and subsequent HCl-hydrolysis. Such fungus-derived ChNs presented an α-chitin crystalline structure with a length of 143 ± 24 nm and a diameter of 10 ± 2 nm. Since the dispersion stability of ChNs suspension determines their further applications, this present study emphasized the dispersity of ChNs in aqueous media evaluated by the viscosity under steady-shear flow and UV–vis absorption, whose results indicated that ChNs in dispersion would aggregate when the concentration of homogeneous dispersion reached 0.5–0.6 wt%. To explore the effect of electrostatic repulsion on interactions between nanoparticles, the maximum energy barriers for parallel and crossed orientations of ChNs in suspension were analyzed using a traditional DLVO theory with additions of NaCl solutions. [ABSTRACT FROM AUTHOR]

The electronic structures, dehydrogenation properties and diffusion path of an H atom in pure and transition metal substituted Mg(BH 4 ) 2 ·2NH 3 were investigated using the first-principles calculations. The occupation energies of dopants indicate that substituting Ti for an Mg1 atom is the easiest, while Ni and Nb substitutions are somewhat difficult. The electronic density of states and the topological analysis of electron density reveal the covalent characteristics of the N–H and B–H bonds and the weak ionic interaction between M (the metal atoms) and the NH 3 and BH 4 groups. The substitutions of Ti, Ni and Nb increase the interaction between metal and N atoms, which stabilize the NH 3 groups and inhibit the release of ammonia during dehydrogenation. The hydrogen removal energies indicate that Ti, Ni or Nb doping weakens the interactions between B and H atoms, thereby facilitating the dissociation of B–H bonds in Mg(BH 4 ) 2 ·2NH 3 . The minimum energy paths of H diffusion demonstrate that the substitutions can reduce the energy barrier and thus favor H diffusion in the bulk phase. Thus, substitution is an effective technique for improving the hydrogenation/dehydrogenation performance of Mg(BH 4 ) 2 ·2NH 3 hydrogen storage material. [ABSTRACT FROM AUTHOR]

Four new tetramic acid analogues neopestalotins A–D ( 1 – 4 ), one new furanone derivative neopestalotin E ( 6 ), and the known compound hymenosetin have been isolated from the solid cultures of the plant endophytic fungus Neopestalotiopsis sp. The structures of the new compounds were determined mainly by nuclear magnetic resonance (NMR) experiments. The absolute configurations of 1 and 2 were assigned by circular dichroism (CD) data, whereas those of 3 and 4 were deduced by a combination of CD and heteronuclear long range coupling (HETLOC) data. Compound 2 showed modest antimicrobial activity against the Gram-positive bacteria, Bacillus subtilis , Staphylococcus aureus col, and Streptococcus pneumoniae . [ABSTRACT FROM AUTHOR]

The spatiotemporal variability and ecological risks related to 16 phthalate esters (PAEs) were investigated in surface water and marine organisms of the Bohai Sea. The average PAE concentrations in the surface water were 8.02, 4.53, and 3.16 μg L−1 in spring, summer, and winter, respectively. Additionally, suspended particle matter was positive related to PAE content in seawater in spring and winter. The predominant PAEs in both water and biota were dimethyl phthalate (DMP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP), and diethylhexyl-phthalate (DEHP). Because they do not exhibit long-distance migratory behavior, Chaeturichthys hexanema , Cynoglossus lighti , and Loligo japonica were good candidate indicator organisms for PAE pollution in Bohai Sea. The risk quotient method revealed that DIBP, DBP, and DEHP posed relatively greater risks to the aquatic system. This research establishes baseline data from which future management strategies to control PAEs in the Bohai Sea can be developed. [Display omitted] • Sixteen PAEs were investigated in surface water and biota samples in Bohai Sea. • The most predominant PAEs in Bohai Sea were DMP, DEP, DIBP, DBP, BBP, and DEHP. • Suspended particle matters are positively related to PAE content in seawater in spring and winter. • C. hexanema , C. lighti , and L. japonica could be indicator organisms in Bohai Sea. • DIBP, DBP, and DEHP present potential risks to sensitive organisms. [ABSTRACT FROM AUTHOR]

Biodegradable plastics (BPs) have seen a continuous increase in annual production and application due to their environmentally sustainable characteristics. However, research on the formation of disinfection byproducts (DBPs) from biodegradable microplastics (BMPs) during chlorination is limited, and the effects of aqueous solution chemistry on this process have yet to be explored. Therefore, two biodegradable microplastics, polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT), were investigated in this study to examine the changes in their physicochemical properties before and after chlorination, and the formation of DBPs under different environmental conditions. The results showed that PLA was more chlorine-responsive, and generated more DBPs. The pH converted some of the intermediates into more stable DBPs by affecting the concentration of HClO and base-catalyzed reactions, whereas ionic strength slightly reduced DBP concentration by ion adsorption and promoting the aggregation of BMPs. Finally, since PLA has a slightly greater volume of mesopores and micropores compared to PBAT, it may more effectively adsorb DBP precursors beyond natural organic matter (NOM), such as some anthropogenic pollutants, thus potentially decreasing the formation of chlorinated DBPs in surface water. This research explored the potentiality for DBP formation by BMPs under different water quality conditions during the disinfection process, which is useful for assessing the environmental hazards of BMPs. [Display omitted] • PLA yields more DBPs than PBAT with its porous structure and reactive ester bonds. • Rising pH converts DBP intermediates to stable DBPs. • NaCl may reduce DBP production by impacting BP reaction sites and agglomeration. • PLA might adsorb non-NOM DBP precursors in surface water to reduce DBP formation. [ABSTRACT FROM AUTHOR]

General transcription factors and core promoter elements play a pivotal role in RNA polymerase II (Pol II)-mediated transcription initiation. In the previous work, we have defined a TFIIA recognition element (IIARE) that modulates Pol II-directed gene transcription in a promoter context-dependent manner. However, how TFIIA interacts with the IIARE and whether the interaction between TFIIA and the IIARE is involved in the regulation of gene transcription by Pol II are not fully understood. In the present study, we confirm that both K348 and K350 residues in TFIIAαβ are required for the interaction between TFIIAαβ and the IIARE. Disruption of the interaction between them by gene mutations dampens TFIIAαβ binding to the AdML-IIARE promoter and the transcriptional activation of the promoter containing a IIARE in vitro and in vivo. Stable expression of the TFIIAαβ mutant containing both K348A and K350A in the cell line with endogenous TFIIAαβ silence represses endogenous gene expression by reducing the occupancies of TFIIAαβ, TBP, p300, and Pol II at the promoters containing a IIARE. The findings from this study provide a novel insight into the regulatory mechanism of gene transcription mediated by TFIIA and the IIARE. • TFIIAαβ K348 and K350 residues are required for TFIIA binding to the AdML-IIARE promoter. • Mutations of TFIIAαβ K348 or K350 residues repress transcription activation of the AdML-IIARE promoter in vitro and in vivo. • Mutations of TFIIAαβ K348 or K350 residues repress transcription activation of the natural promoters containing a IIARE. • Stable expression of the TFIIAαβ mutants containing K348A and K350A inhibits expression of endogenous FDPS gene. [ABSTRACT FROM AUTHOR]

Herein, the microporous structure and gas transport property of a new family of polyimides (PIs) containing bulky tetra- o -isopropyl and naphthalene groups prepared via a microwave-assisted polymerization process are reported. The polyimides were prepared from a naphthalene and isopropyl containing diamine, i.e., 4,4'-(naphthalen-1-ylmethylene)bis(2,6-diisopropylaniline)) (i.e., BAN-3) obtained via a one-step electrophilic substitution reaction, reacting with three commercial dianhydrides. Analysis of fractional free volume (FFV) in conjunction with positron annihilation lifetime spectroscopy (PALS) showed that the resultant BAN-3 based PIs had high FFV values of over 0.19 featuring a bimodal size distribution of microcavities with average diameters in the range of 8.0–9.0 Å and 5.6–6.3 Å, respectively. Wide angle X-ray diffraction (WXRD) further confirmed that the introduction of naphthalene and tetra- o -isopropyl groups effectively enhanced polymeric backbone rigidity and disrupted chain packing, leading to high gas permeabilities in all three PI films. For example, the PI-3F film had high H 2 and CO 2 permeability values of 722 and 849 barrer, respectively while maintaining comparable selectivities for H 2 /CH 4 and CO 2 /CH 4 gas pairs with other reported PIs of the same dianhydride. In addition, the PI-3B film displayed excellent gas separation performance for O 2 /N 2 gas pair approaching the 2008 Robeson upper bound. Image 1 • Robust and highly soluble polyimides containing isopropyl and naphthalene units were readily prepared. • The polyimides had high FFV values featuring a bimodal size distribution of microcavities. • The polyimides showed excellent gas selectivity for O2/N2, approaching the 2008 Robeson upper bound. [ABSTRACT FROM AUTHOR]

Background Triclosan (TCS) has been widely detected in pregnant women. The reproductive endocrine-disrupting effects of TCS have been observed in humans and animals. Little is known about the potential impact of prenatal TCS exposure on fetal reproductive development as well as its potential mechanism. Objectives We investigated the potential effect of prenatal TCS exposure on fetal reproductive hormones in cord blood and its potential mechanism in relation to placental steroidogenic enzymes. Methods Urinary TCS was detected among 537 healthy pregnant women from a prospective cohort in China. Four reproductive hormones in cord blood, namely E 2 (n = 430), T (n = 424), LH (n = 428) and FSH (n = 373), and three steroidogenic enzymes in placenta, namely P450arom (n = 233), 3β-HSD (n = 227) and 17β-HSD (n = 222), were measured. Results Prenatal TCS exposure was associated with increased testosterone concentrations in cord blood in a dose-dependent manner. Infants with prenatal TCS levels > 0.6 μg/L had, on average, a 0.23 ng/mL (95% CI: 0.05, 0.45, p = 0.02) higher testosterone concentrations in cord blood compared to those with prenatal TCS levels < 0.1 μg/L. Of note, prenatal TCS exposure was associated with increased testosterone and decreased E 2 concentrations in cord blood among male infants. Adverse associations were found between the prenatal TCS exposure and concentrations of three placental steroidogenic enzymes. 3β-HSD and P450arom demonstrated mediating effects in the association between prenatal TCS exposure and testosterone concentrations in cord blood. Conclusions Our findings suggested potential impacts of prenatal TCS exposure on reproductive hormones in cord blood mediated by steroidogenic enzymes, and male infants were more vulnerable. [ABSTRACT FROM AUTHOR]

Triclocarban (TCC), an emerging contaminant in water environments, its effects on freshwater biofilms remain insufficiently understood. This study investigates the effects of TCC exposure (at concentrations of 10 μg L−1 and 10 mg L−1) on mature freshwater biofilms. TCC was found to inhibit biofilm activity as evidenced by changes in surface morphology and the ratio of live/dead cells. Moreover, both concentrations of TCC were observed to modify the structure of the biofilm community. Metabolomics analysis revealed an overlap in the toxicity mechanisms and detoxification strategies triggered by various concentrations of TCC in biofilms. However, the higher toxicity induced by 10 mg L−1 TCC resulted from the downregulation of proline betaine, disrupting the homeostasis of cellular osmotic pressure regulation in biofilms. Notably, lipid and lipid-like molecules showed high sensitivity to different concentrations of TCC, indicating their potential as biomarkers for TCC exposure. Annotation of the differential metabolites by KEGG revealed that alterations in amino acid and carbon metabolism constituted the primary response mechanisms of biofilms to TCC. Moreover, the biofilm demonstrated enhanced nucleic acid metabolism, which bolstered resistance against TCC stress and heightened tolerance. Furthermore, elevated TCC concentrations prompted more robust detoxification processes for self-defense. Overall, short-term exposure to TCC induced acute toxicity in biofilms, yet they managed to regulate their community structure and metabolic levels to uphold oxidative homeostasis and activity. This research contributes to a deeper comprehension of TCC risk assessment and policy control in aquatic environments. [Display omitted] • The structure of C-cycling bacteria communities was damaged by triclocarban (TCC). • Rhizobiales were key bacterial communities in biofilm resistance to TCC stress. • Biofilm primarily responded to TCC via changes in amino acid and carbon metabolism. • The unique toxicity of 10 mg L−1 TCC downregulates proline betaine. • Biofilms enhanced nucleic acid metabolism to resist TCC stress. [ABSTRACT FROM AUTHOR]

First-principles calculations were performed to investigate the influences of Al, Ti and Nb doping on the structure, the hydrogen dissociation energy, the electronic structure and the diffusion path of H atom in Mg(BH 4 ) 2 (001) surface. The calculated occupation energies indicate that substitution of Mg atom with Ti is the easiest, with Al is a little harder, and with Nb is the most difficult. The doping can reduce the strengths of B–H bonds around the dopants thus favours the dissociation of these H atoms. In comparison, the Nb doping shows the most outstanding effect and the Al doping has the least influence on the dissociation of hydrogen atoms. The minimum energy pathways (MEP) calculations indicate that the substitutions with Ti and Nb can reduce the energy barriers of hydrogen diffusion and thus facilitate H diffusion in the Mg(BH 4 ) 2 (001) surface, whereas the substitution with Al is not an effective technique for improving the hydrogenation/dehydrogenation performance of Mg(BH 4 ) 2 . [ABSTRACT FROM AUTHOR]

Utilization of aluminosilicate-rich solid waste via geopolymerization, such as mine tailings (MTs), possesses a dual advantage of reducing CO 2 release from cement manufacturing and increasing tailings utilization. However, a major challenge for this technology is the low reactivity of MTs. In this study, an alkali-hydrothermal method at 200 °C was developed for MTs activation, and MTs were converted into an active alkaline aluminosilicate precursor that could play an alkaline activator-like role. Geopolymers were subsequently prepared from activated MTs and slag by simply adding water, and to improve the performance of geopolymers, steel slag (SS) was added as a supplementary alkali source. Results showed that the advantage of SS as a calcium-based alkaline material could be fully exerted in this system. The Ca(OH) 2 phase derived from SS hydration increased the pH of the pore solution, on the one hand, and complexation reactions between Ca2+ ionized from Ca(OH) 2 and Si and Al monomers dissolved from activated MTs might occur and generate calcium aluminosilicate hydrate gel, on the other hand. As a result, the addition of SS accelerated the hydration process, prompted the production of hydration products, and thus enhanced the strength of geopolymers. The 3-day and 28-day strengths of geopolymers achieved as high as 31.10 and 44.79 MPa, respectively, when SS content was kept at 10 wt%. In addition, SS-doped geopolymers had satisfactory soundness because the fast consumption of Ca2+ prevented the growth of Ca(OH) 2 crystals and the resulting expansion effect. • Alkali-hydrothermal activation converted tailings into an active alkaline aluminosilicate precursor. • The advantage of steel slag as a calcium-based alkaline material was fully exerted. • Both the low reactivity of tailings and the poor volume stability of steel slag were overcame. • This study provided a new route to improving the comprehensive utilization of tailings and steel slag. [ABSTRACT FROM AUTHOR]

Molecular chaperones can prevent and repair protein misfolding and aggregation to maintain protein homeostasis in cells. Hsp40 chaperones interact with unfolded client proteins via the dynamic multivalent interaction (DMI) mechanism with their multiple client-binding sites. Here we report that a type I Hsp40 chaperone from Streptococcus pneumonia (spHsp40) forms a concentration-independent polydispersity oligomer state in solution. The crystal structure of spHsp40 determined at 2.75 Å revealed that each monomer has a type I Hsp40 structural fold containing a zinc finger domain and C-terminal domains I and II (CTD I and CTD II). Subsequent quaternary structure analysis using a PISA server generated two dimeric models. The interface mutational analysis suggests the conserved C-terminal dimeric motif as a basis for dimer formation and that the novel dimeric interaction between a client-binding site in CTD I and the zinc finger domain promotes the formation of the spHsp40 oligomeric state. In vitro functional analysis demonstrated that spHsp40 oligomer is fully active and possess the optimal activity in stimulating the ATPase activity of spHsp70. The oligomer state of type I Hsp40 and its formation might be important in understanding Hsp40 function and its interaction with client proteins. • Structure model of spHsp40 reveals two dimeric interfaces. • Interface mutations convert spHsp40 from oligomer to dimer and monomer. • The β3 in zinc finger of spHsp40 have a weak interaction with hydrophobic pocket in CTD I domain. • The oligomeric spHsp40 is fully active and has the optimal activity in stimulating the ATPase activity of spHsp70. [ABSTRACT FROM AUTHOR]

Several per- and polyfluoroalkyl substances (PFAS) have been phased out due to their adverse effects, and replaced by the short-chain perfluorobutanesulfonic acid (PFBS). However, the long-term impacts of PFBS on human health are unknown. We aimed to investigate the association between prenatal exposure to PFAS, especially PFBS and childhood adiposity at 5 years of age. We conducted a prospective birth cohort study involving 1,140 pregnant women from 2012 to 2017 in Shanghai. Fetal umbilical cord blood was collected at birth. A total of 404 children (196 girls) completed the adiposity measurements using a bioelectrical impedance analysis method and cord plasma PFAS measurements using LC-MS/MS. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between PFAS and childhood adiposity. The median concentration of PFAS in the cord plasma ranged from 0.05 (PFBS) to 6.74 ng/mL (PFOA). Results of multivariable linear regression found that in girls, PFBS had a significant positive association with waist circumference and waist to height ratio (P -values < 0.05). Girls in the highest tertile of PFBS concentrations had more fat mass, as well as higher body fat percentage, waist circumference, and waist to height ratio compared to those in the lowest tertile. However, girls in the second tertile of PFDoA had lower body fat percentage, waist circumference and fat mass. Adiposity at 5 years of age shows a positive association with prenatal exposure to PFBS in girls. These findings need to be further verified in larger prospective studies. • We conducted a birth cohort study in Shanghai. • Ten PFAS were measured in cord blood to assess prenatal exposure. • A total of 404 children completed both PFAS measurement and adiposity measurement using a bioelectrical impedance analysis method at 5 years old. • High exposure to PFBS may be of concern for childhood adiposity. [ABSTRACT FROM AUTHOR]

Abstract Gastric cancer (GC) has been an increasingly serious problem in public health. However, there is still a lack of efficient approach to diagnosis and treatment in time, especially in the field of targeted therapy. Increasing evidences demonstrated that DNA methylation plays an essential role in tumorigenesis and progression of GC. Thus the present study aims to identify DNA methylation-based prognostic biomarkers in GC. Two methylation array datasets (GSE25869 and GSE30601) and RNA-seq based gene profiling dataset (TCGA-STAD) were employed for exploring candidate DNA methylation-based biomarkers. Univariate Cox regression analysis was used to select the most efficient prognostic genes in GC patients. Weighted gene correlation network analysis (WGCNA) was performed to screen the cluster of co-expressed genes. As a result, our data proved that NRP1 was a hypomethylated / upregulated gene in GC tissues, and PDGFRB was strongly co-expressed with it. Both of them were significantly associated with the overall survival of patients. More importantly, high expression levels of NRP1 and PDGFRB were associated with malignant phenotypes in GC patients, including Laurén histological diffuse type and higher histological grade. Patients carrying high expression level of NRP1 and PDGFRB had a nearly two-fold increased death risk than others. In summary, the hypomethylated gene, NRP1 , and its co-expressed gene, PDGFRB , were significantly correlated with tumor malignant phenotypes, which might serve as potential prognostic biomarkers for GC patients. [ABSTRACT FROM AUTHOR]

Background Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been widely detected in different populations. However, limited data is available about exposure among family members. Objectives To investigate the PFASs levels in parents and their newborns and to understand their correlation and health implications of in utero exposure to PFASs. Methods Ten PFASs were measured in matched parental and cord serum (N = 369 families) from a birth cohort in Shandong, one of the regions seriously polluted by PFASs in China. The correlation of PFASs levels within families was examined. A questionnaire survey on maternal factors and risk assessment using the hazard quotients (HQs) approach based on maternal PFASs levels was conducted. Results Within a family, the father had the highest levels of all PFASs. Among the 10 PFASs, perfluorooctanoic acid (PFOA) was the highest, with 103.38, 42.83, and 34.67 ng/ml in paternal, maternal and cord serum, respectively. PFASs levels were positively correlated among family members (r = 0.14–0.91, p  < 0.01). Maternal age, body mass index (BMI); smoking history; and intake of fish, milk, poultry, vegetables and tap water were significantly related to PFASs concentrations in cord serum. Twenty-seven (7.3%) HQ values exceeded 1 for both PFOA and the sum of PFOA and perfluorooctane sulfonate (PFOS), indicating potential concern for developmental toxicity in the local newborns. Conclusions PFASs, and especially PFOA levels were extremely high and positively correlated between parents, indicating heavy pollution in this region and common sources of exposure. In utero exposure to PFASs might pose potential concern for developmental toxicity in the local newborns. [ABSTRACT FROM AUTHOR]

Triclosan (TCS) is an antibacterial chemical widely used in personal-care products and an endocrine disruptor. While TCS exposure is associated with insulin resistance and metabolic disorders in animals, few studies have assessed its effect on the risk of gestational diabetes mellitus (GDM) in humans. This study aimed to explore whether maternal urinary TCS level is associated with the risk of GDM and infant birthweight. We examined 620 pregnant women from Shanghai, China in 2012–2013. Urinary TCS level was measured with high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS), and categorized into high, medium and low in tertiles. GDM was defined based on recommendation of International Association of Diabetes and Pregnancy Study Groups (IADPSG). The GDM rate was 12.7%. TCS was detectable (≥0.1 ng/mL) in 97.9% women (median 2.7 ng/mL). There was a positive, but statistically non-significant association between urinary TCS levels and GDM (adjusted odds ratio 1.17; 95%CI: 0.99, 1.39, with each unit increase of log (TCS) ng/mL) with adjustment for urinary creatinine, maternal age, education, passive smoking, parity and prepregnancy BMI categories. 48.1% of infants were females. Birthweight was 122.8 g higher (95% CI: 13.9, 231.6 g) for female infants of women in high TCS (median 13.3 ng/mL) versus low TCS (median 0.77 ng/mL), with adjustment for urinary creatinine, prepregnancy BMI, GDM and other confounders. No association was found between maternal TCS and birthweight in male infants. These results suggested the potential for TCS to be associated with increased risk of GDM and a gender-specific association with higher birthweight among female infants in a population with widespread but moderate exposure to TCS. [ABSTRACT FROM AUTHOR]

Phenolic compounds are among the endocrine disruptors which are widely used in daily life products. Studies in laboratory animals showed reproductive and developmental effects. In spite of widespread exposure to phenols, only few studies examined their effects on human development. This study was designed to investigate the relationship between antenatal phenol exposure and birth outcomes in a Chinese obstetric population. Four hundred ninety-six mother-infant pairs recruited from the Laizhou Wan prospective birth cohort in northern China between 2010 and 2013 were included in the study. We measured two phenol metabolites in maternal urine at delivery and examined their associations with birth outcomes including birth weight, crown–heel length, head circumference, gestational age, and ponderal index. Median levels of bisphenol A (BPA) and triclosan (TCS) in urine were 1.07 and 0.50 μg/g creatinine, respectively. After adjusting for confounders, a 10-fold increase in BPA levels was associated with a 0.63 cm [95% confidence interval (CI): 0.25 to 1.01] increase in birth length among boys, but not among girls. No associations were found between TCS levels and any birth outcomes. The positive association of prenatal low-level BPA exposures with anthropometric measures observed among boys, suggests gender differences in the response to antenatal phenol exposure. Given the variability in urinary phenol levels reported during pregnancy, our findings based on levels of the target biomarkers in a single urine sample need to be confirmed in additional studies. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are commonly used in industrial applications and consumer products, and their potential health impacts are of concern, especially for vulnerable population like fetuses. However, in utero exposure to PFASs and health implications are far from fully characterized in China. To fill in the gap, we analyzed 10 PFASs in cord plasma samples (N = 687) collected in Shanghai between 2011 and 2012, one of the regions widely polluted with PFASs in China. A questionnaire survey on maternal and diet-related factors was conducted. Except for perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (PFOSA), all other PFASs were detected in ˃90% of the samples. Perfluorooctanoic acid (PFOA) was the most predominant PFAS (median value: 6.96 ng/mL), followed by perfluorooctane sulfonate (PFOS) (2.48 ng/mL). PFOA and PFOS combined contributed to 80% of the total PFASs. The final multiple regression models showed that maternal factors including maternal age, body mass index, gestational age, economic status and educational level as well as consumption of fish and wheat were significantly related with concentrations of PFASs in cord blood. The risk assessment using the hazard quotients (HQs) approach on the basis of plasma PFAS levels indicated no potential concern for developmental toxicity in the local newborns. The results demonstrate the unique profiles of local prenatal exposure to PFASs, suggesting that PFOA has been the primary human exposure due to its widespread use and pollution. Special attention to high PFOA exposure and confirmation of potential determinants should be taken as a priority in the future plan for risk management and actions in this area. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pregnant women were widely exposed to NEOs and 6-CN was the most abundant metabolite. • IMI and ACE were adversely associated with neonatal head circumference. • Maternal 8-OHdG mediated the association between NEOs and neonatal head circumference. An increasing number of studies have reported neonicotinoid insecticides (NEOs), the emerging alternatives to conventional insecticides, may increase oxidative stress and cause adverse health effects, but limited is known about the prenatal NEOs exposures and their impact on birth outcomes. We investigated the levels of prenatal exposure to NEOs/metabolites, to assess their associations with birth outcomes, and investigate whether these associations could be mediated by oxidative stress using 8-OHdG as the biomarker. We studied 296 mother-infant pairs recruited from Laizhou Wan Birth Cohort in 2010 – 2013. Two NEOs (IMI and ACE), three metabolites (6-CN, ND-ACE, and 2CTCA), and 8-OHdG were measured in maternal urine collected before delivery. Birth outcomes including birth weight, birth length, ponderal index (PI), head circumference, and gestational age, were acquired. We examined the associations between NEOs/metabolites and birth outcomes using multivariable linear regression. Mediation analysis was conducted to clarify the role of 8-OHdG on the association of NEOs/metabolites exposure and birth outcomes. Highest detection rate was observed for ACE (100.0%), followed by IMI (98.3%) and 6-CN (98.0%), suggesting the common exposure of pregnant women. The highest median concentration was observed for 6-CN with creatinine-adjusted median levels of 9.58 μg/g creatinine. A decrease in newborns' head circumference was observed with a 10-fold increase in IMI (β = -1.83; 95% CI = -3.04, −0.62) and ACE (β = -2.27; 95% CI = -3.56, −0.98). An increase in newborns' PI was observed with a 10-fold increase in IMI (β = 0.40; 95% CI = 0.03, 0.75). Maternal 8-OHdG demonstrated 38.5–65.5% mediating effects in the negative association of IMI, ACE, 2-CTCA with head circumference. These associations might differ between boys and girls. Pregnant women were widely exposed to NEOs/metabolites in China. Results suggested the potential impacts of prenatal exposure to certain neonicotinoid insecticides on head circumference. Urinary 8-OHdG may partly mediate these associations. [ABSTRACT FROM AUTHOR]

Abstract: Germacrone is one of the main bioactive components in the traditional Chinese medicine Rhizoma curcuma. In this study, the anti-proliferative effect of germacrone on the human hepatoma cell lines and the molecular mechanism underlying the cytotoxicity of germacrone were investigated. Treatment of human hepatoma cell lines HepG2 and Bel7402 with germacrone resulted in cell cycle arrest and apoptosis in a dose-dependent manner as measured by MTT assay, flow cytometric and fluorescent microscopy analysis, while much lower effect on normal human liver cell L02 was observed. Flow cytometric analysis revealed that germacrone induced G2/M arrest in the cell cycle progression that was associated with an obvious decrease in the protein expression of cyclin B1 and its activating partner CDK1 with concomitant inductions of p21. Hoechst 33258 and Annexin V/PI staining results showed that the total cell number in apoptosis associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2/Bcl-xl was increased. In the meantime, the up-regulation of p53 and reactive oxygen species increase were observed, which suggested that germacrone might be a new potent chemopreventive drug candidate for liver cancer via regulating the expression of proteins related to G2/M cell cycle and apoptosis, and p53 and oxidative damage may play important roles in the inhibition of human hepatoma cells growth by germacrone. [Copyright &y& Elsevier]

Abstract: Loss-of-function DJ-1 mutations have been linked to autosomal recessive early-onset Parikinsonism. However, the putative function of DJ-1 is not completely understood. Previous studies indicate that DJ-1 overexpression results in upregulation of the tyrosine hydroxylase gene. The mechanism by which DJ-1 affects tyrosine hydroxylase expression remains elusive. In the present study, we show that DJ-1 overexpression induces ERK1/2 activation, along with increased tyrosine hydroxylase expression. The L166P DJ-1 mutant, which has been identified as being responsible for familial Parkinsonism, did not have this effect. Moreover, suppression of ERK1/2 phosphorylation by the pharmacological inhibitor U0126 partially abolished the regulating effect of DJ-1 on tyrosine hydroxylase. Nurr1, a transcriptional factor for tyrosine hydroxylase, can be phosphorylated by ERK1/2 and translocate to the nucleus, where it is activated. Thus, we measured nuclear translocation of Nurr1. Confocal microscopy and Western blotting revealed that Nurr1 translocated to the nucleus and was activated by overexpression of wild-type DJ-1, but not of its L166P mutant. Knockdown of Nurr1 gene expression abolished the effect on tyrosine hydroxylase induced by DJ-1. Taken together, these data suggest that DJ-1 upregulates tyrosine hydroxylase expression by activating its transcription factor Nurr1 via the ERK1/2 pathway. [Copyright &y& Elsevier]

[Display omitted] • Acid-responsive Cab@MPN/CS NPs was prepared via ion crosslinking. • The introduction of CS coating can not only protect the bioactivity of MPN, but also improve the drug loading of Cab. • The zeta-potential of Cab@MPN/CS can be controlled by changing the ratio of CS and Cab@MPN. • The permeability of CS promotes the penetration of Cab@MPN/CS to the deeper tumor spheroids. • The delivery carrier can enhance the retention time in tumor tissues and improve antitumor efficacy of chemotherapy. The safe and effective drug delivery system is important for cancer therapy. Here in, we first constructed a delivery system Cabazitaxel(Cab)@MPN/CS between metal-polyphenol (MPN) and chitosan (CS) to deliver Cab for melanoma therapy. The preparation process is simple, green, and controllable. After introducing CS coating, the drug loading was improved from 7.56 % to 9.28 %. Cab@MPN/CS NPs released Cab continuously under acid tumor microenvironment. The zeta potential of Cab@MPN/CS NPs could be controlled by changing the ratio of Cab@MPN and CS solutions. The positively charged Cab@MPN/CS accelerate B16F10 cell internalization. After internalized, Cab@MPN/CS NPs could escape from lysosomes via the proton sponge effect. The permeability of CS promotes the penetration of Cab@MPN/CS to the deeper B16F10 tumor spheroids. In vivo results showed that Cab@MPN/CS NPs have a longer retention time in tumor tissues and significantly inhibit tumor growth by up-regulating TUNEL expression and down-regulating KI67 and CD31 expression. Thus, this delivery system provides a promising strategy for the tumor therapy in clinic. [ABSTRACT FROM AUTHOR]

• Almost all of pregnant women in Shanghai are exposed to at least one environmental antibiotic. • More than 90% of pregnant women are exposed to multiple environmental antibiotic. • Preferred veterinary antibiotic and veterinary antibiotic are the main contributors to local antibiotics exposure. • About 1% of pregnant women had hazard index value greater than one. • High egg and milk consumption frequency was associated with high-antibiotic-level. Consumption of antibiotics is continuing to increase, with China accounting for approximately one quarter of the global intake. As a class of emerging environmental contaminants, antibiotics may pose a potential threat to human health, especially in children. However, the internal antibiotic exposure levels in pregnant women and their determinants remain unclear. Here we investigated the urinary creatinine-corrected concentration of 15 antibiotics in 762 pregnant women from the Shanghai Prenatal Cohort, by liquid chromatography-tandem mass spectrometry. Logistic regression analysis identified associations between high-antibiotic-level and maternal dietary factors. Results show that cumulatively antibiotics were detected at a frequency of 0.13 – 82.7%, with veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs) detected in 76.9% and 98.2% of samples, respectively; PVAs were the most significant contributors to hazard index values > 1. Further, ciprofloxacin was the predominant antibiotic (median: 73.5 μg/mg creatinine), followed by norfloxacin (54.2 μg/mg creatinine); while sulfamethoxazole, enrofloxacin, and ciprofloxacin levels, used as a PVA or VA, were significantly higher in normal-weight and underweight women compared to overweight and obese women. Also, sulfamethoxazole, sulfadiazine, and ciprofloxacin were more frequently detected in mothers with a relatively low education degree. Interestingly, pregnant women with higher milk intake had a 1.96-times (95% CI: 1.10–3.49) greater risk of high-VA-exposure-level than the lower-intake group. The odds of exposure to high PVA, VA, PVA + VA, and all antibiotics levels for mothers with high egg consumption frequency were more than twice that of low-consumption individuals. Collectively, pregnant women in Shanghai are exposed to multiple environmental antibiotics, primarily as PVAs and VAs. Herein, we provide evidence for the association between dietary factors and maternal environmental antibiotic exposure in China. Special attention to antibiotic exposure and confirmation of potential determinants should be taken in the future. [ABSTRACT FROM AUTHOR]

Neural differentiation from embryonic stem cells (ESCs) is an excellent model for elucidating the key mechanisms involved in neurogenesis, and also provides an unlimited source of progenitors for cell-based nerve regeneration. However, the existing protocols such as small molecule substances, 3D matrix, co-culture technique and transgenic method, are complicated and difficult to operate, thus are limited by laboratory conditions. Looking for an easy-to-operate protocol with easily gained material and high induction efficiency has always been a hot issue in neuroscience research. This paper established an optimized method for embryonic neurogenesis using a strategy of "combinatorial screening". In our study, the whole process of embryonic neurogenesis was divided into two phases, and the differentiation efficiency of seven experimental protocols in phase I and three protocols in phase II were systematically evaluated in A2lox and 129 ESCs. In phase I differentiation, "2-day embryoid bodies formation + 6-day retinoic acid induction" (Phase I-protocol 3) could effectively induce the differentiation of ESCs into neural precursor cells (NPCs). Furthermore, in phase II, N2B27 medium II (Phase II-protocol 3) could better support the subsequent differentiation from NPCs into neurons. Such a combinational method (phase I-protocol 3 and phase II-protocol 3) can realize embryonic neurogenesis with high efficiency, easy implementation and low-cost, and is suitable for promotion in most laboratories. Through "combinatorial screening" strategy, we established an optimized method for embryonic neurogenesis in vitro, which is expected to be a powerful tool for neuroscience research. [ABSTRACT FROM AUTHOR]