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Abstract Objective and methods To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. Results Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. Conclusion A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.

Abstract The exploration of traumatic spinal fractures (TSFs) within the senior demographic has not been thoroughly scrutinized, particularly with respect to variations across genders, age groups, seasonal periods, and causative factors. This retrospective analysis aimed to dissect differences in the prevalence and characteristics of TSFs among the elderly, factoring in gender, age, seasonal timing, and causation. A retrospective analysis was conducted on the medical and imaging records of 1,415 patients, all aged 60 years or older, who were diagnosed with TSFs from 2013 to 2019. This study categorized the data by gender, age groups (60–70, 70–80, and 80 years or older), seasons, and the cause of injuries, including road traffic crashes (RTCs), falls from low heights (LHF), falls from high heights (HHF), and injuries incurred during everyday activities and agricultural labor (DFI). Male patients exhibited notably higher incidences of RTCs, high-height falls (HHFs), outdoor incidents, comas post-injury, fractures of the lower limbs (LLFs), pelvic fractures (PFs), rib fractures (RFs), intra-thoracic injuries (ITIs), intra-abdominal injuries (IAIs), cervical fractures, and spinal cord injuries (SCIs). With advancing age, there was a marked decline in occurrences of RTCs, HHFs, outdoor incidents, RFs, craniocerebral injuries (CCIs), ITIs, cervical fractures, and SCIs, while the incidences of DFIs, indoor incidents, and thoracic and lumbar (T + L) fractures notably increased. During autumn, LLF occurrences were significantly reduced, whereas the winter season saw an increase in thoracic fractures. Spring time was associated with a higher frequency of lumbar fractures and noncontiguous spinal fractures (NSFs). Significant distinctions were observed in the age distribution, injury circumstances, associated injuries, and SCIs between high-energy impacts (RTCs and HHFs) and low-energy traumas (LHFs and DFIs). In the elderly demographic, TSFs exhibited discernible distinctions based on gender, age, seasonal variations, and etiological factors, impacting the nature and circumstances of injuries, associated traumas, complications, fracture sites, and the occurrence of SCIs.

Abstract Objective To describe how mental health and sleep status influence the health-related quality of life (HRQOL) of people living with HIV/AIDS (PLWHA) during the novel coronavirus disease 2019 (COVID-19) pandemic, and to apply targeted interventions to improve the HRQOL. Methods A web-based online questionnaire survey was administered. Descriptive analysis was used to depict the mental health and sleep status. Correlation analysis and the structural equation model (SEM) method were used to analyze the influence of mental health and sleep status on HRQOL in PLWHA. Results After excluding 24 unqualified questionnaires, a total of 490 participants in this survey were included in the statistical analysis. Of the participants, 66.1% and 55.1% reported mild or worse symptoms of depression and anxiety, respectively. Overall, 70.0% had varying degrees of sleep problems. Correlation analysis showed that anxiety had the strongest correlation with sleep disturbances and sleep quality (R = 0.588 and 0.551, respectively), while depression had the strongest correlation with the HRQOL psychological and physical domains (R = − 0.759 and − 0.682, respectively). SEM analysis showed that depression, sleep quality, and psychological domains had the greatest item load on mental health, sleep status, and HRQOL (093, 0.82, and 0.89, respectively). Mental health had a more significant influence than sleep status on HRQOL, as indicated by factor loading (− 0.75 and − 0.15, respectively). Conclusions There were more severe mental health and sleep problems among PLWHA during the COVID-19 pandemic, thus, mental health intervention, especially to relieve depression symptoms, may be the most important approach to improve the HRQOL among PLWHA.

In order to explore the effects of pore size, aromatic lamellar stacking degree, aromatic lamellar ductility, gas temperature and gas pressure on the competitive adsorption of CH4 and CO2, the No.3 coal from Jincheng mining area was taken as the research object. The adsorption process of binary mixed gas of CH4 and CO2 in coal under different temperatures, pressures, pore diameters, aromatic lamellar stacking degrees and aromatic lamellar ductility was studied. The microstructure of coal was tested and analyzed based on industrial analysis and X-ray diffraction experiments. Molecular simulation of the process of gas mixture adsorption in coal using the Grand Canonical Monte Carlo (GCMC) method. The results shown that, the increase of gas pressure was favorable for adsorption, and the adsorption capacity of CO2 was close to saturation at a pressure of 5 MPa. The increase of temperature led to a decrease in the maximum adsorption capacity and adsorption heat of CO2 in coal. The increase of pore size led to the increase of CH4 adsorption capacity in coal, with the fastest increase in CH4 adsorption occurred when pore size increased from 1 nm to 2 nm. With the increase of aromatic lamellar stacking degree, the number of gas molecules adsorbed in coal did not change significantly, but CO2 adsorption capacity of per unit mass in coal decreased rapidly, and the CH4 adsorption capacity decreased slightly. With the increase of aromatic lamellar ductility, the number of CH4 molecules adsorbed in coal increased slowly and the number of CO2 molecules adsorbed increased rapidly, and the change of the two gases adsorption capacity in coal per unit mass was not significant. From the perspective of adsorption capacity and adsorption heat, CO2 is in a dominant position in the competitive adsorption process, so injecting CO2 into coal seam can effectively displace CH4. The results of this paper strengthened the molecular understanding of the adsorption of binary mixed gas of CH4 and CO2, which can lay a theoretical foundation for the enhancement of coalbed methane extraction by CO2 injection.

Background: Current epidemiological results from studies linking per- and poly-fluoroalkyl substances (PFASs) to metabolic syndrome (MetS) remain inconsistent. Objectives: We aim to investigate the association between serum PFASs and MetS using data from the National Health and Nutrition Examination Survey in the United States (US NHANES) 2017–2018. Methods: The Bayesian kernel regression (BKMR) and weighted quantiles sum regression (WQS) models were used to assess the association of serum PFASs with MetS and calculate the weight of each substance. Stratification analysis and sensitivity analysis were used to study the effect modification and the robustness of the study results, respectively. Results: All statistical models used in this study consistently indicated that serum perfluorononanoic acid (PFNA) was positively associated with an increased risk of MetS. The BKMR model revealed that serum PFASs mixtures had a combined toxic effect on MetS and its components, and serum PFNA could contribute the most to driving the overall association. Specifically, the combined exposure of PFASs was significantly associated with lipids (LP), among which serum PFNA contributed significantly to high density lipoprotein cholesterol (HDL-C), and serum perfluorodecanoate (PFDeA) was significantly positively correlated with triglyceride (TG). Besides, a nonlinear dose-response relationship between PFASs and MetS was observed. The final stratified analysis results underscore the critical importance of maintaining a healthy lifestyle, as obesity, smoking, and consume carryout/delivered foods exhibit effect modification on the association between PFASs and MetS. Conclusion: Our findings point to PFNA as a risk factor for metabolic diseases, particularly affecting lipids.

Biotoxins are ranges of toxic substances produced by animals, plants, and microorganisms, which could contaminate foods during their production, processing, transportation, or storage, thus leading to foodborne illness, even food terrorism. Therefore, proposing simple, rapid, and effective detection methods for ensuring food free from biotoxin contamination shows a highly realistic demand. Aptamers are single-stranded oligonucleotides obtained from the systematic evolution of ligands by performing exponential enrichment (SELEX). They can specifically bind to wide ranges of targets with high affinity; thus, they have become important recognizing units in safety monitoring in food control and anti-terrorism. In this paper, we reviewed the technical points and difficulties of typical aptamer screening processes for biotoxins. For promoting the understanding of food control in the food supply chain, the latest progresses in rapid optical detection of biotoxins based on aptamers were summarized. In the end, we outlined some challenges and prospects in this field. We hope this paper could stimulate widespread interest in developing advanced sensing systems for ensuring food safety.

Accumulating research suggested that long-term exposure to fine particulate matter (PM2.5) is related to cardiovascular disease (CVD). However, evidence regarding the relationship between PM2.5 and CVD risk factors remains inconsistent. We hypothesized that this association may be partially modified by socioeconomic status (SES). To investigate the relationships and to test the modifying effect of SES, we included baseline data for 21,018 adults from September 2017 to May 2018. PM2.5 concentrations were determined by employing an amalgamation of linear measurements obtained from monitoring stations located near the participants' residential and workplace addresses. We assessed SES across several domains, including income, education, and occupation levels, as well as through a composite SES index. The results indicated that for every 10 μg/m3 increase in PM2.5 exposure, the risk of hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and hyperhomocysteinemia (HHcy) increased by 7.7% [Odds ratio (OR) = 1.077, 95% Confidence Interval (CI) = 1.011, 1.146], 19.6% (OR = 1.196, 95% CI = 1.091, 1.312), 4.2% (OR = 1.042, 95% CI = 1.002, 1.084), and 17.1% (OR = 1.171, 95% CI = 1.133, 1.209), respectively. Compared to the high SES group, those with low SES are more prone to hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and HHcy. Notably, the disparities in SES appear significant in the relationship between PM2.5 exposure and hypercholesterolemia as well as hyperbetalipoproteinemia. But for diabetes and HHcy, the modification effect of SES on PM2.5 shows an inconsistent pattern. In conclusion, the results confirm the association between PM2.5 and cardiovascular risk factors and low SES significantly amplified the adverse PM2.5 effect on dyslipidemia. It is crucial to emphasize a need to improve the socioeconomic inequality among adults in Beijing and contribute to the understanding of the urgency in protecting the health of vulnerable groups.

An 8-year-old castrated male teddy bear dog presented to our clinic with a persistent cough. The sick dog suffered from vehicular trauma 6 months prior to the visit and had imaging and exploratory laparotomy. Imaging and exploratory laparotomy at the time showed no significant damage. We performed contrast radiography (barium gavage) on the sick dog. Based on the results of a complete contrast radiography (barium gavage), tubular shadows in the thoracic cavity were identified as the small intestine and cecum, and delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax was confirmed with radiographs. Accordingly, the sick dog underwent general anesthesia, manual ventilation and diaphragmatic herniorrhaphy by standard ventral midline abdominal approach. Postoperatively, the dog was given analgesia and antibacterial treatment, and the liver biochemical indexes were monitored to prevent endotoxin. Postoperative radiographs revealed clear contours of thoracic and abdominal organs. The dog moved, ate, and urinated normally within 10 days of the surgery. This case provides a reference for a complete barium meal imaging procedure that clearly shows the position of the organs in the thoracoabdominal cavity after the occurrence of a delayed traumatic diaphragmatic hernia. This paper provides a practical reference for the diagnosis of delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax.

A new method was established for the simultaneous analysis of four homologous benzalkonium chlorides (dodecyldimethylbenzyl ammonium chloride, tetradecyldimethylbenzyl ammonium chloride, hexadecyldimethylbenzyl ammonium chloride, and octadecyldimethylbenzyl ammonium chloride) in compound chemical disinfectants using non-aqueous capillary electrophoresis (CE) based on a micellar electrokinetic chromatography mode with direct ultraviolet detection. The separation was performed on an uncoated fused quartz capillary with a total length of 60.2 cm and a diameter of 25 μm. The separation buffer consisted of a mixture of methanol/acetonitrile (60:40, v/v) containing 70 mmol/L sodium acetate, 60 mmol/L trifluoroacetic acid and 20 mmol/L sodium dodecyl sulfate. The sample buffer was a methanol solution containing only 2 mmol/L trifluoroacetic acid. The separation voltage was set at 8 kV with a working current of approximately 2.3 μA. The detection wavelength was 214 nm. Under optimal conditions, the limit of detection and limit of quantification for these four benzalkonium chlorides (BACs) were 1.0 mg/L and 5.0 mg/L, respectively. Good linearities were observed in the concentration ranges from 5.0 to 100.0 mg/L, with correlation coefficients above 0.999 for all compounds. The recoveries of these four BACs ranged from 92.5 % to 109.1 % with relative standard deviations below 4.7 %. With the new method, all four BACs could be analyzed in a single injection. In contrast, the aqueous CE method in the National Standard GB/T 26369-2020 only allowed for the simultaneous analysis of the first three homologous. The new method demonstrated the improved peak shape compared to the aqueous CE method and then was successfully applied to the analysis of 19 commercially available samples, such as object table disinfectants, hand sanitizers, and disinfectant wipes, which claimed to contain quaternary ammonium compound. The results obtained using the new method were compared with those of the aqueous CE of the National Standard Method, and no statistically significant differences were observed. The new method is simple in pre-treatment and provides accurate results, making it highly suitable for routine analysis.

Broad bean paste (BBP) is a traditional fermented soy food, and its high salt content not only prolongs the fermentation time but also threatens human health. In this study, three BBP-meju with different salt concentrations were prepared, and the effects of varying salinity on fermentation were comprehensively compared. The results showed that salt-reduced fermentation contributed to the accumulation of amino acid nitrogen, reducing sugars, free amino acids, and organic acids. Alcohols, esters, aldehydes, and acids were the main volatile flavor compounds in BBP-meju, and the highest total volatile flavor compounds were found in medium-salt meju. Bacillus, Staphylococcus, Aspergillus, and Mortierella were the dominant microbial communities during fermentation, and there were also three opportunistic pathogens, Enterobacter, Pantoea, and Brevundimonas, respectively. According to Spearman correlation analysis, Wickerhamomyces, Bacillus, Staphylococcus, and Mortierella all showed highly significant positive correlations with ≥3 key flavor compounds, which may be the core functional flora. Furthermore, the dominant microbial genera worked synergistically to promote the formation of high-quality flavor compounds and inhibit the production of off-flavors during salt-reduced fermentation. This study provides a theoretical reference for the quality and safety control of low-salt fermented soy foods.

Purpose The aim of this study was to further assess whether the platelet-to-lymphocyte ratio (PLR) is independently associated with all-cause mortality and cardiovascular mortality in maintenance hemodialysis (MHD) patients.Methods From January 1, 2014, to December 31, 2014, patients undergoing regular hemodialysis in the Blood Purification Center of the General Hospital of Northern Theatre Command were retrospectively selected. A total of 303 MHD patients were enrolled in accordance with the inclusion and exclusion criteria. For each patient, the endpoint of follow-up was either death or December 31, 2021. The primary endpoints were all-cause and cardiovascular death. A receiver operating characteristic (ROC) curve was drawn to detect the predictive ability of PLR, and the optimal critical value of PLR was determined to be 107.57. Kaplan–Meier curves and Cox proportional analysis were used to assess the prognostic value of PLR. We used the same method to evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of MHD patients.Results At the end of follow-up, 128 MHD patients had progressed to all-cause death, and 73 MHD patients had progressed to cardiovascular death. In multivariate Cox regression, both the high PLR group and the high NLR group were independently associated with all-cause mortality (HR 2.608, 95% CI 1.579–4.306, p

Abstract Ring finger protein 31 (RNF31) has been found to play an important role in tumor immunity. However, the role of RNF31 in liver hepatocellular carcinoma (LIHC) has not been reported. Therefore, we investigated the expression and prognostic value of RNF31 in patients with LIHC and explored its relationship with immune cell infiltration. The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset was downloaded to analyse the impact of RNF31 on the prognosis and immune cell infiltration of LIHC. The Tumor Immune Estimation Resource (TIMER) database was used to analyse the correlation between RNF31 and tumor immune cell infiltration in LIHC. Additionally, we analysed the relationship between RNF31 and tumor necrosis factor (TNF) as well as the interferon-gamma (IFN-γ) signaling pathway. The expression of RNF31 in LIHC was significantly higher than that in normal tissues. Increased RNF31 expression was associated with decreased overall survival (OS) and relapse-free survival (RFS). An increase in RNF31 expression was closely related to the infiltration levels of immune cells (e.g., natural killer (NK) cells, CD8 + T cells, and B cells). RNF31 was also positively correlated with the expression of immune checkpoint genes in LIHC. Moreover, RNF31 may participate in TNF and IFN-γ signaling pathways. In conclusion, RNF31 is a potentially valuable prognostic biomarker in LIHC. RNF31 is also associated with immune cell infiltration in LIHC. RNF31 may be a potential target for immunotherapy of LIHC.

Abstract Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer. Graphical Abstract

Abstract As the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.

Aluminum is a neurotoxic food contaminant. Aluminum trichloride (AlCl3) causes hippocampal mitochondrial damage, leading to hippocampal injury. Damaged mitochondria can release mitochondrial reactive oxygen species (mtROS) and activate nucleotide-binding oligomerization domain-like receptor-containing 3 (NLRP3) inflammasomes and apoptosis. E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can attenuate mitochondrial damage. However, the role of mitophagy in AlCl3-induced mice hippocampal damage and its regulatory mechanism remain elusive. First, C57BL/6 N mice were treated with 0, 44.825, 89.65, and 179.3 mg/kg body weight AlCl3 drinking water for 90 d. Apoptosis, NLRP3-inflammasome activation and mitochondrial damage were increased in AlCl3-induced hippocampal damage. In addition, Parkin-mediated mitophagy peaked in the middle-dose group and was slightly attenuated in the high-dose group. Subsequently, we used wild-type and Parkin knockout (Parkin-/-) mice to investigate the AlCl3-induced hippocampal damage. The results showed that Parkin-/- inhibited mitophagy, and aggravated AlCl3-induced mitochondrial damage, NLRP3-inflammasome activation, apoptosis and hippocampal damage. Finally, we administered MitoQ (mtROS inhibitor) and MCC950 (NLRP3 inhibitor) to AlCl3-treated Parkin-/- mice to investigate the mechanism of Parkin-mediated mitophagy. The results showed that inhibition of mtROS and NLRP3 attenuated hippocampal NLRP3-inflammasome activation, apoptosis, and damage in AlCl3-treated Parkin-/- mice. These findings indicate that Parkin-mediated mitophagy protects against AlCl3-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway.

Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.

Summary: Background: RNA viruses account for many human diseases and pandemic events but are often not targetable by traditional therapeutics modalities. Here, we demonstrate that adeno-associated virus (AAV) -delivered CRISPR-Cas13 directly targets and eliminates the positive-strand EV-A71 RNA virus in cells and infected mice. Methods: We developed a Cas13gRNAtor bioinformatics pipeline to design CRISPR guide RNAs (gRNAs) that cleave conserved viral sequences across the virus phylogeny and developed an AAV-CRISPR-Cas13 therapeutics using in vitro viral plaque assay and in vivo EV-A71 lethally-infected mouse model. Findings: We show that treatment with a pool of AAV-CRISPR-Cas13-gRNAs designed using the bioinformatics pipeline effectively blocks viral replication and reduces viral titers in cells by >99.99%. We further demonstrate that AAV-CRISPR-Cas13-gRNAs prophylactically and therapeutically inhibited viral replication in infected mouse tissues and prevented death in a lethally challenged EV-A71-infected mouse model. Interpretation: Our results show that the bioinformatics pipeline designs efficient CRISPR-Cas13 gRNAs for direct viral RNA targeting to reduce viral loads. Additionally, this new antiviral AAV-CRISPR-Cas13 modality represents an effective direct-acting prophylactic and therapeutic agent against lethal RNA viral infections. Funding: Agency for Science, Technology and Research (A∗STAR) Assured Research Budget, A∗STAR Central Research Fund UIBR SC18/21-1089UI, A∗STAR Industrial Alignment Fund Pre-Positioning (IAF-PP) grant H17/01/a0/012, MOE Tier 2 2017 (MOE2017-T2-1-078; MOE-T2EP30221-0005), and NUHSRO/2020/050/RO5+5/NUHS-COVID/4.

Abstract The key to designing and fabricating highly efficient mixed protonic–electronic conductors materials (MPECs) is to integrate the mixed conductive active sites into a single structure, to break through the shortcomings of traditional physical blending. Herein, based on the host–guest interaction, an MPEC is consisted of 2D metal–organic layers and hydrogen‐bonded inorganic layers by the assembly methods of layered intercalation. Noticeably, the 2D intercalated materials (≈1.3 nm) exhibit the proton conductivity and electron conductivity, which are 2.02 × 10−5 and 3.84 × 10−4 S cm−1 at 100 °C and 99% relative humidity, much higher than these of pure 2D metal–organic layers (>>1.0 × 10−10 and 2.01×10−8 S cm−1), respectively. Furthermore, combining accurate structural information and theoretical calculations reveals that the inserted hydrogen‐bonded inorganic layers provide the proton source and a networks of hydrogen−bonds leading to efficient proton transport, meanwhile reducing the bandgap of hybrid architecture and increasing the band electron delocalization of the metal–organic layer to greatly elevate the electron transport of intrinsic 2D metal–organic frameworks.

Fluorinated liquid-crystal monomers (FLCMs), one class of emerging persistent, bioaccumulative and toxic (PBT) compounds, are widely used in liquid-crystal displays (LCDs). As a result, they have been found in the environment and serum from occupational workers. However, little is known about their occurrence in non-occupational exposing populations. Herein, we provided an evaluation of the health risks of FLCMs for infants based on breastfeeding exposure and dust ingestion. The detection frequencies (DF) of FLCMs in indoor dust and breast milk was 100 %, with median concentrations of 12.00 ng/g dry weight (dw) and 133.40 ng/g lipid weight (lw), respectively. 1-butoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (BDPrB) was the predominant pollutant in indoor dust and human breast milk. Significant positive correlations were observed between the dust concentrations of seven FLCMs including BDPrB, and their breast milk concentrations (r = 0.275–0.660, P

Aflatoxin B1 (AFB1) is an extremely hazardous and unavoidable pollutant for cereals and feedstuff. AFB1 can cause testicular lesion, and how to alleviate its testicular toxicity has received much attention in recent years. Lycopene (LYC), a foodborne nutrient derived from red fruits and vegetables, has protective effects against sperm abnormality and testicular lesions. To confirm the beneficial effects and mechanisms of LYC on AFB1-induced testicular lesion, 48 male mice were exposed to 0.75 mg/kg AFB1 or/and 5 mg/kg LYC for consecutive 30 days. Results demonstrated the LYC significantly restored the lesions of testicular microstructure and ultrastructure, and sperm abnormalities in AFB1-exposed mice. Furthermore, LYC effectively attenuated AFB1-induced oxidative stress and mitochondrial damage, including ameliorative mitochondrial structural, and elevated mitochondrial biogenesis for maintaining mitochondrial function. Meanwhile, LYC resisted AFB1-induced mitochondrial-dependent apoptosis. In addition, LYC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and upregulated the Nrf2 signaling pathway. Collectively, our findings demonstrate LYC ameliorates AFB1-induced testicular lesion by attenuating oxidative stress and mitochondrial damage, which is related to the activation of Nrf2.

Despite the widespread use of bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) in various consumer products as protective plasticizer, studies on human dietary exposure to these compounds are scare. In this study, nine bisphenol diglycidyl ethers (BDGEs) including BADGE, BFDGE, and seven of their derivatives were determined in the Chinese adult population based on composite dietary samples collected from the sixth (2016–2019) China total diet study (TDS). Contamination level of nine BDGEs was determined in 288 composite dietary samples from 24 provinces in China. BADGE·2H2O and BADGE are the most frequently detected and BADGE·2H2O presented the highest mean concentration (2.402 μg/kg). The most contaminated food composite is meats, with a mean ∑9BDGEs of 8.203 μg/kg, followed by aquatic products (4.255 μg/kg), eggs (4.045 μg/kg), and dairy products (3.256 μg/kg). The estimated daily intake (EDI) of ∑9BDGEs based on the mean and 95th percentile concentrations are 121.27 ng/kg bw/day and 249.71 ng/kg bw/day. Meats, eggs, and aquatic products are the main source of dietary exposure. Notably, beverages and water, alcohols were the main contributors of dietary exposure to BADGE and BADGE·2H2O, followed by animal-derived foods. Dietary exposure assessment demonstrated that human dietary BDGEs do not pose risks to general population based on the mean and 95th percentile hazard index with

A novel method utilizing non-aqueous capillary electrophoresis (NACE) with indirect ultraviolet detection (IUD) has been developed for the analysis of five quaternary ammonium compounds (QACs). The QACs analyzed in this study include dodecyl trimethyl ammonium bromide, tetradecyl trimethyl ammonium bromide, dioctyl dimethyl ammonium chloride, octyldecyl dimethyl ammonium chloride and didecyl dimethy ammonium bromide. The separation process was carried out on an uncoated fused quartz capillary with a total length of 50.2 cm (effective length 40.0 cm) and a diameter of 50 μm. The separation buffer consisted of a mixture of MeOH/ACN (90:10, v/v) containing 2 mmol/L sodium acetate, 2 mmol/L trifluoroacetic acid (TFA) and 16 mmol/L dodecyl dimethyl benzyl ammonium chloride. The sample buffer utilized a mixture of MeOH/ACN (20:80, v/v) containing 2 mmol/L TFA. During analysis, a separation voltage of 7 kV was applied, resulting in a current of approximately 2.3 μA. The detection wavelength was set at 214 nm to ensure optimal sensitivity. Under optimal conditions, the method exhibited excellent performance characteristics, with a limit of detection of 0.5 mg/L and a limit of quantitation of 5.0 mg/L for the five QACs. Linear calibration curves were obtained in a concentration range of 5.0 to 100.0 mg/L, with correlation coefficients exceeding 0.999 for all compounds. The recoveries of the five QACs ranged from 92.3% to 114.7%, with relative standard deviations below 7.4%. To assess the applicability of the NACE-IUD method, 17 commercially available samples were successfully analyzed. The results confirmed the suitability of the method for accurate determination of the five QACs in disinfectant products. Notably, this method offers an environmentally friendly approach for the analysis of these QACs.

Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. However, little is known about the MACB metabolism in vivo. Here, we determined the metabolism of MACB in zebrafish and microglia cell model. We found that MACB mainly disrupted the metabolism of branched-chain amino acids (Leu, Ile and Val) in zebrafish model and gamma-aminobutyric acid (GABA) pathway-related amino acids in microglia model. Additionally, we demonstrated that MACB can be metabolized by the mixed-function oxidase CYP1A2 enzyme which could be inhibited by estrogen causing the gender-difference in the accumulation of MACB in vivo. These results indicated that MACB perturbed metabolism and induced neurological disorders, particularly in the female zebrafish.

Tremors have been reported even with a low dose of tacrolimus in patients with nephrotic syndrome and are responsible for hampering the day-to-day work of young active patients with nephrotic syndrome. This study proposes a neural network model based on seven variables to predict the development of tremors following tacrolimus. The sensitivity and specificity of this algorithm are high. A total of 252 patients were included in this study, out of which 39 (15.5%) experienced tremors, 181 patients (including 32 patients who experienced tremors) were randomly assigned to a training dataset, and the remaining were assigned to an external validation set. We used a recursive feature elimination algorithm to train the training dataset, in turn, through 10-fold cross-validation. The classification performance of the classifer was then used as the evaluation criterion for these subsets to find the subset of optimal features. A neural network was used as a classification algorithm to accurately predict tremors using the subset of optimal features. This model was subsequently tested in the validation dataset. The subset of optimal features contained seven variables (creatinine, D-dimer, total protein, calcium ion, platelet distribution width, serum kalium, and fibrinogen), and the highest accuracy obtained was 0.8288. The neural network model based on these seven variables obtained an area under the curve (AUC) value of 0.9726, an accuracy of 0.9345, a sensitivity of 0.9712, and a specificity of 0.7586 in the training set. Meanwhile, the external validation achieved an accuracy of 0.8214, a sensitivity of 0.8378, and a specificity of 0.7000 in the validation dataset. This model was capable of predicting tremors caused by tacrolimus with an excellent degree of accuracy, which can be beneficial in the treatment of nephrotic syndrome patients.

In this study, a numerical model of a partial wellbore is developed by coupling computational fluid dynamics (CFD) with the discrete element method (DEM) in order to simulate the operation of a double-circulation system (DCS) in coalbed methane (CBM) well drilling, which is a novel technique used for cuttings transport. The values of the flow field are computed by a fluid solver and the motions of the particle phase are calculated by the DEM, for which an additional multi-sphere particle model is integrated. After verification of the model, the analysis centers on the working mechanism, the DCS parameters, and optimization of the angle θ of the injection nozzles, which is the most critical parameter affecting the efficiency of the DCS. Simulations reveal the working details of the DCS and prove its applicability to cuttings transport, especially in the curved and horizontal parts of the well. The effects of viscosity and particle size are investigated, and a low-viscosity drilling fluid is recommended. The optimal range for θ is obtained as 30° to 50°. This work provides a reference for the engineering application of DCSs, and by feedback from drilling sites the reliability of the results can be verified.

Here, Li et al. perform a genome-wide CRISPR screen to identify host dependency factors for influenza A virus infection and show that the host mRNA cap methyltransferase CMTR1 is important for viral cap snatching and that it affects expression of antiviral genes.

Numerous byproducts resulting from chlorinated disinfection are constantly being generated during water treatment processes. The potential risks of these new emerging pollutions remain largely unknown. Here, we determined the risks of chlorinated disinfection byproducts of diazepam (DZP) in the cellular and zebrafish exposure experiments. The cytotoxicity of disinfection byproducts (MACB and MBCC) was greater than DZP in macrophage raw 264.7 cells at 10 mg/L. We further found that the effects of MBCC on the metabolism of glycine, serine, threonine and riboflavin were far greater than DZP by the targeted metabolomics methods. Moreover, MBCC significantly decreased the peak amplitude of neuronal action potential in primary embryonic rat (Spragu-Dawley SD) hippocampal neurons. We finally determined behavioral toxicity of DZP and byproducts in zebrafish larvae. MBCC significantly decreased the maximal swim-activity and peak duration of zebrafish after 72 h exposure. Altogether, these findings indicate the MBCC pose serious pressures on public health.

Glucocorticoids (GCs) widely exist in animal food including aquatic food. This study aimed to survey the occurrences of cortisone and cortisol in aquatic food and the estimated daily intake (EDI) of cortisone and cortisol due to different habits of aquatic food consumption. The mean levels of cortisone and cortisol in freshwater fish purchased from market were 14.59 μg/kg and 69.15 μg/kg, respectively, which were markedly higher than the levels in marine fish. A test using Zebrafish was performed to compare the concentration of GCs by different killing methods. The results suggested that physically traumatic killing methods are one of the reasons why the levels of GCs in freshwater fish were higher than those in marine fish. The concentrations of cortisone and cortisol in composite aquatic food samples from 12 provincial districts of the fourth China Total Diet Study (TDS) were 0.72~15.75 μg/kg and 4.90~66.13 μg/kg, respectively, which were positively correlated with the distance from the coastline. Further, the correlation coefficient between the levels of cortisone and cortisol in aquatic food and the percentages of freshwater fish consumption were 0.758 (p < 0.01) and 0.908 (p < 0.01), respectively. There was a significant positive correlation between the levels of cortisone and cortisol in aquatic food in the fourth TDS and the percentages of freshwater fish consumption. The calculated average EDIs of cortisone and cortisol from aquatic food in the fourth TDS were 0.16 μg/d and 0.72 μg/d, respectively.

Improving the signal-to-noise ratio (SNR) by amplifying the outputting signal or reducing nonspecific binding (NSB) are the key techniques in multiple immunoassay. Aiming at these issues, this paper presents an improved multiple indirect competitive immune surface-enhanced Raman scattering (ci-SERS) assay for the rapid screening of highly toxic rodenticides in food and biological samples, which ensured remarkable accuracy, ultra-sensitivity and reproducibility. The non-fouling polymer brush grafted magnetic beads (the MB@P-CyM) were prepared as multiple competitive recognition substrates after conjugating triplex haptens (the MB@P-CyM-hap). It was demonstrated that the particular 3D hair-like structures of P-CyM not only facilitate conjugate high-density hapten but reduce the steric hindrance from SERS probes recognition, thus enhancing SNB. On the other hand, Au nanoflowers (AuNFs) of high SERS activity were synthesized using a simple one-pot hydrazine reduction. For simultaneously detecting three highly toxic rodenticides, i.e., diphacinone (DPN), bromadiolone (BRD) and tetramine (TET), the obtained AuNFs were fabricated as a SERS-encoded nanoprobe cocktail after successively labeling mono-antibodies/Raman probes. By integrating the MB@P-CyM-hap with the SERS-encoded cocktail, a highly sensitive multiple SERS assay was achieved in less than 2 h with a limit of detection of 0.62 ng mL−1 for BRD, 0.42 ng mL−1 for TET and 1.37 ng mL−1 for DPN, respectively. The recoveries of these rodenticides in spiked food and biological samples were determined and ranged from 72 to 123%. Above all, the proposed modifications show remarkable improvements for high efficient multiple chemical toxin immunoassay.

Due to the specificity of coal rock containing CBM (coal bed methane), large-sized cuttings from coal bed drilling present abnormal appearances which make the transport of cuttings more troublesome. Simulations of the transport of large-sized and non-spherical drilling cuttings in the horizontal well-bore annulus possesses both theoretical challenges and engineering worth. In this work, a coupled CFD-DEM model is developed and a multi-sphere method is adopted to construct the non-spherical cuttings particles including cubic and long flaky particles. Validation with the experimental data reveals the well applicability of the developed CFD-DEM model. The movements as well as the sedimentations of cuttings are discussed in detail. The influences of fluid velocity and particle shapes on the transport efficiency of cuttings are studied and more attention is paid to flaky cuttings. The results show that, with a consistent equivalent volume, relatively good performance happens to the 20 mm spherical particles while local piled bed appears to the flaky particles; however, cuttings in cubic particles behave the worst. In the chosen conditions, transport efficiency drops dramatically when the volume fraction of the flaky cuttings exceeds 10%. Work in this paper is expected to be able to be applied to CBM drilling engineering.

Shared bikes as a public transport provide convenience for short-distance travel. Whilst they also act as a potential vector for antimicrobial resistant (AR) bacteria and antimicrobial resistance genes (ARGs). However, the understanding of the whole genome sequence of AR strains and ARGs-carrying plasmids collected from shared bikes is still lacking. Here, we used the HiSeq platform to sequence and analyze 24 Escherichia coli isolated from shared bikes around Metro Stations in Beijing. The isolates from shared bikes showed 14 STs and various genotypes. Two blaNDM-5 and blaCTX-M-199-producing ST167 E. coli have 16 resistance genes, four plasmid types and show >95% of similarities in core genomes compared with the ST167 E. coli strains from different origins. The blaNDM-5- or blaCTX-M-199-carrying plasmids sequencing by Nanopore were compared to plasmids with blaNDM-5- or blaCTX-M-199 originated from humans and animals. These two ST167 E. coli show high similarities in core genomes and the plasmid profiles with strains from hospital inpatients and farm animals. Our study indicated that ST167 E. coli is retained in diverse environments and carried with various plasmids. The analysis of strains such as ST167 can provide useful information for preventing or controlling the spread of AR bacteria between animals, humans and environments.

Pseudomonas aeruginosa is one of the most common opportunistic pathogens, which causes severe nosocomial infections because of its well-known multidrug-resistance and hypervirulence. It is critical to curate routinely the epidemic P. aeruginosa clones encountered in the clinic. The aim of the present study was to investigate the connection between virulence factors and antimicrobial resistance profiles in epidemic clones. Herein, we found that ST463 (O4), ST1212 (O11), and ST244 (O5) were prevalent in 30 isolates derived from non-cystic fibrosis patients, based on multilocus sequence type (MLST) and serotype analysis. All isolates were multidrug-resistant (MDR) and each was resistance to at least three classes of antibiotics in antimicrobial susceptibility tests, which was consistent with the presence of the abundant resistance genes, such as blaOXA–50, blaPAO, aph(3′), catB7, fosA, crpP, and blaKPC–2. Notably, all blaKPC–2 genes were located between ISKpn6-like and ISKpn8-like mobile genetic elements. In addition, classical exotoxins encoded by exoU, exoS, and pldA were present in 43.44% (13/40), 83.33% (25/30), and 70% (21/30) of the isolates, respectively. The expression of phz operons encoding the typical toxin, pyocyanin, was observed in 60% of isolates (18/30) and was quantified using triple quadrupole liquid chromatograph mass (LC/MS) assays. Interestingly, compared with other MLST types, all ST463 isolates harbored exoU, exoS and pldA, and produced pyocyanin ranging from 0.2 to 3.2 μg/mL. Finally, we evaluated the potential toxicity of these isolates using hemolysis tests and Galleria mellonella larvae infection models. The results showed that ST463 isolates were more virulent than other isolates. In conclusion, pyocyanin-producing ST463 P. aeruginosa, carrying diverse virulence genes, is a potential high-risk clone.

The emergence and worldwide dissemination of plasmid-mediated colistin resistance gene mcr-1 has attracted global attention. The MCR-1 enzyme mediated colistin resistance by catalyzing phosphoethanolamine (PEA) transfer onto bacterial lipid A. However, the interaction partners of MCR-1 located in membrane protein in E. coli are unknown. Co-immunoprecipitation (Co-IP) and Mass Spectrometry were performed to define the interacting proteins of MCR-1. A total of three different anti-MCR-1 monoclonal antibody (mAbs) were prepared and 3G4 mAb was selected as the bait protein by compared their suitability for Co-IP. We identified 53, 13, and 14 interacting proteins in E. coli BL21 (DE3) (pET28a-mcr-1), E. coli BL21 (DE3) (pET28a-mcr-1-200), and E. coli DH5α (pUC19-mcr-1), respectively. Six proteins, including the stress response proteins DnaK (chaperone protein) and SspB (stringent starvation protein B), the transcriptional regulation protein H-NS, and ribosomal proteins (RpsE, RpsJ, and RpsP) were identified in all these three strains. These MCR-1-interacting proteins were mainly involved in ribosome and RNA degradation, suggesting that MCR-1 influences the protein biosynthesis through the interaction with ribosomal protein. Multidrug efflux pump AcrA and TolC were important interacting membrane proteins of MCR-1 referred to drug efflux during the PEA modification of the bacterial cell membrane. Overall, we firstly identified the functional interactome profile of MCR-1 in E. coli and discovered that two-component AcrA-TolC multidrug efflux pump was involved in mcr-1-mediated colistin resistance.

The environmental effects of additives have attracted increasing attention. Sodium dehydroacetate (DHA-S), as an approved preservative, is widely added in processed foods, cosmetics and personal care products. However, DHA-S has been recently reported to induce hemorrhage and coagulation aberration in rats. Yet little is known about the ecotoxicological effect and underlying mechanisms of DHA-S. Here, we utilized the advantage of zebrafish model to evaluate such effects. DHA-S induced cerebral hemorrhage, mandibular dysplasia and pericardial edema in zebrafish after 24 h exposure (48–72 hpf) at 50 mg/L. We also observed the defective heart looping and apoptosis in DHA-S-treated zebrafish through o-dianisidine and acridine orange staining. Meanwhile, DHA-S induced the deficiency of Ca2+ and vitamin D3 in zebrafish. We further demonstrated that DHA-S stimulated Ca2+ influx resulting in Ca2+-dependent mitochondrial damage in cardiomyocytes. Additionally, DHA-S inhibited glucose uptake and repressed the biosynthesis of amino acids. Finally, we identified that sodium bicarbonate could rescue zebrafish from DHA-S induced cardiovascular toxicity. Altogether, our results suggest that DHA-S is a potential risk for cardiovascular system.

Background: Metabolic syndrome (MetS) patients have a considerably increased risk for noncommunicable diseases, which poses a serious burden on public health. The effects of different elements on MetS have received increasing attention in the field of noncommunicable diseases over the past decade. These elements can exert adverse or favourable effects on human health by synergistic or antagonistic actions. Nevertheless, few studies have explored the relationship between multiple-element exposure and MetS. Method: A total of 2095 MetS patients and 2039 controls free of major cardiovascular disease at baseline and follow-up visits were frequency matched for age (±5 years) and sex. The internal exposure levels of 15 elements in serum were investigated. Logistic regression models were employed to estimate odds ratios (ORs) of MetS for element concentrations categorized according to quartiles in the controls. Result: Magnesium (Mg), selenium (Se), barium (Ba) and mercury (Hg) were significantly associated with MetS in the multi-element exposure model. The ORs for the extreme quartiles of Mg, Se, Ba, and Hg were 0.29 (95% CI: 0.23–0.37, P-trend

The dynamics (rotation and stabilization) of single irregular particles that are constrained to rotate only and until to a quasi-steady state in a two-dimensional channel with viscous flow is numerically investigated using the gradient smoothed method (GSM). The GSM is proved to be computationally stable for arbitrary, irregular geometries discretized with distorted grids and well agreements with others’ work are revealed in validation cases. This work focuses on the influences of irregular particles’ typical shapes, including ellipse, rectangle and triangle, on the relevant surface forces, the flow dynamics, and the response time of the rotation. The effects of aspect ratio and flow velocity are studied in detail for all three typical types of irregular particles. It is found that the imbalance of the total torque on the surface of the particle causes the rotation, and when the particle is approaching the final stable position, the total torque becomes nearly zero with a small fluctuation, which contributes a local oscillation around the stable direction. In our cases, under the constraints, it is found also that the broad side of the elliptical particle always tends to be along the stream. For the rectangular particle, however, the aspect ratio and the flow velocity collectively determine the final orientation which means the major side or the diagonal line is along the flow stream. In addition, the triangular particle is found to behave quite differently in terms of both rotation and stabilization. The ‘response time’ of three types of particles is finally obtained from our GSM simulations. These findings could be helpful for a better understanding on the fluid-particle interactions and maybe advisory for determining the shape factor which is a key parameter for multiple particles motions.

Bike-sharing as a common public transportation has been booming in China in recent years. Previous studies showed that the surfaces of public transport can act as reservoirs of antimicrobial-resistant (AR) bacteria, but AR bacterial contamination of shared bikes has not been investigated. Otherwise, the AR-Enterobacteriaceae is considered as a global health threat for humans. Herein, we aimed to investigate the prevalence of AR Enterobacteriaceae on shared bikes and examine correlations between AR Enterobacteriaceae from shared bikes and public buildings around Metro stations in Beijing. We collected 2117 samples from shared bikes at 240 Metro stations in Beijing. A total of 444 non-duplicate Enterobacteriaceae were isolated from 418 samples at 166 stations. The isolates exhibited low rates of resistance (0.5%–6.3%) to all antimicrobial agents except sulfamethoxazole-trimethoprim (31.5%). Three ceftazidime-resistant E. coli isolates were positive for blaCTX-M-199 and two of them were positive for carbapenemase-producing gene blaNDM-5. Multivariable logistic regression model revealed that variable “secondary/tertiary non-profit hospital nearby” was significantly (p

The microstructures and tensile properties of fresh and aged reformer furnace tubes and a fresh-to-aged welded joint were investigated to assess the weldability of fresh-to-aged reformer furnace tubes. Damage evaluation of the fresh-to-aged welded joint was also carried out using the modified Kachanov–Rabotnov model. The experimental results showed that M7C3 carbide transforms into M23C6 carbide and secondary carbides precipitate in the matrix after aging treatment. With continuous exposure, the interdendritic precipitates coalesced and coarsened and the number of secondary carbides reduced gradually. Microdefects were absent in the fresh-to-aged welded joint, and the tensile properties of the welded joint were close to the as-cast alloy, which confirms the weldability of fresh-to-aged furnace tubes. According to the results of the simulation, stress redistribution occurred during the creep process and the peak damage of the welded joint was located in the aged tube. The maximum damage of the fresh-to-aged welded joint reached 34.01% at 1.5 × 105 h.

Dithiocarbamate-grafted polyurethane (PU) composites were synthesized by anchoring dithiocarbamate (DTC) as a chelating agent to the polyethyleneimine-polydopamine (PE-DA)-functionalized graphene-based PU matrix (PE-DA@GB@PU), as a new adsorbent material for the recovery of Cu2+, Pb2+, and Cd2+ from industrial effluents. After leaching with acidic media to recover Cu2+, Pb2+, and Cd2+, dithiocarbamate-grafted PE-DA@GB@PU (DTC-g-PE-DA@GB@PU) was decomposed and PE-DA@GP was regenerated. The latter was used to recover Pd2+, Pt4+, and Au3+ from the copper leaching residue and anode slime. The present DTC-g-PE-DA@GB@PU and PE-DA@GB@PU composites show high adsorption performance, effective separation, and quick adsorption of the target ions. The morphologies of the composites were studied by scanning electron microscopy and their structures were investigated by Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy. The effects of pH values, contact time, and initial metal ion concentration conditions were also studied. An adsorption mechanism was proposed and discussed in terms of the FT-IR results.

Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth.

To determine the contents of B-vitamins in human milk in China, we analyzed 1778 human milk samples from the sample bank of the National High Technique R & D Program (863 Projects) which was a cross-sectional survey and covered 6419 human milk samples from healthy lactating mothers who were at different stages of lactation (0-330 days postpartum) in 11 provinces of China. The contents of free forms of six B-vitamins in these human milk samples were analyzed by using UPLC-MS/MS. The median concentrations of free form of 6 B-vitamins in colostrums, transitional milk, 15-180 d mature milk and 181-330 d mature milk were respectively as follows: thiamin 5.0 µg/L, 6.7 µg/L, 21.1 µg/L and 40.7 µg/L; riboflavin 29.3 µg/L, 40.6 µg/L, 33.6 µg/L and 29.6 µg/L; niacin 470.7 µg/L, 661.3 µg/L, 687.0 µg/L and 571.3 µg/L; vitamin B-6 4.6 µg/L, 16.1 µg/L, 62.7 µg/L and 80.7 µg/L; flavin adenine dinucleotide (FAD) 808.7 µg/L, 1162.8 µg/L, 1023.9 µg/L and 1057.2 µg/L; pantothenic acid 1770.9 µg/L, 2626.8 µg/L, 2213.0 µg/L and 1895.5 µg/L. The contents of 6 B-vitamins varied significantly among the different lactation stages and different areas (coastal area vs inland area, rural area vs urban area). The present study indicated that the concentrations of B-vitamins in colostrum were generally much lower than those in transitional milk and mature milk. Further studies are warranted for their roles and significance on B-vitamins in colostrum in nutrition and metabolism of neonates.

A total of 181 wheat flour and 142 wheat-based foods including dried noodle, steamed bread and bread collected in China were analyzed for alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN) and tenuazonic acid (TeA) by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. TeA was the predominant toxin found in 99.4% wheat flour samples at levels ranging from 1.76 μg/kg to 520 μg/kg. TEN was another Alternaria toxin frequently detected in wheat flour samples (97.2%) at levels between 2.72 μg/kg and 129 μg/kg. AOH and AME were detected in 11 (6.1%) samples at levels ranging from 16.0 μg/kg to 98.7 μg/kg (AOH) and in 165 (91.2%) samples with a range between 0.320 μg/kg and 61.8 μg/kg (AME). AOH was quantified at higher levels than AME with the ratio of AOH/AME ranging from 1.0 to 3.7. Significant linear regressions of correlation in toxin concentrations were observed between AOH and AME, AME and TeA, TEN and TeA, AOH+AME and TeA. At an average and 95th percentile, dietary exposure to AOH and AME in the Chinese general population and different age subgroups exceeded the relevant threshold value of toxicological concern (TTC), with the highest exposure found in children which deserves human health concern. TEN and TeA seem unlikely to be health concerns for the Chinese via wheat-based products but attention should be paid to synergistic or additive effects of TeA with AOH, AME, TEN and a further assessment will be performed once more data on toxicity-guided fractionation of the four toxins are available. It is necessary to conduct a systemic surveillance of Alternaria toxins in raw and processed foods in order to provide the scientific basis for making regulations on these toxins in China.

Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed "hormesis" effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+.

Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells.

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings.

BACKGROUND:The pair-rule gene, hairy, encodes a basic helix-loop-helix transcription factor and is required for patterning of the early Drosophila embryo and for morphogenesis of the embryonic salivary gland. Although hairy was shown to be expressed in the tracheal primordia and in surrounding mesoderm, whether hairy plays a role in tracheal development is not known. PRINCIPAL FINDINGS:Here, we report that hairy is required for refining the terminal cell fate in the embryonic trachea and that hairy's tracheal function is distinct from its earlier role in embryonic patterning. In hairy mutant embryos where the repressive activity of hairy is lost due to lack of its co-repressor binding site, extra terminal cells are specified in the dorsal branches. We show that hairy functions in the muscle to refine the terminal cell fate to a single cell at the tip of the dorsal branch by limiting the expression domain of branchless (bnl), encoding the FGF ligand, in surrounding muscle cells. Abnormal activation of the Bnl signaling pathway in hairy mutant tracheal cells is exemplified by increased number of dorsal branch cells expressing Bnl receptor, Breathless (Btl) and Pointed, a downstream target of the Bnl/Btl signaling pathway. We also show that hairy genetically interacts with bnl in TC fate restriction and that overexpression of bnl in a subset of the muscle surrounding tracheal cells phenocopied the hairy mutant phenotype. CONCLUSIONS/SIGNIFICANCE:Our studies demonstrate a novel role for Hairy in restriction of the terminal cell fate by limiting the domain of bnl expression in surrounding muscle cells such that only a single dorsal branch cell becomes specified as a terminal cell. These studies provide the first evidence for Hairy in regulation of the FGF signaling pathway during branching morphogenesis.