Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Metabolic engineering of Escherichia coli for 2,4-dinitrotoluene degradation.

2,4-Dinitrotoluene (2,4-DNT) as a common industrial waste has been massively discharged into the environment with industrial wastewater. Due to its refractory degradation, high toxicity, and bioaccumulation, 2,4-DNT pollution has become increasingly serious. Compared with the currently available physical and chemical methods, in situ bioremediation is considered as an economical and environmentally friendly approach to remove toxic compounds from contaminated environment. In this study, we relocated a complete degradation pathway of 2,4-DNT into Escherichia coli to degrade 2,4-DNT completely. Eight genes from Burkholderia sp. strain were re-synthesized by PCR-based two-step DNA synthesis method and introduced into E. coli. Degradation experiments revealed that the transformant was able to degrade 2,4-DNT completely in 12 h when the 2,4-DNT concentration reached 3 mM. The organic acids in the tricarboxylic acid cycle were detected to prove the degradation of 2,4-DNT through the artificial degradation pathway. The results proved that 2,4-DNT could be completely degraded by the engineered bacteria. In this study, the complete degradation pathway of 2,4-DNT was constructed in E. coli for the first time using synthetic biology techniques. This research provides theoretical and experimental bases for the actual treatment of 2,4-DNT, and lays a technical foundation for the bioremediation of organic pollutants.

Azole-Induced Color Vision Deficiency Associated with Thyroid Hormone Signaling: An Integrated In Vivo, In Vitro, and In Silico Study.

Azoles that are used in pesticides, pharmaceuticals, and personal care products can have toxic effects on fish. However, there is no information regarding azole-induced visual disorder associated with thyroid disruption. We evaluated changes in retinal morphology, optokinetic response, transcript abundance of the genes involved in color perception and hypothalamic-pituitary-thyroid (HPT) axis, and thyroid hormone (TH) levels in zebrafish larvae exposed to common azoles, such as climbazole (CBZ, 0.1 and 10 µg/L) and triadimefon (TDF, 50 and 500 µg/L), at environmentally relevant and predicted worst-case environmental concentrations. Subsequently, the effect of azoles on TH-dependent GH3 cell proliferation and thyroid receptor (TR)-regulated transcriptional activity, as well as the in silico binding affinity between azoles and TR isoforms, was investigated. Azole exposure decreased cell densities of the ganglion cell layer, inner nuclear layer, and photoreceptor layer. Zebrafish larvae exposed to environmentally relevant concentrations of CBZ and TDF showed a decrease in optokinetic response to green-white and red-white stripes but not blue-white stripes, consistent with disturbance in the corresponding opsin gene expression. Azole exposure also reduced triiodothyronine levels and concomitantly increased HPT-related gene expression. Molecular docking analysis combined with in vitro TR-mediated transactivation and dual-luciferase reporter assays demonstrated that CBZ and TDF exhibited TR antagonism. These results are comparable to those obtained from a known TR antagonist, namely, TR antagonist 1, as a positive control. Therefore, damage to specific color perception by azoles appears to result from lowered TH signaling, indicating the potential threat of environmental TH disruptors to the visual function of fish.

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.

Investigation of PM2.5 pollution during COVID-19 pandemic in Guangzhou, China.

The COVID-19 pandemic has raised awareness about various environmental issues, including PM2.5 pollution. Here, PM2.5 pollution during the COVID-19 lockdown was traced and analyzed to clarify the sources and factors influencing PM2.5 in Guangzhou, with an emphasis on heavy pollution. The lockdown led to large reductions in industrial and traffic emissions, which significantly reduced PM2.5 concentrations in Guangzhou. Interestingly, the trend of PM2.5 concentrations was not consistent with traffic and industrial emissions, as minimum concentrations were observed in the fourth period (3/01-3/31, 22.45 µg/m3) of the lockdown. However, the concentrations of other gaseous pollutants, e.g., SO2, NO2 and CO, were correlated with industrial and traffic emissions, and the lowest values were noticed in the second period (1/24-2/03) of the lockdown. Meteorological correlation analysis revealed that the decreased PM2.5 concentrations during COVID-19 can be mainly attributed to decreased industrial and traffic emissions rather than meteorological conditions. When meteorological factors were included in the PM2.5 composition and backward trajectory analyses, we found that long-distance transportation and secondary pollution offset the reduction of primary emissions in the second and third stages of the pandemic. Notably, industrial PM2.5 emissions from western, southern and southeastern Guangzhou play an important role in the formation of heavy pollution events. Our results not only verify the importance of controlling traffic and industrial emissions, but also provide targets for further improvements in PM2.5 pollution.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Chronic Exposure to Climbazole Induces Oxidative Stress and Sex Hormone Imbalance in the Testes of Male Zebrafish.

As the main active ingredient for the treatment of fungal infections, climbazole (CBZ) is commonly used in a variety of personal care products. After its use, CBZ enters the receiving environment directly or indirectly through domestic sewage. Its concentration can be up to several nanograms per liter in surface water. So far, the effects of CBZ on the reproductive system of female zebrafish have been systematically studied, but the potential toxicity mechanism of CBZ on male zebrafish still needs to be further explored. In this study, adult male zebrafish were exposed to CBZ at concentrations of 0.1, 10, and 1000 µg·L-1 for 28 days, and their testes were collected for histological, mass-spectrometry-based metabolomics, and biochemical analyses. We found that CBZ caused a significantly abnormal metabolism of purine and glutathione and triggered oxidative stress in zebrafish testes, thereby inducing testicular cell apoptosis. In addition, CBZ could inhibit the synthesis of essential sex hormones in the testis and thus reduce the sperm production. The conclusions of this study fill the data gap on the reproductive toxicity of CBZ to male zebrafish and highlight the ecotoxicological application of untargeted metabolomics in the biomarker discovery.

Crystallography-guided discovery of carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators: insights into different protein behaviors with "short" and "long" inverse agonists.

A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the "short" inverse agonist 6. With the increase in the size of the 6-position substituents, the "short" inverse agonist 6 first reversed its function to agonists and then to "long" inverse agonists. The cocrystal structures of RORγt complexed with the representative "short" inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the "long" inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of "short" inverse agonist 6 and "long" inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that "short" or "long" inverse agonists led to different behaviors of helixes H11, H11', and H12 of RORγt. The "short" inverse agonist 6 destabilizes H11' and dislocates H12, while the "long" inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms.

Uptake, Accumulation, and Biomarkers of PM2.5-Associated Organophosphate Flame Retardants in C57BL/6 Mice after Chronic Exposure at Real Environmental Concentrations.

Although the bioaccumulation of organophosphate flame retardants (OPFRs) in aquatic organisms has been investigated, little information is available about their bioaccumulation in mammals following chronic inhalation exposure. To address this knowledge gap, C57BL/6 mice were exposed to 7 PM2.5-associated OPFRs via the trachea to study their bioaccumulation, tissue distribution, and urinary metabolites. Low (corresponding to the real PM2.5 concentrations occurring during winter in Guangzhou), medium, and high dosages were examined. After 72 days' exposure, ∑OPFR concentrations in tissues from mice in the medium dosage group decreased in the order of intestine > heart > stomach > testis > kidney > spleen > brain > liver > lung > muscle. Of the OPFRs detected in all three exposure groups, chlorinated alkyl OPFRs were most heavily accumulated in mice. We found a significant positive correlation between the bioaccumulation ratio and octanol-air partition coefficient (KOA) in mice tissues for low log KOW OPFR congeners (log KOW ≤ 4, p < 0.05). Three urinary metabolites (di-p-cresyl phosphate: DCrP, diphenyl phosphate: DPhP, dibutyl phosphate: DnBP) were detected from the high dosage group. These results provide important insights into the bioaccumulation potential of OPFRs in mammals and emphasize the health risk of chlorinated alkyl OPFRs.

GC-MS/MS analysis for source identification of emerging POPs in PM2.5.

Emerging POPs have received increasing attention due to their potential persistence and toxicity, but thus far the report regarding the occurrence and distribution of these POPs in PM2.5 is limited. In this study, an extremely sensitive and reliable method, using ultrasonic solvent extraction and silica gel purification followed by gas chromatography coupled with electron ionization triple quadrupole mass spectrometry, was developed and used for the trace analysis of hexachlorobutadiene (HCBD), pentachloroanisole (PCA) and its analogs chlorobenzenes (CBs) in PM2.5 from Taiyuan within a whole year. The limits of detection and limits of quantitation of analytes were 1.14 × 10-4‒2.74 × 10-4 pg m-3 and 3.80 × 10-4‒9.14 × 10-4 pg m-3. HCBD and PCA were detected at the mean concentrations of 3.69 and 1.84 pg m-3 in PM2.5, which is reported for the first time. Based on the results of statistical analysis, HCBD may come from the unintentional emission of manufacture or incineration of chlorinate-contained products but not coal combustion, while O3-induced photoreaction was the potential source of PCA in PM2.5. The temporal distributions of CBs in PM2.5 were closely related to coal-driven or agricultural activities. Accordingly, our study reveals the contamination profiles of emerging POPs in PM2.5 from Taiyuan.

Chemical identity and cardiovascular toxicity of hydrophobic organic components in PM2.5.

Numerous experimental and epidemiological studies have demonstrated that exposure to PM2.5 may result in pathogenesis of several major cardiovascular diseases (CVDs), which can be attributed to the combined adverse effects induced by the complicated components of PM2.5. Organic materials, which are major components of PM2.5, contain thousands of chemicals, and most of them are environmental hazards. However, the contamination profile and contribution to overall toxicity of PM2.5-bound organic components (OCs) have not been thoroughly evaluated yet. Herein, we aim to provide an overview of the literature on PM2.5-bound hydrophobic OCs, with an emphasis on the chemical identity and reported impairments on the cardiovascular system, including the potential exposure routes and mechanisms. We first provide an update on the worldwide mass concentration and composition data of PM2.5, and then, review the contamination profile of PM2.5-bound hydrophobic OCs, including constitution, concentration, distribution, formation, source, and identification. In particular, the link between exposure to PM2.5-bound hydrophobic OCs and CVDs and its possible underlying mechanisms are discussed to evaluate the possible risks of PM2.5-bound hydrophobic OCs on the cardiovascular system and to provide suggestions for future studies.

Acute exposure to triphenyl phosphate inhibits the proliferation and cardiac differentiation of mouse embryonic stem cells and zebrafish embryos.

Attention has recently paid to the interaction of triphenyl phosphate (TPHP) and body tissues, particularly within the reproductive and development systems, due to its endocrine-disrupting properties. However, the acute effects of TPHP on early embryonic development remain unclear. Here, we used mouse embryonic stem cells (mESC) and zebrafish embryos to investigate whether TPHP is an embryo toxicant. First, we found that continuous exposure of TPHP decreased the proliferation and increased the apoptotic populations of mESCs in a concentration-dependent manner. Results of mass spectrometry showed that the intracellular concentration of TPHP reached 39.45 ± 7.72 µg/g w/w after 3 hr of acute exposure with TPHP (38.35 µM) but gradually decreased from 3 hr to 48 hr. Additionally, DNA damage was detected in mESCs after a short-term treatment with TPHP, which in turn, activated DNA damage responses, leading to cell cycle arrest by changing the expression levels of p53, proliferating cell nuclear antigen, and Y15-phosphorylated Cdk I. Furthermore, our results revealed that short-term treatment with TPHP disturbed cardiac differentiation by decreasing the expression levels of Oct4, Sox2, and Nanog and transiently reduced the glycolysis capacity in mESCs. In zebrafish embryos, exposure to TPHP resulted in broad, concentration-dependent developmental defects and coupled with heart malformation and reduced heart rate. In conclusion, the two models demonstrate that acute exposure to TPHP affects early embryonic development and disturbs the cardiomyogenic differentiation.

In Situ Detection and Imaging of PFOS in Mouse Kidney by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry.

Perfluorooctanesulfonic acid (PFOS) is an emerging environmental organic pollutant that has been widely used in daily life products in the last century. Numerous studies showed that the accumulation of PFOS in human through food chain would lead to various disease. However, there is currently no report about its in situ localization in the tissue. In present study, we aimed to develop a reproductive and less-cost method to quantitatively detect and determine the spatial distribution of PFOS in mouse kidney by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) with a commercially available matrix. α-Cyano-4-hydroxycinnamic acid (CHCA) matrix was optimized for PFOS detection in MALDI-IMS analysis. Compared to other organic matrices, CHCA used in negative ion mode showed less background interference and enhanced MS signal intensity and high spatial resolution (80 µm) for PFOS analysis. The use of a CHCA matrix with an autospray system led to successful identification of the PFOS ion signals on the perfusion kidney tissue. The detection limit was at the µg/mL level, with direct visualization from a MS image. The developed method with the optimized parameters was successfully employed to obtain the PFOS spatial distribution in the kidney collected from mice after the PFOS exposure for 14 days. PFOS was mainly distributed in the kidney cortex region, which was consistent with the histological analysis results. Taken together, a rapid, economic, and efficient method was developed for PFOS detection by MALDI-IMS using a CHCA matrix. Mapping the distribution of PFOS by MALDI-IMS with a CHCA matrix provides an innovative approach for the analysis of environmental pollutants in animal or human tissues.

Investigation of the interaction between the fate of antibiotics in aquafarms and their level in the environment.

China is the largest freshwater aquaculture producer and antibiotics consumer in the world, and rivers in China are generally polluted by antibiotics. However, there is little information available regarding the linkage of antibiotics in aquaculture and the aquatic environment. Therefore, this study investigated the fate of antibiotics in several open water culture-based freshwater aquafarms, including integrated livestock/fish systems and non-integrated fish ponds, and explored the contamination profiles of antibiotics in the Beijiang River. Then the study tried to clarify the two-way interaction of antibiotics in aquaculture and the environment. The results showed that, when compared with the effluent from livestock farms and wastewater treatment plants, the contribution of antibiotics from non-integrated fish pond water without livestock sewage input was limited, while that of effluent from the integrated livestock/fish system was quite high. The total concentrations of antibiotics detected in the aquafarm source water were similar to those in the upper river water and generally higher than those in the corresponding fish pond water, implying that the occurrence of antibiotics in intensive aquafarms can mainly be attributed to the antibiotic residues in nearby river water. Overall, the results underscore the need to develop a sewage infrastructure for the treatment of effluent from integrated livestock/fish aquafarms, and suggest that open water culture-based fish farms should be located far from seriously contaminated sections of rivers.

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion-Induced Acute Lung Injury.

Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines. In this study, we found that enhanced endoplasmic reticulum (ER) stress was observed in infiltrated neutrophils in the early stage of an ALI mice model. In neutrophils, complement 5a (C5a) inspires strong ER stress through inositol-requiring kinase 1a and, to a less extent, the protein kinase R-like ER kinase signaling pathway. The granule release induced by C5a was ER stress mediated. Knowkdown of X-box-binding protein 1, a downstream signaling molecule of inositol-requiring kinase 1a, impaired granule release, based on myeloperoxidase production. Further analysis revealed that C5a induced ER stress by binding to C5a receptor in neutrophils. Using xbp(f/f) MRP8-cre mice in which X-box-binding protein 1 is deficient specifically in neutrophils and ER stress is deprived, we confirmed that ER stress in neutrophils was required for granule release in vivo and led to ALI, whereas dampening ER stress in neutrophils substantially alleviated ALI. Taken together, our results demonstrated that C5a receptor-mediated ER stress induced granule release in neutrophils, contributing to the development of ALI. This novel mechanism suggests a new potential therapeutic target in autophagy regulation for ALI.

[Cardioprotective Effect and Its Mechanism of Total Saponins of Panacis Majoris Rhizoma in Myocardial Infarction Rats].

OBJECTIVE: To explore the cardioprotective effect and its mechanism of total saponins of Panacis Majoris Rhizoma in myocardial infarction (MI) rats. METHODS: The MI model rats induced by ligating anterior descending branch of coronary artery were randomly divided into four group:model group, total saponins of Panacis Majoris Rhizoma (100 and 200 mg/kg) groups and compound Danshen dripping pills group. The rats were orally administrated with drugs once a day for four weeks. Another rats were selected as sham operation group. After four weeks intervention, cardiac function was examined, the serum levels of TNF-α, IL-1ß, IL-6 and IL-8 were measured by using ELISA, respectively. The myocardial hypertrophy index was investigated, the myocardial infarct size, degree of ventricular dilatation, myocardial interstitial collagen volume fraction and tissue morphology were investigated by HE, Masson, picric acid-sirius red staining and observing with alight microscope and electron microscope. Protein expressions of phosphorylation IκB-α( pIκB-α) and NF-κB p65 in heart tissue were detected by Western blotting. RESULTS: Total saponins of Panacis Majoris Rhizoma might significantly decrease the levels of serum TNF-α, IL-1ß, IL-6 and IL-8; decrease myocardial hypertrophy indexes, myocardial infarct size, degree of ventricular dilatation and myocardial interstitial collagen volume fraction; improve heart tissue morphology and cardiac function; downregulate protein expression of pIκB-α and NF-κBp65; and upregulate protein expression of SIRT1. The aforementioned action effects of total saponins of Panacis Majoris Rhizoma (200 mg/kg) were similar with compound Danshen dripping pills. CONCLUSION: Total saponins of Panacis Majoris Rhizoma possesses cardioprotective effect against ligating left anterior descending branch induced MI in rats. The mechanism may be related to strengthening SIRT1 expression, inhibiting the phosphorylation of IκB-α, and finally inhibiting the activation of NF-κB and proinflammatory production.

Hsa-miR-196a2 functional SNP is associated with the risk of ESCC in individuals under 60 years old.

BACKGROUND AND AIM: The miR-196a2 gene contains a C/T polymorphism (rs11614913). Its presence could change the conformation of secondary structure of miR-196a2 RNA, and directly affect the binding to target mRNAs and the miRNA maturation process. Both of which eventually alter protein expression and contributed to cancer susceptibility. This study assessed whether the rs11614913 single nucleotide polymorphism (SNP) could affect an individual's susceptibility to esophageal squamous cell carcinomas (ESCC). METHODS: SNP rs11614913 was genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) in 597 ESCC patients and 597 control subjects. RESULTS: Overall, there were no significant differences in the frequency of the miRNA-196a2 SNP rs11614913 genotype between the ESCC cases and the controls (χ(2) = 1.395, p = 0.498). The TT genotype, CT genotype and CT/TT combined genotype (dominant model) did not modify the risk of ESCC as compared with the CC genotype. Comparisons of the TT genotype to the CT/CC combined genotype did not reveal a significant association to ESCC, too. However, further analyses revealed an increased risk of ESCC in the dominant model (OR = 1.56, 95% CI = 1.08-2.26) and the allele frequency comparison (OR = 1.31, 95% CI = 1.06-1.63) in the ≤60-year-old group. CONCLUSIONS: These results suggest that the miRNA-196a2 functional polymorphism rs11614913 might be an effective genetic marker for ESCC risk assessment in individuals younger than 60 years of age from a region of high ESCC incidence in northern China.

Analysis of 21 progestagens in various matrices by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) with diverse sample pretreatment.

In this study, a highly sensitive and robust method using an ultra-high-performance liquid chromatography-tandem mass spectrometry combined with solid-phase extraction and ultrasonic extraction for pretreatment and silica gel purification steps has been developed for determination of 21 natural and synthetic progestagens in river surface water and sediments, and influents, effluents, and sludge from municipal wastewater treatment plants, and flush water and feces from swine farms. For the various matrices considered, the optimized method showed satisfactory performance with recoveries of 70-129 % (except AD, 5α-DHP, DPT, HPC), the limits of quantification below 2.30 ng/L for liquid samples and 2.59 ng/g for solid samples (except AD), and good linearity and reproducibility. This developed method was successfully applied in the analysis of progestagens in environmental samples from Liuxi Reservoir, Xintang municipal wastewater treatment plant, and Shunfeng swine farm in South China. Six analytes were detected at trace levels in surface water, effluent, and sediment samples. Seven analytes (0.7 (HPA)-35.1 ng/L (DGT)) were found in the influent samples and three analytes (5.6 (DGT)-11.8 ng/g (5α-DHP)) in the dewatered sludge samples. Moreover, 13 analytes were detected in swine farm, with high concentrations ranging from 23.8 ng/L (ET) to 5,024 ng/L (P) in flush water, and from 20.0 ng/g (MPA) to 1952 ng/g (P) in feces.

Efficacy and safety of dexmedetomidine versus propofol for the sedation of tube-retention after oral maxillofacial surgery.

PURPOSE: To compare the safety and efficacy of sedation induced by dexmedetomidine and propofol after oral and maxillofacial surgery. MATERIALS AND METHODS: In this trial, 66 patients 18 to 50 years old received oral and maxillofacial surgery and required postoperative nasal endotracheal intubation under overnight sedation with dexmedetomidine or propofol. The dexmedetomidine group (group D) received dexmedetomidine 1.0 µg/kg intravenously for 10 minutes after entering the recovery room. The dose was maintained by giving an intravenous injection of dexmedetomidine 0.4 µg/kg. The injection rate could be modulated from 0.2 to 0.7 µg/kg/hour in the intensive care unit (ICU). If the Ramsay score was lower than 2 and involuntary limb movement occurred, other sedatives were used. The propofol group (group P) was given propofol 0.1 mg/kg intravenously for 10 minutes after entering the recovery room and then maintained with intravenous injections of propofol 1 to 2 mg/kg/hour in the recovery room and ICU. RESULTS: The oxygen desaturation of group P was higher than that of group D (at the first sedation time of 30 minutes), but the mean blood pressure of group P was significantly lower than that of group D at the 10-minute time point. The Ramsay score was higher in group D after the first 3 hours of sedation than in group P (P < .05). CONCLUSION: Dexmedetomidine showed similar safety and efficacy as propofol and could be used for tube-retaining sedation after oral and maxillofacial surgery.

Bioaccumulation and risk assessment of per- and polyfluoroalkyl substances in wild freshwater fish from rivers in the Pearl River Delta region, South China.

Per- and polyfluoroalkyl substances (PFASs) are used in various industries, which results in their ubiquitous occurrence in the environment. This study determined the concentrations of eighteen PFASs in muscle and liver of nine wild freshwater fish species collected from rivers in the Pearl River Delta (PRD) region, South China, and assessed their bioaccumulation and potential health risks to local people. The results showed that eight and twelve PFASs were detected in the fish muscle and liver samples, respectively. Perfluorooctane sulfonate (PFOS) was found to be the predominant PFAS both in muscle and liver with its highest concentrations of 79ng/g wet weight (ww) in muscle and 1500ng/g ww in liver, followed by Perfluoroundecanoic acid (PFUnDA) and Perfluorotridecanoic acid (PFTrDA) with trace concentrations. The mean PFOS concentrations in fish muscle and liver tissues of the nine collected species ranged from 0.40ng/g in mud carp to 25ng/g in snakehead, and from 5.6ng/g in mud carp to 1100ng/g in snakehead, respectively. Significant positive correlations were found among PFASs both in water and fish, indicating a similar pollution source for these PFASs. In tilapia samples, PFOS concentrations showed an increasing trend with increasing length and weight, but no significant difference between genders. Bioaccumulation factors (logBAF) in fish for the PFASs were in the range from 2.1 to 5.0. The calculated hazard ratios (HR) of PFOS for all fishes were in the range of 0.05-2.8, with four out of nine species (tilapia, chub, leather catfish and snakehead) having their HR values more than 1.0. The results suggest that frequent consumption of these four fish species may pose health risks to local population.