The m6A Reader YTHDF1 Improves Sevoflurane-Induced Neuronal Pyroptosis and Cognitive Dysfunction Through Augmenting CREB-BDNF Signaling.

Sevoflurane is one of the most widely used anesthetics in surgery which is the main cause of postoperative cognitive dysfunction (POCD). Previous reports confirmed that YTHDF1 is differently expressed in sevoflurane-induced POCD, while the roles and mechanistic details remain unclear. The molecular expressions were assessed using qRT-PCR, western blot, immunofluorescence and immunohistochemistry. Pathological change in the hippocampus tissues was analyzed using HE staining. Cognitive ability in rats was measured using MWM test. Hippocampal neuronal viability and apoptosis were measured by MTT assay and flow cytometry, respectively. The levels of pro-inflammatory cytokines were assessed using ELISA. The interaction between YTHDF1 and CREB was analyzed by RNA immunoprecipitation assay. YTHDF1 was significantly decreased in hippocampus tissues by sevoflurane exposure, and its overexpression could improve sevoflurane-induced neuron damage and cognitive dysfunction. Meanwhile, YTHDF1 upregulation repressed sevoflurane-induced activation of NLRP3 inflammation and pyroptosis in hippocampus tissues. Subsequently, YTHDF1 directly interacted to CREB mRNA to augment its stability and translation via a m6A-dependent manner, thus activating CREB/BDNF pathway. In addition, the inactivation of CREB/BDNF pathway could reverse the protective effects of YTHDF1 overexpression on sevoflurane-mediated neuronal damage and pyroptosis. These findings revealed that YTHDF1 improved sevoflurane-induced neuronal pyroptosis and cognitive dysfunction through activating CREB-BDNF signaling.

Propofol Versus Remimazolam on Cognitive Function, Hemodynamics, and Oxygenation During One-Lung Ventilation in Older Patients Undergoing Pulmonary Lobectomy: A Randomized Controlled Trial.

OBJECTIVES: To investigate the effects of remimazolam on postoperative cognitive function, intraoperative hemodynamics, and oxygenation in older patients undergoing lobectomy. DESIGN: A prospective, double-blind, randomized, controlled study. SETTING: A university hospital. PARTICIPANTS: Eighty-four older patients with lung cancer who underwent lobectomy, aged ≥65 years. INTERVENTIONS: Patients were divided randomly into the remimazolam (group R) and propofol (group P) groups. Group R underwent remimazolam anesthesia induction and maintenance, whereas group P underwent propofol anesthesia induction and maintenance. Cognitive function was assessed with neuropsychological tests 1 day before surgery and 7 days after surgery. The Clock Drawing Test, Verbal Fluency Test (VFT), Digit Symbol Switching Test (DSST), and Auditory Verbal Learning Test-Huashan (AVLT-H) assessed visuospatial ability, language function, attention, and memory, respectively. The systolic blood pressure (SBP), heart rate, mean arterial pressure (MAP), and cardiac index were recorded 5 minutes before induction of anesthesia (T0), 2 minutes after sedation (T1), 5 minutes after intubation with two-lung ventilation (T2), 30 minutes after one-lung ventilation (OLV) (T3), 60 minutes after OLV (T4), and at the end of surgery (T5), and the incidences of hypotension and bradycardia were recorded. The PaO2, oxygenation index (OI), and intrapulmonary shunt (Qs/Qt) were assessed at T0, T2, T3, T4, and T5. The levels of S-100ß and interleukin 6 were measured by enzyme-linked immunosorbent assay at T0, T5, 24 hours after surgery (T6), and on day 7 after surgery (T7). MEASUREMENTS AND MAIN RESULTS: The VFT, DSST, immediate recall AVLT-H, and short-delayed recall AVLT-H scores were significantly higher in group R than in group P on day 7 after surgery (p < 0.05). The SBP and MAP at T2 to T5 were significantly higher in group R than in group P, the incidence of hypotension was significantly lower in group R (9.5%) than in group P (35.7%) (p = 0.004), and remimazolam significantly reduced the dose of phenylephrine used (p < 0.05). The PaO2 and OI at T4 were significantly higher in group R than in group P, and Qs/Qt was significantly lower in group R than in group P. The levels of S-100ß at T5 were significantly lower in group R than in group P (p < 0.05). CONCLUSION: The results showed that remimazolam (versus propofol) may lessen the degree of short-term postoperative cognitive dysfunction measured by standard neuropsychological tests, better optimize intraoperative hemodynamics, and lead to improved oxygenation during OLV.

miR-182-5p Delivered by Plasma Exosomes Promotes Sevoflurane-Induced Neuroinflammation and Cognitive Dysfunction in Aged Rats with Postoperative Cognitive Dysfunction by Targeting Brain-Derived Neurotrophic Factor and Activating NF-κB Pathway.

The objective of this study was to discuss the possible mechanism and effect of miR-182-5p delivered by plasma exosomes on sevoflurane-induced neuroinflammation and cognitive disorder in aged rats with postoperative cognitive dysfunction (POCD). Firstly, aged POCD rat models were constructed by sevoflurane anesthesia and superior mesenteric artery occlusion. Subsequently, exosomes and miR-182-5p were inhibited by injection of GW4869 and miR-182-5p-sponge, respectively. Then, exosomes were extracted from the plasma of rats in each group, followed by the determination of the morphology and diameters of exosomes as well as the expression of exosome markers CD63 and CD81 by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Besides, the Morris water maze (MWM) and fear conditioning test were used to evaluate the learning and memory ability of rats; Western blot to detect the expression levels of neurotrophic factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) as well as NF-κB pathway-related proteins (p65 and p-p65) in rat hippocampal tissues or PC-12 cells; qRT-PCR to assess the expression levels of miR-182-5p and BDNF in rat plasma, plasma exosomes, hippocampal tissues, and PC-12 cells; ELISA to evaluate the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in rat hippocampal tissues; and dual-luciferase reporter assay to verify the targeting relationship between miR-182-5p and BDNF. After examination, the results were obtained as follows. miR-182-5p expression was up-regulated in POCD rats and could be delivered by plasma exosomes. Inhibition of plasma exosomes or miR-182-5p could significantly ameliorate learning and memory disorders; decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß; increase the expression of BDNF and NGF; and inhibit the activity of NF-κB signaling pathway in POCD rat hippocampus. In addition, miR-182-5p could also target and inhibit BDNF. All in all, miR-182-5p delivered by plasma exosomes promotes sevoflurane-induced neuroinflammation and cognitive dysfunction in aged POCD rats by targeting BDNF and activating the NF-κB pathway.

External Exposure to BTEX, Internal Biomarker Response, and Health Risk Assessment of Nonoccupational Populations near a Coking Plant in Southwest China.

Benzene, toluene, ethylbenzene and xylene isomers (BTEX) have raised increasing concern due to their adverse effects on human health. In this study, a coking factory and four communities nearby were selected as the research area. Atmospheric BTEX samples were collected and determined by a preconcentrator GC-MS method. Four biomarkers in the morning urine samples of 174 participants from the communities were measured by LC-MS. The health risks of BTEX exposure via inhalation were estimated. This study aimed to investigate the influence of external BTEX exposure on the internal biomarker levels and quantitatively evaluate the health risk of populations near the coking industry. The results showed that the average total BTEX concentration in residential area was 7.17 ± 7.24 µg m-3. Trans,trans-muconic acid (T,T-MA) was the urinary biomarker with the greatest average level (127 ± 285 µg g-1 crt). Similar spatial trends can be observed between atmospheric benzene concentration and internal biomarker levels. The mean values of the LCR for male and female residents were 2.15 × 10-5 and 2.05 × 10-5, respectively. The results of the risk assessment indicated that special attention was required for the non-occupational residents around the area.

Source identification of pollution and health risks to metals in household indoor and outdoor dust: A cross-sectional study in a typical mining town, China.

Dust is regarded as an important pathway of heavy metal(loid)s to the human body. Health risks posed by metal(loid)s from household dust are of particular concern. However, the contamination and sources of heavy metal(loid)s in household dust environments, as well as source identification of health risks related to heavy metal(loid)s from household dust for vulnerable populations such as children, have not been thoroughly studied in China, particularly for the areas involved with industrial activities such as ore mining. Thus, a cross-sectional study was conducted in a rural area famous for Pb/Zn ore mining, to assess the pollution sources and health risks of heavy metal(loid)s from household indoor and outdoor dust and to identify the contribution of household dust to the health risks for children. The results indicated that household environment was heavily contaminated by metal(loid)s, which were mainly attributed to mining activity. Meanwhile, the indoor/outdoor ratio and the redundancy analysis indicated that there were other pollution sources in indoor environments such as coal combustion, materials for interior building and decoration. Vapor inhalation was the main exposure pathway for Hg, while ingestion was the predominant pathway for other metal(loid)s. Although the cancer risks were relatively low, the HIt from household indoor and outdoor dust (2.19) was about twice the acceptable limit (1) and was primarily from Pb (64.52%) and As (23.42%). Outdoor dust was a larger contributor to the HI of Sb, As, Cr, Cd, Zn and Pb, which accounted for 51.37%, 58.63%, 52.14%, 59.66%, 52.87% and 64.47%, respectively, and the HIt was mainly from outdoor dust (60.76%). These results indicated that non-cancer health risks were largely from outdoor dust exposure, and strengthened the notion that concern should be given to the potential health risks from metal(loid)s in household dust both originating from mining activity and indoor environmental sources.

Density functional theory study of active sites on nitrogen-doped graphene for oxygen reduction reaction.

Oxygen reduction reaction (ORR) remains challenging due to its complexity and slow kinetics. In particular, Pt-based catalysts which possess outstanding ORR activity are limited in application with high cost and ease of poisoning. In recent years, nitrogen-doped graphene has been widely studied as a potential ORR catalyst for replacing Pt. However, the vague understanding of the reaction mechanism and active sites limits the potential ORR activity of nitrogen-doped graphene materials. Herein, density functional theory is used to study the reaction mechanism and active sites of nitrogen-doped graphene for ORR at the atomic level, focusing on explaining the important role of nitrogen species on ORR. The results reveal that graphitic N (GrN) doping is beneficial to improve the ORR performance of graphene, and dual-GrN-doped graphene can demonstrate the highest catalytic properties with the lowest barriers of ORR. These results provide a theoretical guide for designing catalysts with ideal ORR property, which puts forward a new approach to conceive brilliant catalysts related to energy conversion and environmental catalysis.

Level, Source, and Spatial Distribution of Potentially Toxic Elements in Agricultural Soil of Typical Mining Areas in Xiangjiang River Basin, Hunan Province.

The concentrations, chemical availability, distribution, and sources of potentially toxic elements (PTEs) in the soil of Xiangjiang Basin in Hunan Province, China were investigated at 85 sites. The highest mean concentrations of Cd, Cu, Zn, As, and Pb were observed in Hengyang, whereas those for Mn, Co, and Hg were observed in Changde. The pollution index values followed the order: Cd > Hg > Cu > Zn > As > Pb; the mean geo-accumulation index values were in the order: Cd > Hg > Pb > Cu > Zn > As > Co > Mn. Cd was associated with moderate contaminated level, Hg and Pb were associated with moderate contaminated to uncontaminated level, and Cu, Zn, As, Co, and Mn were associated with uncontaminated level of pollution. Furthermore, 64.5% of Cd was water-soluble and exhibited exchangeable fractions; its chemical availability posed a risk to the ecosystem. Spatial analysis, principal component analysis, and a positive matrix factorization model were used to assess the PTE sources. Four principal components contributed to 88.8% of the 8 PTEs concentrations. Mining, smelting, industrial, and agricultural activities, alongside sewage irrigation, the use of agrochemicals, and vehicular emissions are the possible anthropogenic sources that pollute agricultural products and threaten human health in the Xiangjiang Basin.

Effect of perfluorocarbon partial liquid ventilation-induced hypothermia on dogs with acute lung injury.

BACKGROUND: Acute lung injury (ALI) is the damage of alveolar epithelial cells and capillary endothelial cells caused by various direct and indirect injury factors, resulting in diffuse pulmonary interstitial and alveolar edema, resulting in acute hypoxic respiratory insufficiency. This study aimed to investigate the effects of hypothermia induced by partial fluid ventilation on dogs with ALI. METHODS: The experimental dogs were randomly divided into a conventional mechanical ventilation group (CMV) group, a normal temperature perfluorocarbon liquid ventilation group (NPLV) group, and a hypothermic perfluorocarbon liquid ventilation group (HPLV) group. After induction of ALI, the dogs of the CMV group was treated with CMV for respiratory support, the HPLV group was given a 15 °C low-temperature perfluorocarbon partial liquid ventilation (PLV), and the NPLV group was given partial fluid permeation of perfluorocarbon (PFC) at a room temperature of 37 °C. Anesthesia was stable at 0.5 h (T0), and successful modeling (T1), at 1 h (T2), 2 h (T3), 3 h (T4) and 4 h (T5) was completed. Blood gas analysis was performed, and rectum temperature, peak airway pressure (PIP), and lung compliance were measured. We performed enzyme-linked immunosorbent assay (ELISA) for peripheral blood and postoperative bronchoalveolar lavage fluid (BALF), calculation of lung tissue wet weight/dry weight ratio, and Western blot detection of NF-κB p65. RESULTS: In the HPLV group, the blood gas index of dogs with ALI was close to normal. In T2¬-T5, the rectal temperature of the HPLV group was significantly lower than that of the NPLV group and the CMV group the lung compliance in the HPLV group and the NPLV group was lower than that in the CMV group at the T2-T5 time point, while the CLst value was significantly increased. The detection of peripheral blood and BALF in dogs showed that interleukin-10 (IL-10) was significantly increased and TNF-α was significantly decreased in the HPLV group compared with the CMV group and NPLV group. Compared with CMV group, the wet/dry ratio of lung tissue in the BALF of HPLV group was decreased. CONCLUSIONS: The results indicate that mild hypothermia caused by partial fluid ventilation can increase oxygenation capacity, oxygen partial pressure, the expression of anti-inflammatory factor IL-10 and improve lung compliance in dogs with ALI.

Characterization of outdoor air pollution from solid fuel combustion in Xuanwei and Fuyuan, a rural region of China.

Outdoor air pollution is a growing public health concern, particularly in urban settings. However, there are limited epidemiological data on outdoor air pollution in rural areas with substantial levels of air pollution attributed to solid fuel burning for household cooking and heating. Xuanwei and Fuyuan are rural counties in China where the domestic combustion of locally sourced bituminous ("smoky") coal has been associated with the highest lung cancer rates in China. We previously assessed indoor and personal air pollution exposures in this area; however, the influence of indoor coal combustion and household ventilation on outdoor air pollution has not been assessed. Therefore, we measured outdoor fine particulate matter (PM2.5), species of polycyclic aromatic hydrocarbons (PAHs) including naphthalene (NAP) and the known carcinogen benzo(a)pyrene (BaP), sulfur dioxide (SO2), and nitrogen dioxide (NO2) over two consecutive 24-h sampling periods in 29 villages. Just over half of the villages were revisited two to nine months after the initial sampling period to repeat all measurements. The overall geometric mean (GM) of outdoor PM2.5, BaP, NAP, and NO2 were 45.3 µg/m3, 9.7 ng/m3, 707.7 ng/m3, and 91.5 µg/m3, respectively. Using linear mixed effects models, we found that burning smoky coal was associated with higher outdoor BaP concentrations [GM ratio (GMR) = 2.79] and lower outdoor SO2 detection rates (GMR = 0.43), compared to areas burning smokeless coal. Areas with predominantly ventilated stoves (> 50% of stoves) had higher outdoor BaP (GMR = 1.49) compared to areas with fewer ventilated stoves. These results show that outdoor air pollution in a rural region of China was associated with the type of coal used for cooking and heating indoors and the presence of stove ventilation. Our findings suggest that efforts of household stove improvement to reduce indoor air pollution have resulted in higher outdoor air pollution levels. Further reducing adverse health effects in rural villages from household coal combustion will require the use of cleaner fuel types.

Temporal and spatial distribution characteristics and source origins of volatile organic compounds in a megacity of Sichuan Basin, China.

As important pollution gases and represented precursors of both ozone and second organic aerosol (SOA), the component characteristics, source origins, environmental health and emission control of volatile organic compounds (VOCs), are gaining more and more attention in Chinese megacities. In order to understand the concentration, composition and temporal and spatial distribution characteristics of VOCs in the atmosphere of Chengdu, a megacity located in Sichuan basin in southwest China, the offline sampling measurements of VOCs were carried out at 28 different field sites covering all the districts and counties of Chengdu during special periods from May 2016 to January 2017. Speciated VOCs measurement was performed by the GC-FID/MS, and 99 species were identified. The averaged total VOC mixing ratios of each sampling site were in the range from 35.03 to 180.57 ppbv. Based on these observational data, the distribution characteristics of VOCs in different months and different regions of Chengdu were clarified. The VOCs data were used to estimate the potential amount of ozone, secondary aerosol formation and health risk assessment in Chengdu. Furthermore, the positive matrix factorization (PMF) model was used to identify the dominant emission sources and evaluate their contribution to VOCs in the city. The two main sources of VOCs in Chengdu were motor vehicle exhaust and solvent utilization. These accounted for 43% of all emission sources. In the summertime, due to higher temperatures and stronger sunlight, the contribution of natural sources and secondary emissions were also relatively high, which were supported by the regional emission inventories. Finally, the controlling direction of VOCs and O3 pollution in Chengdu was discussed, and the VOCs pollution control strategy was proposed for the near future.

Quantificational exposure, sources, and health risks posed by heavy metals in indoor and outdoor household dust in a typical smelting area in China.

Contamination of metals in household dust remains a concern for human health. However, few studies to date have been conducted on the contribution of both indoor and outdoor environments to the health risks posed by metals. This study was carried out to assess the potential health risks from both indoor and outdoor household dust and the respective contribution to the health risks for children. The results showed that household dusts were heavily polluted by metal(loid)s, which were up to 30 times higher than the relative background level, and were attributed to smelting activity. However, there are other pollution sources in indoor environments, since the I/O ratio values of Pb, Cd, and As were significantly higher than 1. HI values of Pb and As exceeded the threshold of (1) and accounted for approximately 60% and 24% to the HIt, respectively. The HIts of Zn, Cr, Mn, Hg, and Cu were mainly attributable to indoor dust exposure, particularly for Hg (73.44%), indicating non-carcinogenic health risks could be attributed more to the indoor dust exposure. This study highlights the potential risks of metal contamination in household environment, particularly indoor environment, on the health of children who live in the vicinity of smelting activity.

Photodynamic Modification of Native HCN Channels Expressed in Thalamocortical Neurons.

The photodynamic process requires three elements: light, oxygen, and photosensitizer, and involves the formation of singlet oxygen, the molecular oxygen in excited electronic states. Previously, we reported that heterologously expressed hyperpolarization-activated cAMP-gated (HCN) channels in excised membrane patches are sensitive to photodynamic modification (PDM). Here we extend this study to native HCN channels expressed in thalamocortical (TC) neurons in the ventrobasal (VB) complex of the thalamus and dopaminergic neurons (DA) of the ventral tegmental area (VTA). To do this, we introduced the photosensitizer FITC-cAMP into TCs or DAs of rodent brain slices via a whole-cell patch-clamp recording pipette. After illumination with blue light pulses, we observed an increase in the voltage-insensitive, instantaneous Iinst component, accompanied by a long-lasting decrease in the hyperpolarization-dependent Ih component. Both Ih and the increased Iinst after PDM could be blocked by the HCN blockers Cs+ and ZD7288. When FITC and cAMP were dissociated and loaded into neurons as two separate chemicals, light application did not result in any long-lasting changes of the HCN currents. In contrast, light pulses applied to HCN2-/- neurons loaded with FITC-cAMP generated a much greater reduction in the Iinst component compared to that of WT neurons. Next, we investigated the impact of the long-lasting increases in Iinst after PDM on the cellular physiology of VB neurons. Consistent with an upregulation of HCN channel function, PDM elicited a depolarization of the resting membrane potential (RMP). Importantly, Trolox-C, an effective quencher for singlet oxygen, could block the PDM-dependent increase in Iinst and depolarization of the RMP. We propose that PDM of native HCN channels under physiological conditions may provide a photodynamic approach to alleviate HCN channelopathy in certain pathological conditions.

Partial liquid ventilation-induced mild hypothermia improves the lung function and alleviates the inflammatory response during acute respiratory distress syndrome in canines.

Background Acute respiratory distress syndrome (ARDS), which is the severest form of pulmonary injury, is the leading cause of death in critical care. At present, the mortality remains high in ARDS. Partial liquid ventilation (PLV) using perfluorocarbon (PFC) has been proven to improve gas exchange and respiratory dynamics of the lungs during ARDS. However, PLV has not been shown to reduce the mortality of ARDS. Some studies have shown that mild hypothermia therapy can reduce lung injuries in animal models of ARDS by reducing inflammatory cytokine levels in lung tissues. However, hypothermia cannot produce a lung protection effect alone, and it may have a synergistic effect with other protective measures. To explore the possible role of PLV combined with mild hypothermia in the treatment of ARDS, in this study, we used PFC liquid ventilation to induce mild hypothermia in dogs suffering from ARDS and analyzed the effects of PFC liquid ventilation-induced mild hypothermia on the levels of inflammatory factors and lung histopathology in dogs with ARDS. The experimental dogs were randomly divided into conventional mechanical ventilation (CMV), normal temperature PFC liquid ventilation (NPLV), hypothermic PFC liquid ventilation (HPLV), and mechanical ventilation (MV) groups. After induction of ARDS, the CMV group was treated with CMV for respiratory support, the HPLV group was treated with PLV-induced mild hypothermia using 15 °C PFC and maintained the rectal temperature at 34-36 °C, the NPLV group was treated with PLV using 36 °C PFC and maintained the rectal temperature at 36-38 °C. The MV group served as the control group. Analyses of the pulmonary pathology, partial pressure of oxygen in the blood, and lung wet-dry weight ratio (W/T) of each dog revealed that PLV-induced mild hypothermia significantly increased the PaO2 values and attenuated lung injury, and there were no adverse effects on hemodynamics. Furthermore, treatment with PLV-induced mild hypothermia significantly increased the expression of the anti-inflammatory factor IL-10 in bronchoalveolar lavage fluid (BALF) and attenuated the expression of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood and in lung BALF. Moreover, the results showed that the expression of myeloperoxidase (MPO) and NF-κB p65 in lung tissues was significantly decreased by PLV-induced mild hypothermia compared with NPLV and CMV. Our results indicated that PLV combined with mild hypothermia can provide protection against oleic acid-induced ARDS in dogs.

Cellulose-Nanofiber-Mediated Sorption-Benefitting Holed Silicalite-1 Crystals.

Silicalite-1-type zeolites with unique intracrystal holes or cracks were successfully prepared using a cellulose nanofiber (CNF) as an additional mediating material, and their vapor phase adsorption properties toward methyl tert-butyl ether (MTBE) and n-nitrosodimethylamine (NDMA) were examined. It was found that the mixing protocol of CNF and structure-directing agents (SDAs), the addition amount of CNF, and the CNF/SDAs amount ratio play important roles in forming the holed silicalite-1. The synthesis route that preliminarily mixes CNF with SDAs in a series of controlled conditions is particularly beneficial for the formation of the holed silicalite-1 with mesoporosity and larger pores because the CNF-SDAs composite structure benefits the zeolite growth closely encompassing CNF inside the crystal structure. It also promotes the preferential formation of the orthorhombic phase vicinal to the CNF surface, namely, the surface of the formed internal holes or cracks, with the twin-type crystal size reduced as compared to the non-CNF-templated sample. On the contrary, the synthesis route that mixes CNF with SDAs-silicate composite ions tends to modify the twin-type crystal shape at the same time to form small but uniform well-crystallized particles with less holes or cracks and a dominative monoclinic phase. It was considered that both the inter-subunit structural defect and silanol defect whose content is increased with CNF addition influence the adsorptivity of MTBE and NDMA. Owing to the small twin-type crystal size, the smaller crystal subunits, and the favored short path from the surface of internal holes or cracks, the holed silicalite-1 derived from the CNF and SDA premixture assures the easiest access of adsorbate molecules to the most energetically favored sites and is most appropriate for the adsorption of both MTBE and NDMA among the examined zeolites.

Internal biomarkers and external estimation of exposure to polycyclic aromatic hydrocarbons and their relationships with cancer mortality in a high cancer incidence area.

This study aimed to evaluate internal biomarkers and external estimation of exposure to polycyclic aromatic hydrocarbons (PAH) in a high cancer mortality area in southeast China and identify which of these showed a stronger association of PAH with cancer mortality. A retrospective death survey was conducted to determine the mortality rate of cancer. Cumulative and aggregate external exposures to PAHs of local residents were estimated by field sampling. Three regions in southwest China with gradient PAH exposure levels from high to low (H, M, and L) were selected in this study. Research participants were selected from these three regions using a statistical sampling method. To determine the internal exposure, urinary OH-PAHs were measured using the first morning urine samples. From the retrospective death survey, the highest age-standardized lung cancer mortality rate occurred in Region H (78 per 100,000 person-years), followed by that in Regions M (33 per 100,000 person-years) and L (15 per 100,000 person-years), and the rate was nearly four times China's national mortality rate (20 per 100,000 person-years). Residents estimated daily aggregate exposure doses per unit body weight to carcinogenic benzo(a)pyrene equivalent concentration were 159 ±â€¯14 ng-kg-1-day-1, 7.41 ±â€¯2.76 ng-kg-1-day-1, and 6.13 ±â€¯2.89 ng-kg-1-day-1 in Region H, M, and L, respectively. The participants in Region M had the greatest urinary OH-PAH concentration (9.10 ±â€¯4.92 µg-g-1 crt), followed by Region H (8.01 ±â€¯4.22 µg-g-1 crt) and L (7.12 ±â€¯3.10 µg-g-1 crt). The spatial difference in the total OH-PAHs was not statistically significant. Aggregate and cumulative exposure to 16 PAHs from external routes were found, and external exposure had a stringer relationship with lung cancer mortality than internal exposure.

The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural china.

We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1-V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02-14.48], ORlow = 3.78 [1.03-13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67-8.48], ORlow = 2.01 [0.58-6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85-10.92], ORlow = 2.53 [0.72-8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42-3.66], ORlow = 2.01 [0.63-6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Health risk from dietary exposure to polycyclic aromatic hydrocarbons (PAHs) in a typical high cancer incidence area in southwest China.

This study was designed to test whether the dietary intake of polycyclic aromatic hydrocarbons (PAHs) is a potential exposure source relating to the high cancer incidence area in southwest China. Duplicate plate method was used to collect food samples in rural and urban sites in the region. Questionnaire surveys were conducted among 300 local residents to obtain their dietary habits and 50 subjects were chosen to collect the samples. The 16 priority PAHs (PAH16) in composite food samples for each individual subject were measured, and non-carcinogenic and carcinogenic risks were analyzed based on the results of Monte Carlo method. The average concentration of the PAH16 in food samples was 12.04 ±â€¯8.52 ng g-1. The life time average daily benzo(a)pyrene equivalent (BaPeq) exposure dose was 6.07 × 10-6 mg kg-1 day-1. Although non-carcinogenic risk was found to be within a controllable range, the average incremental lifetime cancer risk (ILCR) was 3.7 × 10-5 for rural subjects and 6.1 × 10-5 for urban subjects, which is comparable with other regions in China. The serious risk level of 10-4 was exceeded by 10.7% of urban residents and 2.1% of rural residents. This study implies that dietary exposure to PAHs is a potential exposure source to the high cancer in the region, and further cancer risk control strategies need to be formulated.

Developmental toxicity of synthetic phenolic antioxidants to the early life stage of zebrafish.

Synthetic phenolic antioxidants (SPAs) have gained high concerns due to their extensive usages and unintended environmental release via various routes. Their contamination in water system could pose potential threat to aquatic organisms, therefore, the studies on the aquatic toxicology of this kind of chemicals are of high importance. In this research, the developmental toxicities of four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ), and 2,2'-methylenebis (6-tert-butyl-4-methylphenol) (AO2246) were investigated using the zebrafish embryo toxicity test (ZFET). The results showed that these four SPAs exerted different acute toxicities to zebrafish, and the toxic order, based on their 96 h LC50 values, was AO2246 > TBHQ > BHA > BHT, and decreased hatching rates were induced for the embryos in BHA, TBHQ and AO2246 exposure groups. Non-lethal exposures of BHA (≤20 µM), TBHQ (≤20 µM), BHT (≤200 µM) and AO2246 (≤2 µM) decreased the heart rates and body lengths of zebrafish in exposure concentration-dependent manners. Diverse morphological deformities, including uninflated swim bladder, pericardial edema, spinal curvature, severe yolk deformation, or abnormal pigmentation, were induced in zebrafish larvae upon SPA treatments. The transcriptional levels of the related genes, examined by quantitative PCR, indicated that the interferences of SPAs with hypothalamic-pituitary-thyroid axis (HPT axis), GH/PRL synthesis and Hedgehog (hh) pathway contributed to their developmental toxicities in zebrafish. The up-regulation of pluripotency biomarker, Oct4, caused the developmental retardation during the early stages of zebrafish embryos in BHA and TBHQ exposure groups. The results obtained herein provided important information on the developmental toxicity of SPAs, which could be very helpful in guiding the risk assessment on their aquatic toxicology.

Shank3-deficient thalamocortical neurons show HCN channelopathy and alterations in intrinsic electrical properties.

KEY POINTS: Shank3 increases the HCN channel surface expression in heterologous expression systems. Shank3Δ13-16 deficiency causes significant reduction in HCN2 expression and Ih current amplitude in thalamocortical (TC) neurons. Shank3Δ13-16 - but not Shank3Δ4-9 -deficient TC neurons share changes in basic electrical properties which are comparable to those of HCN2-/- TC neurons. HCN channelopathy may critically mediate events downstream from Shank3 deficiency. ABSTRACT: SHANK3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in the SHANK3 gene have been linked to neuropsychiatric disorders especially the autism spectrum disorders. SHANK3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different mouse Shank3 isoforms, Shank3A and Shank3C, significantly increase the surface expression of the mouse hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel. In Shank3Δ13-16 knockout mice, which lack exons 13-16 in the Shank3 gene (both Shank3A and Shank3C are removed) and display a severe behavioural phenotype, the expression of HCN2 is reduced to an undetectable level. The thalamocortical (TC) neurons from the ventrobasal (VB) complex of Shank3Δ13-16 mice demonstrate reduced Ih current amplitude and correspondingly increased input resistance, negatively shifted resting membrane potential, and abnormal spike firing in both tonic and burst modes. Impressively, these changes closely resemble those of HCN2-/- TC neurons but not of the TC neurons from Shank3Δ4-9 mice, which lack exons 4-9 in the Shank3 gene (Shank3C still exists) and demonstrate moderate behavioural phenotypes. Additionally, Shank3 deficiency increases the ratio of excitatory/inhibitory balance in VB neurons but has a limited impact on the electrical properties of connected thalamic reticular (RTN) neurons. These results provide new understanding about the role of HCN channelopathy in mediating detrimental effects downstream from Shank3 deficiency.

Evaluation of acute normovolemic hemodilution in patients undergoing intracranial meningioma resection: A quasi-experimental trial.

The aim of this study was to evaluate the safety of acute normovolemic hemodilution (ANH) for patients undergoing intracranial meningioma resection.Eighty patients (aged 48-65 years) with American Society of Anesthesiologists physical status I-II undergoing intracranial meningioma resection were included in this prospective observational study. The patients were randomly divided into group A (ANH group), which underwent a combination of ANH and intraoperative cell salvage (ICS), and group B (control group), which underwent ICS alone. The study parameters were recorded as baseline values before blood drainage (T0), after blood drainage (T1), and before (T2) and after (T3) retransfusion in group A. Whereas in group B, the same parameters were measured 10 minutes after anesthesia induction (T0), before surgery (T1), and before (T2) and after (T3) transfusion of autologous blood.When intraoperative blood loss was <2000 mL, the mean volume of homologous blood transfused in group A patients was 100.8 ±â€Š82.3 mL, compared with the 190.0 ±â€Š91.8 mL in group B. Reduction in homologous blood used in group A was statistically significant (P < .05). In group B, 15.1% patients received homologous blood, whereas only 5.9% patients received homologous blood in group A. The difference in heart rate between both groups at different time points was statistically nonsignificant (P > .05). The mean hemoglobin and hematocrit levels at T1 and T2 in group A were lower than in group B (P < .05). The prothrombin time and activated partial thromboplastin time in both groups were prolonged significantly after T2 (all P < .05), but were all within normal range. There were no significant differences in postoperative hospital stay, mortality, and postoperative infection between the 2 groups.For patients undergoing excision of intracranial meningioma, ANH is an effective procedure to reduce the need for allogeneic transfusions.