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.

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.

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.

Personal exposure to fine particulate matter and benzo[a]pyrene from indoor air pollution and leukocyte mitochondrial DNA copy number in rural China.

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-µg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.

Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.

In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a]pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.

Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

Polycyclic aromatic hydrocarbon exposure in household air pollution from solid fuel combustion among the female population of Xuanwei and Fuyuan counties, China.

Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning "smoky" (bituminous) coal has been implicated as a cause of the high lung cancer incidence in the counties of Xuanwei and Fuyuan, China. Little is known about variations in PAH exposure from throughout the region nor how fuel source and stove design affects exposure. Indoor and personal PAH exposure resulting from solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h particle bound and gas-phase PAH measurements, which were collected from 163 female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266 personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed effect models indicated that PAH exposure was up to 6 times higher when burning smoky coal than smokeless coal and varied by up to a factor of 3 between different smoky coal geographic sources. PAH measurements from unventilated firepits were up to 5 times that of ventilated stoves. Exposure also varied between different room sizes and season of measurement. These findings indicate that PAH exposure is modulated by a variety of factors, including fuel type, coal source, and stove design. These findings may provide valuable insight into potential causes of lung cancer in the area.

Personal and indoor PM2.5 exposure from burning solid fuels in vented and unvented stoves in a rural region of China with a high incidence of lung cancer.

The combustion of biomass and coal is the dominant source of household air pollution (HAP) in China, and contributes significantly to the total burden of disease in the Chinese population. To characterize HAP exposure related to solid fuel use and ventilation patterns, an exposure assessment study of 163 nonsmoking female heads of households enrolled from 30 villages was conducted in Xuanwei and Fuyuan, two neighboring rural counties with high incidence of lung cancer due to the burning of smoky coal (a bituminous coal, which in health evaluations is usually compared to smokeless coal--an anthracite coal available in some parts of the area). Personal and indoor 24-h PM2.5 samples were collected over two consecutive days in each household, with approximately one-third of measurements retaken in a second season. The overall geometric means (GM) of personal PM2.5 concentrations in Xuanwei and Fuyuan were 166 [Geometric Standard Deviation (GSD):2.0] and 146 (GSD:1.9) µg/m(3), respectively, which were similar to the indoor PM2.5 air concentrations [GM(GSD):162 (2.1) and 136 (2.0) µg/m(3), respectively]. Personal PM2.5 was moderately highly correlated with indoor PM2.5 (Spearman r = 0.70, p < 0.0001). Burning wood or plant materials (tobacco stems, corncobs etc.) resulted in the highest personal PM2.5 concentrations (GM:289 and 225 µg/m(3), respectively), followed by smoky coal, and smokeless coal (GM:148 and 115 µg/m(3), respectively). PM2.5 levels of vented stoves were 34-80% lower than unvented stoves and firepits across fuel types. Mixed effect models indicated that fuel type, ventilation, number of windows, season, and burning time per stove were the main factors related to personal PM2.5 exposure. Lower PM2.5 among vented stoves compared with unvented stoves and firepits is of interest as it parallels the observation of reduced risks of malignant and nonmalignant lung diseases in the region.

Biomass fuels and coke plants are important sources of human exposure to polycyclic aromatic hydrocarbons, benzene and toluene.

Large amounts of carcinogenic polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) might be emitted from incomplete combustion reactions in both coal tar factories and biomass fuels in rural China. The health effects arising from exposure to PAHs and BT are a concern for residents of rural areas close to coal tar plants. To assess the environmental risk and major exposure sources, 100 coke plant workers and 25 farmers in Qujing, China were recruited. The levels of 10 mono-hydroxylated PAHs (OH-PAHs), four BT metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine collected from the subjects were measured. The 8-OHdG levels in the urine were determined to evaluate the oxidative DNA damage induced by the PAHs and BT. The results showed that the levels of the OH-PAHs, particularly those of 1-hydroxynathalene and 1-hydroxypyrene, in the farmers were 1-7 times higher than those in the workers. The concentrations of the BT metabolites were comparable between the workers and farmers. Although the exact work location within a coke oven plant might affect the levels of the OH-PAHs, one-way ANOVA revealed no significant differences for either the OH-PAHs levels or the BT concentrations among the three groups working at different work sites. The geometric mean concentration (9.17 µg/g creatinine) of 8-OHdG was significantly higher in the farmers than in the plant workers (6.27 µg/g creatinine). The levels of 8-OHdG did not correlate with the total concentrations of OH-PAHs and the total levels of BT metabolites. Incompletely combusted biomass fuels might be the major exposure source, contributing more PAHs and BT to the local residents of Qujing. The estimated daily intakes (EDIs) of naphthalene and fluorene for all of the workers and most of the farmers were below the reference doses (RfDs) recommended by the U.S. Environmental Protection Agency (EPA), except for the pyrene levels in two farmers. However, the EDIs of benzene in the workers and local farmers ranged from 590 to 7239 µg/day, and these levels were 2- to 30-fold higher than the RfDs recommended by the EPA. Biomass fuel combustion and industrial activities related to coal tar were the major sources of the PAH and BT exposure in the local residents. Using biomass fuels for household cooking and heating explains the higher exposure levels observed in the farmers relative to the workers at the nearby coal tar-related industrial facility.

Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.

The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 µmol/L), and KN-62 (10 µmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.

Ambient particulate matter and lung function growth in Chinese children.

BACKGROUND: Exposure to particulate matter (PM) has been associated with deficits in lung function growth among children in Western countries. However, few studies have explored this association in developing countries, where PM levels are often substantially higher. METHODS: Children (n = 3273) 6-12 years of age were recruited from 8 schools in 4 Chinese cities. The lung function parameters of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured using computerized spirometers twice a year for up to 3 years (1993-1996). Dichotomous samplers placed in each schoolyard were used to measure PM2.5 and PM10 (PM with diameter ≤ 2.5 µm and ≤ 10 µm, respectively). Multivariable generalized estimating equations were used to examine the association between the quarterly average PM levels and lung function growth during the period of follow-up. RESULTS: Annual average PM2.5 and PM10 levels in the 4 cities ranged from 57 to 158 µg/m and 95 to 268 µg/m, respectively. In multivariable models, an increase of 10 µg/m of PM2.5 was associated with decreases of 2.7 mL FEV1 (95% confidence interval = -3.5 to -2.0), 3.5 mL FVC (-4.3 to -2.7), 1.4 mL/year FEV1 growth (-1.8 to -0.9), and 1.5 mL/year FVC growth (-2.0 to -1.0). Similar results were seen with PM10 exposure. CONCLUSIONS: Exposure to ambient particulate matter was associated with decreased growth in lung function among Chinese children.

A single molecule scaffold for the maize genome.

About 85% of the maize genome consists of highly repetitive sequences that are interspersed by low-copy, gene-coding sequences. The maize community has dealt with this genomic complexity by the construction of an integrated genetic and physical map (iMap), but this resource alone was not sufficient for ensuring the quality of the current sequence build. For this purpose, we constructed a genome-wide, high-resolution optical map of the maize inbred line B73 genome containing >91,000 restriction sites (averaging 1 site/ approximately 23 kb) accrued from mapping genomic DNA molecules. Our optical map comprises 66 contigs, averaging 31.88 Mb in size and spanning 91.5% (2,103.93 Mb/ approximately 2,300 Mb) of the maize genome. A new algorithm was created that considered both optical map and unfinished BAC sequence data for placing 60/66 (2,032.42 Mb) optical map contigs onto the maize iMap. The alignment of optical maps against numerous data sources yielded comprehensive results that proved revealing and productive. For example, gaps were uncovered and characterized within the iMap, the FPC (fingerprinted contigs) map, and the chromosome-wide pseudomolecules. Such alignments also suggested amended placements of FPC contigs on the maize genetic map and proactively guided the assembly of chromosome-wide pseudomolecules, especially within complex genomic regions. Lastly, we think that the full integration of B73 optical maps with the maize iMap would greatly facilitate maize sequence finishing efforts that would make it a valuable reference for comparative studies among cereals, or other maize inbred lines and cultivars.

The physical and genetic framework of the maize B73 genome.

Maize is a major cereal crop and an important model system for basic biological research. Knowledge gained from maize research can also be used to genetically improve its grass relatives such as sorghum, wheat, and rice. The primary objective of the Maize Genome Sequencing Consortium (MGSC) was to generate a reference genome sequence that was integrated with both the physical and genetic maps. Using a previously published integrated genetic and physical map, combined with in-coming maize genomic sequence, new sequence-based genetic markers, and an optical map, we dynamically picked a minimum tiling path (MTP) of 16,910 bacterial artificial chromosome (BAC) and fosmid clones that were used by the MGSC to sequence the maize genome. The final MTP resulted in a significantly improved physical map that reduced the number of contigs from 721 to 435, incorporated a total of 8,315 mapped markers, and ordered and oriented the majority of FPC contigs. The new integrated physical and genetic map covered 2,120 Mb (93%) of the 2,300-Mb genome, of which 405 contigs were anchored to the genetic map, totaling 2,103.4 Mb (99.2% of the 2,120 Mb physical map). More importantly, 336 contigs, comprising 94.0% of the physical map ( approximately 1,993 Mb), were ordered and oriented. Finally we used all available physical, sequence, genetic, and optical data to generate a golden path (AGP) of chromosome-based pseudomolecules, herein referred to as the B73 Reference Genome Sequence version 1 (B73 RefGen_v1).

Detailed analysis of a contiguous 22-Mb region of the maize genome.

Most of our understanding of plant genome structure and evolution has come from the careful annotation of small (e.g., 100 kb) sequenced genomic regions or from automated annotation of complete genome sequences. Here, we sequenced and carefully annotated a contiguous 22 Mb region of maize chromosome 4 using an improved pseudomolecule for annotation. The sequence segment was comprehensively ordered, oriented, and confirmed using the maize optical map. Nearly 84% of the sequence is composed of transposable elements (TEs) that are mostly nested within each other, of which most families are low-copy. We identified 544 gene models using multiple levels of evidence, as well as five miRNA genes. Gene fragments, many captured by TEs, are prevalent within this region. Elimination of gene redundancy from a tetraploid maize ancestor that originated a few million years ago is responsible in this region for most disruptions of synteny with sorghum and rice. Consistent with other sub-genomic analyses in maize, small RNA mapping showed that many small RNAs match TEs and that most TEs match small RNAs. These results, performed on approximately 1% of the maize genome, demonstrate the feasibility of refining the B73 RefGen_v1 genome assembly by incorporating optical map, high-resolution genetic map, and comparative genomic data sets. Such improvements, along with those of gene and repeat annotation, will serve to promote future functional genomic and phylogenomic research in maize and other grasses.

Combustion-derived nanoparticle exposure and household solid fuel use in Xuanwei and Fuyuan, China.

Combustion-derived nanoparticles (CDNPs) have not been readably measurable until recently. We conducted a pilot study to determine CDNP levels during solid fuel burning. The aggregate surface area of CDNP (µm(2)/cm(3)) was monitored continuously in 15 Chinese homes using varying fuel types (i.e. bituminous coal, anthracite coal, wood) and stove types (i.e. portable stoves, stoves with chimneys, firepits). Information on fuel burning activities was collected and PM(2.5) levels were measured. Substantial exposure differences were observed during solid fuel burning (mean: 228.1 µm(2)/cm(3)) compared to times without combustion (mean: 14.0 µm(2)/cm(3)). The observed levels during burning were reduced by about four-fold in homes with a chimney (mean: 92.1 µm(2)/cm(3); n = 9), and effects were present for all fuel types. Each home's CDNP measurement was only moderately correlated with the respective PM(2.5) measurements (r (2) = 0.43; p = 0.11). Our results indicate that household coal and wood burning contributes to indoor nanoparticle levels, which are not fully reflected in PM(2.5) measurements.

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.

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.