Overexpression of Bmp4 induces microphthalmia by disrupting embryonic neural retina.

Microphthalmia, mostly an autosomal dominant disorder, is a worldwide severe congenital ocular malformation that causes visual impairment. Our investigation unveiled a total of 30 genes associated with microphthalmia. Employing the CytoHubba and PPI network, we identified Bmp4 as the most pivotal hub gene. Subsequently, the conditional overexpression of Bmp4 in the retina caused highly distinctive microphthalmia, manifested by retinal disorganization with ganglion cell misalignment. Significant reduction in the number and abnormal distribution location of retinal cells in microphthalmia model mice. Elevated Bmp4 was associated with an increase in retinal apoptosis and a decrease in proliferating cells, which exacerbates the development of microphthalmia. Here we identify Bmp4 as an extremely important gene responsible for microphthalmia and the involved mechanisms. Overexpression of Bmp4 induces retinal cell ectopic expression and developmental defects, highlighting the importance of a well-balanced Bmp4 level in shaping the embryonic retina during early development.

Secondary Organic Aerosol Formation of Fleet Vehicle Emissions in China: Potential Seasonality of Spatial Distributions.

Vehicle emissions are an important source of urban particular matter. To investigate the secondary organic aerosol (SOA) formation potential of real-world vehicle emissions, we exposed on-road air in Beijing to hydroxyl radicals generated in an oxidation flow reactor (OFR) under high-NOx conditions on-board a mobile laboratory and characterized SOA and their precursors with a suite of state-of-the-art instrumentation. The OFR produced 10-170 µg m-3 of SOA with a maximum SOA formation potential of 39-50 µg m-3 ppmv-1 CO that occurred following an integrated OH exposure of (1.3-2.0) × 1011 molecules cm-3 s. The results indicate relatively shorter photochemical ages for maximum SOA production than previous OFR results obtained under low-NOx conditions. Such timescales represent the balance of functionalization and fragmentation, possibly resulting in different spatial distributions of SOA in different seasons as the oxidant level changes. The detected precursors may explain as much as 13% of the observed SOA with the remaining plausibly contributed by the oxidation of undetected intermediate-volatility organic compounds. Extrapolation of the results suggests an annual SOA production rate of 0.78 Tg yr-1 from mobile gasoline sources in China, highlighting the importance of effective regulation of gaseous vehicular precursors to improve air quality in the future.

Precursors and Pathways Leading to Enhanced Secondary Organic Aerosol Formation during Severe Haze Episodes.

Molecular analyses help to investigate the key precursors and chemical processes of secondary organic aerosol (SOA) formation. We obtained the sources and molecular compositions of organic aerosol in PM2.5 in winter in Beijing by online and offline mass spectrometer measurements. Photochemical and aqueous processing were both involved in producing SOA during the haze events. Aromatics, isoprene, long-chain alkanes or alkenes, and carbonyls such as glyoxal and methylglyoxal were all important precursors. The enhanced SOA formation during the severe haze event was predominantly contributed by aqueous processing that was promoted by elevated amounts of aerosol water for which multifunctional organic nitrates contributed the most followed by organic compounds having four oxygen atoms in their formulae. The latter included dicarboxylic acids and various oxidation products from isoprene and aromatics as well as products or oligomers from methylglyoxal aqueous uptake. Nitrated phenols, organosulfates, and methanesulfonic acid were also important SOA products but their contributions to the elevated SOA mass during the severe haze event were minor. Our results highlight the importance of reducing nitrogen oxides and nitrate for future SOA control. Additionally, the formation of highly oxygenated long-chain molecules with a low degree of unsaturation in polluted urban environments requires further research.

Resting frontal EEG asymmetry and schizotypal traits: a test-retest study.

Introduction: Increase in right relative to left frontal electroencephalography (EEG) activity has been observed in patients with schizophrenia, both in cognitive tasks and during rest; and this lateralisation may be related to the severity of schizotypal traits. Methods: We used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits, and examined the correlation between these traits and resting EEG frontal asymmetry (left-right) in 52 college students, as well as the reliability of this correlation over a three-month interval. Results: A higher total score on the SPQ was correlated with reduced asymmetry in different frequency bands: gamma and beta2 frequency bands at baseline, and delta and alpha frequency bands three months later. Additionally, the reduced left relative to right frontal gamma and beta2 asymmetry was correlated with the participants' verbal fluency ability. However, this correlation was no longer statistically significant after the total SPQ score was controlled. Conclusions: These findings suggest that resting frontal EEG asymmetry is correlated with powers in different frequency bands, and may be an endophenotype for schizophrenia spectrum disorders.

Multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid with high-performance liquid chromatography for the determination of steroid sex hormones in water and urine.

The development of a simple and sensitive analytical approach that combines multiple monolithic fiber solid-phase microextraction with liquid desorption followed by high-performance liquid chromatography with diode array detection is proposed for the determination of trace levels of seven steroid sex hormones (estriol, 17ß-estradiol, testosterone, ethinylestradiol, estrone, progesterone and mestranol) in water and urine matrices. To extract the target analytes effectively, multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid was used to concentrate hormones. Several key extraction parameters including desorption solvent, extraction and desorption time, pH value and ionic strength in sample matrix were investigated in detail. Under the optimal experimental conditions, the limits of detection were found to be in the range of 0.027-0.12 µg/L. The linear range was 0.10-200 µg/L for 17ß-estradiol, 0.25-200 µg/L estriol, ethinylestradiol and estrone, and 0.50-200 µg/L for the other hormones. Satisfactory linearities were achieved for analytes with the correlation coefficients above 0.99. Acceptable method reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations of both less than 8%. The enrichment factors ranged from 54- to 74-fold. Finally, the proposed method was successfully applied to the analysis of steroid sex hormones in environmental water samples and human urines with spiking recoveries ranged from 75.6 to 116%.

Semantic processing features and schizotypal traits: A test-retest study.

Semantic processing abnormalities have been observed across the schizophrenia spectrum. However, it is unclear whether associations between semantic processing measures and schizotypal traits are stable over time. The current study aimed to explore the temporal stability of semantic processing measures and their correlations with schizotypal traits. In this study, we used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits and explored the association between schizotypal traits and semantic processing measures (i.e., N400- a large negativity with a broad scalp distribution, peaking around 400 ms after the presentation of any potentially meaningful stimulus) at baseline (Time 1; n = 63) and 3 months later (Time 2; n = 44). Repeated-measure ANOVA was conducted to examine the stability of the semantic processing measures; the intraclass correlation coefficient (ICC) was used to examine test-retest reliability; Pearson's r was calculated to explore associations between schizotypal traits and semantic processing measures. Results showed that both behavioral (reaction times) and N400 measures showed high reliability but low temporal stability. N400 latency for semantically unrelated stimuli was correlated with the cognitive-perceptual and the disorganized dimensions of schizotypal traits at Time 2. In conclusion, semantic processing measures generally showed good reliability. Schizotypal traits were correlated with N400 latencies in the current sample, but further studies are needed to examine whether this association is stable.

Rest but busy: Aberrant resting-state functional connectivity of triple network model in insomnia.

Introduction: One classical hypothesis among many models to explain the etiology and maintenance of insomnia disorder (ID) is hyperarousal. Aberrant functional connectivity among resting-state large-scale brain networks may be the underlying neurological mechanisms of this hypothesis. The aim of current study was to investigate the functional network connectivity (FNC) among large-scale brain networks in patients with insomnia disorder (ID) during resting state. Methods: In the present study, the resting-state fMRI was used to evaluate whether patients with ID showed aberrant FNC among dorsal attention network (DAN), frontoparietal control network (FPC), anterior default mode network (aDMN), and posterior default mode network (pDMN) compared with healthy good sleepers (HGSs). The Pearson's correlation analysis was employed to explore whether the abnormal FNC observed in patients with ID was associated with sleep parameters, cognitive and emotional scores, and behavioral performance assessed by questionnaires and tasks. Results: Patients with ID had worse subjective thought control ability measured by Thought Control Ability Questionnaire (TCAQ) and more negative affect than HGSs. Intriguingly, relative to HGSs, patients with ID showed a significant increase in FNC between DAN and FPC, but a significant decrease in FNC between aDMN and pDMN. Exploratory analysis in patients with ID revealed a significantly positive correlation between the DAN-FPC FNC and reaction time (RT) of psychomotor vigilance task (PVT). Conclusion: The current study demonstrated that even during the resting state, the task-activated and task-deactivated large-scale brain networks in insomniacs may still maintain a hyperarousal state, looking quite similar to the pattern in a task condition with external stimuli. Those results support the hyperarousal model of insomnia.

Understanding the Influences of EEG Reference: A Large-Scale Brain Network Perspective.

The influence of reference is a critical issue for the electroencephalography (EEG) and event-related potentials (ERPs) studies. However, previous investigations concentrated less on the location of source at a systematic neuroscience level. Our goal was to examine the EEG signal associated with the locations from a common network parcellation of the human brain function, offering a system perspective of the influence of EEG reference. In our simulation, vertices uniformly distributed in eight large-scale brain networks were adopted to generate the scalp EEG. The brain networks contain the visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal, default networks, and the deep brain structure. The distributions of the most sensitive and neutral electrodes were calculated for each network based on the lead-field matrix. While the most sensitive electrode had a network-specific symmetric pattern, the electrodes in scalp surface had approximately equal chance to be the most neutral electrode. Simulated data were referenced at the FCz, the Oz, the mean mastoids (MM), the average (AVE), and the infinity reference obtained by the reference electrode standardization technique (REST). Intriguingly, the relative error followed the pattern REST

Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development.

Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s) are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae). Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma from Sinonatrix annularis to snake envenomation.

SaPLIγ is a novel gamma phospholipase A2 inhibitor (PLI) recently isolated from Sinonatrix annularis, a Chinese endemic non-venomous snake. To explore the neutralization effects of saPLIγ in snakebite envenomation, a dose equivalent to LD50 of Deinagkistrodon acutus, Agkistrodon halys and Naja atra venom with/without saPLIγ was inoculated into the gastrocnemius muscle of female Kunming mice. The ability of saPLIγ to inhibit myonecrosis and systemic toxicity were evaluated through investigations of muscle histopathology, and determination of the serum levels of creatine kinase (CK), lactate dehydrogenase isoenzyme1 (LDH1) and aspartate transferase (AST). Edema of the gastrocnemius muscle was evaluated by calculating the width difference between the inoculated limb and the contralateral leg. Desmin loss in the gastrocnemius muscle was determined by Western blot analysis. Co-immunoprecipitation and shotgun LC-MS/MS analyses were performed to identify venom proteins that interact with saPLIγ. All the envenomed mice had significantly elevated serum CK, LDH1 and AST levels, whereas the levels were decreased significantly in the presence of saPLIγ. Histopathological evaluation of gastrocnemius muscle sections showed severe snake venom-induced damage, characterized by leukocyte infiltration and erythrocyte leakage, leading to local edema. Myonecrosis, hemorrhage and desmin loss were significantly attenuated by saPLIγ. SaPLIγ interacted with a wide range of venom proteins, including PLA2s, metalloproteinases and C type lectins, which may contribute to broad anti-venom effects.

Sensitive monitoring of benzoylurea insecticides in water and juice samples treated with multiple monolithic fiber solid-phase microextraction and liquid chromatographic analysis.

In present study, a convenient, sensitive and environmentally friendly method for the determination of five benzoylurea insecticides (BUs) in water and juice samples was developed. To extract trace benzoylurea insecticides effectively, poly(methacrylic acid-co-ethylene dimethacrylate) monolith was prepared and used as the sorbent of multiple monolithic fiber solid-phase microextraction (MMF-SPME). The influences of preparation conditions of monolith and extraction parameters of MMF-SPME on BUs were studied thoroughly. Under the optimized conditions, the combination of MMF-SPME with high performance liquid chromatography-diode array detection (MMF-SPME-HPLC-DAD) showed expected analytical performance for target analytes. The limits of detection (S/N=3) of the developed method were 0.026-0.075 µg L(-1) in water and 0.053-0.29 µg L(-1) in juice samples. Good linearity was obtained for analytes with the correlation coefficients (R(2)) above 0.99. Satisfactory repeatability and reproducibility was achieved, with relative standard deviations (RSD) of both less than 10%. Finally, the established MMF-SPME-HPLC-DAD method was successfully applied for the determination of BUs residues in juice and environmental water samples. Recoveries obtained for the determination of BUs in spiking samples ranged from 65.1% to 118%, with RSD below 10% in all cases.