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CD147 is thought to promote tumor angiogenesis mostly through its ability to increase expression of vascular endothelial growth factor (VEGF) in tumor cells. In the present study, we found that the expression of CD147 was significantly higher in hepatocellular carcinoma (HCC) tissue samples than in normal tissues. We also found a significantly larger number of CD147-positive small extracellular vesicles (CD147+ sEVs) in the plasma of HCC patients than those from live cirrhosis (LC) patients and healthy donors (HD). Our data demonstrate a close correlation between ration of CD147+ sEVs with progression of HCC. The index of CD147+ sEVs combined with that of alpha-fetoprotein (AFP) improves the diagnostic efficiency for HCC. and When AFP is negative, the index of CD147+ sEVs still remains a good diagnostic power. Furthermore, we show that hepatocellular carcinoma cell (HepG2)-derived CD147+ sEVs promote cell proliferation, migration, invasion and angiogenesis of human umbilical vein endothelial cells. The CD147+ sEVs up-regulates vascular endothelial growth factor A (VEGFA) by activating PI3K/Akt pathway, thereby promoting angiogenesis. Taken together, our data suggest that HCC-derived sEVs is able to promote angiogenesis through CD147 and demonstrate a diagnostic value of plasma CD147+ sEVs for HCC.

A potential use of small extracellular vesicles (sEVs) for diagnostic and therapeutic purposes has recently generated a great interest. sEVs, when purified directly from various tissues with proper procedures, can reflect the physiological and pathological state of the organism. However, the quality of sEV is affected by many factors during isolation, including separation of sEV from cell and tissues debris, the use of enzymes for tissue digestion, and the storage state of tissues. In the present study, we established an assay for the isolation and purification of liver cancer tissues-derived sEVs (tdsEVs) and cultured explants-derived sEVs (cedsEVs) by comparing the quality of sEVs derived from different concentration of digestion enzyme and incubation time. The nano-flow cytometry (NanoFCM) showed that the isolated tdsEVs by our method are purer than those obtained from differential ultracentrifugation. Our study thus establishes a simple and effective approach for isolation of high-quality sEVs that can be used for analysis of their constituents. Graphical abstract

Objective. To investigate the difference of cabin environment between a large transport aircraft (A) and a previous transport aircraft (B) and its impact on the workload of flight personnel by questionnaire, so as to provide reference for the formulation of aviation and health support measures. Methods. A self-administered questionnaire was used to conduct on-the-spot investigation. The grade data were tested by nonparametric test, with P < 0.05 as the statistical difference. Results. The results of cockpit environment investigation showed that there was no significant difference in the evaluation of cockpit noise and vibration changes between the two types of transport aircraft, but there was significant difference in the evaluation of cockpit temperature comfort, instrument airworthiness and control convenience between the two types of transport aircraft (Z = −3.136, P = 0.002; Z = −3.556, P < 0.001; Z = −3.556, P < 0.001); There was no significant difference in the effects of cockpit environment on hearing and vision between the two types of transport aircraft; there was significant difference in the evaluation of seat comfort between the two types of transport aircraft (Z = −2.395, P = 0.017). Conclusion. The noise and vibration of the cockpit environment of transport A have no obvious change compared with that of transport B, but the temperature comfort of the cockpit of transport A has been greatly improved; the instrument airworthiness and convenient control of the cockpit of transport A have been greatly improved compared with that of transport B; the influence of the cockpit environment of two types of transport on the hearing and vision of flight personnel is not obvious, and The comfort of the seats of transport A has been improved significantly compared with that of transport B.

Background In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of the middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM2.5 (fine particulate matter) and O3 (ozone) on non-accidental mortality and respiratory mortality of the middle-aged and elderly people in Lishui District of Nanjing and provide the evidence for potential prevention and control measures of air pollution. Method Using daily mortality and atmospheric monitoring data from 2015 to 2019, we applied a generalized additive model with time-series analysis to evaluate the association of PM2.5 and O3 exposure with daily non-accidental mortality and respiratory mortality in Lishui District. Using the population attributable fractions to estimate the death burden caused by short-term exposure to O3 and PM2.5。. Result For every 10 μg/m3 increase in PM2.5, non-accidental mortality increased 0.94% with 95% confidence interval (CI) between 0.05 and 1.83%, and PM2.5 had a more profound impact on females than males. For every 10 μg/m3 increase in O3, respiratory mortality increased 1.35% (95% CI: 0.05, 2.66%) and O3 had a more profound impact on males than females. Compared with the single pollutant model, impact of the two-pollutant model on non-accidental mortality and respiratory mortality slightly decreased. In summer and winter as opposed to the other seasons, O3 had a more obvious impact on non-accidental mortality. The population attributable fractions of non-accidental mortality were 0.84% (95% CI:0.00, 1.63%) for PM2.5 and respiratory mortality were 0.14% (95% CI:0.01, 0.26%) for O3. For every 10 μg/m3 decrease in PM2.5, 122 (95% CI: 6, 237) non-accidental deaths could be avoided. For every 10 μg/m3 decrease in O3, 10 (95% CI: 1, 38) respiratory deaths could be avoided. Conclusion PM2.5 and O3 could significantly increase the risk of non-accidental and respiratory mortality in the middle-aged and elderly people in Lishui District of Nanjing. Exposed to air pollutants, men were more susceptible to O3 damage, and women were more susceptible to PM2.5 damage. Reduction of PM2.5 and O3 concentration in the air may have the potential to avoid considerable loss of lives.

Background In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM2.5 and O3 on non-accidental mortality and respiratory mortality of the middle-aged and elderly in Lishui district of China and provide the scientific basis for the prevention and control measures of air pollution. Method: Using daily mortality and atmospheric monitoring data from 2015 to 2019, we applied a generalized additive model with time-series analysis to study the association of PM2.5 and O3 exposure with daily non-accidental mortality and respiratory mortality in Lishui district of China. Using attributable risk to estimate the death burden attributable to short-term exposure to O3 and PM2.5。 Result PM2.5 and O3 were associated with non-accidental and respiratory mortality. For every 10µg/m3 increased in PM2.5, non-accidental mortality increased 0.94% (95%CI: 0.05%-1.83%), and PM2.5 had a more significant impact on women. For every 10µg/m3 increased in O3, respiratory mortality increased 1.35% (95%CI: 0.05%-2.66%). and O3 had a more significant impact on men. Compared with single pollutant model, the impact of the two-pollutant model on non-accidental mortality and respiratory mortality slightly decreased. Besides, in summer and winter, O3 had a more obvious impact on non-accidental mortality. The Population Attributable Fractions of non-accidental mortality were 0.839% (95%CI:0.004–1.626%) for PM2.5 and the PAF of respiratory mortality were 0.135% (95%CI:0.005–0.263%) for O3. Conclusion PM2.5 and O3 could significantly increase the risk of non-accidental and respiratory mortality in middle-aged and elderly people in Lishui district, China. Exposing to air pollutants, men were more susceptible to O3 damage, and women were more susceptible to PM2.5 damage.

The synthetic pyrethroid derivative, fenpropathrin, is a widely used insecticide. However, a variety of toxic effects in mammals have been reported. In particular, fenpropathrin induces degeneration of dopaminergic neurons and parkinsonism. However, the mechanism of fenpropathrin-induced parkinsonism has remained unknown. In the present study, we investigated the toxic effects and underlying mechanisms of fenpropathrin on perturbing the dopaminergic system both in vivo and in vitro. We found that fenpropathrin induced cellular death of dopaminergic neurons in vivo. Furthermore, fenpropathrin increased the generation of reactive oxygen species, disrupted both mitochondrial function and dynamic networks, impaired synaptic communication, and promoted mitophagy in vitro. In mice, fenpropathrin was administered into the striatum via stereotaxic (ST) injections. ST-injected mice exhibited poor locomotor function at 24 weeks after the first ST injection and the number of tyrosine hydroxylase (TH)-positive cells and level of TH protein in the substantia nigra pars compacta were significantly decreased, as compared to these parameters in vehicle-treated mice. Taken together, our results demonstrate that exposure to fenpropathrin induces a loss of dopaminergic neurons and partially mimics the pathologic features of Parkinson’s disease. These findings suggest that fenpropathrin may induce neuronal degeneration via dysregulation of mitochondrial function and the mitochondrial quality control system.

Fenpropathrin is an insecticide that is widely used in agriculture. It remains unknown whether fenpropathrin exposure increases the risk of Parkinson's disease. We found that fenpropathrin increased oxidative stress both in vitro and in vivo. Additionally, fenpropathrin increased production of ROS, NOS2, and HO-1, and decreased SOD and GSH in astrocytes. We further found that fenpropathrin-mediated oxidative stress might inhibit autophagic flow, including decreased expression of LC3A/B and enhanced expression of SQSTM1 via down-regulation of CDK-5, an upstream marker of autophagy. In mice, autophagy was slightly different from that found in astrocytes, as reflected in the increased expressions of LC3A/B and SQSTM1. Our findings elucidate the toxicological phenomena and pathogenic mechanisms of fenpropathrin and may provide guidance for improved pesticide control and environmental protection.

Parkinson's disease (PD) is a common neurodegenerative disease that is characterized by pathological dopaminergic (DA) neuronal death and α-synuclein aggregation. Glutamate excitotoxicity is a well-established pathogenesis of PD that involves dysfunctional expression of glutamate transporters. Glutamate transporter-1 (GLT-1) is mainly responsible for clearance of glutamate at synapses, including DA synapses. However, the role of GLT-1 in the aberrant synaptic transmission in PD remains elusive. In the present study, we generated small-interfering RNAs (siRNAs) to knockdown GLT-1 expression in primary astrocytes, and we report that siRNA knockdown of astrocytic GLT-1 decreased postsynaptic density-95 (PSD-95) expression in neuron-astrocyte cocultures in vitro. Using adeno-associated viruses (AAVs) targeting GLT-1 short-hairpin RNA (shRNA) sequences with a glial fibrillary acidic protein (GFAP) promoter, we abolished astrocytic GLT-1 expression in the substantia nigra pars compacta (SNpc) of mice. We found that GLT-1 deficiency in the SNpc induced parkinsonian phenotypes in terms of progressive motor deficits and nigral DA neuronal death in mice. We also found that there were reactive astrocytes and microglia in the SNpc upon GLT-1 knockdown. Furthermore, we used RNA sequencing to determine altered gene expression patterns upon GLT-1 knockdown in the SNpc, which revealed that disrupted calcium signaling pathways may be responsible for GLT-1 deficiency-mediated DA neuronal death in the SNpc. Taken together, our findings provide evidence for a novel role of GLT-1 in parkinsonian phenotypes in mice, which may contribute to further elucidation of the mechanisms of PD pathogenesis.

Jet formation is the decisive factor of penetrating power of shaped charge, coherence and stability contribute to penetration. In the same condition, multiple penetrating tests of the shaped charge with depleted uranium(DU) liner did not get the expected results. In order to study the jet forming characteristics of DU liner under static explosion condition, an X-ray photography experiment was designed, which turned out to show the jet being badly incoherent. To research the incoherence of DU shaped charge jet from principles of jet incoherence, supersonic collision worked out to be the reasons for incoherence of the shaped charge jet. This paper provides a method for structural optimization of DU shaped charge and DU liner processing, which has guiding significance for application of DU liner in high explosive antitank projectile.

Many publications reported that genetic dysfunction mediates abnormal immune responses in the brain, which is important for the development of neurodegenerative diseases, especially for Parkinson's disease (PD). This immune disorder results in subsequent inflammatory reaction, which stimulates microglia or other immune cells to secrete cytokines and chemokines and disturbs the proportion of peripheral blood lymphocyte subsets contributing to dopaminergic (DA) neuron apoptosis. Furthermore, the abnormal immune related signal pathways caused by genetic variants promote chronic inflammation destroying the blood-brain barrier, which allows infiltration of different molecules and blood cells into the central nervous system (CNS) exerting toxicity on DA neurons. As a result, the inflammatory reaction in the CNS accelerates the progression of Parkinson's disease and promotes α-synuclein aggregation and diffusion among DA neurons in the procession of Parkinson's disease. Thus, for disease evaluation, the genetic mediated abnormal immune response in PD may be assessed based on the multiple immune molecules and inflammatory factors, as well as the ratio of lymphocyte subsets from PD patient's peripheral blood as potential biomarkers.

Objectives This study aimed to identify patients with major depressive disorder (MDD) by developing different machine learning (ML) models based on tryptophan hydroxylase-2 (TPH2) methylation and environmental stress. Methods The data were collected from 291 patients with MDD and 100 healthy control participants: individual basic information, the Negative Life Events Scale (NLES) scores, the Childhood Trauma Questionnaire (CTQ) scores and the methylation level at 38 CpG sites in TPH2. Information gain was used to select critical input variables. Support vector machine (SVM), back propagation neural network (BPNN) and random forest (RF) algorithms were used to build recognition models, which were evaluated by the 10-fold cross-validation. SHapley Additive exPlanations (SHAP) method was used to evaluate features importance. Results Gender, NLES scores, CTQ scores and 13 CpG sites in TPH2 gene were considered as predictors in the models. Three ML algorithms showed satisfactory performance in predicting MDD and the BPNN model indicated best prediction effects. Conclusion ML models with TPH2 methylation and environmental stress were identified to possess great performance in identifying patients with MDD, which provided precious experience for artificial intelligence to assist traditional diagnostic methods in the future.

Parkinson's disease (PD) features the degeneration and death of dopamine neurons in the substantia nigra pars compacta and the formation of Lewy bodies that contain α-synuclein. Among the numerous PD etiologies, glutamate excitotoxicity is a research hot spot, and glutamate transporters play key roles in this theory. It has been shown that the expression of the glutamate transporter is regulated by microRNAs. In this study, we found that the levels of expression and function of glutamate transporter type 1 (GLT-1) were significantly reduced and miR-543-3p was upregulated during the development of PD. Furthermore, our results indicated that GLT-1 plays an important role in the pathomechanism of PD. We found that miR-543-3p can suppress the expression and function of GLT-1 in MPP+-treated astrocytes and MPTP-treated mice. Inhibition of miR-543-3p can rescue the expression and function of GLT-1 and relieve dyskinesia in the PD model, which suggests that inhibition of miR-543-3p could serve as a potential therapeutic target for PD.

Objective To investigate workload changes of subjects during simulated long-haul flights at daytime and nighttime. Methods Eight volunteers were completed the simulated long-haul flight experiments at the same time periods of day and night. The parameters of measurements included flight simulation performance, additional task performance, ratings of perceived exertion scale (RPE), Stanford Sleepiness Scale (SSS), and critical flicker fusion frequency (CFF). Results There were no significant changes of the simulated flight performance between daytime group and nighttime group. The achievement of additional task was significantly lower than that of the same time period in daytime group. RPE and SSS scores in nighttime group were increased and CFF decreased. Conclusions Simulated long-haul flight at nighttime could aggravate the flight workload and reduce the reserved operating capacity.

In order to solve the identification of projectile surface defect category of which body defect detection system, the classifier of the body defect detection system was designed. The mathematical model of BP neural network and support vector machine (SVM) network classifier were established respectively and realized by using VC + + program and MATLAB, the number of nodes in the middle layer were determined, and the detection performance of the two kinds of classifiers were tested. Test samples were collected from magnetic particle detection images of 3 models which included 20 samples containing cracks and 600 without defects. The results show that the SVM defect classification network classifier has higher recognition rate than the BP neural network, but BP network has stronger stability classification than the SVM.

An intelligent vehicle system is deeloped, where five single-row laser scannners are mounted on the car to profile object geometry along the streets from different viewpoints and with different directions; a GPS (Global Positioning System)/IMU (Inertial Measurement Unit) based navigation unit is also applied to give outputs of vehicle pose. This paper focus on sensor alignment in order to achieve an omni-directional laser measurement of dynamic urban environment using an intelligent vehicle. An algorithm is proposed, where the laser scanners that facing towards different directions are aligned through horizontal and vertical matching of laser points. Experimental results are presented demonstrating that a comprehensive knowledge of the environment can be achieved, and shortages of each individual sensor can be compensated through such a sensor fusion.

Axially chiral N,N'-dioxide Lewis base promoters have been developed and have for the first time been applied to the asymmetric synthesis of alpha-amino nitriles through cyanide addition to aldimines. The chiral 3,3'-dimethyl-2,2'-biquinoline N,N'-dioxide 2 exhibited high enantioselectivity for asymmetric Strecker reactions between N-benzhydrylimines and trimethylsilyl cyanide. In the presence of 1 equiv. of chiral promoter 2, the cyanosilylation of aldimines afforded the corresponding alpha-amino nitriles with ee values of up to 95%. Optically pure products (99% ee) were obtained simply by recrystallization in the cases of some of the products. Moreover, the promoter 2 could be recovered and reused at least four times without any loss of enantioselectivity and reactivity. A putative mechanism for the enantioselective Strecker reactions is also discussed. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).