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This paper presents a detailed characterization of the size and shape distributions, and chemical compositions of ambient fine and ultrafine particles collected at the site of a building demolition and construction project at the Pennsylvania State University. Particle samples were collected with a nine-stage cascade impactor, characterized via transmission electron microscopy and energy dispersive spectroscopy for elemental compositions, and images analyzed for morphological features. 89.3% of the particles collected by count were ultrafine particles or aggregates of ultrafine particles that disaggregated during the collection process. The mean particulate matter mass and count concentrations were 167.2 µg/m3 and 16,232 particles/cm3, respectively. 72.2% of the particles by count were morphologically circular on two-dimensional images and 74.0% of the particles by count had an aspect ratio of between 1:1 and 2:1. The five most prevalent elements found in the samples were carbon, oxygen, silicon, sulfur, and calcium, with corresponding mass fractions of 40.8%, 26.4%, 7.6%, 5.1%, and 4.7%. Based on the current regulatory occupational exposure limits, the particulate matter at the construction site was within permissible concentrations. These results enable a comparison of a real-world particulate exposure environment to hazard levels determined through single-particle-type exposure studies.

Different from systems that directly provide online shared courses such as MOOC, online learning systems such as Tencent Classroom simulate a real classroom environment for students and teachers to realize online face-to-face teaching, utilized during the COVID-19 pandemic. Nevertheless, due to the limitation of physical distance, the intelligent design of online learning systems is necessary to provide students with a good learning experience. This study notes that an unexpected optimization effect is the impact of system characteristics on the flow experience of online learning systems, which has not been studied, but plays a vital role in the effectiveness of online learning systems. In the study, a questionnaire was created and multi-stage sampling was used to investigate 623 college students. Based on the DeLone and McLean model of IS success and flow theory, a model for optimizing system characteristics and flow experience was constructed and its effectiveness was tested. The results reveal that system characteristics have a positive impact on continuance intention and flow experience. Additionally, flow experience and learning effect have a positive impact on continuance intention. Furthermore, flow experience has a positive impact on the learning effect. This study emphasizes the flow experience of online learning systems and reveals the optimization direction of online virtual face-to-face classrooms to provide references for the Ministry of Education, schools, and enterprises providing education systems.

Point spread function (PSF) engineering is an important technique to encode the properties (e.g., 3D positions, color, and orientation) of a single molecule in the shape of the PSF, often with the help of a programmable phase modulator. A deformable mirror (DM) is currently the most widely used phase modulator for fluorescence detection as it shows negligible photon loss. However, it relies on careful calibration for precise wavefront control. Therefore, design of an optimal PSF not only relies on the theoretical calculation of the maximum information content, but also the physical behavior of the phase modulator, which is often ignored during the optimization process. Here, we develop a framework for PSF engineering which could generate a device specific optimal PSF for 3D super-resolution imaging using a DM. We use our method to generate two types of PSFs with depths of field comparable to the widely used astigmatism and tetrapod PSFs, respectively. We demonstrate the superior performance of the DM specific optimal PSF over the conventional astigmatism and tetrapod PSF both theoretically and experimentally.

We report a high-yield synthesis of gold (Au) nanosheets with tunable size and surface morphology in the aqueous phase. In particular, crumpled and flat Au nanosheets with a thickness of ∼10 nm could be selectively produced in high purity when the reaction was conducted at room temperature and in an ice-water bath, respectively. Unlike Au nanoplates/nanoprisms in the form of well-defined triangles or hexagons documented in previous studies, the current products exhibit random in-plane branches or holes, together with wavy edges. Strong absorbance in the NIR region was observed for all the Au nanosheet products. When serving as electrocatalysts for the ethanol oxidation reaction, the current products exhibited an enhanced activity and operation stability, as compared to quasi-spherical counterparts.

Synthesis of the unconventional phase of noble metal nanocrystals may create new opportunities in exploring intriguing physicochemical properties but remains challenging. In the research field of thin film growth, the interface strain offers a general driving force to stabilize the metastable phase of epitaxial film. Herein we extend this concept to the field of noble metal nanocrystals and report the solution synthesis of metastable face-centered tetragonal Au that has not been discovered before. The successful synthesis relies on the formation of intermetallic AuCu3@Au core-shell structure, where the interface strain stabilizes the metastable fct Au overlayer. Compared with the face-centered cubic Au counterpart, the metastable fct Au shows greatly improved catalytic activity toward CO2 reduction to CO. The density functional theory calculations and spectroscopic studies reveal that the metastable fct Au upshifts the d-band center, which lowers the energy barrier of key intermediate COOH* formation and thus facilitates the reaction kinetics.

Our previous study established an asynchronous BCI system by using the oddball paradigm to simultaneously induce event-related potentials (ERPs) and visual evoked potentials (VEPs) (E-V BCIs). We found that stimulus onset asynchrony (SOA) is an important factor for performance since it significantly affects the ERP and VEP. Increasing the SOA increases the ERP, which improves the accuracy of detecting target stimuli. However, a larger SOA leads to a lower VEP frequency, which causes the VEP to have poor accuracy when discriminating between the brain states. How to balance the two potentials and accuracies is a problem. This study established eight SOAs from 100 ms to 375 ms that were composed of different interstimulus intervals and the same stimulus duration of 80 ms. We used a probability-based Fisher linear discriminant analysis (P-FLDA) classifier to calculate the classification accuracies of the ERP-based visual speller, VEP-based brain state discrimination, and E-V BCI. The results show that as the SOA increases, the amplitudes of N200 and P300 increase, and the accuracy also shows an increasing trend. However, the frequency of the VEP and the accuracies of state discrimination show downward trends. The change in accuracies of the E-V BCI system combining these two parts is nonlinear, and the SOA optimal value is 125 ms. The SOA of 125 ms yields the best accuracies of 95.83% and practical bit rate of 57.17 bits/min in the E-V BCI system, which provides a guideline for selecting the SOA to improve the performance.

A simple and efficient methodology for the synthesis of 2-aryl-perfluorobenzoxazoles was developed via a direct dual C–F functionalization of perfluorobenzene with arylformamide in the presence of a Fe(II)/NaH/DMSO system. Various substituted aryl formamides are tolerated giving good yields. The preliminary fluorescence properties (up to 99% fluorescence quantum yield of 3d) of the products and their applications in the synthesis of uniform cubic platinum nanoparticles indicate that these perfluorobenzoxazole derivatives may have certain potential applications in materials chemistry.

Objective. Motor imagery (MI)-based brain-computer interfaces (BCIs) provide an additional control pathway for people by decoding the intention of action imagination. The way people imagine greatly affects MI-BCI performance. Action itself is one of the factors that influence the way people imagine. Whether the different actions cause a difference in the MI performance is unknown. What is more important is how to manifest this action difference in the process of imagery, which has the potential to guide people to use their individualized actions to imagine more effectively. Approach. To explore action differences, this study proposes a novel paradigm named as action observation based delayed matching posture task. Ten subjects are required to observe, memorize, match, and imagine three types of actions (cutting, grasping and writing) given by visual images or videos, to accomplish the phases of encoding, retrieval and reinforcement of MI. Event-related potential (ERP), MI features, and classification accuracy of the left or the right hand are used to evaluate the effect of the action difference on the MI difference. Main results. Action differences cause different feature distributions, resulting in that the accuracy with high event-related (de)synchronization (ERD/ERS) is 27.75% higher than the ones with low ERD/ERS (p < 0.05), which indicates that the action difference has impact on the MI difference and the BCI performance. In addition, significant differences in the ERP amplitudes exists among the three actions: the amplitude of P300-N200 potential reaches 9.28 μV of grasping, 5.64 μV and 5.25 μV higher than the cutting and the writing, respectively (p < 0.05). Significance. The ERP amplitudes derived from the supplementary motor area shows positive correlation to the MI classification accuracy, implying that the ERP might be an index of the MI performance when the people is faced with action selection. This study demonstrates that the MI difference is related to the action difference, and can be manifested by the ERP, which is important for improving MI training by selecting suitable action; the relationship between the ERP and the MI provides a novel index to find the suitable action to set up an individualized BCI and improve the performance further.

The complement system plays a crucial role in cognitive impairment in obstructive sleep apnea (OSA). The present study aimed to investigate the connections between complement component 8 gamma (C8G) levels in astrocyte-derived exosomes (ADEs) and cognitive impairment in OSA patients without dementia. This cross-sectional cohort study recruited 274 participants without dementia, including 124 OSA patients with mild cognitive impairment (MCI), 100 OSA patients without MCI, and 50 healthy control subjects. Enrolled participants underwent polysomnography (PSG) evaluation, neuropsychological scale assessment, magnetic resonance imaging scanning, and collection of peripheral blood samples for quantification of complement proteins in ADEs. The findings showed higher C8G concentrations in ADEs from OSA patients with MCI than in the controls and OSA without MCI group. Logistic regression analysis suggested that C8G levels in ADEs were independently associated with MCI in OSA patients. Multivariable linear regression analysis demonstrated that C8G levels in ADEs were significantly correlated with global cognitive scores and all cognitive subdomain scores after adjusting for demographic factors (age, sex, education), vascular risk factors (Body mass index, history of hypertension, diabetes, dyslipidemia), depressive symptoms measures, and apnea-hypopnea index (AHI) values. The levels of C8G were linearly positively related to the white matter hyperintensity (WMH) volumes in Pearson's correlation analysis. Our research confirmed that C8G levels are significantly associated with cognitive impairment in OSA patients, which paves the way for novel therapeutic targets for neurocognitive dysfunction progression in OSA patients in the future.

This study characterizes particles emitted from three commercial sunscreen sprays with a sun protection factor (SPF) of 30. Sample collection and measurement were made at 20 cm longitudinally and 36 cm laterally from the emission point to simulate the point of inhalation for an application on one’s arm. Over 85% of all particles by count had a diameter of less than 100 nm. The three products had a mass median diameter of 0.65 µm, 1.40 µm, and 1.70 µm, respectively. The collected aerosols in the breathing zone from application of the sunscreen sprays with TiO2 and ZnO contained less than advertised. The product containing only TiO2 as active ingredient generated aerosols with a higher mass fraction of TiO2. The total particle mass concentrations of the sunscreens were 0.77 µg/m3, 0.57 µg/m3, and 0.80 µg/m3, respectively. The PM2.5 mass concentrations were 0.45 µg/m3, 0.30 µg/m3, and 0.37 µg/m3, respectively. The estimated mass concentrations for total particles, PM2.5, TiO2, ZnO, and SiO2 did not exceed the regulatory limits by the Occupational Health and Safety Administration (OSHA) or the recommended limits by the National Institute for Occupational Safety and Health (NIOSH), meaning 8-h daily average exposures at these levels throughout a typical career would comply with current regulations. Consequently, applying the three sunscreen sprays does not pose a significant hazard via respiratory exposure under these conditions, and considering the transient and relatively infrequent use by most consumers, a substantial factor of safety exists.

The loss of tight junction (TJ) and adherens junction (AJ) proteins leads to the damage of the blood-brain barrier (BBB) during cerebral ischemia. Inhibition of cyclic nucleotide phosphodiesterase 4 (PDE4) by roflumilast (Roflu) protects against ischemic stroke-induced neuronal damage. However, the effects of Roflu on vascular endothelial injury and BBB integrity remain unknown. Here, we investigated whether and how Roflu protects against cerebrovascular endothelial injury caused by cerebral ischemia/reperfusion. We demonstrated that PDE4B knocking-down increased the expression of TJ and AJ proteins in human brain microvascular endothelial cells (HBMECs) subjected to oxygen-glucose deprivation reperfusion (OGD/R). Inhibition of PDE4 by Roflu (1.0 μM) showed similar effects as PDE4B knocking-down. We then found that Roflu activated Notch1/Hairy and enhancer of split 1 (Hes1) signaling. Consistently, the effects of Roflu on TJ and AJ proteins were reversed by the γ-secretase inhibitor DAPT or Hes1 knocking-down. Furthermore, Roflu (1.0 mg/kg) improved neurobehavioral outcomes and ameliorated BBB disruption in rats following ischemic stroke. Roflu also increased the levels of TJ proteins and AJ proteins in vivo. Collectively, these data suggest that Roflu is a promising compound for the prevention of BBB damage. The protective effects of Roflu are mediated through activation of the Notch1/Hes1 pathway.

Coexistence of heavy metals in aquatic environments exert complex effects on amphibians. Here, the adverse effects of Pb (0.14 μM) combined with Cu at concentrations of 0, 0.25, and 1.0 μM were investigated in Bufo gargarizans tadpoles. Tadpoles were chronically exposed from Gosner stage (Gs) 26 to Gs 38, and morphology of tadpoles as well as intestinal histology and bacterial community were assessed. Our results indicated that Pb+Cu1.0 exposure induced significant retardation of somatic mass, total length, intestine mass, and intestine length as well as intestinal histological alterations. Pb+Cu0.25 and Pb+Cu1.0 exposure were associated with the loss of gut bacterial diversity. Proteobacteria and Bacteroidetes were two dominant phyla in tadpoles independently of heavy metal exposure, but the abundance of Proteobacteria increased significantly in Pb+Cu1.0 group and Bacteroidetes decreased significantly in all treatment groups. Furthermore, functional prediction indicated that metabolic disorders were associated with Pb+Cu0.25 and Pb+Cu1.0 exposure. Overall, relative limited shifts in intestinal bacterial diversity, composition, and functionality caused by Pb+Cu0 exposure, while coexistence of Pb and Cu induced gut dysbiosis and might further cause disturbance of metabolic homeostasis. The findings of this study provide insights into the effects of Pb and Cu coexistence on the health of amphibians.

Alcohol-water solution-mediated transformation of gypsum into α-hemihydrate (α-HH) whiskers provides a green alternative for the high-value-added recycling of flue gas desulfurization (FGD) gypsum. However, the role of non-lattice cations during the transformation is still unclear. We report an evolution from "boosting-retarding" to "boosting-retarding-boosting" and finally to "boosting only" effect of non-lattice Na

Electrocatalytic energy conversion is one of the most promising pathways to develop clean and renewable energy technologies, and the development of high-performance electrocatalysts to improve the energy conversion efficiency is of paramount importance. Metal nanocrystals with twin defects possess unique features, including lattice strain and high density of low-coordinated atoms at the twin boundary, endowing them with excellent catalytic performance in various electrocatalytic reactions. Herein, we briefly summarize recent advances in the synthesis of metal nanocrystals with various twin structures, recent breakthroughs related to electrocatalytic applications of twin metal nanocrystals are also overviewed. Finally, the major challenges and perspectives for future development of twin metal nanocrystals in electrochemical applications are proposed.

Lithium-ion batteries play an important role in large-scale energy storage systems. However, the power inconsistency of the battery packs restricts the developments of modern technologies in energy storage area. The motivation of the present study is to serve the growing needs of the energy balance for lithium-ion battery packs. The present study proposes a flexible multiphase interleaved converter for the energy equalization of a lithium battery pack with series configuration. Moreover, the graph theory is applied to the analysis of equalization circuits. It is intended to establish a unified standard for the comparison. The parameter of average efficiency is considered as an important indicator to evaluate the characteristics of the equilibrium system. The proposed method is verified by constructing a lithium-ion battery pack with the equalization circuit. It is observed that the proposed multiphase interleaved converter has flexible characteristics, while it has low energy loss compared with the conventional methods. It is found that the proposed method simplifies the complex equalization circuits into graphs and facilitates the comparison of the average efficiency of the system. It is concluded that this method is a feasible and powerful method for evaluating the battery equalization circuit. This approach can be applied for solving complex problems in other engineering applications.

This study aims to identify lower risk exterior shelter areas and building air intake locations by modeling particulate matter (PM) dispersion in a three-dimensional street canyon from a point source and comprises a wind tunnel experiment and a computational fluid dynamics (CFD) simulation. The model street canyon was a two-by-two building array of constant height with aspect ratios of 0.35, 0.70, and 1.05. A PM emission source external to the street canyon was simulated with water droplets from an ultrasonic humidifier in the wind tunnel. The CFD simulation, using the standard turbulence k-ϵ turbulence model and the Discrete Phase Model, showed that, inside the street canyon, the sidewalks had the lowest PM concentration at the breathing level of 1.5 m above the ground. Regardless of wind direction and PM source location, the roofs had the lowest PM concentration among all building surfaces with access to the internal intersection. Therefore, if an accidental point release of PM outside the street canyons occurs, pedestrians that could not enter buildings should stay on the sidewalks. For building construction and renovation, new ventilation air intakes should be installed on the roofs, and the intakes that are already installed on other building facade surfaces should be advised to be closed during such episode.

The purpose of our study was to investigate the correlation between neural-derived plasma exosomal amyloid-β (Aβ)42, total tau (T-tau) and tau phosphorylated at threonine 181 (P-T181-tau) protein levels and cognitive impairment in patients with obstructive sleep apnea (OSA).There were 122 subjects without dementia included in the study: 27 patients with OSA and mild cognitive impairment (MCI), 52 OSA patients without MCI, and 43 subjects diagnosed with simple snoring but not MCI as the control group. Neuronal-derived exosomal proteins were measured by ELISA kits for Aβ42, T-tau and P-T181-tau. The cognitive function was evaluated by a Chinese version of the Montreal Cognitive Assessment (MoCA) questionnaire, and a normal cognitive score was ≥26.The exosomal Aβ42, T-tau and P-T181-tau levels in the OSA with MCI group were higher than those in the OSA group. The Aβ42, T-tau, and P-T181-tau levels in the plasma neuronal-derived exosomes were associated with an increased risk of cognitive impairment in OSA patients after additional adjustment for age, gender, education, vascular risk factors, apnea-hypopnea index (AHI) or oxygen reduction index (ODI). Furthermore, there were also significant associations between Aβ42, T-tau, and P-T181-tau in neural-derived plasma exosomes and Epworth Sleepiness Scale, AHI, and ODI in OSA patients. After 1 year of continuous positive airway pressure (CPAP) intervention, the neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau were significantly lower than those at baseline (P = 0.001, P = 0.012, and P = 0.034).These findings indicate that peripheral blood levels of neuronal-derived exosomal Aβ and tau proteins were increased in OSA patients with cognitive impairment. CPAP interventions could possibly improve cognitive function and be associated with decreased levels of exosomal Aβ and tau proteins.

There is accumulating evidence that mitochondrial dysfunction is associated with the contribution of diabetes to Alzheimer disease (AD) progression. Neuronal mitochondrial proteins are found in plasma neuronal-derived exosomes (NDEs) at levels that reflect those in brain neurons. Here, we tested the performance of mitochondrial proteins in plasma NDEs to predict cognitive decline and brain injury in participants with diabetes. The study participants with type 2 diabetes mellitus (T2DM) included 41 cognitively normal control subjects, 97 individuals with mild cognitive impairment (MCI) (68 individuals with stable MCI; 29 individuals with progressive MCI), and 36 patients with AD dementia. Plasma neuroexosomal proteins were measured by ELISA kits. Spearman correlation was used to test associations between plasma neuroexosomal mitochondrial proteins and other core biomarkers of AD. Diagnostic accuracy for progressive MCI and AD was obtained for mitochondrial proteins using receiver operating characteristic curve analyses. The associations of mitochondrial proteins with the conversion from MCI to AD were assessed by Cox proportional hazard regression analysis. Plasma levels of neuroexosomal NADH ubiquinone oxidoreductase core subunit S3 (NDUFS3) and succinate dehydrogenase complex subunit B (SDHB) were significantly lower in patients with T2DM with AD dementia and progressive MCI than in cognitively normal subjects (P < 0.001 for both groups). We also found that plasma neuroexosomal NDUFS3 and SDHB levels were lower in progressive MCI subjects than in stable MCI subjects. Both plasma neuroexosomal NDUFS3 and SDHB offer diagnostic utility for AD. Low plasma neuroexosomal SDHB levels significantly predicted conversion from MCI to AD. In addition, low mitochondrial protein levels were associated with the rate of hippocampal and gray matter atrophy and reduced AD signature cortical thickness in progressive MCI over the follow-up period. These data suggest that both plasma neuroexosomal NDUFS3 and SDHB are already increased at the early clinical stage of AD, and indicate the promise of plasma neuroexosomal mitochondrial proteins as diagnostic and prognostic biomarkers for the earliest symptomatic stage of AD in participants with diabetes.

Background There is accumulating evidence that mitochondrial dysfunction is associated with the contribution of diabetes to Alzheimer's disease (AD) progression. Neuronal mitochondrial proteins found in plasma neuronal-derived exosomes(NDEs) at levels that reflect those in brain neurons. Here, we tested the performance of mitochondrial proteins in plasma NDEs to predict cognitive decline and brain injury in diabetic participants. Methods The type 2 diabetes mellitus (T2DM) participants in the study included 41 cognitively normal controls, 97 individuals with mild cognitive impairment (MCI) (68 individuals with stable MCI; 29 individuals with progressive MCI) and 36 patients with AD dementia. Plasma neuroexosomal proteins were measured by ELISA kits. Spearman’s correlation was used to test associations between mitochondrial proteins and other core biomarkers of AD in plasma neuronal-derived exosomes. Diagnostic accuracy (the area under the curve (AUC)) for progressive MCI and AD was obtained for mitochondrial proteins using receiver operating curve (ROC) analyses. The associations of mitochondrial proteins with the conversion from MCI to AD were assessed by Cox proportional hazard regression analysis. Results Plasma neuroexosomal NADH ubiquinone oxidoreductase core subunit S3 (NDUFS3) and succinate dehydrogenase complex subunit B (SDHB) levels were significantly lower in T2DM patients with AD dementia (232.7 ± 63.4, 1360.7 ± 328.5, pg/ml) and progressive MCI (274.4 ± 78.6, 1536.7 ± 342.8, pg/ml) than in cognitively normal subjects (333.9 ± 96.7, 2050.4 ± 628.9, pg/ml) (P < 0.001 for both groups). We also found that plasma neuroexosomal NDUFS3 and SDHB levels were lower in progressive MCI (274.4 ± 78.6 pg/ml, 1536.7 ± 342.8 pg/ml) than in stable MCI (319.9 ± 109.8 pg/ml, P < 0.05; 1824.7 ± 606.4 pg/ml, P < 0.05) subjects. Both plasma neuroexosomal NDUFS3 and SDHB offer diagnostic utility for AD. Low plasma neuroexosomal SDHB levels significantly predicted conversion from MCI to AD. In addition, low mitochondrial proteins levels were associated with the rate of hippocampal and gray matter atrophy, reduced AD signature cortical thickness in progressive MCI over the follow-up period. Conclusions These data suggest that both plasma neuroexosomal NDUFS3 and SDHB are already increased at the early clinical stage of AD, and indicate the promise of plasma neuroexosomal mitochondrial proteins as diagnostic and prognostic biomarkers for the earliest symptomatic stage of AD in diabetic participants .

We have previously shown that roflupram (ROF) protects against MPP(+)-induced neuronal damage in models of Parkinson’s disease (PD). Since impaired degradation of α-synuclein (α-syn) is one of the key factors that lead to PD, here we investigated whether and how ROF affects the degradation of α-syn in rotenone (ROT)-induced PD models in vivo and in vitro. We showed that pretreatment with ROF (10 μM) significantly attenuated cell apoptosis and reduced the level of α-syn in ROT-treated SH-SY5Y cells. Furthermore, ROF significantly enhanced the lysosomal function, as evidenced by the increased levels of mature cathepsin D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1) through increasing NAD(+)/NADH and the expression of sirtuin 1 (SIRT1). Pretreatment with an SIRT1 inhibitor selisistat (SELI, 10 μM) attenuated the neuroprotection of ROF, ROF-reduced expression of α-syn, and ROF-increased expression levels of LAMP1 and mature CTSD. Moreover, inhibition of CTSD by pepstatin A (20 μM) attenuated ROF-reduced expression of α-syn. In vivo study was conducted in mice exposed to ROT (10 mg·kg(−1)·d(−1), i.g.) for 6 weeks; then, ROT-treated mice received ROF (0.5, 1, or 2 mg·kg(−1)·d(−1); i.g.) for four weeks. ROF significantly ameliorated motor deficits, which was accompanied by increased expression levels of tyrosine hydroxylase, SIRT1, mature CTSD, and LAMP1, and a reduced level of α-syn in the substantia nigra pars compacta. Taken together, these results demonstrate that ROF exerts a neuroprotective action and reduces the α-syn level in PD models. The mechanisms underlying ROF neuroprotective effects appear to be associated with NAD(+)/SIRT1-dependent activation of lysosomal function.

We have previously shown that inhibition of cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4) protects against cellular toxicity in neuronal cells. Since α-synuclein (α-syn) toxicity contributes to the neurodegeneration of Parkinson's disease (PD). The aim of this study was to explore the effects and mechanisms of PDE4 on α-syn-induced neuronal toxicity. Using mutant human A53T α-syn overexpressed SH-SY5Y cells, we found that PDE4B knockdown reduced cellular apoptosis. Roflupram (ROF, 20 μM), a selective PDE4 inhibitor, produced similar protective effects and restored the morphological alterations of mitochondria. Mechanistic studies identified that α-syn enhanced the phosphorylation of Parkin at Ser131, followed by the decreased mitochondrial translocation of Parkin. Whereas both PDE4B knockdown and PDE4 inhibition by ROF blocked the effects of α-syn on Parkin phosphorylation and mitochondrial translocation. Moreover, PDE4 inhibition reversed the increase in the phosphorylation of p38 mitogen-activated protein kinase (MAPK) induced by α-syn. ROF treatment also reduced the binding of p38 MAPK to Parkin. Consistently, overexpression of PDE4B blocked the roles of ROF on p38 MAPK phosphorylation, Parkin phosphorylation, and the subsequent mitochondrial translocation of parkin. Furthermore, PDE4B overexpression attenuated the protective role of ROF, as evidenced by reduced mitochondria membrane potential and increased cellular apoptosis. Interestingly, ROF failed to suppress α-syn-induced cytotoxicity in the presence of a protein kinase A (PKA) inhibitor H-89. Our findings indicate that PDE4 facilitates α-syn-induced cytotoxicity via the PKA/p38 MAPK/Parkin pathway in SH-SY5Y cells overexpressing A53T mutant α-synuclein. PDE4 inhibition by ROF is a promising strategy for the prevention and treatment of α-syn-induced neurodegeneration.

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.

Overtaking behavior between non-motorized vehicles is one of the main characteristics of the cycling path, and unsafe overtaking behavior has a certain negative impact on riders’ safety. However, little is known about the factors affecting riders’ overtaking decisions. This study aimed to identify the influence of road facilities, types of non-motorized vehicles, and human factors on the characteristics of overtaking behavior on bicycle lanes. DJI drone-based naturalistic riding research was explored in China and a random parameter logit regression model was estimated to model the overtaking decisions of non-motorized vehicle riders. The results showed that gender, age, professional deliverer, type of lead non-motor vehicle, type of non-motorized vehicles, and width of cycling lane influence overtaking behavior significantly. The present study provides theoretical evidence to strengthen the safety design and evaluation of cycling lane infrastructure.

Dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) are important components of dissolved organic matter (DOM) in soil. A change in the concentration of soil DOM leads to changes in the soil carbon (C) and nitrogen (N) pools and the emergence of potential pollution. Many studies have reported that the concentrations of soil DOM could be significantly influenced by land management practices. However, the results obtained from these studies are inconsistent, and the effects of environmental factors on the responses of DOM concentrations to such management practices remain unclear. The aims of this study were to: (1) synthesize the available datasets and elucidate the general patterns of changes in soil DOM concentrations in response to different land management practices; and (2) probe how the responses of DOM concentrations to management practices were affected by environmental factors (e.g., altitude, climate, and soil properties). Data from 942 observations in 184 publications were collected, integrated, and statistically analyzed. The meta-analysis result shows that overall, N fertilization, liming, organic amendment addition, and vegetation cover significantly increased the concentrations of soil DOM, whereas tillage decreased DOC concentrations. The magnitude of all positive and negative effects was driven by implemented management practices. Generally, a threshold range might exist for the application rate and duration of the management measures that could cause significant changes in DOM concentrations. In addition, DOC concentrations were more responsive to N fertilization and liming than were DON concentrations, indicating that the changes in the two variables were not correlated in each management practice. The results also indicate that the responses of DOM concentrations to management practices could be regulated by the altitude, climate (e.g., mean annual temperature and precipitation), and soil property factors (e.g., total C, total N, C:N ratio, clay content, and initial soil pH). In conclusion, our study suggests that in order to maintain proper soil DOM concentrations in an ecosystem, not only the type and implementation of management practices but also the local environmental factors should be considered when proposing a land management plan.

Multiband carrierless amplitude and phase (MultiCAP) modulation is a modulation mode based on Carrierless Amplitude and Phase (CAP). To improve the capability of a short distance optical communication system for communication capacity and frequency band utilization, multiband CAP modulation technology is adopted. In this article, the diagram for MultiCAP modulation signal of signal-to-noise ratio and bit error rate was analyzed under the condition of Gamma–Gamma atmospheric turbulence channel model. The bit error rate of 4 the band CAP modulation system has been discussed under conditions of different intensity fluctuation variance and signal-to-noise ratio. The simulation results show that when the total bandwidth is constant, the larger the frequency band is, the lower bit error rate is. When the value of σ R 2 is small, the system error rate decreases with increasing signal-to-noise ratio. When the σ R 2 is larger, the system error rate decreases with decreasing σ R 2 . The experimental results of atmospheric laser communication show that the receiver branch signal phase shift are well compensated and intersymbol interference is effectively suppressed after using MMA algorithm for equilibrium, and the bit error rate of each branch signal is decreased from 1 0 − 3 to 2 . 4462 × 1 0 − 4 . Consequently, the system transmission performances improve.

NiFe layered double hydroxides (LDHs) have received widespread attention due to their unique structures and inherent electrocatalytic activity towards the oxygen evolution reaction (OER). Extensive studies have been reported to further improve the electrocatalytic activity of NiFe-LDHs via various strategies. However, controlling the degree of amorphization and stabilizing the amorphous zone during the electrocatalytic process are still challenging. Here, we report a facile method to synthesize a space-confined amorphous NiFe-LDH (SCA-NiFe-LDH) by selectively etching the surfaces of electrocatalysts. Due to the successful anchoring of amorphous zones onto the basal planes of the two-dimensional NiFe-LDH, the optimized SCA-NiFe-LDH exhibits high electrocatalytic activity with a low overpotential of 190 mV at 10 mA cm-2, a Tafel slope of 31 mV dec-1 and excellent long-term stability. The substantially enhanced OER performance is attributed to the increased amount of active sites and the modified electronic structure of NiFe-LDH after amorphization.

In this study, a stitching method based on dual quaternion is proposed. The application of a dual quaternion in sub-aperture stitching interferometry is analyzed in detail, and a calculation method for sub-aperture stitching based on a dual quaternion is deduced. The experimental results demonstrate the accuracy of the stitching method proposed in this study (residuals of overlapping area approximately 0.22 nm RMS). Finally, the residual differences of 0.79 nm RMS between the figure errors are acquired with a stitching by parts algorithm based on the dual quaternion and long trace profiler (FSP at HEPS). The high-accuracy and high-efficiency stitching method proposed in this study will expand its application in the metrology and manufacture of long cylindrical mirrors.

The addition of graphene oxide (GO) and fly ash (FA) to SFRC (steel fiber reinforced concrete) increases frost resistance. Based on the analysis of the amelioration of GO on the frost resistance of SFRC, the improvement mechanism and the effects of GO and FA on the durability of SFRC were studied in depth. The test blocks’ compressive strength, relative dynamic modulus of elasticity, and mass-loss rate were tested through experiments. The pore distribution and morphological characteristics of concrete were captured by industrial CT scanning technology. The effects of GO and FA on the pore distribution and morphology of the SFRC are discussed. The results show that the compressive strength of GO-SFRC(graphene oxide and steel fiber reinforced concrete)with GO proportion of 0.03% is 28.20% higher than that of ordinary SFRC without freezing and thawing; after 100 freeze-thaw cycles, the compressive strength of the G0.03S25 increased by 31.70% compared with the compressive strength of the G0.00S25, and pore shape of G0.03S25 presents a spherical shape and an elliptical spherical shape; based on the data analysis of the strength loss, relative dynamic elastic modulus loss and mass-loss rate, it is considered that the properties of ordinary SFRC are the worst under freezing and thawing; as FA admixture increases, the porosity decreases; with FA of 30% and GO of 0.03%, the GO-FA-SFRC has the best frost resistance, as well as most of the pores are closed which resemble spheres and ellipsoids.

An asynchronous event-related potential-based brain computer interface (ERP-BCI) permits the subjects to output intentions at their own pace, which provides a more free and practical communication pathways without the need for muscle activity. The core of constructing this type of system is to discriminate both the intentions and brain states.This study proposes a fisher linear discriminant analysis classification algorithm fused with naïve Bayes (B-FLDA) for the ERP-BCI to simultaneous recognize the subjects' intentions, working and idle states. This method uses the spectral characteristics of visual-evoked potential and the time-domain characteristics of ERP to simultaneously detect brain states and target stimulus, and obtain the final discrimination result through probability fusion.The accuracy and the information transfer rate increase to 98.61% and 62.80 bits/min under 10 repetitions and 1 repetition, respectively. The three parameters of receiver operator characteristic curve have achieved better performance.Ten subjects participate in this study with the proposed algorithms and two other control methods. The accuracy and information transfer rate of this algorithm are better than the other methods.It indicates that the naïve Bayes-FLDA algorithm is able to improve the performance of an asynchronous BCI system by detecting the intentions and states simultaneously.

A major challenge for sustainable development is providing adequate energy services while mitigating adverse environmental effects, which unquestionably requires a reduction in the energy consumed per unit of real GDP (i.e. energy intensity) and novel energy technologies. However, our knowledge of how energy technologies influence energy intensity is incomplete. This paper thus empirically investigates the effects of energy technologies on energy intensity by dividing them into energy-conservation and energy-substitution technologies. Additionally, we classify energy technologies according to their executors, as having two purposes. Using a China's provincial dataset over 2000–2018, we find that energy-conservation technologies play a more important role in decreasing energy intensity compared to energy-substitution technologies. In addition, from the purposes of these energy technologies, the energy technologies coming from utility-type enterprises exert the most significant effect on energy intensity reduction. Since the effect of energy technologies on energy intensity may be related to technology absorptive ability, an additional analysis based on the dynamic panel threshold model indicates that technology absorptive ability shows an important effect on energy intensity.

Synthesis of the unconventional phase of noble metal nanocrystals may create new opportunities in exploring intriguing physicochemical properties but remains challenging. In the research field of thin film growth, the interface strain offers a general driving force to stabilize the metastable phase of epitaxial film. Herein we extend this concept to the field of noble metal nanocrystals and report the solution synthesis of metastable face-centered tetragonal Au that has not been discovered before. The successful synthesis relies on the formation of intermetallic AuCu

Somatic embryogenesis is a type of plant cell totipotency where embryos develop from nonreproductive (vegetative) cells without fertilization. Somatic embryogenesis can be induced in vitro by auxins, and by ectopic expression of embryo-expressed transcription factors like the BABY BOOM (BBM) AINTEGUMENTA-LIKE APETALA2/ETHYLENE RESPONSE FACTOR domain protein. These different pathways are thought to converge to promote auxin response and biosynthesis, but the specific roles of the endogenous auxin pathway in somatic embryogenesis induction have not been well-characterized. Here we show that BBM transcriptionally regulates the YUCCA3 (YUC3) and YUC8 auxin biosynthesis genes during BBM-mediated somatic embryogenesis in Arabidopsis (Arabidopsis thaliana) seedlings. BBM induced local and ectopic YUC3 and YUC8 expression in seedlings, which coincided with increased DR5 auxin response and indole-3-acetic acid (IAA) biosynthesis and with ectopic expression of the WOX2 embryo reporter. YUC-driven auxin biosynthesis was required for BBM-mediated somatic embryogenesis, as the number of embryogenic explants was reduced by ca. 50% in yuc3 yuc8 mutants and abolished after chemical inhibition of YUC enzyme activity. However, a detailed YUC inhibitor time-course study revealed that YUC-dependent IAA biosynthesis is not required for the re-initiation of totipotent cell identity in seedlings. Rather, YUC enzymes are required later in somatic embryo development for the maintenance of embryo identity and growth. This study resolves a long-standing question about the role of endogenous auxin biosynthesis in transcription factor-mediated somatic embryogenesis and also provides an experimental framework for understanding the role of endogenous auxin biosynthesis in other in planta and in vitro embryogenesis systems.

Objective: The purpose of this study is exploring the influence of physical exercise on the Traditional Chinese Medicine (TCM) constitution of college students and providing evidence for the intervention methods of college students' TCM constitution by the survey of the TCM Constitution and exercise habits of 672 students in the college of Shaanxi province. Methods: All 672 students who are from three grades in the university were investigated by using the Traditional Chinese Medicine Constitution Scale and the self-made questionnaire on exercise habits. Results: Among 672 college students, 203 students were in gentleness type (30.2%), 447 students were in biased types (66.5%).Among 447 biased types of students, 252 cases (37.5%) were in Yang-deficiency constitution, 236 cases (35.1%) were in Yin-deficiency constitution and 224 cases (33.3%) were in Qi-deficiency constitution. The probability of gentleness type of college students with exercise habit is higher than those doing little exercise, and the probability of biased types are lower than that without exercise habit. Among the college students who have the habits of exercising, the students doing aerobic exercises showed a lower level of biased types than those doing strength training or flexibility training. The exercise frequency was negatively correlated with Qi-deficiency constitution, Yang-deficiency constitution, Phlegm-dampness constitution and Qi-stagnation constitution (r=0.041, 0.003, 0.005, 0.024), the exercise time was negatively correlated with Phlegm-dampness constitution (r=0.026), and positively correlated with Special-diathesis constitution (r=0.038), all the differences were statistically significant (P

Somatic embryogenesis is a form of totipotency that can be induced by applying plant growth regulators or by ectopic overexpression of specific transcription factors. It has a great value in commercial plant breeding for clonal propagation of valuable germplasm. This thesis aims to extend the knowledge of the molecular components of transcription factor-induced somatic embryogenesis, in particular the different levels of BBM-mediated somatic embryogenesis.BBM is one of the eight AIL family transcription factors found in arabidopsis. Chapter 1 introduces the AIL transcription factor family and describes the functions of arabidopsis AIL genes during plant developmental processes, like embryo development, root and shoot development, flower development and regeneration. Some of the signaling pathways in which these proteins function are also presented.Chapter 2 identifies BBM target genes in somatic embryos and characterizes the function of these targets. We show that BBM binds to and regulates expression of the LAFL embryo identity transcription factors, which themselves are positive regulators of (somatic) embryo identity. We uncovered positive (LEC1, LEC2, FUS) and negative (ABI3) roles for these transcription factors in BBM-mediated somatic embryogenesis. We also show that the BBM-PLT clade of AIL proteins are functionally equivalent for somatic embryogenesis induction and that BBM and PLT2 induce somatic embryogenesis in a dose- and context-dependent manner, as was demonstrated previously for root development.We also identified BBM target genes in other signaling pathways, among which auxin pathways genes that were found in early and late stages of somatic embryogenesis. In Chapter 3 we identify BBM target genes during the initiation phase of BBM-mediated somatic embryogenesis in imbibed seeds. We show that genes involved in two tryptophan-dependent pathways, IAA biosynthesis and IAOx metabolism, are some of the earliest target genes during BBM-mediated somatic embryo induction, and that these genes are positive regulators of somatic embryogenesis. We show that auxin is not required for the initial reinstatement of totipotency in cotyledons, despite the early induction of YUCCA auxin biosynthesis genes and auxin accumulation. Rather, auxin is essential for maintaining embryonic identity and for embryo patterning. This chapter also shows that loss of function mutants in the IAOx pathway genes regulated by BBM, negatively affect BBM-induced somatic embryogenesis, even though some of these genes are repressed by BBM. This data identifies a new role for the IAOx pathway in cell totipotency and suggests that the extent and/or timing of these metabolic changes is tightly regulated.BBM and other AILs interact with HOMEODOMAIN GLABROUS (HDG) transcription factors. They act antagonistically to regulate plant cell proliferation and differentiation via protein-protein interaction and regulation of common target genes. Functional analysis of the HDG protein family has been limited by the functional redundancy in this gene family and by the use of T-DNA insertion alleles with different activities. Chapter 4 characterizes the functions of HDG transcription factors in arabidopsis seedling cotyledons. Using CRISPR-Cas9 induced null mutants, we confirmed previously reported seedling phenotypes observed in presumed dominant negative and partial T-DNA insertion lines and also uncovered new interactions and functions. This study highlights the utility of genome editing for targeted and simultaneous mutation of multigene families.A chromatin remodeling protein, PICKLE-RELATED1 (PKR1), was also identified as BBM protein interactor in the same in vitro screen that identified the HDG proteins. In Chapter 5, we use in vivo immunoprecipitation followed by MS/MS of a BBM:GFP protein to identify the components of BBM protein complexes in somatic embryos. We identified PKR1 as BBM protein complex partner, as well as a large number of additional chromatin remodeling proteins. We show that PKR1 regulates the timing of zygotic embryo development and promotes BBM-induced somatic embryogenesis.Finally, Chapter 6 summarizes and discusses the major results of this thesis. We discuss the remaining questions and provide a perspective on future research that can help to better understand BBM function.

Proton exchange membrane fuel cells (PEMFCs) with high efficiency and nonpollution characteristics have attracted massive attention from both academic and industrial communities due to their irreplaceable roles in building the future sustainable energy system. However, the stability issue of Pt-based catalysts for oxygen reduction reaction (ORR) has become a central constraint to the widespread deployment of the devices relative to the catalytic activity. This review aims to provide comprehensive insights into how to improve the stability of Pt-based catalysts for ORR. First, the basic physical chemistry behind the catalyst degradation, including the fundamental understandings of carbon corrosion, catalyst dissolution, and particle sintering, is highlighted. After a discussion of advanced characterization techniques for the catalyst degradation, the design strategies for improving the stability of Pt-based catalysts are summarized. Finally, further insights into the remaining challenges and future research directions are also provided.

Inhibition of phosphodiesterase 4 (PDE4) protects against neuronal apoptosis induced by cerebral ischemia. However, the exact mechanisms responsible for the protection of PDE4 inhibition have not been completely clarified. Roflumilast (Roflu) is an FDA-approved PDE4 inhibitor for the treatment of chronic obstructive pulmonary disease. The potential protective role of Roflu against ischemic stroke-associated neuronal injury remains unexplored. In this study, we investigated the effect and mechanism of Roflu against ischemic stroke using in vitro oxygen-glucose deprivation reperfusion (OGD/R) and in vivo rat middle cerebral artery occlusion (MCAO) models. We demonstrated that Roflu significantly reduced the apoptosis of HT-22 cells exposed to OGD/R, enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2), and reduced oxidative stress. Treatment with Roflu increased the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3β (GSK3β) but decreased the level of phosphorylated inositol requiring enzyme 1α (IRE1α). Interestingly, constitutively active GSK3β (S9A) mutation abolished the effects of Roflu on oxidative stress and IRE1α phosphorylation. Moreover, Roflu decreased the binding of IRE1α to tumor necrosis factor receptor-associated factor 2 (TRAF2) and attenuated the phosphorylation of c-Jun N-terminal kinase (JNK). We also found that PDE4B knockdown reduced the phosphorylation of both IRE1α and JNK, while overexpression of PDE4B antagonized the role of PDE4B knockdown on the activation of IRE1α and JNK. Besides, the inhibition of PDE4 by Roflu produced similar effects in primary cultured neurons. Finally, Roflu ameliorated MCAO-induced cerebral injury by decreasing infarct volume, restoring neurological score, and reducing the phosphorylation of IRE1α and JNK. Collectively, these data suggest that Roflu protects neurons from cerebral ischemia reperfusion-mediated injury via the activation of GSK3β/Nrf-2 signaling and suppression of the IRE1α/TRAF2/JNK pathway. Roflu has the potential as a protective drug for the treatment of cerebral ischemia.