Transcriptomic and neuroimaging data integration enhances machine learning classification of schizophrenia.

Background: Schizophrenia is a polygenic disorder associated with changes in brain structure and function. Integrating macroscale brain features with microscale genetic data may provide a more complete overview of the disease etiology and may serve as potential diagnostic markers for schizophrenia. Objective: We aim to systematically evaluate the impact of multi-scale neuroimaging and transcriptomic data fusion in schizophrenia classification models. Methods: We collected brain imaging data and blood RNA sequencing data from 43 patients with schizophrenia and 60 age- and gender-matched healthy controls, and we extracted multi-omics features of macroscale brain morphology, brain structural and functional connectivity, and gene transcription of schizophrenia risk genes. Multi-scale data fusion was performed using a machine learning integration framework, together with several conventional machine learning methods and neural networks for patient classification. Results: We found that multi-omics data fusion in conventional machine learning models achieved the highest accuracy (AUC ~0.76-0.92) in contrast to the single-modality models, with AUC improvements of 8.88 to 22.64%. Similar findings were observed for the neural network, showing an increase of 16.57% for the multimodal classification model (accuracy 71.43%) compared to the single-modal average. In addition, we identified several brain regions in the left posterior cingulate and right frontal pole that made a major contribution to disease classification. Conclusion: We provide empirical evidence for the increased accuracy achieved by imaging genetic data integration in schizophrenia classification. Multi-scale data fusion holds promise for enhancing diagnostic precision, facilitating early detection and personalizing treatment regimens in schizophrenia.

Mental health problems of front-line medical staff in the early stage of public health emergencies.

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention.

AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

Differential expression of diacylglycerol kinase ζ is involved in inferior parietal lobule-related dysfunction in schizophrenia with cognitive impairments.

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

The Association Between Lentiform Nucleus Function and Cognitive Impairments in Schizophrenia.

Introduction: Cognitive decline is the core schizophrenia symptom, which is now well accepted. Holding a role in various aspects of cognition, lentiform nucleus (putamen and globus pallidus) dysfunction contributes to the psychopathology of this disease. However, the effects of lentiform nucleus function on cognitive impairments in schizophrenia are yet to be investigated. Objectives: We aim to detect the fractional amplitude of low-frequency fluctuation (fALFF) alterations in patients with schizophrenia, and examine how their behavior correlates in relation to the cognitive impairments of the patients. Methods: All participants underwent magnetic resonance imaging (MRI) and cognitive assessment (digit span and digit symbol coding tests). Screening of brain regions with significant changes in fALFF values was based on analysis of the whole brain. The data were analyzed between Jun 2020 and Mar 2021. There were no interventions beyond the routine therapy determined by their clinicians on the basis of standard clinical practice. Results: There were 136 patients (75 men and 61 women, 24.1 ± 7.4 years old) and 146 healthy controls (82 men and 64 women, 24.2 ± 5.2 years old) involved in the experiments seriatim. Patients with schizophrenia exhibited decreased raw scores in cognitive tests (p < 0.001) and increased fALFF in the bilateral lentiform nuclei (left: 67 voxels; x = -24, y = -6, z = 3; peak t-value = 6.90; right: 16 voxels; x = 18, y = 0, z = 3; peak t-value = 6.36). The fALFF values in the bilateral lentiform nuclei were positively correlated with digit span-backward test scores (left: r = 0.193, p = 0.027; right: r = 0.190, p = 0.030), and the right lentiform nucleus was positively correlated with digit symbol coding scores (r = 0.209, p = 0.016). Conclusion: This study demonstrates that cognitive impairments in schizophrenia are associated with lentiform nucleus function as revealed by MRI, involving working memory and processing speed.

Shaping the Trans-Scale Properties of Schizophrenia via Cerebral Alterations on Magnetic Resonance Imaging and Single-Nucleotide Polymorphisms of Coding and Non-Coding Regions.

Schizophrenia is a complex mental illness with genetic heterogeneity, which is often accompanied by alterations in brain structure and function. The neurobiological mechanism of schizophrenia associated with heredity remains unknown. Recently, the development of trans-scale and multi-omics methods that integrate gene and imaging information sheds new light on the nature of schizophrenia. In this article, we summarized the results of brain structural and functional changes related to the specific single-nucleotide polymorphisms (SNPs) in the past decade, and the SNPs were divided into non-coding regions and coding regions, respectively. It is hoped that the relationship between SNPs and cerebral alterations can be displayed more clearly and intuitively, so as to provide fresh approaches for the discovery of potential biomarkers and the development of clinical accurate individualized treatment decision-making.

Complete chloroplast genome sequence and phylogenetic analysis of winter oil rapeseed (Brassica rapa L.).

Winter oil rapeseed '18 R-1' (Brassica rapa L.) is a new variety that can survive in northern China where the extreme low temperature is -20 °C to -32 °C. It is different from traditional B. rapa and Brassica napus. In this study, the complete chloroplast (cp) genome of '18 R-1' was sequenced and analyzed to assess the genetic relationship. The size of cp genome is 153,494 bp, including one large single copy (LSC) region of 83,280 bp and one small single copy (SSC) region of 17,776 bp, separated by two inverted repeat (IR) regions of 26,219 bp. The GC content of the whole genome is 36.35%, while those of LSC, SSC, and IR are 34.12%, 29.20%, and 42.32%, respectively. The cp genome encodes 132 genes, including 87 protein-coding genes, eight rRNA genes, and 37 tRNA genes. In repeat structure analysis, 288 simple sequence repeats (SSRs) were identified. Cp genome of '18 R-1' was closely related to Brassica chinensis, B. rapa and Brassica pekinesis.

Chest computed tomography (CT) findings and semiquantitative scoring of 60 patients with coronavirus disease 2019 (COVID-19): A retrospective imaging analysis combining anatomy and pathology.

In this study, we ascertained the chest CT data of 60 patients admitted to 3 hospitals in Chongqing with confirmed COVID-19. We conducted anatomical and pathological analyses to elucidate the possible reasons for the distribution, morphology, and characteristics of COVID-19 in chest CT. We also shared a semiquantitative scoring of affected lung segments, which was recommended by our local medical association. This scoring system was applied to quantify the severity of the disease. The most frequent imaging findings of COVID-19 were subpleural ground glass opacities and consolidation; there was a significant difference in semiquantitative scores between the early, progressive, and severe stages of the disease. We conclude that the chest CT findings of COVID-19 showed certain characteristics because of the anatomical features of the human body and pathological changes caused by the virus. Therefore, chest CT is a valuable tool for facilitating the diagnosis of COVID-19 and semiquantitative scoring of affected lung segments may further elucidate diagnosis and assessment of disease severity. This will assist healthcare workers in diagnosing COVID-19 and assessing disease severity, facilitate the selection of appropriate treatment options, which is important for reducing the spread of the virus, saving lives, and controlling the pandemic.

[Effects of Different Levels of Nitrogen Fertilization on Soil Respiration Rates and Soil Biochemical Properties in an Alfalfa Grassland].

Understanding the effects of different levels of nitrogen fertilizer applications on soil respiration rates and soil biochemical properties is of great importance for providing a theoretical basis for accurate assessments of the soil respiration intensity and carbon recycling in grassland ecosystems. A field experiment was performed from April 2017 to March 2018, in which four different levels of nitrogen applications were investigated, including 0 kg·hm-2 (N0), 60 kg·hm-2 (N1), 120 kg·hm-2 (N2), and 180 kg·hm-2 (N3). The seasonal changes in the soil respiration rate, soil temperature, and soil moisture in the alfalfa grassland under different levels of nitrogen applications were observed, and soil biochemical characteristics were observed after each harvest in the growing season. The results showed that soil respiration rate of the alfalfa grassland displayed significant seasonal variation under different nitrogen levels. In particular, the soil respiration rate reached a peak during the last 10-day period of July and then decreased to the minimum in mid-December. During the growing season of alfalfa, the soil respiration rate of the alfalfa grassland increased with the increases in the nitrogen application rate. The mean soil respiration rates of the N1, N2, and N3 treatments were 0.97, 1.04, and 1.07 g·(m2·h)-1, respectively, and these values were 10.2%, 18.2%, and 21.6% greater than that of N0[0.88 g·(m2·h)-1], respectively. The results from ANOVA testing indicated that nitrogen applications had no significant effect on the soil respiration rate during the non-growing season of alfalfa (P>0.05). According to the statistical analysis, the soil respiration rate had a significant exponential positive relationship with soil temperature during the growing season, non-growing season, and entire year of alfalfa grassland observations under different nitrogen application rates (P<0.01); the coefficients of determination were ranked as follows:growing season (0.46-0.62) < non-growing season (0.66-0.76) < whole year (0.80-0.86). Soil temperature (T) and soil moisture (W) interacted with each other and ultimately affected the soil respiration (RS), and by using a two-factor linear model of soil temperature and soil moisture, a better fit was obtained for the change in the soil respiration rate. Both of the two factors explained 68%-80% of the variation in the seasonal soil respiratory rate during the growing season of alfalfa. Nitrogen fertilization decreased the soil pH and available phosphorus content (AP) to varying degrees, but it increased the available potassium (AK), soil organic matter (SOM), and soil urease (URE) and invertase activity (INV). Total nitrogen (TN) and available nitrogen (AN) showed different trends under different nitrogen levels. The TN and AN contents increased considerably in soils; however, when the nitrogen rate was higher than N2 (120 kg·hm-2), TN and AN decreased with the increases in the nitrogen application rate. According to the correlation matrix analysis between soil respiration and soil biochemical properties during the growth period of alfalfa, data showed that the soil respiration rate (RS) was significantly and negatively correlated with soil pH (P<0.01), and it was significantly and positively correlated with soil TN and URE (P<0.01). Simultaneously, there was a significant positive correlation between the soil respiration rate (RS) and SOM (P<0.05), and there was a significant negative correlation with INV (P<0.05). The soil nutrient and enzyme activities of the alfalfa grassland explained the variations in the soil respiration rate under different nitrogen application levels to varying degrees.

Meta-Analysis of Randomized Controlled Trials on the Efficacy and Safety of Donepezil, Galantamine, Rivastigmine, and Memantine for the Treatment of Alzheimer's Disease.

To study the impact of donepezil, rivastigmine, galantamine, and memantine on cognitive, functional, behavioral, global changes and adverse effects in patients with mild, moderate and severe Alzheimer's disease (AD), we screened the literature published before September 2017 in the Pubmed, Embase, Cochrane library and Web of Science Electronic databases according to the inclusion criteria. Thirty-six studies were finally determined from 1560 preliminary screened articles. The AD Assessment Scale-cognitive Subscale (ADAS-cog), AD Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), and Clinician's Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+) were used as valid endpoints. Of the 36 trials included, meta-analyses of these placebo-control trials showed that there were significant differences between the donepezil, rivastigmine and placebo groups using ADAS-cog, ADCS-ADL, and CIBIC+. Meta-analyses of these placebo-controlled trials showed that there were significant differences between the galantamine and placebo groups using ADAS-cog, ADCS-ADL, NPI, and CIBIC+. These observations suggest that memantine is beneficial for stabilizing or slowing the decline in ADAS-cog and ADCS-ADL19 changes in AD patients. However, there was no significant effect according to the ADCS-ADL23, NPI, and CIBIC+ tests, which indicated that memantine treatment has no significant effect on these cognitive aspects of AD patients. Different effects of donepezil, rivastigmine, galantamine, or memantine on AD were found in this study. According to the results, we conclude that galantamine is effective in treating all aspects of AD and is the first choice for the treatment of AD. However, due to limited data, we should consider additional data to obtain more stable results.

Copper chelators promote nonamyloidogenic processing of AßPP via MT1/2 /CREB-dependent signaling pathways in AßPP/PS1 transgenic mice.

Copper is essential for the generation of reactive oxygen species (ROS), which are induced by amyloid-ß (Aß) aggregation; thus, the homeostasis of copper is believed to be a therapeutic target for Alzheimer's disease (AD). Although clinical trials of copper chelators show promise when applied in AD, the underlying mechanism is not fully understood. Here, we reported that copper chelators promoted nonamyloidogenic processing of AßPP through MT1/2 /CREB-dependent signaling pathways. First, we found that the formation of Aß plaques in the cortex was significantly reduced, and learning deficits were significantly improved in AßPP/PS1 transgenic mice by copper chelator tetrathiomolybdate (TM) administration. Second, TM and another copper chelator, bathocuproine sulfonate (BCS), promoted nonamyloidogenic processing of AßPP via inducing the expression of ADAM10 and the secretion of sAßPPα. Third, the inducible ADAM10 production caused by copper chelators can be blocked by a melatonin receptor (MT1/2 ) antagonist (luzindole) and a MT2 inhibitor (4-P-PDOT), suggesting that the expression of ADAM10 depends on the activation of MT1/2 signaling pathways. Fourth, three of the MT1/2 -downstream signaling pathways, Gq/PLC/MEK/ERK/CREB, Gs/cAMP/PKA/ERK/CREB and Gs/cAMP/PKA/CREB, were responsible for copper chelator-induced ADAM10 production. Based on these results, we conclude that copper chelators regulate the balance between amyloidogenic and nonamyloidogenic processing of AßPP via promoting ADAM10 expression through MT1/2 /CREB-dependent signaling pathways.

Tetrathiomolybdate Treatment Leads to the Suppression of Inflammatory Responses through the TRAF6/NFκB Pathway in LPS-Stimulated BV-2 Microglia.

Although the positive relationship between copper and Alzheimer's disease (AD) was reported by a lot of epidemiological data, the mechanism is not completely known. Copper is a redox metal and serves as a mediator of inflammation. Because the homeostasis of copper is altered in Aß precursor protein (APP) and presenilin 1 (PS1) transgenic (Tg) mice, the using of copper chelators is a potential therapeutic strategy for AD. Here we report that a copper chelator, tetrathiomolybdate (TM), is a potential therapeutic drug of AD. We investigated whether TM treatment led to a decrease of pro-inflammatory cytokines in vivo and in vitro, and found that TM treatment reduced the expression of iNOS and TNF-α in APP/PS1 Tg mice through up-regulating superoxide dismutase 1 (SOD1) activity. In vitro, once stimulated, microglia secretes a variety of proinflammatory cytokines, so we utilized LPS-stimulated BV-2 cells as the inflammatory cell model to detect the anti-inflammatory effects of TM. Our results indicated that TM-pretreatment suppressed the ubiquitination of TRAF6 and the activation of NFκB without affecting the expression of TLR4 and Myd88 in vitro. By detecting the activity of SOD1 and the production of reactive oxygen species (ROS), we found that the anti-inflammatory effects of TM could be attributed to its ability to reduce the amount of intracellular bioavailable copper, and the production of ROS which is an activator of the TRAF6 auto-ubiquitination. Hence, our results revealed that TM-treatment could reduce the production of inflammatory cytokines by the suppression of ROS/TRAF6/AKT/NFκB signaling pathway.

Clustered repetitive transcranial magnetic stimulation for the prevention of depressive relapse/recurrence: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) may have the potential to prevent depressive relapse. This assessor-blinded, randomized controlled study was designed to evaluate the efficacy and safety of rTMS as a mono- and combination therapy in the prevention of depressive relapse/recurrence. A total of 281 depressed patients who had achieved stable full or partial remission on a 6-month antidepressant (ADP) run-in treatment were randomly assigned to an rTMS (n = 91), ADP (n = 108), or combined (rTMS + ADP, n = 82) treatment group for 12 months. Monthly clustered rTMS was conducted in 5-10 sessions over a 3-5-day period. Maintenance outcomes were assessed using time to relapse/recurrence and relapse/recurrence rate. Overall, 71.2% (200/281) of the participants completed the treatment per the protocol. rTMS + ADP and rTMS significantly reduced the risk of relapse/recurrence compared with ADP (P = 0.000), with hazard ratios of 0.297 and 0.466, respectively. Both rTMS-containing regimens produced significantly lower relapse/recurrence rates than ADP (15.9% and 24.2% vs. 44.4%, P < 0.001). In the relapsed/recurrent subgroup, first-episode depressed, rTMS-treated patients had a markedly lower relapse/recurrence rate than ADP-treated patients. Five patients on the ADP-containing regimens, but none on rTMS alone, developed acute mania. The rTMS-containing regimens had considerably more certain side effects than did the ADP group. We concluded that TMS, whether as a mono- or additional therapy, is superior to antidepressants in preventing depressive relapse/recurrence, particularly in first-episode depressed patients. The treatment does not increase the risk of manic switch, but may increase the risk of certain side effects.

Isoflurane exposure regulates the cell viability and BDNF expression of astrocytes via upregulation of TREK­1.

Neonatal isoflurane exposure in rodents disrupts hippocampal cognitive functions, including learning and memory, and astrocytes may have an important role in this process. However, the molecular mechanisms underlying this disruption are not fully understood. The present study investigated the role of TWIK­related K+ channel (TREK­1) in isoflurane­induced cognitive impairment. Lentiviruses were used to overexpress or knockdown TREK­1 in astrocytes exposed to increasing concentrations of isoflurane or O2 for 2 h. Subsequently, the mRNA and protein expression of brain­derived neurotrophic factor (BDNF), caspase­3, Bcl­2­associated X (Bax) and TREK­1 was measured by reverse transcription­ quantitative polymerase chain reaction and western blot analysis, respectively. In addition, cell viability was assessed by a 2­(4­Iodophenyl)­3­(4­nitrophenyl)­5­(2,4­disulfophenyl)­ 2H­tetrazolium monosodium salt assay. The results demonstrated that, prior to manipulating TREK­1, isoflurane significantly decreased the cell viability and BDNF expression, and increased Bax, caspase­3 and TREK­1 expression was observed. However, TREK­1 overexpression in astrocytes significantly downregulated BDNF expression, and upregulated Bax and caspase­3 expression. Furthermore, lentiviral­mediated short hairpin RNA knockdown of TREK­1 effectively inhibited the isoflurane­induced changes in BDNF, Bax and caspase­3 expression. Taken together, the results of the present study indicate that isoflurane­induced cell damage in astrocytes may be associated with TREK­1­mediated inhibition of BDNF and provide a reference for the safe use of isoflurane anesthesia in infants and children.

Fractal MTW Zeolite Crystals: Hidden Dimensions in Nanoporous Materials.

Screw dislocation structures in crystals are an origin of symmetry breaking in a wide range of dense-phase crystals. Preparation of such analogous structures in framework-phase crystals is of great importance in zeolites but is still a challenge. On the basis of crystal-structure solving and model building, it was found that the two specific intergrowths in MTW zeolite produce this complex fractal and spiral structure. With the structurally determined parameters (spiral pitch h, screw angle θ, and spatial angle ψ) of Burgers circuit, the screw dislocation structure can be constructed by two different dimensional intergrowth sections. Thus the reported complexity of various dimensions in diverse crystals can be unified.

An assessor-blinded, randomized comparison of efficacy and tolerability of switching from olanzapine to ziprasidone and the combination of both in schizophrenia spectrum disorders.

BACKGROUND: Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited. OBJECTIVE: This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD). METHODS: In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared. RESULTS: The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens. CONCLUSIONS: We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.

Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 µmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 µmol/L) nor artemisinin (50 µmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication, thus is a candidate anti-HFMD drug.

[Diurnal and Seasonal Dynamic Variation of Soil Respiration and Its Influencing Factors of Different Fenced Enclosure Years in Desert Steppec].

The fenced measures could improve the ecological environment of degraded grassland, it's a main measure for restoration of degraded grassland vegetation in China. Soil respiration (Rs) is an important component of an ecosystem's carbon cycle and the main pathway for carbon moving from the ecosystem to the atmosphere. In order to explore soil respiration characteristics and influencing factors of the different fenced years in arid desert grassland, we continuously observed Rs rate and environmental factors in the growing season of fenced enclosure 11a, 7a and no fenced (CK) desert steppe in Ningxia. The results showed that: (1) Both the diurnal andseasonal variations of Rs rate showed a single asymmetric peak changing in fenced enclosure of 11 years, 7 years, CK desert steppe. On the daily scale, the maximum and minimum values of Rs rate were found in the periods of 12:00-16:00 and 00:00-06:00,respectively. On the seasonal variation scale, the maximum value of Rs rate occurred in August with suitable precipitation and temperature conditions. And the Rs rate of the growing season of different fenced enclosure years was in the order of 11a [0.143 g · (m² · h)⁻¹] > 7a [0.138 g · (m² · h)⁻¹] > CK [0.106 g · (m2 - h)⁻¹]. (2) According to statistical analysis, it indicated that R² rate had a significant exponential positive relationship with air and soil temperature in fenced enclosure of 11 years, 7 years, CK desert steppe (P < 0.01). The order of the correlation of Rs rate and temperature was shown as soil surface temperature (R²: 0.408-0.413) > air temperature (R2: 0.355-0.376) > 5-20 cm soil temperature (R2: 0.263-0.394). The temperature sensitivity coefficient Q, increased gradually with the soil depth, and Q1, of different fenced enclosure years was showed as 11 a (2.728) > 7a (2.436) > CK (2.086). (3) A significant quadratic function model (P < 0.05) was observed for the relationship between Rs rate and relative air humidity, soil moisture content of fenced enclosure 11a, 7a and CK desert steppe in the whole growing season. Rs rate had a significant linear negative correlation with air carbon dioxide concentration (P < 0.01), a linear positive correlation with the windspeed (P < 0.05), and a significant weak linear positive correlation with light intensity (P < 0.01). (4) It showed that Rs increasedwith increasing fenced closure years in arid desert steppe, and temperature sensitivity coefficient Q10 also increased with increasing fenced enclosure years. To sum up, 0-20 cm soil temperature and moisture were the main influencing factors of soil respiration of desert steppe. This study has important implications to understand the role that different fenced enclosure years play in carbon emission. Such information will lay a foundation for assessing carbon source or carbon sequestration of different fenced enclosure years in desert steppe. Therefore, our research results have important function for better managing grassland in desert steppe in Ningxia and other arid and semiarid areas of North China.

Down-regulation of Homer1 attenuates t-BHP-induced oxidative stress through regulating calcium homeostasis and ER stress in brain endothelial cells.

Endothelial dysfunction in brain endothelial cells contributes to vasogenic cerebral edema and increased mortality after various neurological diseases. The postsynaptic density protein Homer1 plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigated the role of Homer1 in modulating cell survival using an in vitro endothelial dysfunction model in murine brain endothelial cells (mBECs). Treatment with tert-butyl hydroperoxide (t-BHP) induced a dose-dependent toxicity in mBECs, with no effects on Homer1 expression and distribution. Knockdown of Homer1 using specific siRNA significantly alleviated lactate dehydrogenase (LDH) release, increased cell viability, and ultimately decreased apoptosis after t-BHP treatment. Moreover, Homer1 knockdown attenuated t-BHP-induced ROS generation, lipid peroxidation and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential (MMP), ATP synthesis collapse and mitochondrial swelling. The results of Ca(2+) imaging showed that Homer1 was involved in inositol trisphosphate receptors (IP3R)- and ryanodine receptor (RyR)-mediated intracellular Ca(2+) release, and also mediated t-BHP-induced Ca(2+) release from the endoplasmic reticulum (ER). In addition, knockdown of Homer1 significantly prevented activation of ER stress markers induced by t-BHP exposure. All these results showed that Homer1 is involved in t-BHP-induced endothelial dysfunction in mBECs, and may be an ideal candidate for searching gene intervention strategy for preventing endothelial oxidative stress in vitro.