cPKCγ Inhibits Caspase-9-Initiated Neuronal Apoptosis in an Ischemia Reperfusion Model In Vitro Through p38 MAPK-p90RSK-Bad Pathway.

Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.

Influence of urban morphological parameters on the distribution and diffusion of air pollutants: A case study in China.

Air pollution has a serious fallout on human health, and the influences of the different urban morphological characteristics on air pollutants cannot be ignored. In this study, the relationship between urban morphology and air quality (wind speed, CO, and PM2.5) in residential neighborhoods at the meso-microscale was investigated. The changes in the microclimate and pollutant diffusion distribution in the neighborhood under diverse weather conditions were simulated by Computational Fluid Dynamics (CFD). This study identified five key urban morphological parameters (Building Density, Average Building Height, Standard Deviation of Building Height, Mean Building Volume, and Degree of Enclosure) which significantly impacted the diffusion and distribution of pollutants in the neighborhood. The findings of this study suggested that three specific strategies (e.g. volume of a single building should be reduced, DE should be increased) and one comprehensive strategy (the width and height of the single building should be reduced while the number of single buildings should be increased) could be illustrated as an optimized approach of urban planning to relief the air pollution. The result of the combined effects could provide a reference for mitigating air pollution in sustainable urban environments.

EVALUATION OF THE INHIBITORY EFFECTS OF SIX NATURAL PRODUCT EXTRACTS AGAINST BABESIA GIBSONI IN VITRO AND IN VIVO.

New antibabesial drugs are required to fight resistant parasites, and plant-derived natural products are a robust source. Six kinds of natural product extracts derived from herbal medicines that are traditionally used for the treatment of malaria were selected to test the antibabesial effect on Babesia gibsoni in vitro and in vivo. Parasitized blood was collected from dogs infected with B. gibsoni to evaluate the inhibitory effect of verbenalin, catechin hydrate, dihydrolycorine, embelin, ursolic acid, agrimol B, and bruceine H in vitro. The expression levels of the 18S rRNA gene in all drug-treated groups were determined by relative quantification using a real-time PCR method. Significant inhibition of the in vitro growth of B. gibsoni was observed after treatment by those natural product extracts (200 nM concentration) (P < 0.05). Catechin hydrate showed the highest activity in vitro due to the lowest expression levels of the 18S rRNA gene. The IC50 value of catechin hydrate against B. gibsoni was 273 nM. In B. gibsoni infected dogs, intravenous administrations of catechin hydrate and diminazene aceturate showed significant (P < 0.05) inhibition of B. gibsoni growth at a dose of 11 mg/kg and 10 mg/kg, respectively, compared to the control group. The results of our study may suggest that catechin hydrate may be a promising alternative to treat canine babesiosis caused by B. gibsoni.

The Association between Long Noncoding RNA over Expression and Poor Prognosis of Liver Cancer: A Meta-Analysis.

Background: Long noncoding RNA (lncRNA) is considered to be a mediator of carcinogenesis, which may be associated with liver cancer survival. However, the relationship remains inconclusive. Meta-analysis was conducted to analytically review the association between the lncRNA expression level and clinicopathological characteristics and prognostic value of hepatic carcinoma. Materials and Methods: Four databases including Embase, PubMed, Web of Science, and the Cochrane Library were searched to collect studies about the relation between lncRNA overexpression and prognosis of liver cancer, dating from the earliest records of these databases to March 2021. Two researchers independently screened the data and literature to perform a stringent evaluation of the quality of material involved in the study. Meta-analysis was performed by Stata 16.0 software on 42 case-control studies with 6293 samples. Results: The outcomes of meta-analysis are presented as follows: lncRNA overexpression patients had later TNM stage (OR = 0.36, 95% CI (0.31, 0.41), P < 0.001), lower histological grade (OR = 0.56, 95%CI (0.49, 0.65), P < 0.001), more vascular invasion (OR = 2.02, 95% CI (1.74, 2.35), P < 0.001), bigger tumor size (OR = 2.28, 95% CI (2.00, 2.60), P < 0.001), more severe liver cirrhosis (OR = 1.39, 95% CI(0.1.16, 1.66), P < 0.001), more likely to metastasize (OR = 1.80, 95%CI(1.49, 2.18), P < 0.001), and more tumor numbers (OR = 0.72, 95% CI (0.62, 0.84), P < 0.05). lncRNA over expression patients had shorter OS (HR = 2.32, 95 CI% (2.08, 2.59), P < 0.01, RFS (HR = 2.19, 95 CI% (1.72, 2.78), P < 0.01), and DFS (HR = 2.01, 95 CI% (1.57, 2.57), P < 0.01). Conclusions: Overexposure of lncRNA is a poor prognostic feature for patients with hepatic carcinoma. The scope of our study was limited because of a lack of relevant research and the poor representativeness and varying quality of the studies involved in the current meta-analysis. Our conclusion still requires higher studies for further validation. This trial is clinically registered with CRD4201920620.

Factor analysis of the relationship between PANSS score and family burden of patients with schizophrenia.

OBJECTIVE: This study aims to investigate the burden of family caregivers of patients with schizophrenia, and its influencing factors METHODS: A total of 105 patients with schizophrenia and their caregivers were investigated using the positive and negative symptom scale (PANSS) and family burden scale of disease (FBS) RESULTS: There was a strong correlation between the patient's recovery and family burden, especially between positive and negative symptoms and family financial burden, family daily activities, family recreational activities, and family relationship CONCLUSION: There is a strong correlation between the patient's recovery and family burden, and this is especially correlated to family economic burden, family daily activities, family recreational activities, and family relationship. Medical staff should pay attention to the psychological characteristics of patients and fully understand and avoid the adverse effects of family burden on the rehabilitation of patients.

Molecular Characterization of Fructose-1,6-bisphosphate Aldolase From Trichinella spiralis and Its Potential in Inducing Immune Protection.

Trichinella spiralis is a major food-borne parasite worldwide. Trichinellosis caused by T. spiralis is not only a public health problem, but also an economic hazard in food safety. The development of effective vaccines to prevent Trichinella infection in domestic animals and humans is urgently needed for controlling of this zoonosis. Fructose-1, 6-bisphosphate aldolase (FBPA) is involved in energy production in glycolysis and is also associated with many non-glycolysis functions in the parasite, such as adhesion to host cells, plasminogen binding, and invasion. FBPA has been considered as a potential vaccine candidate or as a target for chemotherapeutic treatment. Here, we report for the first time the characterization of FBPA of T. spiralis and an evaluation of its potential as a vaccine candidate antigen against T. spiralis infection in mice. The results of qPCR and western blot analysis showed that the Ts-FBPA gene was expressed at various developmental stages of T. spiralis and was also detected in excretory-secretory products (ES) of T. spiralis muscle larvae (ML). Immunostaining with anti-Ts-FBPA mouse sera indicated that it localized principally to the surface and embryos of this parasitic nematode. Vaccination of mice with recombinant Ts-FBPA (rTs-FBPA) resulted in a Th1/Th2 mixed humoral and cellular immune response with Th2 predominant, as well as remarkably elevated IgE levels. Moreover, mice vaccinated with rTs-FBPA displayed a 48.7% reduction in adult worm burden and 52.5% reduction in muscle larval burden. These studies indicated that Ts-FBPA is a promising target for developing an effective vaccine to prevent and control Trichinella infection.

Neuroprotective effects of Astilbin on MPTP-induced Parkinson's disease mice: Glial reaction, α-synuclein expression and oxidative stress.

Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii, Engelhardia roxburghiana, Smilax corbularia and Erythroxylum gonocladum, and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i.p) daily for 5 days, to establish a subacute Parkinson's disease model, followed by daily treatment with AST or saline for 7 days. Pole and traction tests showed that AST ameliorated the impaired motor functions in MPTP-induced Parkinson's disease mice. High performance liquid chromatography analysis revealed that AST treatment prevented MPTP-induced decreases in striatal dopamine levels. Immunofluorescence assays showed that AST reduced the loss of dopaminergic neurons and the activation of microglia and astrocytes in the substantia nigra. Western blot analyses revealed that AST suppressed α-synuclein overexpression and activated PI3K/Akt in the striatum following MPTP treatment. AST also prevented the MPTP-induced reduction in total superoxide dismutase and glutathione activity in the striatum. AST exerts neuroprotective effects on MPTP-induced PD mice by suppressing gliosis, α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD.

Design and laboratory testing of a MEMS accelerometer array for subsidence monitoring.

The in situ monitoring of displacement variation is important for studying the seabed subsidence mechanism. To meet the multi-point measurement requirements for vertical displacement in subsidence monitoring of the seabed surface, a Micro-Electro-Mechanical Systems accelerometer array was designed. By sensing the tilt angles, displacements on the array can be calculated. The subsidence is calculated as the difference in the displacements from the initial values. To improve the accuracy of the displacement calculation, a calibration model of the tilt angle was presented. The model parameters are computed through a least squares estimation method, which is solved by the Levenberg-Marquardt algorithm. Experimental results show that the calibration model performs excellently with the maximum error of tilt angle being less than 1° in the measurement range (-90°, 90°). The displacement measurement accuracy of the array (2.1 m long) is almost less than 1 cm. Thus, the results show a strong agreement between the detected data and actual deformation in the test.

Aucubin alleviates glial cell activation and preserves dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian mice.

Aucubin (AUC) is a major bioactive ingredient in Eucommia ulmoides, Plantain asiatica, and Aucuba japonica, and has been shown to exert anti-inflammatory, antioxidative, and neuroprotective effects. We explore the neuroprotective effects of AUC in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Mice were administered MPTP (30 mg/kg) daily for 5 days, followed by treatment with AUC for 7 days. Measurement of dopamine levels was performed by high-performance liquid chromatography and tyrosine hydroxylase expression was assessed by western blot. Our results showed that AUC treatment improved mobility in the pole descent test and the traction test, and reduced the loss of dopaminergic neurons in MPTP-induced parkinsonian mice. AUC treatment rescued the decreased dopamine and tyrosine hydroxylase levels in the striatum of parkinsonian mice. Furthermore, AUC treatment reduced both microglia and astrocyte activation in the substantia nigra of parkinsonian mice. These findings suggest that AUC exerts neuroprotective effects, in part by reducing inflammation and preserving dopaminergic neurons. Possible protection mechanisms involved in MPTP-induced parkinsonian mice need to be clarified further.

Comprehensive Proteomic Analysis of Lysine Acetylation in the Foodborne Pathogen Trichinella spiralis.

Lysine acetylation is a dynamic and highly conserved post-translational modification that plays a critical role in regulating diverse cellular processes. Trichinella spiralis is a foodborne parasite with a considerable socio-economic impact. However, to date, little is known regarding the role of lysine acetylation in this parasitic nematode. In this study, we utilized a proteomic approach involving anti-acetyl lysine-based enrichment and highly sensitive mass spectrometry to identify the global acetylated proteome and investigate lysine acetylation in T. spiralis. In total, 3872 lysine modification sites were identified in 1592 proteins that are involved in a wide variety of biological processes. Consistent with the results of previous studies, a large number of the acetylated proteins appear to be involved in metabolic and biosynthetic processes. Interestingly, according to the functional enrichment analysis, 29 acetylated proteins were associated with phagocytosis, suggesting an important role of lysine acetylation in this process. Among the identified proteins, 15 putative acetylation motifs were detected. The presence of serine downstream of the lysine acetylation site was commonly observed in the regions surrounding the sites. Moreover, protein interaction network analysis revealed that various interactions are regulated by protein acetylation. These data represent the first report of the acetylome of T. spiralis and provide an important resource for further explorations of the role of lysine acetylation in this foodborne pathogen.