Pseudorabies virus UL38 attenuates the cGAS-STING signaling pathway by recruiting Tollip to promote STING for autophagy degradation.

Natural immunity is the first defense line of the host immune system, which plays a significant role in combating foreign pathogenic microorganisms. The IFN-ß (interferon-beta) signaling pathway, being a typical example of innate immunity, plays a vital function. This study aimed to elucidate the function of pseudorabies virus (PRV) UL38 protein (unique long region 38) in suppressing the activation of the IFN-ß signaling pathway. The findings from our study indicate that the PRV UL38 protein effectively hampers the activation of IFN-ß by poly (dA: dT) (poly(deoxyadenylic-deoxythymidylic)) and 2'3'-cGAMP (2'-3'-cyclic GMP-AMP). Furthermore, UL38 exhibits spatial co-localization with STING (stimulator of interferon genes) and effectively hinders STING dimerization. Subsequently, STING was downgraded to suppress the production of IFN-ß and ISGs (interferon stimulated genes). Immunoprecipitation analysis revealed that the interaction between UL38 and STING, which subsequently initiated the degradation of STING via selective autophagy mediated by TOLLIP (toll interacting protein). To summarize, this research elucidates the function of UL38 in counteracting the cGAS (cGAMP synthase)-STING-induced IFN-ß pathway. The PRV UL38 protein may attenuate the activation of IFN-ß as a means of regulating the virus's persistence in the host.

Prognostic and immune infiltration features of disulfidptosis-related subtypes in breast cancer.

Breast cancer (BC) is a prominent cause of cancer incidence and mortality around the world. Disulfidptosis, a type of cell death, can induce tumor cell death. The purpose of this study was to analyze the potential impact of disulfidptosis-related genes (DRGs) on the prognosis and immune infiltration features of BC. Based on DRGs, we conducted an unsupervised clustering analysis on gene expression data of BC in TCGA-BRCA dataset and identified two BC subtypes, cluster1 and cluster2, with cluster1 showing a higher likelihood of favorable survival. Through immune analysis, we found that cluster1 had lower proportions of infiltration in immune-related cells, including aDCs, DCs, NK_cells, Th2_cells, and Treg. Based on the immunophenoscore (IPS) results, we inferred that cluster1 might benefit more from immune checkpoint inhibitors targeting CTLA-4 and PD1. Targeted small molecule prediction results showed that patients with cluster2 BC might respond better to antagonistic small molecule compounds, including clofazimine, lenalidomide, and epigallocatechin. Differentially expressed genes between the two subtypes were found to be enriched in signaling pathways related to steroid hormone biosynthesis, ovarian steroidogenesis, and neutrophil extracellular trap formation, according to enrichment analyses. In conclusion, this study identified BC subtypes based on DRGs so as to help predict patient prognosis and provide valuable tools for guiding clinical management and precise treatment of BC patients.

Induced regulatory T cells modified by knocking down T-bet in combination with ectopic expression of inhibitory cytokines effectively protect graft-versus-host disease.

Induced regulatory T (iTreg) cells play a vital role in immune tolerance and in controlling chronic inflammation. Generated in the periphery, iTreg cells are suitable for responding to alloantigens and preventing transplant rejection. Nevertheless, their clinical application has been impeded by the plasticity and instability attributed to the loss of forkhead box protein 3 expression, raising concerns that iTreg may be converted to effector T cells and even exert a pathogenic effect. Herein, second-generation short hairpin RNAs loaded with 3 pairs of small interfering RNAs were utilized to target the T-box transcription factor TBX21. In addition, 2 immunosuppressive cytokines, namely, transforming growth factor beta and interleukin 10, were constitutively expressed. This novel engineering strategy allowed the generation of stably induced regulatory T (SI Treg) cells, which maintained the expression of forkhead box protein 3 even in an unfavorable environment and exerted potent immunosuppressive functions in vitro. Furthermore, SI Treg cells demonstrated an effector transcriptional profile. Finally, SI Treg cells showed a significant protective effect against graft-versus-host disease-related deaths in a xenotransplantation model. Collectively, these results signify that SI Treg cells hold great promise for future clinical application and offer a rational therapeutic approach for transplant rejection.

Mitigating Ion Migration with an Ultrathin Self-Assembled Ionic Insulating Layer Affords Efficient and Stable Wide-Bandgap Inverted Perovskite Solar Cells.

Wide-bandgap perovskite solar cells (PSCs) are attracting increasing attention because they play an irreplaceable role in tandem solar cells. Nevertheless, wide-bandgap PSCs suffer large open-circuit voltage (VOC ) loss and instability due to photoinduced halide segregation, significantly limiting their application. Herein, a bile salt (sodium glycochenodeoxycholate, GCDC, a natural product), is used to construct an ultrathin self-assembled ionic insulating layer firmly coating the perovskite film, which suppresses halide phase separation, reduces VOC loss, and improves device stability. As a result, 1.68 eV wide-bandgap devices with an inverted structure deliver a VOC of 1.20 V with an efficiency of 20.38%. The unencapsulated GCDC-treated devices are considerably more stable than the control devices, retaining 92% of their initial efficiency after 1392 h storage under ambient conditions and retaining 93% after heating at 65 °C for 1128 h in an N2 atmosphere. This strategy of mitigating ion migration via anchoring a nonconductive layer provides a simple approach to achieving efficient and stable wide-bandgap PSCs.

Relationships of leisure activities with physical and cognitive functions among Chinese older adults: A prospective community-based cohort study.

OBJECTIVES: Based on a prospective design, this study aimed to investigate the relationships of leisure activities with physical and cognitive functions among Chinese older adults. METHODS: The respondents aged 65 years or more were selected from the 2014-2018 of the Chinese Longitudinal Healthy Longevity Survey. Physical function measurement indicators were reflected by activities of daily living (ADL), instrumental activities of daily living (IADL), and physical performance (PP), while cognitive function was assessed by Mini-Mental State Examination. Fine-Gray competing risk regression models were used to analyze the data. RESULTS: Using the figures for 2014 as a baseline for the study, we included 6047, 6216, 5951, and 5916 respondents in the ADL, IADL, PP, and cognitive function analyses, respectively. The prospective results showed that keeping domestic animals or pets was related to a lower risk of ADL disability of respondents after adjustment (SHR: 0.619, 95% CI: 0.486, 0.788). Similarly, taking part in social activities (SHR: 0.781, 95%CI: 0.658, 0.929) and reading books or newspapers (SHR: 0.793, 95% CI: 0.656, 0.958) were associated with a lower risk of IADL disability. Playing cards or mahjong was correlated with a lower risk of cognitive impairment (SHR: 0.669, 95% CI: 0.507, 0.882), while keeping domestic animals or pets was related to a higher risk of cognitive impairment (SHR: 1.279, 95% CI: 1.047, 1.562). CONCLUSION: Participation in leisure activities moderately may decrease the risk of a decline in physical and cognitive functions among Chinese older adults.

Encephalomyocarditis Virus Abrogates the Interferon Beta Signaling Pathway via Its Structural Protein VP2.

Type I interferon (IFN)-mediated antiviral responses are critical for modulating host-virus responses, and indeed, viruses have evolved strategies to antagonize this pathway. Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen, which causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs. This study aims to understand how EMCV interacts with the IFN pathway. EMCV circumvents the type I IFN response by expressing proteins that antagonize cellular innate immunity. Here, we show that EMCV VP2 is a negative regulator of the IFN-ß pathway. This occurs via the degradation of the MDA5-mediated cytoplasmic double-stranded RNA (dsRNA) antiviral sensing RIG-I-like receptor (RLR) pathway. We show that structural protein VP2 of EMCV interacts with MDA5, MAVS, and TBK1 through its C terminus. In addition, we found that EMCV VP2 could significantly degrade RLRs by the proteasomal and lysosomal pathways. For the first time, EMCV VP2 was shown to play an important role in EMCV evasion of the type I IFN signaling pathway. This study expands our understanding that EMCV utilizes its capsid protein VP2 to evade the host antiviral response.IMPORTANCE Encephalomyocarditis virus is an important pathogen that can cause encephalitis, myocarditis, neurological diseases, and reproductive disorders. It also causes huge economic losses for the swine industry worldwide. Innate immunity plays an important role in defending the host from pathogen infection. Understanding pathogen microorganisms evading the host immune system is of great importance. Currently, whether EMCV evades cytosolic RNA sensing and signaling is still poorly understood. In the present study, we found that viral protein VP2 antagonized the RLR signaling pathway by degrading MDA5, MAVS, and TBK1 protein expression to facilitate viral replication in HEK293 cells. The findings in this study identify a new mechanism for EMCV evading the host's innate immune response, which provide new insights into the virus-host interaction and help develop new antiviral approaches against EMCV.

Promoting the anode performance of microbial fuel cells with nano-molybdenum disulfide/carbon nanotubes composite catalyst.

The design and manufacture of advanced anode materials with superior quality are significant for assembling high-performance microbial fuel cells (MFCs). The present study aims to investigate the synergistic effect of MoS2/CNTs nanocomposite as a novel anode-modifying material of MFCs. XRD, XPS, SEM, TEM and electrochemical analyses were performed to confirm the nanocomposite, to understand the morphology and to study the electrochemical properties of the modified electrodes. The performance of the MoS2/CNTs/carbon paper (CP)-MFCs was investigated and compared with that of MoS2/CP-MFCs, CNTs/CP-MFCs and CP-MFCs. The densest biofilm was formed on MoS2/CNTs-modified anode compared to MoS2/CP, CNTs/CP and CP anode, and MFCs with MoS2/CNTs-modified anodes achieved the maximum power density of 645 ± 32 mW m-2, which is three times greater than MFCs with bare carbon paper anodes (213 ± 10 mW m-2). These results demonstrate that the synthesized MoS2/CNTs nanocomposite could be exploited as an efficient anode catalyst for improving the performance of MFCs.

Effects of Comprehensive Swallowing Intervention on Obstructive Sleep Apnea and Dysphagia After Stroke: A Randomized Controlled Trial.

OBJECTIVE: This study aims to explore the effects of comprehensive swallowing intervention on obstructive sleep apnea (OSA) and dysphagia in stroke patients. METHODS: We performed a randomized controlled trial in stroke patients with obstructive sleep apnea (OSA) complicated by dysphagia, divided into treatment group and control group. The treatment group underwent comprehensive swallowing intervention and received swallowing care for 4 weeks, while the control group received only swallowing care. Outcome measurements were obtained at baseline and after the 4-week intervention, evaluated by polysomnography (PSG), videoendoscopic swallowing study (VFSS) synchronized surface electromyography (sEMG), oropharyngeal magnetic resonance imaging (MRI) and swallowing assessment scales. RESULTS: Sixty patients with stroke (30 treatment and 30 control) were eligible to participate in this study. There were no significant differences in any assessment between two groups at baseline. After a 4-week intervention, compared with to control group, there was a significant decrease in the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), and increased mean and minimal oxygen saturation (SaO2), amplitudes of suprahyoid muscle group (ASUPMG) and subhyoid muscle group (ASUBMG). Moreover, the posterior palatal distance (PPD), posterior lingual distance (PLD) and minimal cross-sectional area (MCSA) were obviously elevated in the treatment group. Additionally, the scores of Gugging swallowing screen (GUSS) and VFSS were significantly increased in the treatment group, compared to control group. CONCLUSIONS: The comprehensive swallowing intervention had therapeutic effects on OSA and dysphagia after stroke, and the mechanism was related to enhancing oropharyngeal muscle strength and changing upper airway structure.

How Do Presenteeism and Family Functioning Affect the Association Between Chinese Nurses' Job Stress and Intention to Stay?

BACKGROUND: Despite a great deal of existing research on nurses' job stress and intention to stay, it is still unclear how the association between Chinese nurses' job stress and intention to stay is affected by presenteeism and family functioning. AIMS: This study aimed to investigate the correlations of Chinese nurses' job stress, presenteeism, and family functioning with their intention to stay and clarify the mediating effect of presenteeism and the moderating effect of family functioning on the association between their job stress and intention to stay. METHOD: A cross-sectional study of 1,008 nurses was performed in a major general hospital in Qiqihar City, Heilongjiang Province, China. The participants were invited to engage in a questionnaire survey regarding job stress, presenteeism, family functioning, and intention to stay. A moderated mediation analysis was conducted through multiple linear regression analysis and the PROCESS macro. RESULTS: Job stress and presenteeism were negatively correlated with intention to stay, whereas family functioning was positively correlated with intention to stay. The effect of job stress on intention to stay was partially mediated by presenteeism (Effect = -0.147, 95% CI = [-0.305, -0.003]). In addition, family functioning moderated the direct effect of job stress on intention to stay (Index = -0.134, 95% CI = [-0.274, -0.001]). CONCLUSIONS: Presenteeism and family functioning were found to play mediating and moderating roles, respectively, in the relationship between job stress and intention to stay. Relevant interventions or family-friendly programs should be developed to enhance nurses' intention to stay.

Associations of job satisfaction and burnout with psychological distress among Chinese nurses.

Nurses' mental health is related to the quality of medical care and the outcome of treatment, and has become an important issue in nursing management. However, the role of burnout in the relationship between job satisfaction and psychological distress have not been evaluated. This study aimed to examine the prevalence of psychological distress among Chinese nurses and explore the associations of job satisfaction and burnout with psychological distress. A cross-sectional survey of 866 nurses was conducted in Qiqihar City, Heilongjiang Province of China. Job satisfaction, burnout, and psychological distress were assessed via the single-item, the Maslach Burnout Inventory-Human Services Survey, and the 12-item General Health Questionnaire respectively, followed by a mediation analysis through the multiple regression analysis and a PROCESS macro method. The prevalence of psychological distress was 35.2% among the participants. After controlling the potential confounding factors, job satisfaction and burnout were found to be still associated with psychological distress (P < 0.001). Furthermore, psychological distress was negatively correlated with both job satisfaction (r = -0.312) and personal accomplishment (r = -0.422) but positively correlated with both emotional exhaustion (r = 0.491) and depersonalization (r = 0.449). Burnout may mediate the association between job satisfaction and psychological distress (B = 0.139, ß = 0.440, P < 0.001 for emotional exhaustion; B = 0.226, ß = 0.382, P < 0.001 for depersonalization; and B = -0.105, ß = -0.368, P < 0.001 for personal accomplishment). The mental health status of Chinese nurses remains to be improved. Low job satisfaction and burnout could increase the risk of psychological distress among Chinese nurses. Moreover, job satisfaction may partially affect psychological distress among Chinese nurses through emotional exhaustion, personal accomplishment, and depersonalization. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04006-w.

Robust Self-Assembled Molecular Passivation for High-Performance Perovskite Solar Cells.

Defect passivation via post-treatment of perovskite films is an effective method to fabricate high-performance perovskite solar cells (PSCs). However, the passivation durability is still an issue due to the weak and vulnerable bonding between passivating functional groups and perovskite defect sites. Here we propose a cholesterol derivative self-assembly strategy to construct crosslinked and compact membranes throughout perovskite films. These supramolecular membranes act as a robust protection layer against harsh operational conditions while providing effective passivation of defects from surface toward inner grain boundaries. The resultant PSCs exhibit a power conversion efficiency of 23.34 % with an impressive open-circuit voltage of 1.164 eV. The unencapsulated devices retain 92 % of their initial efficiencies after 1600 h of storage under ambient conditions, and remain almost unchanged after heating at 85 °C for 500 h in a nitrogen atmosphere, showing significantly improved stability.

Relationships of organisational justice, psychological capital and professional identity with job burnout among Chinese nurses: A cross-sectional study.

AIMS AND OBJECTIVES: The present study was aimed at describing the status of job burnout and exploring the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout. BACKGROUND: With the shortage of nurses all over the world, nurses' job burnout has become the focus of studies in recent years. However, limited published research has examined the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout within hospital contexts in China. DESIGN: A cross-sectional design. METHODS: A total of 1,009 nurses were enrolled from a major general hospital located in Qiqihar City in the northeast of China from March-July 2018, and asked to complete questionnaires regarding organisational justice, psychological capital, professional identity and job burnout. The STROBE checklist was adhered to in this study. RESULTS: It was observed that the overall proportion of nurses with job burnout was 58.8%. All the correlations among organisational justice, psychological capital, professional identity and job burnout were statistically significant, with coefficients ranging between -0.487-0.863. Psychological capital and professional identity had indirect effects equal to -0.072 and -0.142, respectively, on the association between organisational justice and job burnout, taking up 13.7% and 26.9% of the total effect, respectively. The serial indirect effect of psychological capital and professional identity was -0.129, accounting for 24.5% of the total effect. CONCLUSIONS: This study showed the necessity of addressing the status of job burnout among Chinese nurses. Psychological capital and professional identity may mediate the linkage between organisational justice and job burnout independently and accumulatively. RELEVANCE TO CLINICAL PRACTICE: Nursing managers should strengthen organisational justice and improve the psychological capital and professional identity of nurses through effective strategies to prevent the job burnout of nurses.

Relationships of professional identity and psychological reward satisfaction with subjective well-being among Chinese nurses.

AIM: This study aimed at exploring the impact of professional identity and psychological reward satisfaction on subjective well-being and clarifying the effect of psychological reward satisfaction on this relationship. BACKGROUND: People know little about the effect of psychological reward satisfaction on the relationship between professional identity and subjective well-being. METHODS: A cross-sectional survey was carried out on 1,009 nurses from Qiqihar City, Heilongjiang Province of China. Professional Identity Scale, Psychological Reward Satisfaction Scale and General Well-Being Schedule were used to assess professional identity, psychological reward satisfaction and subjective well-being, respectively. Associations were explored by using structural equation modelling. RESULTS: The subjective well-being of 436 (43.2%) nurses was at low and moderate levels. After the adjustment of potential confounding factors, professional identity was still associated with subjective well-being (B = 3.035, ß = 0.215, p < .001). Professional identity (r = .308) and psychological reward satisfaction (r = .309) were positively correlated with subjective well-being. Psychological reward satisfaction mediated the association between professional identity and subjective well-being (effect = 0.114, p < .001). CONCLUSION: This study suggested that the subjective well-being of nurses should be improved by paying special attention to them and taking targeted support measures. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers can help enhance the professional identity of nurses by organising nursing education activities, and pay more attention to psychological reward satisfaction to improve the subjective well-being of nurses.

Establishment and associated factors of health records among young Chinese migrants.

BACKGROUND: Most Chinese migrants have been faced with obstacles to getting access to local public health services. Young migrants among internal migrants make a major contribution to the economy. However, the establishment of their health records has been ignored. This research was aimed at exploring the status and associated factors of the establishment of health records among young Chinese migrants. METHODS: Data were obtained from the 2017 China Migrants Dynamic Survey (CMDS). Chi-square test and binary logistic regression were performed to investigate the associated factors of the establishment of health records among young Chinese migrants. RESULTS: Approximately 30.2% of young migrants had their health records established in inflow communities. Urban residence, medical insurance (insured), and lower average monthly household income were attributed to the establishment of more health records. Young migrants who were in northeast China and across provinces and immigrated for working or engaging in trade were less likely to have health records established. Young migrants who participated in social activities and public affairs activities and took type of people in touch as natives in the inflow area showed a higher possibility of establishing health records. Meanwhile, receiving health education and hearing about national basic public health services (BPHSs) were beneficial for establishing the health records of more young migrants. CONCLUSION: This study showed that the health records of young migrants had a relatively low establishment rate. Sociodemographic and migration characteristics, health status, public health services, and social integration factors were all related to the health record establishment of young Chinese migrants.

Associations of negative life events and coping styles with sleep quality among Chinese adolescents: a cross-sectional study.

BACKGROUND: Limited published research has examined the relationships of negative life events and coping styles with sleep quality in Chinese junior high school students. We aimed to investigate the prevalence of poor sleep quality and to clarify the role of coping styles between negative life events and sleep quality. METHODS: A cross-sectional study of 3081 students was conducted in Ganzhou City, Jiangxi Province, Southeastern China. Adolescent Self-Rating Life Events Checklist, Simplified Coping Style Questionnaire, and Pittsburg Sleep Quality Index were applied to assess negative life events, coping styles, and sleep quality, respectively. Descriptive analyses, independent-samples t tests, one-way analyses of variance, Pearson correlation analyses, and structural equation modeling (SEM) were applied to analyze the data. RESULTS: The prevalence of poor sleep quality was 26.7%. Negative life events (B = 0.038, P < 0.001) and negative coping style (B = 0.049, P < 0.001) demonstrated a positive association with poor sleep quality, while positive coping style indicated a negative association with poor sleep quality (B = -0.029, P < 0.001). Interactions of negative life events and coping styles with sleep quality were not found (all P > 0.05). The association between negative life events and sleep quality was mediated by negative coping styles. CONCLUSIONS: Our results indicated that poor sleep quality was common in these Chinese adolescents. Negative life events and negative coping style were associated with an increased prevalence of poor sleep quality, while the positive coping style was related to a decreased prevalence of poor sleep quality. A negative coping style mediated the association between negative life events and sleep quality.

Risk factors and control of seizures in 778 Chinese patients undergoing initial resection of supratentorial meningiomas.

This retrospective study explored the risk factors for the occurrence of seizures in the pre- and postoperative period in patients undergoing supratentorial meningiomas surgery to investigate those who are likely to benefit from prophylactic antiepileptic drugs (AEDs). We reviewed the medical records of 778 supratentorial meningiomas patients who were operated at our institution between 2011 and 2012. A total of 100 (12.9%) patients experienced preoperative seizures; 41 patients (5.3%) experienced postoperative in-hospital seizures, and 91 (13.5%, n = 673) patients experienced postoperative seizures after discharge. Multivariate analysis revealed that motor cortex involvement (odds ratio [OR] 3.243, P < 0.001) and peritumoral edema ≥ 1 cm (OR 3.936, P < 0.001) were significant risk factors of preoperative seizures. Whereas presenting with headache (OR 0.259, P < 0.001) and age ≥ 55 years at surgery (OR 0.514, P = 0.009) showed decreased incidence of preoperative seizures. The involvement of motor cortex (OR 3.290, P = 0.003), postoperative Karnofsky Performance Scale (KPS) ≤ 70 (OR 5.389, P < 0.001), preoperative seizure (OR 4.003, P < 0.001), and occurrence of any medical/surgical complication (OR 3.925, P = 0.001) were significant risk factors for postoperative in-hospital seizures. Postoperative seizures after discharge were associated with tumor maximal diameter ≥ 3.5 cm (OR 1.903, P = 0.022), preoperative seizures (OR 4.350, P < 0.001), postoperative in-hospital seizures (OR 6.385, P < 0.001), and tumor recurrence/progression (OR 7.642, P < 0.001). The probability of seizure freedom in the 5-year follow-up was roughly 59% among patients with preoperative seizures, and 87% among patients without preoperative seizures. Cox regression analysis showed that tumor recurrence/progression (relative risk 2.987, 95% CI 1.517, 5.879, P = 0.002) was the only predictor of postoperative seizures in patients without a history of preoperative epilepsy. The use of postoperative prophylactic antiepileptic drug (AED) did not reduce the incidence of seizures in our analysis. Understanding the risk factors for seizures might help clinicians to predict their occurrence and develop effective anti-epileptic treatment strategies. Further prospective randomized controlled trials are needed to determine the risk factors for seizures and the efficacy of AED prophylaxis.

Alteration of liver immunity by increasing inflammatory response during co-administration of methamphetamine and atazanavir.

Objective: Use of methamphetamine (METH) is prevalent among HIV-infected individuals. Previous research has shown that both METH and HIV protease inhibitors exert influences on mitochondrial respiratory metabolism and hepatic nervous system. This study aims to study the joint effect of METH and HIV protease inhibitors on hepatic immune function.Materials and methods: Based on the differentially expressed genes obtained from RNA-seq of the liver from mouse model, the expression levels of CD48 and Macrophage Receptor with Collagenous Structure (MARCO) were examined using qRT-PCR and flow cytometry, and the expression and secretion of cytokines IL-1ß, IL-6, IL-8, IL-10, IFN-γ, IFN-ß, and TNF-α were determined using qRT-PCR and ELISA in THP-1-derived macrophages.Results: Our results indicated that compared with the control group, CD48 molecules were significantly down-regulated by METH-atazanavir co-treatment, and the expression level of CD48 decreased as METH concentration increases. MARCO molecules were increased, especially at larger doses of METH and atazanavir treatment. In addition, in the presence of METH-atazanavir, the expression and secretion of a series of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-8 increased while the expression and secretion of anti-inflammatory cytokine IL-10 decreased.Conclusion: These results demonstrated that METH and atazanavir had a combined impact on the liver immunity, suggesting that the co-treatment could enhance inflammatory response and suppress NK cell activation via CD48.

Comparative study of striatum GABA concentrations and magnetic resonance spectroscopic imaging in Parkinson's disease monkeys.

BACKGROUND: Parkinson's disease is a progressive degenerative nervous system disease. Recent studies have shown that secondary changes in the GABA system play directly affect the pathogenesis of PD. There is still much debate about GABA concentrations because currently, GABA concentrations in the brain tissue are obtained indirectly by measuring its concentration in the blood and cerebrospinal fluid. These results are unreliable. Magnetic resonance spectroscopy (MRS) is the only noninvasive method for evaluating the concentration of metabolites in living brain tissue and has been widely applied in research and clinical practice. In addition, combining MEGA-PRESS technology with LCModel software for quantitative GABA measurements is largely recognized. At present, the PD monkeys model in primates has been increasingly proficient. Primates are more similar to humans in terms of brain structure and function than other animals. However, 3.0 T MRS studies involving the PD monkey model to measure metabolites in living subjects with PD are still rare. The study was performed at 3.0 T MRI with control monkeys and PD monkeys that were injected methyl-phenyl-tetrahydropyridine (MPTP) in one side of common carotid artery before and 3 months after successful model establishment to measure GABA concentrations in the bilateral striatum. Behavioral observations were performed for all animals, and the behavioral score was recorded. After 3 months, the GABA concentration in the bilateral striatum was measured in both groups by high-performance liquid chromatography (HPLC). The data obtained from magnetic resonance spectroscopy (MRS) were compared with the actual measured GABA concentrations in tissues isolated from the corresponding regions, and their correlations with the behavior score were analyzed. The research objectives are to investigate the changes of γ-aminobutyric acid (GABA) concentration in the bilateral striatum of monkeys with Parkinson's disease (PD) and the value of quantitatively measuring its concentration by noninvasive 3.0 T spectroscopy. RESULTS: (1) The MRS results showed that the GABA concentration in the injured side of the striatum of the PD monkeys was higher than in the contralateral side, but the difference was not statistically significant (P = 0.154). Compared with that the blank control group, the GABA concentration in the striatum of the PD monkeys increased, but there was no difference between the groups (P = 0.381; P = 0.425). (2) The GABA concentration that determined from the isolated specimens by HPLC in the injured side of the striatum of the PD monkeys was significantly higher than that in the contralateral side (P < 0.01). Compared with the blank control group, the PD monkeys had higher GABA concentrations in both sides of the striatum, and there was a significant difference in the lesion side (P = 0.004), while there was a non-significant difference in the contralateral side (P = 0.475). (3) The mean GABA concentration in the injured striatum of PD monkeys determined by MRS was not significantly correlated with the behavioral score (r = 0.146, P = 0.688). The mean GABA concentration in the injured striatum determined from the isolated specimens was positively correlated with the behavioral score in the same period (r = 0.444, P = 0.038). CONCLUSION: The GABA concentration in the injured striatum of PD monkeys is increased and positively correlated with behavioral changes. Validity of noninvasive 3.0 T MRS to detect PD neurotransmitter changes is limited.

Characteristic features and proposed classification in 69 cases of intracranial microcystic meningiomas.

Microcystic meningioma (MM) is a rare subtype of intracranial meningiomas, with clinical and radiologic features not well characterized in the literature. Based on our experience, we propose a classification system of intracranial MMs. We reviewed the medical records, radiographic studies, and operative notes of a group of consecutive patients with intracranial MM. The mean age of the 69 patients was 46.8 ± 10.6 years (range, 21-75 years). Three types of intracranial MMs could be identified. Type 1 MMs presented as a solid lesion, hypointense or isointense on T1WI, hyperintense on T2WI, and homogeneous or heterogeneous enhancement, and were found in 43 patients (67.2%). Type 2 MMs represented signals similar to CSF both on T1WI and T2WI, and faint reticular enhancement with marginal enhancement, and these were found in 7 patients (10.9%). Type 3 MMs consisted of cystic-solid or cystic lesion and were found in 14 patients (21.9%). Significant differences were observed among the different types of MMs for the following variables: sex, presence of severe peritumoral brain edema (PTBE), and extent of tumor resection. Females were found in all of patients with type 2 MMs, but were only 35.7% of those with type 3 MMs (P = 0.018). Severe PTBEs were more common among patients with type 1 MMs (55.8%) than among those with type 2 (14.3%) and type 3 MMs (14.3%) (P = 0.007). Type 1 MMs (97.7%) were associated with a significantly higher rate of gross total resection compared with the other two types (71.4 and 78.6%) (P = 0.019). Total length of hospital stay after craniotomy ranged from 4 to 30 days (median, 8 days). There were no significant differences in progression-free survival among the three types of MMs (P = 0.788). The current classification identifies three distinct types of intracranial MM based on their radiological findings and growth patterns. The type 1 MMs are more commonly associated with severe PTBE. Type 2 and Type 3 MMs have a higher predilection towards parasaggital location with venous involvement and therefore have a lower rate of gross total resection.

Construction, expression, and characterization of a single-chain variable fragment (ScFv) antibody targeting to the encephalomyocarditis virus.

Encephalomyocarditis virus (EMCV) is as a potential zoonotic agent with a wide host range. Here, applying gene splicing by overlap extension PCR (SOE-PCR), we describe a simple method for producing single-chain variable fragment (scFv) antibody against EMCV that configurates in the orientation of VH-(GGGGS)4 -VL. DNA template was resverse transcribed by total RNA that derived from hyperimmunized antibody positive mice spleen after inoculation inactivated EMCV-PV21 as antigen. Using the degenerate primers designed for the variable regions of IgG of murine antibody, the 417 bp of gene encoding VH-linker (VHL) and 360 bp of gene encoding linker-VL (LVL) of the anti-EMCV was individually amplified from DNA template by PCR, repectively. The 762 bp gene encoding anti-EMCV scFv was constructed by SOE-PCR when the mixed VHL and LVL genes were used as the template. The amplified gene subcloned into pGEX-6P1 to yield pGEX-6P1/EMCV-scFv. Recombinant vector transformed into the Escherichia coli BL21 (DE3) and a 53 KDa GST-scFv fusion protein was obtained by SDS-PAGE electrophoresis. Animal experiment results showed that the pretective rate of mice in group A which challenged 500 µL 104 TCID50 EMCV per mouse for 7 d post-inoculation scFv 3 d (0.5 mg purified recombinant scFv per mouse) was 91.67% (11/12). The serum anti-EMCV antibody titer in group A mice was most significantly higher than that in positive control mouse (P < 0.01), coversely the serum relative mRNA copies were significantly lower than that in positive control mouse (P < 0.05). These findings indicated that recombinant anti-EMCV scFv has remarkable anti-EMCV effect in mice.