Mechanisms for phase separation between TDP-43 and ubiquitin in vitro / 军事医学

Objective To explore the characteristics and mechanism of phase separation between TAR DNA binding protein-43(TDP-43)and ubiquitin.Methods The TARDBP gene and its truncated genes were inserted into vectors to construct recombinant plasmids for expression and protein purification.The phase separation system of ubiquitin and TDP-43 was constructed in vitro.The characteristics of the droplets formed via liquid-liquid phase separation were observed by fluorescence microscopy.The plasmids of ubiquitin and TDP-43 were co-transfected into HEK293T cells to observe aggregates containing TDP-43 and ubiquitin and find out whether TDP-43 could be ubiquitinated.Results The GFP-8Ub,TDP-43 full-length(FL)and truncated proteins were purified.TDP-43 FL and C-terminal domain(CTD)proteins were able to form droplets via phase separation with ubiquitin.The droplets changed into solid-like aggregates after prolonged incubation.Insolvable aggregates containing TDP-43 and ubiquitin were formed.TDP-43 was ubiquitinated under stress conditions in HEK293T cells after being co-transfected with ubiquitin and TDP-43 recombinant plasmids.Conclusion TDP-43 undergoes co-phase separation with ubiquitin,mainly driven by the multivalent interaction between TDP-43′s CTD structural domain and ubiquitin.The droplets finally form aggregates with solid-like properties.Under stress conditions,especially when the protein homeostasis is disrupted,TDP-43 and ubiquitin form aggregates while TDP-43 is ubiquitinated.This study reveals the basic mechanism of TDP-43 co-phase separation with ubiquitin and liquid-solid transformation.

Transcranial magnetic stimulation can alleviate sleep disorders in children with cerebral palsy / 中华物理医学与康复杂志

Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on sleep disorders among children with cerebral palsy (CP).Methods:A total of 102 children with CP and disordered sleep were randomly divided into an experimental group and a control group, each of 51. All were given routine rehabilitation and sleep health education, but the experimental group additionally received rTMS for two weeks. The polysomnography (PSG) results of the two groups were recorded and analyzed.Results:The PSG parameters had improved greatly in both groups after the treatment. The percentage of N2 sleep (depth of sleep during light sleep) in the severe cerebral palsy group and of N3 sleep (depth of sleep during deep sleep) in the moderate cerebral palsy group had increased significantly more than in the mild cerebral palsy group, on average. After the intervention the percentages of N2 and N3 in those with mixed cerebral palsy and of N3 in those with involuntary motor cerebral palsy had increased significantly more than in those with spastic cerebral palsy, on average.Conclusion:rTMS treatment can improve the sleep disorders of children with cerebral palsy, especially N2 sleep among children with moderate to severe cerebral palsy, N3 sleep in cases of mixed or dyskinetic CP.

Intervention of Traditional Chinese and Western Medicine in NLRP3 Inflammasome-mediated Digestive System Diseases： A Review / 中国实验方剂学杂志

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

Magnetic resonance imaging of children with cerebral palsy and their clinical characteristics / 中华物理医学与康复杂志

Objective:To document the clinical features of children with cerebral palsy (CP) using magnetic resonance imaging (MRI).Methods:The gross motor functioning of 325 children diagnosed as having CP was graded using the gross motor function classification system (GMFCS). The GMFCS grades were correlated with MRI results in univariate and multivariate logistic regression analyses. The significance of any relationship between the MRI results and co-morbidities was tested using chi-squared tests.Results:Cerebral dysplasia, cerebroventricular enlargement, periventricular leukomalacia (PVL), abnormal signals in the thalami, and morphological changes after hypoxic ischemic encephalopathy were all found to be significantly correlated with GMFCS grading. Moreover, the chi-squared tests indicated that PVL children, children with thinning of the corpus callosum and/or abnormal signals in the thalami were significantly more likely to have visual, auditory or speech impairment complications and/or mental retardation.Conclusions:The findings from MRI correlate well with types of CP, GMFCS grades and co-morbidities among CP children. MRI can be an effective tool for early diagnosis and prognosis of CP in children, indicating needs for clinical rehabilitation.

Diagnostic value of C-reactive protein and procalcitonin for bacterial infection in acute exacerbations of chronic obstructive pulmonary disease / 中南大学学报(医学版)

OBJECTIVE@#To investigate the value of C-reactive protein (CRP) and procalcitonin (PCT) in diagnosis of the bacterial infection in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients by detecting the change of CRP and PCT.@*METHODS@#A total of 369 AECOPD patients were divided into infective group and non-infective group. The values of CRP, PCT, WBC, N and ESR were tested and compared before and after treatment in each group.@*RESULTS@#Before treatment, the levels of CRP, PCT, WBC, and N in the infective group were significantly higher than that in the non-infective group (P0.05). In the infective group, the levels of CRP, PCT, WBC, N and ESR after the treatment were much lower than those before treatment (P0.05). There was a positive relationship between PCT and CRP, ESR and WBC (r=0.46, 0.38, 0.20; P<0.05), CRP and WBC as well as N and ESR (r=0.56, 0.43, 0.30; P<0.05).@*CONCLUSION@#It is a sensitive method for diagnosis and treatment of the bacterial infection in AECOPD patients through the combination of CRP with PCT and also for evaluation of the prognosis of patients with AECOPD.

Dextran sulfate attenuates ischemia-reperfusion injury after lung transplantation in rats / 中华器官移植杂志

Objective To investigate the effects of dextran sulfate on lung ischemia-reperfusion injury after lung transplantation in rats.Method A total of 32 male Wistar rats were subjected to unilateral left lung orthotopic transplantation.They were randomly divided two groups (n =16 each):DXS group [DXS (10 mg/kg) was given prior to the reperfusion],and the control group (the same volume of normal saline was given).After animals were sacrificed,the lung graft was harvested 2 h after reperfusion.Oxygenation indexes,wet/dry ratio (W/D),myeloperoxidase (MPO) activity,malondialdehyde (MDA) and endothelin 1 (ET-1) in the transplanted lung,and tumor necrosis factor a (TNF-α) and interleukin 8 (IL-8) in serum were measured.The lung injury scores were evaluated and complement deposition was observed.Result After 2-h reperfusion,compared to the control group,oxygenation indexes were improved significantly in DXS group (P＜0.05),but there were no significant differences in W/D between two groups.In DXS group,the activity of MPO was significantly reduced,and the contents of MDA and ET-1 in the lung tissue were significantly reduced as compared with the control group.DXS reduced the level of TNF-α and IL-8 markedly in serum (P ＜0.05).There was no significant difference in lung injury score between two groups (4.53 ± 0.46 vs.5.28 ±0.49,P＞0.05).Compared to the control group,DXS reduced the deposition of C3c (0.8 ±0.2vs1.5±0.3) andC6 (1.2±0.4vs.2.4±0.5) (P＜0.05).Conclusion Administration of DXS attenuated ischemia-reperfusion injury after lung transplantation by inhibiting complement deposition,and improved the oxygenation of the transplanted lung.This protection was associated with inhibition of inflammation and oxidation and endothelial cytoprotection.