Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.
Animals ; Swine ; African Swine Fever Virus/metabolism* ; Membrane Proteins/metabolism* ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction/genetics*

Novel coronavirus pneumonia (COVID-19) is currently raging worldwide, and the prevention and control situation is very grim. Gratifying achievements of organ donation have been made in China since its implementation. Due to the characteristics of potential donors, such as complicated personnel structure, sudden onset and critical illness, it is necessary for multi-department to contact with the donors and their families during the work link of donor evaluation, family communication, donor transportation, organ function maintenance and organ procurement, which raises higher requirement for the screening and management of potential donors under COVID-19 epidemic. During the outbreak, Beijing Youan Hospital, Capital Medical University has completed 9 cases of organ donation, formulated the relevant screening process, established the prevention and control requirements, and gained certain experience and effects, which benefits the orderly and smooth development of organ donation under the COVID-19 epidemic.

Objective To identify the plasma miRNAs which are differentially expressed in the patients with traumatic avascular necrosis of the femoral head by means of high-throughput screening so as to provide data for further research into the pathogenesis of traumatic avascular necrosis of the femoral head.Methods We selected 10 patients with femoral neck fracture who had been treated from January to April 2015 for traumatic avascular necrosis of the femoral head following manual reduction and internal fixation with percutaneous hollow screws (necrosis group) and another contemporary age-matched 10 patients with femoral neck fracture who had been treated in the similar way but did not develop traumatic avascular necrosis of the femoral head for over 2 years (control group).After the peripheral blood was obtained from the 20 patients,Axon GenePix 4000B chip scanner was used for peripheral blood chip screening to identify the miRNAs which were differentially expressed.QPCR technique was used to verify the top 5 miRNAs which were significantly up-regulated and the top 5 miRNAs which were significantly down-regulated.Results The Harris score for the necrosis group was significantly lower than that for the control group while the Visual Analog Scale score for the former significantly higher than that for the latter (P ＜ 0.05).There were no significant differences between the 2 groups in general data (P ＞ 0.05).In comparison of the 2 groups,the chip screening identified 95 miRNAs which were significantly up-regulated and 413 miRNAs which were significantly down-regulated.The "volcano" analysis screened out 147 miRNAs differentially expressed of which 35 were up-regulated genes and 112 down-regulated genes.Of the 10 genes selected,8 were found in line with the results of microarray screening:hsa-miR-93-5p,hsa-let-7i-5p,hsa-miR-320a,hsa-miR-25-3p,hsa-miR-16-2-3p,hsa-miR-122-5p,hsa-miR-4711-3p and hsa-miR-3191-5p.Conclusion This study indentified 8 differentially expressed miRNAs associated with traumatic osteonecrosis of the femoral head,providing data for further study.

Objective:To evaluate the safety of cardiac catheterization intervention therapy and transthoracic small incision surgery in the occlusion bydomestic occluder under echocardiography guiding in patients with atrial septal defect (ASD).Methods:A total of 1 080 patients with ASD in the occlusion by domestic occluder were analyzed retrospectively,and the interventional treatment were performed in 734 cases through cardiac catheterization intervention therapy and 346 cases through transthoracic small incision surgery.The patients undergone cardiac catheterization intervention therapy were guided under the digital substraction angiography (DSA) and were monitored by transthoracic echocardiography (TTE) in the whole interventional process,and the efficacy was evaluated with TTE.The occlusion of transthoracic small incision surgery was guided under the transesophageal echocardiography (TEE),which was used to monitor the position of occluder and evaluate the efficacy immediately.Results:Two kinds of intervention in the occlusion by domestic occluder had achieved satisfactory results in patients with ASD.There was no statistically difference in the longest size of ASD between the 2 intervention methods,while there were statistically differences in the ratio between ASD longest diameter and atrial septal length,and the size of the occlusion,and the disparity between the size of the occluder and ASD longest diameter (D value),respectively (all P＜0.05).When the size of arithmetic mean of the ASD was ＜30 mm,the success rate of the 2 methods was both 100％.When the size of arithmetic mean of the ASD was ≥ 30 mm,the success rate was 100％ in the transthoracic small incision surgery and 50％ in the cardiac catheterization intervention therapy.Conclusion:Domestic occluder is safe.Compared with the imported one,its cost is lower.When the size of the defects is same,the occlusion is smaller in the transthoracic small incision surgery compared with that in the cardiac catheterization intervention therapy.When the size of arithmetic mean of the ASD is ≥ 30 mm,the success rate of the transthoracic small incision surgery is higher compared with the cardiac catheterization intervention therapy.When the cardiac catheterization intervention therapy fails,the transthoracic small incision surgery may be a better choice.

Objective To study the effect of black granule capsules(BGCs) on growth of transplanted mouse hepatocarcinoma cells, cell proliferation cycle and apoptosis.Methods KM mouse were subcutaneously inoculated with Hepatocarcinoma cells (H22) and randomly divided into the model control group, the positive control group, the low, medium and high does of BGC group after 24h. The positive control group received intraperitoneal injection with 30 mg/kg cyclophosphamide. Mice of BGC groups were intragastricaly with different dosage of BGC (400, 800, 1 600 mg/kg). The model control group received intragastricaly with normal saline. The drugs were administrated once a day for seven days. The tumor inhibition rate was calculated at 24 h after the last administration. Flow cytometry was used to detect changes of cell cycle and apoptosis in harvested H22 tumor cells.Results The group of high does showed significant inhibitory effect on the growth of transplanted H22 tumor cells withthe inhibitory rate 38.78% (male) and 43.57% (female). Compared with model control group, groups of different dosages decreased time of G0-G1 phase (58.06% ± 9.65%, 55.10% ± 5.89%, 61.36% ± 15.95%vs. 74.47% ± 2.63%), increased tiem of Sphase (33.96% ± 11.90%, 32.67% ± 4.04%, 33.89% ± 9.82%vs. 14.37% ± 4.92%), and increased the apoptosis rate (31.12% ± 1.85%, 31.89% ± 2.16%, 40.64% ± 0.55%vs.21.75% ± 2.64%).Conclusion BGC has antitumor effect on mouse hepatocarcinoma H22 tumor cells, and its mechanism was to regulate cell proliferation cycle and induce the apoptosis.

ObjectiveTo investigate the effects of Saposhnikovia divaricata extract combined with arsenic trioxide (ATO) on the proliferation and apoptosis in chronic myelogenous leukemia K562 cells. MethodsSaposhnikovia divaricata extract was prepared.Cultured K562 cells were treated with different concentration of Saposhnikovia divaricataextract or/and ATO for 48h. Cell proliferation was determined using the MTT assay. Apoptosis and cell cycle were detected using flow cytometry.ResultsThe MTT assay showed that Saposhnikovia divaricata extract of 750,1 000,1 250,1 500 μg/ml had a significantly proliferation inhibitory effect compared with control group, the inhibitory rates were 23.29% ± 3.31%, 48.30% ± 2.50%, 79.62% ± 3.41% and 88.94% ± 0.06%, respectively (allP<0.05); Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 1.0, 0.5 μg/ml significantly increased inhibitor rates compared with ATO of 1.0, 0.5 μg/ml (64.99% ± 5.18%vs. 44.48% ± 3.31%,38.59% ± 3.88%vs.26.30% ± 5.03%; allP<0.05). FCM showed that Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 2.0, 1.0, 0.5 μg/ml significantly increased apoptotic rate compared with ATO group of 2.0, 1.0, 0.5 μg/ml (33.97% ± 0.59%vs.20.97% ± 2.17%, 13.53% ± 0.47%vs.9.77%±0.64%、6.63%±&0.40%vs.4.00%±0.46%; allP<0.05 ). Cell cycle results showed that Saposhnikovia divaricata extract of 500μg/ml combined with ATO of 2.0,1.0, 0.5μg/ml significantly increased the rate of S phase compared with ATO group of 2.0, 1.0, 0.5 μg/ml (60.25 ± 2.59%vs.55.61 ± 1.28%, 60.89 ± 1.53%vs.37.96 ± 1.02%, 47.76 ± 0.87%vs.39.90 ± 0.92%; allP<0.05).ConclusionsSaposhnikovia divaricataextract could obviously inhibit the proliferation of K562 cells and enhance the apoptotic effect of ATO. ATO could induce a G2/M phase arrest, while Saposhnikovia divaricata extract combined with ATO could induce a S phase arrest in K562 cells.

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity of the β-hydroxyacyl-ACP dehydratase HadAB complex. How this inhibition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2',4,4'-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon mutation to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site. The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; metabolism ; Catalytic Domain ; Enzyme Inhibitors ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Hydro-Lyases ; antagonists & inhibitors ; chemistry ; Molecular Sequence Data ; Mycobacterium tuberculosis ; drug effects ; enzymology ; Protein Binding ; drug effects ; Protein Multimerization ; drug effects ; Protein Structure, Secondary ; Sequence Alignment

Objective To observe the changes of serum superoxide dismutase (SOD) levels in typeⅡdiabetic patients with peripheral arterial disease (PAD) before and after interventional therapy, and to investigate the effects of oxidative stress level and interventional treatment on serum SOD level. Methods During the period from July 2011 to December 2012 at authors’ hospital, a total of 40 patients with type Ⅱ angiography together with balloon dilation and/or stenting was carried out in 24 patients (group B, with Fontaine stage of Ⅱb - Ⅲ). Of the 24 patients in group B, lower limb arterial angiography together with balloon dilation was employed in 16 (group B1) and lower limb arterial angiography together with balloon dilation and stenting was adopted in 8 (group B2). Twenty healthy clinical subjects were used as control group (group C). Before interventional treatment, elbow venous blood samples of patients in group A and B were collected to determine serum lipid, HbA1c and SOD levels. The same tests were also carried out in the subjects of group C. During percutaneous lower extremity arterial intervention , through arterial sheath 3 ml arterial blood specimen was collected in all patients of both group A and B before intervention started. Twenty-four hours after the treatment, venous blood specimen was also collected in all patients to determine serum SOD levels. The results were statistically analyzed. Results Lower limb arterial angiography showed that no obvious arterial stenosis was seen in the patients of group A. The interventional procedures were all successfully completed in all patients of group B. SOD levels of group A, B and C were (46.1 ± 3.13)U/ml, (35.37 ± 3.58)U/ml and (60.50 ± 6.99)U/ml respectively. SOD levels of both group A and B were significantly lower than that of group C (t = 8.420, P < 0.01; t = 14.324, P < 0.01). The level of SOD in group A was significantly higher than that in group B (t = 10.092, P < 0.01). The ankle-brachium indexes (ABI) of group A, B and C were (0.70 ± 0.12), (0.58 ± 0.13) and (1.15 ± 0.07) respectively. ABI of group A and B was significantly lower than that of group C (t = 14.324, P < 0.01; t = 17.392, P < 0.01). ABI of group B was significantly lower than that of group A (t=3.027, P<0.05). SOD level bore a negative correlation with HbA1c level (r=-0.541, P<0.01). In both group A and group B, no significant difference in SOD level existed between the venous blood and arterial blood. The preoperative arterial SOD levels in group B1 and group B2 were (35.70 ± 3.04)U/ml, and (36.07 ± 2.14)U/ml respectively, and the difference between the two groups was not statistically significant. The preoperative SOD levels in the ischemic arterial region in group B1 and group B2 were (32.95 ± 3.52)U/ml and (33.59 ± 2.64)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative arterial SOD levels(t=2.741, P<0.05; t=2.704, P<0.05). After the interventional treatment, the SOD levels in the ischemic arterial region in group B1 and group B2 were (29.40 ± 5.49)U/ml and (26.68 ± 2.31)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative SOD levels in the ischemic arterial region (t = 2.536, P < 0.05; t = 5.005, P < 0.01). No statistically significant differences in SOD levels at each corresponding site existed between group B1 and group B2. Conclusion No significant difference in SOD level exists between the venous blood and the arterial blood. Serum SOD level carries a negative linear correlation with HbA1c level. Before interventional treatment , the SOD level in ischemic region is low, which becomes lower after the interventional procedure, which may be caused by the enhanced oxidative stress reaction that is resulted from the damage of the vascular wall due to interventional manipulations. The enhanced oxidative stress reaction may play an important role in the occurrence of restenosis.

Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
Acids ; chemistry ; Amino Acid Sequence ; Animals ; Capsid Proteins ; chemistry ; genetics ; metabolism ; Enterovirus A, Human ; genetics ; metabolism ; physiology ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Lysosome-Associated Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Protein Structure, Tertiary ; RNA, Viral ; genetics ; metabolism ; Receptors, Scavenger ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Sf9 Cells ; Static Electricity ; Virion ; genetics ; metabolism ; Virus Attachment