Attenuating Neuronal Autophagy Alleviates Inflammatory Injury in OGDDeprived Co-culture of HT22 with BV2.

Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1ß, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.

[Analysis of the epidemiological characteristics of scarlet fever in Yantai City, Shandong Province from 2015 to 2019].

From 2015 to 2019, the annual average incidence rate of scarlet fever was 7.80/100 000 in Yantai City, which showed an increasing trend since 2017 (χ2trend=233.59, P<0.001). The peak period of this disease was from April to July and November to January of the next year. The ratio of male to female was 1.49∶1, with a higher prevalence among cases aged 3 to 9 years (2 357/2 552, 92.36%). Children in kindergartens, primary and middle school students, and scattered children were the high risk population, with the incidence rate of 159.86/100 000, 25.57/100 000 and 26.77/100 000, respectively. The global spatial auto-correlation analysis showed that the global Moran's I index of the reported incidence rate of scarlet fever in Yantai from 2015 to 2019 was 0.28, 0.29, 0.44, 0.48, and 0.22, respectively (all P values<0.05), suggesting that the incidence rate of scarlet fever in Yantai from 2015 to 2019 was spatial clustering. The local spatial auto-correlation analysis showed that the "high-high" clustering areas were mainly located in Laizhou City, Zhifu District, Haiyang City, Fushan District and Kaifa District, while the "low-high" clustering areas were mainly located in Haiyang City and Fushan District.

[Clinical features and CT findings of Takayasu's arteritis associated pulmonary hypertension].

Objective: Takayasu's arteritis involving the pulmonary artery (PTA) is uncommon, and those with pulmonary hypertension (PH) are even rarer. This study investigated the clinical features and CT findings in PTA patients with PH. Methods: A total of 40 PTA patients were retrospective selected in the First Hospital of Air Force Medical University from January 2008 to January 2018. There were 14 PTA patients with PH, including 3 male and 11 female cases, aged from 18 to 53 (29.7±9.4) years, as the study group (PTA+PH group). There were 26 PTA patients without PH, including 4 males and 22 females, aged 15-52 (28.9±8.5) years, as the control group (PTA group). The Chi-square or Fisher's test, T test of two independent samples and Mann-Whitney U rank sum test were used to compare the general information, symptoms, signs, laboratory examination data, right ventricular and pulmonary artery measurement data, and pulmonary artery CT findings between the two groups. Results: Compared with the PTA group, the patients in the PTA+PH group had longer disease duration, fewer active cases, more shortness of breath, chest distress and lower limb edema, lower blood oxygen partial pressure (PaO2) and lower ESR (all P<0.05). The width of right atrium and right ventricle in PTA+PH group was greater than that in PTA group (all P<0.05). The main CT findings of the involved pulmonary artery included lumen stenosis (39 cases, 97.5%), lumen occlusion (16 cases, 40%), wall thickening (9 cases, 22.5%), and lumen dilation (2 cases, 5.0%). Patients in the PTA+PH group had less wall thickening and mild lumen stenosis (<50%), more severe lumen stenosis (≥50%) and occlusion than those in the PTA group (all P<0.05). Conclusions: PTA patients with PH showed certain characteristics in clinical, laboratory and CT findings, which may be correlated to the stage of the disease duration, the severity, and the prognosis.

LncRNA DSCAM-AS1 promoted cell proliferation and invasion in osteosarcoma by sponging miR-101.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play critical roles in osteosarcoma (OS) progression. LncRNA DSCAM-AS1 has been reported to function as a tumor promoter in various cancers. However, the potential mechanism of DSCAM-AS1 in OS remains rarely know. PATIENTS AND METHODS: The expression levels of DSCAM-AS1 and miR-101 were detected by RT-qPCR. The correlation between DSCAM-AS1 and miR-101 expression was analyzed by Pearson's correlation. Kaplan-Meier analysis was used to assess the overall survival rate. Cell viability and invasion were assessed by MTT assay and transwell assays, respectively. A Luciferase reporter assay was used to identify the relationship between DSCAM-AS1 and miR-101. RESULTS: In the present study, it was demonstrated that DSCAM-AS1 expression was significantly upregulated in OS tissues and cells and high expression of DSCAM-AS1 predicted poor prognosis in OS patients. In addition, the silencing of DSCAM-AS1 suppressed the viability and invasion of OS cells, while DSCAM-AS1 overexpression promoted cell viability and invasion. Furthermore, we found that DSCAM-AS1 inhibited miR-101 expression by direct interaction and DSCAM-AS1 promoted OS progression by sponging miR-101. In addition, miR-101 expression was negatively correlated with DSCAM-AS1 expression. Patients with low miR-101 expression had a shorter overall survival time compared with those with high miR-101 expression. CONCLUSIONS: The present study demonstrated that DSCAM-AS1 accelerated OS cell progression by sponging miR-101, which might provide a new sight in the treatment of OS.

[Pleural amoebic empyema: a case report].

In this paper, a case of pleural amoebic empyema and its diagnosis and treatment were reported.

[Prevalence of tonsilloliths and CT diagnosis].

Objective: To investigate the prevalence, gender and age distribution characteristics of tonsilloliths and its CT diagnosis, in order to improve the knowledge of clinicians. Methods: The images of 2 710 patients who underwent head and neck CT scans from November 2015 to November 2016 were retrospectively reviewed, the prevalence, gender and age distribution of tonsilloliths and CT manifestation were analyzed. SPSS 18.0 was used for statistical analysis. Results: Tonsilloliths were found in 383 (14.1%) of the 2 710 patients, including 217 men and 166 women. The prevalence was 15.1% in men and 13.1% in women, and no gender difference was seen. The age of patients with tonsilloliths ranged from 6-88 years, and the mean age was (51.1±16.8) years. The prevalence of tonsilloliths in patients 40 years and younger was significantly lower than in those who were over 40 years (χ(2)=15.201, P<0.001), and the prevalence of tonsilloliths was positively correlated with age(r=0.812, P=0.008). One hundred and twenty eight cases of tonsilloliths were located on the right side, and 157 were located on tleft side. Tonsilloliths were detected bilaterally in 98 patients. There was no significant difference between left and right sides(χ(2)=1.919, P=0.166). Most of tonsilloliths showed a single small tonsillolith, 60.6% of tonsilloliths showed only one tonsillolith, whereas 39.4% showed two or more. The size of tonsilloliths ranged from 1.0 to 10.0 mm, the mean maximum diameter was (2.3±1.2) mm, and 86.7% of tonsilloliths with a maximum diameter of no more than 3.0 mm. Tonsilloliths showed dot, round or oval hyperdense in tonsillar crypt or parenchyma. CT attenuation of majority tonsilloliths was over 120 Hu. Conclusion: Tonsilloliths are more common than previously suggested, its CT diagnosis is not difficult, and the knowledge of clinician and radiologist needs to be improved.

[CT findings and clinical features of Takayasu's arteritis with pulmonary artery involvement].

Objective: To explore the CT findings of the Takayasu's arteritis (TA)with pulmonary artery (PA) involvement and its clinical significance. Methods: A total of 35 patients with TA involving the PA in Xijing Hospital from November 2007 to November 2016, 6 male cases, 29 female cases, the age was 15-52 (28±9) years old, were retrospectively collected and included in the study group (TA+ P group), meanwhile 40 patients with TA but not involving the pulmonary artery in this hospital from January 2015 to November 2016 were collected as control group, 5 male cases, 35 female cases, the age was 7-67 (28±12) years old.The clinical and laboratory data, the pulmonary artery and right heart measurement data of the two groups were compared by using t test, χ(2) test , and rank sum test.The CT signs of pulmonary artery involvement in the TA+ P group were analyzed. Results: TA+ P group patients had shortness of breath, wheezing(54.3% vs 10.0%), cough(31.4% vs 12.5%)and palpitations(11.4% vs 0)mostly, and there were statistical difference between TA+ P group and TA group (all P<0.05), However, there was no difference between the two groups in the activity and duration of disease (all P>0.05). In TA+ P group, a total of 312 pulmonary artery segments were involved in 35 patients.The lumen stenosis of PA was more common(35 cases, 211 segments), followed by occlusion(14 cases, 94 segments), bilateral PA (23 cases, 217 segments) and multiple branches of PA involvement(34 cases, 311 segments) were more common.The PA systolic pressure, the diameter of main pulmonary artery, right atrium and right ventricular width of the TA+ P group patients were significantly higher than those of the TA group (all P<0.05). Conclusions: There are some CT certain characteristics in TA pulmonary arterial involvement, and they are not related to the activity and duration of the disease.Most patients with PA involvement present pulmonary hypertension and a series of special clinical manifestations.

Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling.

Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27. Additionally, we found that ActRIB activation could reverse TSP50-mediated cell proliferation and tumor growth. Furthermore, analysis of human breast cancer specimens by immunohistochemistry indicated that TSP50 expression was negatively related to p-Smad2/3 and p27 protein levels. Most importantly, breast cancer diagnosis-related indicators such as tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer.

Risk of developing psoriasis in patients with schizophrenia: a nationwide retrospective cohort study.

BACKGROUND: Schizophrenia is a complex disease which proceeds from an interaction between genetic background and environmental factors. Recent studies showed T helper 17 (Th17) signalling, which is the main downstream immune response of psoriasis, is activated in schizophrenia. OBJECTIVE: To investigate whether patients with schizophrenia have higher risk of psoriasis. METHODS: In this nationwide retrospective cohort study, we analysed the 1 million enrollees' cohort from Taiwan's National Health Insurance Research Database. Psoriasis and schizophrenia were ascertained by International Classification of Diseases, 9th revision, Clinical Modification coding. The study cohort was comprised of enrollees diagnosed with schizophrenia during the period from 1 January 1996 through 31 December 2010, while the comparison population consisted of enrollees who had not been diagnosed with schizophrenia during the study period. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for the risk of psoriasis associated with schizophrenia using Cox proportional hazard regression. RESULTS: The adjusted HR of psoriasis associated with schizophrenia was 2.32 (95% CI = 1.81-2.98). After 15 years, the cumulative incidence of psoriasis in patients with schizophrenia and comparison population was 2.82% and 1.17%, respectively. The Kaplan-Meier curves for the cumulative incidence of psoriasis in individuals with and without schizophrenia differed significantly (P < 0.0001, log-rank test). CONCLUSIONS: Patients with schizophrenia have higher risk of psoriasis, which may be due to common genetic susceptibilities and/or immunologic mechanisms in both diseases. Th17 signalling and pro-inflammatory cytokines may act as a link between these two diseases and are potential therapeutic targets for schizophrenia.

[Application of the BACspreader™ Microbe Dispersion Counter in drug susceptibility test on Mycobacterium tuberculosis].

Objective: To evaluate the application of the BACspreader™ Microbe Dispersion Counter in drug susceptibility test (DST) on Mycobacterium tuberculosis (MTB). Methods: The MTB strains were dispersed and diluted to 1.0 McFarland standard turbidity, by means of BACspreader™ Microbe Dispersion Counter and manual grinding method, respectively. The bacterial dispersion effect and bacterial activity were tested by microscope and colony counting method. During Jan. 2015 to June 2015, a total of 726 isolates of MTB were collected in all district tuberculosis hospitals of Shanghai. The bacterial suspension dispersed by instrument and manual grinding, were inoculated in slant medium for DST (Proportion Method), and then incubated in 37 ℃ incubator for 28 days and the DST results were reported. The effects of the 2 different bacterial dispersion methods were compared by comparing DST results and counting the bacterial colony which grew in high and low concentration control media. Paired chi-square test was used for statistical analysis, and the significance level was 0.05. Results: Compared to the manual grinding method, the MTB colony could be better dispersed by BACspreader™ Microbe Dispersion Counter, without reducing the bacterial activity. The DST results of 726 mycobacterial isolates were the same by different bacterial dispersion methods. The count of bacterial colony growing in high concentration control medium was significantly different between of the 2 dispersion methods (χ(2)=8.0, P<0.01). When counting the bacterial colony growing in low concentration control medium, the numerable rate was 97.7% by BACspreader™ Microbe Dispersion Counter, and 4.3% by manual grinding method; the difference being significant between the 2 dispersion methods (χ(2)=674, P<0.001). Conclusions: Compared to the manual grinding method, the slant medium inoculated with bacterial suspension obtained by BACspreader™ Microbe Dispersion Counter had better countability in low concentration control slants, and had more significant contrast between high and low concentration control slants, which was useful to determine the DST results. Introducing the BACspreader™ Microbe Dispersion Counter to MTB DST could automate the DST process, make the testing results objective and standardized, and reduce personal error in the tests.

Rapid Proteomics to Prospect and Validate Novel Bacterial Metabolism Induced by Environmental Burden.

Understanding the pathophysiology of genes and enzymes involved in caffeine metabolism can have extracurricular benefits, such as providing distinct methylxanthines as intermediates for pharmaceutical synthesis, and also improve environmental waste remediation. The strains Pseudomonas putida CBB5 and CES may provide insights into these applications because they may both be induced to degrade caffeine, yet the latter thrives in concentrations >8.0gL-1; threefold higher than any other bacteria. We took a novel approach toward identifying the enzymatic pathways in both Pseudomonas sp. CES and a deletion mutation of strain CBB5, which largely circumvented the need for exhaustive isolation of enzymes and the stepwise reconstitution of their activities to determine caffeine response elements. Here, we describe two optimized, rapid alternative strategies based on multiplexed SIL assays and demonstrate their application by discovering caffeine-degrading enzymes in the CES strain based on quantitative comparison between enriched lysate fractions drawn from bacterial proteomes grown in the absence and presence of caffeine. Comparisons were made using stable isotope dimethyl labeling and expression differences were substantiated by reciprocal labeling experiments. The role of the identified proteins in caffeine degradation was independently verified by genetic sequencing. Multiple new components of N-demethylase system were discovered within a fraction of the lysate enriched specifically for this activity. We also describe how to expand the biological context (and reduce systemic bias) by adapting the protocol for total lysate analysis. We combined off-line prefractionation with the speed and resolution advantages of the Orbitrap LUMOS. The global protocol revealed 2406 proteins 1789 of which were quantified between treatments revealing, among other insights, a new antagonistic degradation pathway for vanillin that is completely suppressed by caffeine treatment.

Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the role of aberrant expression of non-coding RNAs in T cells.

Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are RNA molecules that do not translate into protein. Both miRNAs and lncRNAs are known to regulate gene expression and to play an essential role in T cell differentiation and function. Both systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease, and rheumatoid arthritis (RA), a representative disease of inflammatory arthritis, are characterized by a complex dysfunction in the innate and adaptive immunity. T cells play a central role in cell-mediated immune response and multiple defects in T cells from patients with SLE and RA have been observed. Abnormality in T cell signalling, cytokine and chemokine production, T cell activation and apoptosis, T cell differentiation and DNA methylation that are associated closely with the aberrant expression of a number of miRNAs and lncRNAs have been implicated in the immunopathogenesis of SLE and RA. This review aims to provide an overview of the current state of research on the abnormal expression of miRNAs and lncRNAs in T cells and their roles in the immunopathogenesis of SLE and RA. In addition, by comparing the differences in aberrant expression of miRNAs and lncRNAs in T cells between patients with SLE and RA, controversial areas are highlighted that warrant further investigation.

Formation of long single quantum dots in high quality InSb nanowires grown by molecular beam epitaxy.

We report on realization and transport spectroscopy study of single quantum dots (QDs) made from InSb nanowires grown by molecular beam epitaxy (MBE). The nanowires employed are 50-80 nm in diameter and the QDs are defined in the nanowires between the source and drain contacts on a Si/SiO2 substrate. We show that highly tunable QD devices can be realized with the MBE-grown InSb nanowires and the gate-to-dot capacitance extracted in the many-electron regimes is scaled linearly with the longitudinal dot size, demonstrating that the devices are of single InSb nanowire QDs even with a longitudinal size of ∼700 nm. In the few-electron regime, the quantum levels in the QDs are resolved and the Landég-factors extracted for the quantum levels from the magnetotransport measurements are found to be strongly level-dependent and fluctuated in a range of 18-48. A spin-orbit coupling strength is extracted from the magnetic field evolutions of a ground state and its neighboring excited state in an InSb nanowire QD and is on the order of ∼300 µeV. Our results establish that the MBE-grown InSb nanowires are of high crystal quality and are promising for the use in constructing novel quantum devices, such as entangled spin qubits, one-dimensional Wigner crystals and topological quantum computing devices.

Parity independence of the zero-bias conductance peak in a nanowire based topological superconductor-quantum dot hybrid device.

We explore the signatures of Majorana fermions in a nanowire based topological superconductor-quantum dot-topological superconductor hybrid device by charge transport measurements. At zero magnetic field, well-defined Coulomb diamonds and the Kondo effect are observed. Under the application of a finite, sufficiently strong magnetic field, a zero-bias conductance peak structure is observed. It is found that the zero-bias conductance peak is present in many consecutive Coulomb diamonds, irrespective of the even-odd parity of the quasi-particle occupation number in the quantum dot. In addition, we find that the zero-bias conductance peak is in most cases accompanied by two differential conductance peaks, forming a triple-peak structure, and the separation between the two side peaks in bias voltage shows oscillations closely correlated to the background Coulomb conductance oscillations of the device. The observed zero-bias conductance peak and the associated triple-peak structure are in line with Majorana fermion physics in such a hybrid topological system.

Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production.

We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines.

Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3(+) anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3(+) anti-CD28(+) lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3(+) anti-CD28(+) LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.

Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant-expressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR-516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE.

Anomalous zero-bias conductance peak in a Nb-InSb nanowire-Nb hybrid device.

Semiconductor InSb nanowires are expected to provide an excellent material platform for the study of Majorana fermions in solid state systems. Here, we report on the realization of a Nb-InSb nanowire-Nb hybrid quantum device and the observation of a zero-bias conductance peak structure in the device. An InSb nanowire quantum dot is formed in the device between the two Nb contacts. Due to the proximity effect, the InSb nanowire segments covered by the superconductor Nb contacts turn to superconductors with a superconducting energy gap Δ(InSb) ∼ 0.25 meV. A tunable critical supercurrent is observed in the device in high back gate voltage regions in which the Fermi level in the InSb nanowire is located above the tunneling barriers of the quantum dot and the device is open to conduction. When a perpendicular magnetic field is applied to the devices, the critical supercurrent is seen to decrease as the magnetic field increases. However, at sufficiently low back gate voltages, the device shows the quasi-particle Coulomb blockade characteristics and the supercurrent is strongly suppressed even at zero magnetic field. This transport characteristic changes when a perpendicular magnetic field stronger than a critical value, at which the Zeeman energy in the InSb nanowire is E(z) ∼ Δ(InSb), is applied to the device. In this case, the transport measurements show a conductance peak at the zero bias voltage and the entire InSb nanowire in the device behaves as in a topological superconductor phase. We also show that this zero-bias conductance peak structure can persist over a large range of applied magnetic fields and could be interpreted as a transport signature of Majorana fermions in the InSb nanowire.

Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca(2+) -calcineurin-nuclear factor of activated T cells pathway.

Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca(2+) signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca(2+) level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca(2+) influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+) channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.

The prognostic values of soft tissue sonography for adult cellulitis without pus or abscess formation.

Abstract The current practice for cellulitis in diagnosis and treatment is mainly based on subjective clinical judgement without validated objective guidance. For patients with non-purulent cellulitis needing intravenous antibiotic treatment in hospital, we found soft tissue sonography performed around 4 days after initiation of antibiotics might have prognostic values. The patients with soft tissue sonographic pattern of subcutaneous thickening alone had shorter duration of antibiotic treatment and higher rate of early treatment response to antibiotics than those with the pattern of cobblestone appearance. Larger-scale research may be warranted to validate the prognostic roles of sonography in cellulitis management.