Monitoring mild cognitive impairment of workers exposed to occupational aluminium based on quantitative susceptibility mapping.

AIM: To investigate the diagnostic value of quantitative susceptibility mapping (QSM) in mild cognitive impairment (MCI) of aluminium (Al) workers. MATERIALS AND METHODS: The basic data of 53 workers in an Al factory were collected and divided into the MCI group and normal control (NC) group by Montreal Cognitive Assessment (MoCA) scores. All participants were tested for plasma Al concentration and had magnetic resonance imaging (MRI). The QSM values of many areas of the brain were delineated and measured. Independent two-sample t-tests or non-parametric tests were used to compare the parameter values between the two groups. Spearman's correlation analysis was performed between QSM values, MoCA scores, and plasma Al concentration. The receiver operating characteristic curve and z test were performed to assess diagnostic efficacy and the best parameter. RESULTS: There was no difference in age and educational level. Plasma Al concentration of the MCI group was higher than that of NC group (p=0.057). QSM values of the left hippocampus, left dentate nucleus, right substantia nigra, and left putamen in MCI group were higher than that of NC group (p<0.05), and the left hippocampus had the best diagnostic efficacy. QSM values correlated negatively with MoCA scores. No correlation was found between QSM values and plasma Al concentration (p>0.05). CONCLUSION: QSM might be a neuroimaging marker for the diagnosis of MCI. The left hippocampus showed the best diagnostic efficacy. Plasma Al concentration of the MCI group was higher than that of the NC group. A correlation between QSM and plasma Al concentration was not found.

Quantum error correction in a solid-state hybrid spin register.

Error correction is important in classical and quantum computation. Decoherence caused by the inevitable interaction of quantum bits with their environment leads to dephasing or even relaxation. Correction of the concomitant errors is therefore a fundamental requirement for scalable quantum computation. Although algorithms for error correction have been known for some time, experimental realizations are scarce. Here we show quantum error correction in a heterogeneous, solid-state spin system. We demonstrate that joint initialization, projective readout and fast local and non-local gate operations can all be achieved in diamond spin systems, even under ambient conditions. High-fidelity initialization of a whole spin register (99 per cent) and single-shot readout of multiple individual nuclear spins are achieved by using the ancillary electron spin of a nitrogen-vacancy defect. Implementation of a novel non-local gate generic to our electron-nuclear quantum register allows the preparation of entangled states of three nuclear spins, with fidelities exceeding 85 per cent. With these techniques, we demonstrate three-qubit phase-flip error correction. Using optimal control, all of the above operations achieve fidelities approaching those needed for fault-tolerant quantum operation, thus paving the way to large-scale quantum computation. Besides their use with diamond spin systems, our techniques can be used to improve scaling of quantum networks relying on phosphorus in silicon, quantum dots, silicon carbide or rare-earth ions in solids.

The epidemiology of hepatitis B virus infection in women of reproductive age in highly endemic areas in China.

We describe the epidemiology of hepatitis B virus (HBV) infection among women of reproductive age residing in areas of China that are highly endemic for chronic HBV, and provide evidence useful for decision-makers to guide strategies for preventing mother-to-child transmission of HBV, and assess the impact of perinatal transmission PMTCT by projecting HBsAg prevalence trends without interventions. We conducted a cross-sectional HBV serological survey of women, 15-49 years of age, residing in Fujian, Guangdong, Guangxi and Hainan provinces. Demographic and other subject-level data were collected in face-to-face interviews, after which we obtain blood specimens. Specimens were tested for HBV sero-markers by ELISA (Beijing Wantai Biological Pharmacy), and HBV DNA was tested with PCR (Hunan Sansure Biotech). Weighted HBsAg and HBV (either HBsAg+ or anti-HBc+ indicating either present or past infection) prevalences were 11.82% and 57.16%, respectively. Among the HBsAg-positive women, 27% were also HBeAg positive. The proportion of individuals with HBV DNA loads >105 IU/mL declined with increasing age. Among HBsAg-negative women, 0.9% had occult HBV infection. The prevalence of chronic HBV infection among reproductive women in these highly endemic provinces is high, posing a threat to maternal health and risk of mother-to-child transmission. Prevention of mother-to-child transmission remains critically important.

Improvement of heart allograft acceptability associated with recruitment of CD4+CD25+ T cells in peripheral blood by recipient treatment with granulocyte colony-stimulating factor.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF), an important hematopoietic growth factor of the myeloid lineage, exerts profound immunoregulatory effects in T-cell tolerance. The study objective was to investigate the potential mechanism of G-CSF's antirejection effects in a fully mismatched rat cardiac allograft model. METHODS: The allograft recipients were treated with subcutaneous injection of recombinant human G-CSF (rh-G-CSF) at a dose of 250 microg/kg/d for 6 days starting from the day of cardiac transplantation. The alloreactive T-cell response and rejection level of G-CSF-treated rats were compared with those of control rats using mixed lymphocyte reactions (MLR) and histological examinations. Cytokine and cellular profiles were determined using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The presence and suppressive functions of regulatory T cells were determined by adoptive cell transfer experiments. RESULTS: Posttransplantation treatment of recipients with rh-G-CSF alone prolonged allograft survival, improved allograft biopsy grading scores, and induced alloreactive T-cell hyporesponsiveness accompanied by high levels of interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) production in MLR. It also enhanced CD4+CD25+ T cells in peripheral blood. The splenocytes from rh-G-CSF-treated recipients transferred antirejection effects to secondary recipients. CONCLUSIONS: Posttransplantation treatment of cardiac allograft recipients with rh-G-CSF leads to alloreactive T-cell hyporesponsiveness in vivo and in vitro associated with recruitment of CD4+CD25+ T cells in the peripheral blood. This study may provide insight into the application of G-CSF to control acute rejection of solid organ transplantations.

Clinical efficacy of sequential therapy with voriconazole on COPD patients in acute phase with pulmonary aspergillosis and effects on cytokines and pulmonary functions.

OBJECTIVE: To explore the clinical efficacy of sequential therapy with voriconazole on chronic obstructive pulmonary disease (COPD) patients in acute phase with pulmonary aspergillosis and its effects on cytokines and pulmonary functions. PATIENTS AND METHODS: A total of 110 COPD patients in acute phase with pulmonary aspergillosis who were admitted to the hospital between February 2015 and November 2016 were enrolled. We divided them randomly into two groups, i.e., the control group (n = 55) and the treatment group (n = 55). Patients in the control group took itraconazole capsules orally (200 mg/time, twice per day for three days followed by once per day). Patients in treatment group underwent sequential treatment with voriconazole through intravenous infusion at a dose of 5 mg/kg/time twice a day for 3 days followed by a dose of 4 mg/kg/time, twice a day for 8 days. Then, patients took voriconazole orally at a dose of 150 mL/time, twice a day for 6 days. Patients in two groups received the treatment for a total of 14 days. After treatment, we evaluated the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-8. The total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLco), and arterial oxygen saturation (SaO2), were measured as well. RESULTS: The total effectiveness rates of the treatment group and the control group were 83.63% and 61.82%. The differences had statistical significance (p < 0.01). After treatment, the incidence of chest pain, cough, sputum-coughing, hemoptysis, cyanosis, and dyspnea in the treatment group was significantly fewer than that in the control group (p < 0.05). TCL, DLco, and SaO2 in the two groups were significantly ameliorated by treatment (p < 0.05). The amelioration in the treatment group was more prominent than that in the control group (p < 0.05). The levels of TNF-α, IL-8, and IL-6 in the two groups were decreased dramatically by the treatments. The decrease in the treatment group was significantly lower than those in the control group (p < 0.05). Occurrence of adverse reactions in treatment group and control group were 8.33% and 6.25%, respectively; (p > 0.05). CONCLUSIONS: Sequential therapy with voriconazole exhibits promising clinical efficacy in COPD patients in acute phase with pulmonary aspergillosis. The treatment ameliorated the clinical symptoms and vital signs of patients significantly. It also improved the pulmonary functions and inhibited the inflammatory responses of patients with evident clinical efficacy.

Nuclear magnetic resonance spectroscopy with single spin sensitivity.

Nuclear magnetic resonance spectroscopy and magnetic resonance imaging at the ultimate sensitivity limit of single molecules or single nuclear spins requires fundamentally new detection strategies. The strong coupling regime, when interaction between sensor and sample spins dominates all other interactions, is one such strategy. In this regime, classically forbidden detection of completely unpolarized nuclei is allowed, going beyond statistical fluctuations in magnetization. Here we realize strong coupling between an atomic (nitrogen-vacancy) sensor and sample nuclei to perform nuclear magnetic resonance on four (29)Si spins. We exploit the field gradient created by the diamond atomic sensor, in concert with compressed sensing, to realize imaging protocols, enabling individual nuclei to be located with Angstrom precision. The achieved signal-to-noise ratio under ambient conditions allows single nuclear spin sensitivity to be achieved within seconds.

Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor-specific transfusion with impaired inducible costimulator/B7 homologous protein allorecognition.

OBJECTIVE: To investigate apoptosis of the CD8(+) T cells (Tc) subpopulation in rodent cardiac allograft recipients, which were treated by donor specific transfusion combined with blockade of Inducible costimulator (ICOS)/B7 homologous protein (B7h) costimulation. METHODS: Donor hearts were heterotopically transplanted into the necks of recipient mice using Chen's technique. Postoperative graft survival was recorded. Both the percentage of CD3(+)CD8(+)ICOS(+) Tc in recipients' peripheral blood and the apoptosis of CD8(+) Tc in recipient draining lymph nodes were detected by flow cytometry analysis. RESULTS: In comparison with the allogeneic group, the survival of cardiac grafts was prolonged by combined treatment with 5 × 10(6) ICOS-Fc-targeted B cells on day 0 of transplantation and 10 mg/kg/d ICOS-Fc on days 0 to 6 (84.38 ± 29.14 days versus 7.00 ± 0.76 days, P < .01). The treatment group showed a stable CD8(+)Tc clone size in recipient peripheral blood (49.4% ± 3.11% versus 50.0% ± 2.46%, P > .05); however, the percentage of CD3(+)CD8(+)ICOS(+) Tc decreased significantly compared with the allogeneic group (7.5% ± 2.02% versus 14.0% ± 3.03%, P < .05). Compared with allogeneic group, apoptosis of the CD8(+) Tc subpopulation in recipient draining lymph nodes was up-regulated significantly at postoperative 7 days in the treatment group (19.53% ± 5.10% versus 8.70 ± 3.14%, P < .05). CONCLUSION: Apoptosis of CD8(+) Tc in recipient draining lymph nodes was enhanced by pretreatment with donor specific transfusion and impaired ICOS/B7h allorecognition, which may have been associated with the variation in the CD3(+)CD8(+)ICOS(+) Tc subpopulation in peripheral blood and at least partially contributed to unresponsiveness toward cardiac allograft.

Inhibition of T-cell expansion caused by inducible costimulator/B7h costimulation blockade in direct allorecognition pathway.

OBJECTIVE: Inducible costimulator (ICOS)/B7h costimulation plays a crucial role in acute and chronic allograft rejection. To test the role of the ICOS signal in T-cell activation and expansion, we used ICOS-Fc-targeted B cells as donor antigen presenting cells to challenge the allogeneic response in vitro. METHODS: In vitro, the binding of ICOS-Fc with B7h on splenic B cells was confirmed by flow cytometry analysis. To evaluate the capacity of ICOS-Fc-targeted B cells to elicit an allogeneic response in vitro, we performed mixed lymphocyte reactions. RESULTS: The binding of B7h on splenic B cells by ICOS-Fc was confirmed at a saturating concentration of 100 µg/mL. Blockade of ICOS/B7h in direct allorecognition depressed proliferation of alloreactive T cells in vitro. CONCLUSIONS: ICOS/B7h signal plays an important role in direct allorecognition, eliciting allogeneic responses in vitro.

Transferable cardiac allograft acceptance induced by transfusion of donor B cells with impaired inducible costimulator/B7h allorecognition.

OBJECTIVE: Donor-specific transfusion (DST) of leukocytes with an impaired costimulatory signal has been proven to be an effective way to improve allograft survival. Inducible costimulator (ICOS) has been shown to play a crucial role in acute and chronic allograft rejection. To test the role of ICOS signaling during DST, we employed ICOS-Fc-targeted B cells as antigen of DST to challenge the allogeneic engraftment in vivo. MATERIALS AND METHODS: A murine cardiac allograft model was employed using BALB/c donors and C57BL/6 recipients, while various transfusions were performed according to treatment protocols. RESULTS: Allograft survival was prolonged by infusion of ICOS-Fc-targeted B cells; however, allograft acceptance could not be achieved unless additional systemic injections of ICOS-Fc were given. Adoptive transfer of splenic CD4(+) but not CD4(+)CD25(-) subsets from long-term allograft survival (LTAS) mice to lightly irradiated naive recipients resulted in subsequent BALB/c allograft acceptance without additional immunosuppression. CONCLUSIONS: ICOS/B7h signaling during direct allorecognition played an important role in prolonging allograft survival, and an allograft acceptance can be established by DST with complete blockade of ICOS/B7h in both direct and indirect allorecognition. Interestingly, this allograft acceptance was transferable and maintained at least partly by the immune regulation of CD4(+)CD25(+) T cells. These findings may help to design a potential therapeutic treatment to prevent allograft rejection by DST in combination with ICOS/B7h blockade.

Pharmacokinetics of 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil in woodchucks.

1-(2-Fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) is a nucleoside analog with potent in vitro activity against hepatitis B virus (HBV) and Epstein-Barr virus. The purpose of this study was to characterize the disposition of L-FMAU following oral and intravenous administration in the woodchuck animal model. The numerous similarities between woodchuck hepatitis virus and HBV infection justify the use of the woodchuck as an animal model for preclinical studies of anti-HBV agents in vivo. Woodchucks were given 25 mg of L-FMAU per kg of body weight intravenously and orally. Concentrations of L-FMAU in urine and plasma were determined by high-performance liquid chromatography. Following intravenous administration of 25 mg of L-FMAU per kg to woodchucks, total clearance was moderate, averaging 0.23 +/- 0.07 liter/h/kg. Renal clearance and nonrenal clearance averaged 0.13 +/- 0.08 and 0.10 +/- 0.06 liter/h/kg, respectively. The steady-state volume of distribution averaged 0.99 +/- 0.17 liter/kg, indicative of intracellular distribution of the nucleoside. The terminal-phase half-life of L-FMAU following intravenous administration averaged 6.2 +/- 2.0 h, and mean residence time averaged 4.5 +/- 0.8 h. Absorption of L-FMAU after oral administration was incomplete, and bioavailability was approximately 20%. Concentrations of L-FMAU in plasma remained above the in vitro 50% effective concentration of 0.026 microg/ml for HBV (C. K. Chu, T. Ma, K. Shanmuganathan, C. Wang, Y. Xiang, S. B. Pai, G.-Q. Yao, J.-P. Sommadossi, and Y.-C. Cheng, Antimicrob. Agents Chemother. 39:979-981, 1995) for 24 h after both intravenous and oral administration of 25 mg of L-FMAU per kg.