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Airway epithelial cells are the first cells to be challenged upon contact with the conidia of Aspergillus . In response, they express pattern-recognition receptors that play fundamental roles as sentinels and mediators of pulmonary innate immunity. The C-type lectin Dectin-1 is expressed predominantly on the surface of myeloid lineage cells. We examined the induction, regulation, and functions of Dectin-1 in pulmonary epithelial cells by challenging human bronchial epithelial (HBE) cells with A. fumigatus . Inflammatory, antimicrobial peptide genes and reactive oxygen species (ROS) were quantified, with and without knockdown of Dectin-1. We found that A. fumigatus induced the expression of Dectin-1 mRNA and protein in HBE cells in a toll-like receptor (TLR) 2-dependent manner. In addition, A. fumigatus -mediated generation of ROS was dependent on the upregulation of Dectin-1. Moreover, A. fumigatus actively induced the expression of TNFα, GM-CSF, IL8, HBD2, and HBD9. Knockdown of Dectin-1 inhibited TNFα, IL8, HBD2, and HBD9 expression. Hence, Dectin-1 was required for the upregulation of pro-inflammatory cytokines and antimicrobial peptides. Finally, knockdown of TLR2 significantly inhibited Dectin-1 upregulation. Our results demonstrate the novel induction of Dectin-1 in human bronchial epithelial cells and its critical role in the innate immune response against A. fumigatus in non-phagocytic cells.

To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III–IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1–23.1%) than in the ATG-10 group (4.5%, CI, 0.7–8.3%, P =0.005, 95% CI for the difference, −19.4% to −3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1–33.5%) than in the ATG-6 group (9.6% (4.0–15.2%), P =0.001). The 1-year disease-free survival rates were 84.3% (77.3–91.3%) and 86.0% (79.2–92.8%) for the ATG-6 group and ATG-10 groups, respectively ( P =0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.

There is conflicting evidence regarding the association between vitamin D status and cognitive function in population studies. The use of one-time vitamin D measurement in cognitive health studies may not reflect long-term vitamin D status in the body. We aimed to examine the relationship of vitamin D status measured over time with the risk of neurocognitive disorders (NCDs) in Norwegian older adults. Prospective cohort study. Regional, Trøndelag Health Study. This study followed a random cohort of 717 participants from HUNT2 (1995–97) and HUNT3 (2006–08) to HUNT4 70+ (2017–19). The mean age at HUNT4 70+ was 77.7 years. Seasonal-standardized serum 25-hydroxyvitamin D [25(OH)D] levels in HUNT2 and HUNT3 were averaged and used as either a categorical variable (<50 and ≥50 nmol/L) or a continuous variable (per 25 nmol/L decrease). In the cohort aged 70 years or over (HUNT4 70+), NCDs consisting of mild cognitive impairment (MCI) and dementia were diagnosed by clinical experts according to the DSM-5 criteria. Logistic and linear regression models were used to estimate odds ratios (ORs) and regression coefficients (beta) with 95% confidence intervals (CIs) to assess the relationship between 25(OH) D levels and the risk of NCDs or the Montreal Cognitive Assessment (MoCA) score. In total, 347 (48.4%) had NCDs in HUNT4, with 33.3% having MCI and 15.1% having dementia. Compared with participants with serum 25(OH)D ≥50 nmol/L, those with 25(OH)D <50 nmol/L had a similar risk of NCDs (OR 1.05, 95% CI 0.76 to 1.46). No association was observed with the risk of MCI (OR 1.01, 95% CI 0.71 to 1.44) or dementia (OR 1.16, 95% CI 0.70 to 1.92), respectively. In a subsample of participants evaluated with the MoCA (n=662), a 25 nmol/L decrease in serum 25(OH)D was not associated with a change in MoCA score (beta 0.33, 95% CI −0.17 to 0.85). Vitamin D insufficiency defined by two times measurements of serum 25(OH)D with a 10-year interval was not associated with the risk of NCDs in a cohort of older Norwegian adults. Future studies utilizing multiple vitamin D measurements with a longer follow-up duration and larger sample size are warranted.

Primary ovarian insufficiency (POI) is a common cause of infertility in around 1–2% of women aged <40 years. However, the mechanisms that cause POI are still poorly understood. Here we showed that germ cell-specific knockout of an essential autophagy induction gene Atg7 led to subfertility in female mice. The subfertility of Atg7 deletion females was caused by severe ovarian follicle loss, which is very similar to human POI patients. Further investigation revealed that germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal transition period. In addition, our in vitro studies also demonstrated that autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries under the starvation condition. Taken together, our results uncover a new role for autophagy in the regulation of ovarian primordial follicle reservation and hint that autophagy-related genes might be potential pathogenic genes to POI of women.

We conducted a retrospective analysis to evaluate outcomes of haploidentical transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults received haploidentical transplantation between May 2011 and December 2016. Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti-thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and peripheral blood transplantation. The patients’ median age was 25 years. Forty-nine patients survived for more than 28 days and all achieved donor myeloid engraftment. The median time for myeloid engraftment and platelet recovery was 13 days (range, 10–21) and 17.5 (range, 7–101) days. The cumulative incidence (CI) of grade II–IV and III–IV acute GvHD) was 20.00±0.33% and 6.00±0.12%, respectively. The incidence of chronic GvHD was 14.00±0.36% and 25.90±0.71%, and that of moderate-severe chronic GvHD was 2.51±0.06% and 6.92±0.25% at 1 and 3 years, respectively. The 3-year estimated overall survival and failure-free survival were both 83.5±5.4% with a median follow-up of 21.1 months. Multivariate analysis showed hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of ⩾3 was significantly associated with worse outcome. Haploidentical transplantation conditioning including Bu/Cy/ATG was a safe and effective strategy for adult SAA patients, and HCT-CI might be an outcome predictor in these patients.

The FY3 (Feng-Yun-3) GNOS (GNSS Occultation Sounder) mission is a GNSS (Global Navigation Satellite System) radio occultation mission of China for remote sensing of Earth's neutral atmosphere and the ionosphere. GNOS will use both the global positioning system (GPS) and the Beidou navigation satellite systems on the China Feng-Yun-3 (FY3) series satellites. The first FY3-C was launched at 03:07 UTC on 23 September 2013. GNOS was developed by the Center for Space Science and Applied Research, Chinese Academy of Sciences (CSSAR). It will provide vertical profiles of atmospheric temperature, pressure, and humidity, as well as ionospheric electron density profiles on a global basis. These data will be used for numerical weather prediction, climate research, and ionospheric research and space weather. This paper describes the FY3 GNOS mission and the GNOS instrument characteristics. It presents simulation results of the number and distribution of GNOS occultation events with the regional Beidou constellation and the full GPS constellation, under the limitation of the GNOS instrument occultation channel number. This paper presents the instrument performance as derived from analysis of measurement data in laboratory and mountain-based occultation validation experiments at Mt. Wuling in Hebei Province. The mountain-based GNSS occultation validation tests show that GNOS can acquire or track low-elevation radio signal for rising or setting occultation events. The refractivity profiles of GNOS obtained during the mountain-based experiment were compared with those from radiosondes. The results show that the refractivity profiles obtained by GNOS are consistent with those from the radiosonde. The rms of the differences between the GNOS and radiosonde refractivities is less than 3%.

Only 30% of high-risk adult ALL patients in their first complete remission (CR1) are able to receive an HLA-matched sibling stem cell transplant. The role of haploidentical hematopoietic SCT (haplo-HSCT) in post-remission therapy is not well established. Recently, we developed a novel protocol for unmanipulated haploidentical transplantation. In this study, we compared haplo-HSCT with conventional consolidation and maintenance chemotherapy in adult high-risk ALL patients. Between January 2000 and December 2012, 104 patients received conventional chemotherapy and 79 patients received haplo-HSCT. Patients who underwent haplo-HSCT had significantly improved 3-year OS (72.5% vs 26.6%; P< 0.001), 3-year disease-free survival (DFS) (63.9% vs 21.1%; P< 0.001) and 3-year relapse (18.7% vs 60.5%; P< 0.001) rates. The non-relapse mortality (NRM) rate was not different between patients treated with haplo-HSCT vs chemotherapy (19.2% vs 14.4%; P= 0.80). In multivariate analysis, the only factor associated with improved OS, better DFS and low risk of relapse was haplo-HSCT. The only factor associated with high NRM was enrollment before 2006. In conclusion, haplo-HSCT may be an option for adults with high-risk ALL in CR1 who do not have an HLA-matched donor.