Explore the vast range of titles available.

Ultrafine-grained (UFG) and coarse-grained (CG) AA2024 samples are prepared by powder metallurgy process involving high-energy ball milling, spark plasma sintering and hot extrusion, as well as subsequent T6 heat treatment. The microstructural evolution, precipitation behavior, and tensile mechanical properties of the samples are investigated. During T6 heat treatment, recrystallization and grain growth occur, leading to a grain coarsening in the CG2024 sample and a slight grain refinement in the UFG2024 sample. After T6 heat treatment, the UFG2024 sample demonstrated an accelerated precipitation behavior with the formation of lens-shaped and round Sʹ phases due to the high density of dislocations and grain boundaries. This consequently resulted in an improvement in both strength and tensile ductility. Based on the analysis, nanoparticle strengthening and grain boundary strengthening make the major contributions to the improved yield strength of the UFG2024-HT sample. Graphical abstract

Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood–brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.

Previous studies have demonstrated that type 1 diabetes mellitus (T1DM) could be triggered by an early childhood infection. Whether maternal infection during pregnancy is associated with T1DM in offspring is unknown. Therefore, we aimed to study the association using a systematic review and meta-analysis. Eighteen studies including 4304 cases and 25 846 participants were enrolled in this meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were synthesised using random-effects models. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of associations. Overall, the pooled analysis yielded a statistically significant association between maternal infection during pregnancy and childhood T1DM (OR 1.31, 95% CI 1.07–1.62). Furthermore, six studies that tested maternal enterovirus infection showed a pooled OR of 1.54 (95% CI 1.05–2.27). Heterogeneity from different studies was evident ( I 2 = 70.1%, P < 0.001) and was mainly attributable to the different study designs, ascertaining methods and sample size among different studies. This study provides evidence for an association between maternal infection during pregnancy and childhood T1DM.

IntroductionRenal calculi are the predominant urological ailment in air force pilots. Flexible ureteroscopy (FURS) constitutes a valuable approach for renal calculi treatment. This study presents a decade-long exploration of using FURS for renal calculi treatment in air force pilots. Additionally, it investigates the safety and feasibility of granting waiver flights to pilots with renal parenchyma calcification.MethodsFrom December 2009 to December 2019, a retrospective review was conducted on Chinese air force pilots undergoing treatment for renal calculi. Among the pilots assessed, a total of 71 individuals underwent FURS. Endoscopic methodology involved the insertion of a flexible ureteroscope into the ureter and renal pelvis, guided by a safety wire. Stone fragmentation was achieved using a holmium laser fibre, followed by extraction using a soft stone basket. Postoperative non-enhanced CT (NECT) scans was used to confirm stone clearance. Furthermore, clinical diagnoses were classified based on endoscopic findings and postoperative NECT results. All data were presented as mean (SD) or median (minimum-maximum) for continuous variables and frequency counts and percentages for categorical variables.ResultsFURS identified free kidney stones in 60 cases among all patients. The remaining 11 cases, without free stones detected during ureteroscopy, exhibited persistent high-density spots on postoperative NECT. Of the 60 cases with stones, renal calculi were successfully cleared in 30 pilots, while the remaining 30 exhibited persistent high-density spots on NECT postsurgery. Pilots with completely cleared free stones were deemed fit for flight. Pilots with diagnosed renal parenchyma calcification were granted permission to fly under waivers following a meticulous evaluation.ConclusionsFURS could not only effectively eliminate renal calculi but also accurately diagnose renal parenchyma calcification, facilitating a prompt return to flight for pilots. A protocol for managing pilot renal calculi, informed by FURS and our experience, is proposed.

Objective: The objective of this study was to determine whether a dietary vitamin E (VE) supplement could alleviate any detrimental effects of aged corn on lipid metabolism and antioxidant status in laying hens.Methods: The experiment consisted of a 2×3 factorial design with two corn types (normal corn and aged corn (stored for 4 yr) and three concentrations of VE (0, 20, and 100 IU/kg). A total of 216 Lohmann laying hens (50 wk of age) were randomly allocated into six treatment diets for 12 wk. Each treatment had 6 replicates of 6 hens per replicate.Results: The results show that aged corn significantly decreased the content of low-density lipoprotein cholesterol (p<0.05), and reduced chemokine-like receptor 1 (CMKLR1) mRNA expression (p<0.05) in the liver compared to controls. Diet with VE did not alter the content of crude fat and cholesterol (p>0.05), or acetyl-CoA carboxylase, lipoprotein lipase, fatty acid synthase or CMKLR1 mRNA expression (p>0.05) in the liver among treatment groups. Aged corn significantly increased the content of malondialdehyde (MDA) (p<0.05) and decreased superoxide dismutase (SOD) activity (p<0.05) in the liver. The VE increased the content of MDA (p<0.05) but decreased glutathione peroxidase (GSH-Px) activity in serum (p<0.01) and in the ovaries (p<0.05). Adding VE at 20 and 100 IU/kg significantly increased GSH-Px activity (p<0.05) in liver and in serum (p<0.01), 100 IU/kg VE significantly increased SOD activity (p<0.05) in serum. Aged corn had no significant effects on GSH-Px mRNA or SOD mRNA expression (p<0.01) in the liver and ovaries. Addition of 100 IU/kg VE could significantly increase SOD mRNA expression (p<0.01) in the liver and ovary.Conclusion: Aged corn affected lipid metabolism and decreased the antioxidant function of laying hens. Dietary VE supplementation was unable to counteract the negative effects of aged corn on lipid metabolism. However, addition of 100 IU/kg VE prevented aged corninduced lipid peroxidation in the organs of laying hens.

Correction to: Gene Therapy (2016) 23, 380–392; doi:10.1038/gt.2016.11 The initial Figure 2a was erroneously generated from a file from a mouse injected with conventional AAV9-GFP and not exo-AAV9-GFP, as described in the manuscript. We have therefore reformatted this specific panel, and corrected Figure 2a and the figure legend accordingly, now showing an image of the GFP signal detected by 2-photon microscopy after intravenous injection of exo-AAV9-GFP in a mouse.

Cotransfer of thyroid-specific transcription factor (TTF)-1 and Pax-8 gene to tumor cells, resulting in the re-expression of iodide metabolism-associated proteins, such as sodium iodide symporter (NIS), thyroglobulin (Tg), thyroperoxidase (TPO), offers the possibility of radioiodine therapy to non-iodide-concentrating tumor because the expression of iodide metabolism-associated proteins in thyroid are mediated by the thyroid transcription factor TTF-1 and Pax-8. The human TTF-1 and Pax-8 gene were transducted into the human thyroid carcinoma (K1 and F133) cells by the recombinant adenovirus, AdTTF-1 and AdPax-8. Re-expression of NIS mRNA and protein, but not TPO and Tg mRNA and protein, was detected in AdTTF-1-infected F133 cells, following with increasing radioiodine uptake (6.1–7.4 times), scarcely iodide organification and rapid iodide efflux ( t 1/2 ≈8-min in vitro , t 1/2 ≈4.7-h in vivo ). On contrast, all of the re-expression of NIS, TPO and Tg mRNA and proteins were detected in F133 cells coinfected with AdTTF-1 and AdPax-8. AdTTF-1- and AdPax-8-coinfected K1 and F133 cells could effectively accumulate radioiodine (6.6–7.5 times) and obviously retarded radioiodine retention ( t 1/2 ≈25–30-min in vitro , t 1/2 ≈12-h in vivo ) ( P <0.05). Accordingly, the effect of radioiodine therapy of TTF-1 and Pax-8 cotransducted K1 and F133 cells (21–25% survival rate in vitro ) was better than that of TTF-1-transducted cells (40% survival rate in vitro ) ( P <0.05). These results indicate that single TTF-1 gene transfer may have limited efficacy of radioiodine therapy because of rapid radioiodine efflux. The cotransduction of TTF-1 and Pax-8 gene, with resulting NIS-mediated radioiodine accumulation and TPO and Tg-mediated radioiodine organification and intracellular retention, may lead to effective radioiodine therapy of thyroid carcinoma.