Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study

Introduction Avascular necrosis of femoral head (ANFH) is a progressive disease that often leads to hip joint dysfunction and even disability in young patients. Although the standard treatment, which is core decompression, has the advantage of minimal invasion, the efficacy is variable. Recent studies have shown that implantation of bone marrow containing osteogenic precursors into necrotic lesion of ANFH may be promising for the treatment of ANFH. Methods A prospective, double-blinded, randomized controlled trial was conducted to examine the effect of bone-marrow buffy coat (BBC) grafting combined with core decompression for the treatment of ANFH. Forty-five patients (53 hips) with Ficat stage I to III ANFH were recruited. The hips were allocated to the control group (core decompression + autologous bone graft) or treatment group (core decompression + autologous bone graft with BBC). Both patients and assessors were blinded to the treatment options. The clinical symptoms and disease progression were assessed as the primary and secondary outcomes. Results At the final follow-up (24 months), there was a significant relief in pain (P \u3c0.05) and clinical joint symptoms as measured by the Lequesne index (P \u3c0.05) and Western Ontario and McMaster Universities Arthritis Index (P \u3c0.05) in the treatment group. In addition, 33.3% of the hips in the control group have deteriorated to the next stage after 24 months post-procedure, whereas only 8% in the treatment group had further deterioration (P \u3c0.05). More importantly, the non-progression rates for stage I/II hips were 100% in the treatment group and 66.7% in the control group. Conclusion Implantation of the autologous BBC grafting combined with core decompression is effective to prevent further progression for the early stages of ANFH. Trial registration ClinicalTrials.gov identifier NCT01613612. Registered 13 December 2011

Continuous and Distribution-free Probabilistic Wind Power Forecasting: A Conditional Normalizing Flow Approach

We present a data-driven approach for probabilistic wind power forecasting based on conditional normalizing flow (CNF). In contrast with the existing, this approach is distribution-free (as for non-parametric and quantile-based approaches) and can directly yield continuous probability densities, hence avoiding quantile crossing. It relies on a base distribution and a set of bijective mappings. Both the shape parameters of the base distribution and the bijective mappings are approximated with neural networks. Spline-based conditional normalizing flow is considered owing to its non-affine characteristics. Over the training phase, the model sequentially maps input examples onto samples of base distribution, given the conditional contexts, where parameters are estimated through maximum likelihood. To issue probabilistic forecasts, one eventually maps samples of the base distribution into samples of a desired distribution. Case studies based on open datasets validate the effectiveness of the proposed model, and allows us to discuss its advantages and caveats with respect to the state of the art.Comment: The second revision to IEEE Transactions on Sustainable Energ

Electrospun chitosan-graft-poly (ɛ-caprolactone)/poly (ɛ-caprolactone) nanofibrous scaffolds for retinal tissue engineering

A promising therapy for retinal diseases is to employ biodegradable scaffolds to deliver retinal progenitor cells (RPCs) for repairing damaged or diseased retinal tissue. In the present study, cationic chitosan-graft-poly(ɛ-caprolactone)/polycaprolactone (CS-PCL/PCL) hybrid scaffolds were successfully prepared by electrospinning. Characterization of the obtained nanofibrous scaffolds indicated that zeta-potential, fiber diameter, and the content of amino groups on their surface were closely correlated with the amount of CS-PCL in CS-PCL/PCL scaffolds. To assess the cell–scaffold interaction, mice RPCs (mRPCs) were cultured on the electrospun scaffolds for 7 days. In-vitro proliferation assays revealed that mRPCs proliferated faster on the CS-PCL/PCL (20/80) scaffolds than the other electrospun scaffolds. Scanning electron microscopy and the real-time quantitative polymerase chain reaction results showed that mRPCs grown on CS-PCL/PCL (20/80) scaffolds were more likely to differentiate towards retinal neurons than those on PCL scaffolds. Taken together, these results suggest that CS-PCL/PCL(20/80) scaffolds have potential application in retinal tissue engineering

Free energy landscape for the binding process of Huperzine A to acetylcholinesterase

Drug-target residence time (t = 1/koff, where koff is the dissociation rate constant) has become an important index in discovering betteror best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, koff and activation free energy of dissociation (ΔG≠ off). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated.We applied this method to simulate the binding event of the anti-Alzheimer’s disease drug (−)−Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/ mol. The method also provides atomic resolution information for the (−)−Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect thismethodology to be widely applicable to drug discovery and development

Heat wave, electricity rationing, and trade-offs between environmental gains and economic losses: The example of Shanghai

In recent decades, many megacities in the world have suffered from increasingly frequent heat waves. During heat waves, air-conditioners, refrigerators, and electric fans add a considerable peak demand on electrical utility grids, and on the supply side, high temperatures exert adverse effects on electricity generation, transmission, and distribution. Without proactive planning and mitigation measures, the overloading would result in more frequent blackouts (the complete failure of electricity distribution) and brownouts (voltage reductions). To facilitate a pro-active planning, which aims to replace blackouts and brownouts by a rationing regime in selected sectors, this research proposes an integrated modeling tool which couples a regression model between daily electricity use and maximum temperature over the summer and a mixed input–output model with supply constraints. With the help of available data in Shanghai, China, we show that this tool is capable of quantitatively estimating the overall economic effects and sequential changes in carbon emissions, which a given magnitude of power rationing in a specific sector can exert across all sectors. The availability of such information would enable decision makers to plan an electricity rationing regime at the sector level to meet the double criterions of minimizing the overall economic losses and maximizing the extent of carbon emission reduction

Functional Analysis of General Odorant Binding Protein 2 from the Meadow Moth, Loxostege sticticalis L. (Lepidoptera: Pyralidae)

Odorant binding proteins play a crucial role in transporting semiochemicals across the sensillum lymph to olfactory receptors within the insect antennal sensilla. In this study, the general odorant binding protein 2 gene was cloned from the antennae of Loxostege sticticalis, using reverse transcription PCR and rapid amplification of cDNA ends. Recombinant LstiGOBP2 was expressed in Escherichia coli and purified by Ni ion affinity chromatography. Real-time PCR assays indicated that LstiGOBP2 mRNA is expressed mainly in adult antennae, with expression levels differing with developmental age. Ligand-binding experiments using N-phenyl-naphthylamine (1-NPN) as a fluorescent probe demonstrated that the LstiGOBP2 protein has binding affinity to a broad range of odorants. Most importantly, trans-11-tetradecen-1-yl acetate, the pheromone component of Loxostege sticticalis, and trans-2-hexenal and cis-3-hexen-1-ol, the most abundant plant volatiles in essential oils extracted from host plants, had high binding affinities to LstiGOBP2 and elicited strong electrophysiological responses from the antennae of adults

Wild Type and Mutant 2009 Pandemic Influenza A (H1N1) Viruses Cause More Severe Disease and Higher Mortality in Pregnant BALB/c Mice

BACKGROUND: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. PRINCIPAL FINDINGS: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. CONCLUSION: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation

Corrigendum to: The TianQin project: current progress on science and technology

In the originally published version, this manuscript included an error related to indicating the corresponding author within the author list. This has now been corrected online to reflect the fact that author Jun Luo is the corresponding author of the article