Allergic rhinitis (AR) is a growing public health, medical and economic problem worldwide. The current review describes the major discoveries related to AR during the past 2 years, including risk ...factors for the prevalence of AR, the corresponding diagnostic strategy, precise underlying immunological mechanisms, and efficient therapies for AR during the ongoing global “coronavirus disease 2019” (COVID‐19) pandemic. The review further attempts to highlight future research perspectives. Increasing evidence suggests that environmental exposures, climate changes, and lifestyle are important risk factors for AR. Consequently, detailed investigation of the exposome and the connection between environmental exposures and health in the future should provide better risk profiles instead of single predictors, and also help mitigate adverse health outcomes in allergic diseases. Although patients with dual AR, a newly defined AR phenotype, display perennial and seasonal allergens‐related nasal symptoms, they are only allergic to seasonal allergens, indicating the importance of measuring inflammation at the local sites. Herein, we suggest that a combination of precise diagnosis in local sites and traditional diagnostic methods may enhance the precision medicine‐based approach for management of AR; however, this awaits further investigations. Apart from traditional treatments, social distancing, washing hands, and disinfection are also required to better manage AR patients in the ongoing global COVID‐19 pandemic. Despite recent advances in understanding the immune mechanisms underlying the effects of allergen immunotherapy (AIT), further understanding changes of cell profiles after AIT and accurately evaluate the efficacy of AIT are required.
Allergic rhinitis (AR) is a global health problem with increasing prevalence and association with an enormous medical and socioeconomic burden. New recognition of immune cells such as type 2 innate ...lymphocytes (ILC2s), T helper (Th2) 2 cells, follicular helper T cells, follicular regulatory T cells, regulatory T cells, B cells, dendritic cells, and epithelial cells in AR pathogenesis has been updated in this review paper. An in‐depth understanding of the mechanisms underlying AR will aid the identification of biomarkers associated with disease and ultimately provide valuable parameters critical to guide personalized targeted therapy. As the only etiological treatment option for AR, allergen‐specific immunotherapy (AIT) has attracted increasing attention, with evidence for effectiveness of AIT recently demonstrated in several randomized controlled trials and long‐term real‐life studies. The exploration of biologics as therapeutic options has only involved anti‐IgE and anti‐type 2 inflammatory agents; however, the cost‐effectiveness of these agents remains to be elucidated precisely. In the midst of the currently on‐going COVID‐19 pandemic, a global life‐threatening disease, although some studies have indicated that AR is not a risk factor for severity and mortality of COVID‐19, this needs to be confirmed in multi‐centre, real‐life studies of AR patients from different parts of the world.
Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be ...heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
Direct phase modulation is one of the most urgent and difficult issues in the terahertz research area. Here, we propose a new method employing a two-dimensional electron gas (2DEG) perturbation ...microstructure unit coupled to a transmission line to realize high-precision digital terahertz phase manipulation. We induce local perturbation resonances to manipulate the phase of guided terahertz waves. By controlling the electronic transport characteristics of the 2DEG using an external voltage, the strength of the perturbation can be manipulated, which affects the phase of the guided waves. This external control permits electronic manipulation of the phase of terahertz waves with high precision, as high as 2−5° in the frequency range 0.26–0.27 THz, with an average phase error of only 0.36°, corresponding to a timing error of only 4 fs. Critically, the average insertion loss is as low as 6.14 dB at 0.265 THz, with a low amplitude fluctuation of 0.5 dB, so the device offers near-ideal phase-only modulation.A terahertz phase modulator based on the switchable perturbation resonance in two-dimensional electron gas is demonstrated. Phase manipulation with precision ranging from 2° to 5° is obtained at frequencies in the range from 0.26 to 0.27 THz.
Weight loss is often key in the management of obese or overweight patients with type 2 diabetes, yet few treatments for diabetes achieve clinically meaningful weight loss. We aimed to assess the ...efficacy, tolerability, and safety of treatment with MEDI0382, a balanced glucagon-like peptide-1 and glucagon receptor dual agonist developed to provide glycaemic control and weight loss, in patients with type 2 diabetes.
This randomised, placebo-controlled, double-blind, combined multiple-ascending dose (MAD) and phase 2a study was done at 11 study sites (hospitals and contract research organisations) in Germany. We enrolled patients aged 18–65 years with controlled type 2 diabetes (glycated haemoglobin A1c HbA1c levels of 6·5–8·5% at screening) and a body-mass index between 27 kg/m2 and 40 kg/m2. An interactive web-response system was used to randomly assign patients to receive MEDI0382 or placebo. Patients were randomly assigned 2:1 in cohorts A–C and 3:1 in cohorts D and E in the MAD portion of the study, and 1:1 in the phase 2a portion. Randomisation was done by a contracted third-party operator who was not involved in the clinical operations of the study. The pharmacists, participants, and study site personnel involved in treating and assessing participants were masked to treatment allocation. Patients received once-daily subcutaneous injections of the study drug at doses of no more than 300 μg for 22 days or less in the MAD portion of the study, and a dose of no more than 200 μg for 41 days or less in the phase 2a portion. The two primary endpoints of the phase 2a portion were the change from baseline to day 41 in glucose area under the curve at 0–4 h (AUC0–4 h) after a mixed-meal tolerance test (MMTT), assessed in all participants who received at least one dose of study drug and whose measurements were taken at baseline and day 41, and change from baseline in bodyweight, assessed in the intention-to-treat (ITT) population. Safety analyses were done in all participants who received any study drug analysed according to the treatment they received. This study is registered with ClinicalTrials.gov, number NCT02548585.
Patients were recruited between Dec 9, 2015, and Feb 24, 2017. 61 patients were randomly assigned to the MAD part of the study (42 to MEDI0382 and 19 to placebo). 51 patients were randomly assigned to the phase 2a part, of whom 25 were randomly assigned to MEDI0382 and 26 to placebo. In the phase 2a study, three patients in the MEDI0382 group and one in the placebo group discontinued, all as a result of adverse events. 22 (88%) patients in the MEDI0382 group and 25 (96%) in the placebo group received at least one dose and had measurements taken at baseline and day 41. Glucose AUC0–4 h post MMTT decreased significantly with MEDI0382 versus placebo (least squares LS mean −32·78% 90% CI −36·98 to −28·57 vs −10·16% –14·10 to −6·21, and the mean difference was −22·62% –28·40 to −16·85; p<0·0001). In the ITT population, reduction in bodyweight was significantly greater with MEDI0382 than with placebo (LS mean −3·84 kg 90% CI −4·55 to −3·12 vs −1·70 kg –2·40 to −1·01 and mean difference of 2·14 kg –3·13 to −1·31; p=0·0008). The proportion of patients who had a treatment-emergent adverse event (TEAE) was similar between treatment groups (22 88% of 25 in the MEDI0382 group vs 23 88% of 26 in the placebo group); gastrointestinal disorders (18 72% vs 13 40%) and decreased appetite (five 20% vs none) occurred more frequently with MEDI0382 than placebo. No participants in the MEDI0382 group had a grade 3 or worse TEAE (vs two 8% in the placebo group).
MEDI0382 has the potential to deliver clinically meaningful reductions in blood glucose and bodyweight in obese or overweight individuals with type 2 diabetes.
MedImmune.
The flexible Li‐air battery (FLAB) with ultrahigh energy density is a hopeful candidate for flexible energy storage devices. However, most current FLAB operate in a pure oxygen atmosphere, which is ...limited by safety and corrosion issues from the metallic lithium anode and has thus greatly impeded the application of FLAB. Now, inspired by the protection effect of the umbrella, a stable hydrophobic composite polymer electrolyte (SHCPE) film with high flexibility, hydrophobicity, and stability was fabricated to protect the lithium anode. The SHCPE mitigated lithium corrosion and improved the capacity, rate performance, and cycle life (from 24 cycles to 95 cycles) of a battery in the ambient air. Based on the protection of SHCPE and the catalysis of MnOOH, the prepared pouch‐type FLAB displayed high flexibility, stable performances, long cycling life (180 cycles), and excellent safety; the battery can bear soaking in water, high temperature, and nail penetration.
Hold up an umbrella! A stable hydrophobic composite polymer electrolyte inspired by umbrellas was designed and fabricated on a lithium anode for a flexible Li‐air battery that can safely operate in the ambient air. Based on the in situ fabricated multifunctional electrolyte, the pouch‐type flexible Li‐air battery showed stable electrochemical performance and safety even under extreme conditions.
Highly specific Cas9 nucleases derived from SpCas9 are valuable tools for genome editing, but their wide applications are hampered by a lack of knowledge governing guide RNA (gRNA) activity. Here, we ...perform a genome-scale screen to measure gRNA activity for two highly specific SpCas9 variants (eSpCas9(1.1) and SpCas9-HF1) and wild-type SpCas9 (WT-SpCas9) in human cells, and obtain indel rates of over 50,000 gRNAs for each nuclease, covering ~20,000 genes. We evaluate the contribution of 1,031 features to gRNA activity and develope models for activity prediction. Our data reveals that a combination of RNN with important biological features outperforms other models for activity prediction. We further demonstrate that our model outperforms other popular gRNA design tools. Finally, we develop an online design tool DeepHF for the three Cas9 nucleases. The database, as well as the designer tool, is freely accessible via a web server, http://www.DeepHF.com/ .
Sodium‐ion batteries (SIBs) are considered as promising alternatives to lithium‐ion batteries (LIBs) for large‐scale electrical‐energy‐storage applications due to the wide availability and the low ...cost of Na resources. Along with the avenues of research on flexible LIBs, flexible SIBs are now being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. Here, the recent progress on flexible electrodes based on metal substrates, carbonaceous substrates (i.e., graphene, carbon cloth, and carbon nanofibers), and other materials, as well as their applications in flexible SIBs, are summarized. Also, some future research directions for constructing flexible SIBs are proposed, with the aim of providing inspiration to the further development of advanced flexible SIBs.
Flexible sodium‐ion batteries (SIBs) are being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. The recent progress on flexible electrodes based on metal substrates, carbonaceous substrates, and other materials, is summarized, along with their applications in flexible SIBs.
Stem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell ...transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in MI. In this review, we retrospectively summarized the current applications and strategy of stem cell-derived cell sheet technology for heart tissue repair in MI.
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