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Abstract Asthma is a chronic airway inflammation disease and the diagnosis and treatment strategies remain difficult. MicroRNAs play important roles in many biological and pathological processes including asthma development. There is no study confirming the contribution of genetic variants in miR-145 to asthma etiology. We hypothesize that single nucleotide polymorphisms (SNPs) in the promoter region of miR-145 may be associated with the risk of asthma in Taiwanese. We used a case–control study to test this hypothesis. In 198 asthma patients and 453 healthy controls, the genotypes of miR-145 rs4705342 and rs4705343 were determined, and the associations of miR-145 genotypes with asthma risk and severity were evaluated. The distribution of miR-145 rs4705342 genotypes between asthma patients and non-asthmatic control groups were significantly different (p = 0.0187). In multivariable logistic regression analysis, compared with the wild-type TT genotype, individuals carrying the variant genotypes had progressively decreased risks of asthma: the odds ratio (OR) for the heterogeneous variant genotype (CT) and homozygous variant genotype (CC) was 0.77 (95% CI 0.55–1.10, p = 0.1788) and 0.41 (95% CI 0.21–0.79, p = 0.0102), respectively (p for trend = 0.0187). In allelic test, the C allele was associated with a 31% reduced risk of asthma (OR = 0.69, 95% CI 0.53–0.90, p = 0.0070). In addition, the rs4705342 variant genotypes were correlated with the symptom severity (p = 3 × 10–5). Furthermore, the variant genotypes correlated with lower miR-145-5p expression level in serum (p = 0.0001). As for rs4705343, there was no differential distribution of genotypes between cases and controls. Our data provide evidence for miR-145 rs4705342 to serve as a novel biomarker for asthma risk prediction.

Abstract Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.

Abstract Ovarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2+ tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2+ ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2+ ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2+ ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P

Abstract Spiro-OMeTAD with symmetric spiro-bifluorene unit has dominated the investigation of hole-transporting material (HTM) for efficient perovskite solar cells (PSCs) despite of its low intrinsic hole conductivity and instability. In this study, we designed and synthesized three asymmetric spiro-phenylpyrazole/fluorene base HTMs, namely: WY-1, WY-2 and WY-3. They exhibit excellent electrochemical properties and hole conductivities. Moreover, the PSC based on WY-1 exhibits the highest power conversion efficiency (PCE) of 14.2%, which is comparable to the control device employing spiro-OMeTAD as HTM (14.8%). These results pave the way to further optimization of both molecular design and device performance of the spiro-based HTMs.

In this study, Kinesio tape (KT) was applied in two different directions to the gastrocnemius muscle, the most important muscle in stance stability, to investigate the effect of different taping directions on overall balance and sensation systems before versus after muscle fatigue. The participants, comprising 45 healthy athletes, were randomly divided into three groups: the placebo taping group (PTG), the facilitation KT group (FKTG), and the inhibition KT group (IKTG). The tests involved in this study were a balance test, a superficial sensory function test, and a combined cortical sensation test. The data from these tests were collected before taping, after taping and a 10-min rest, and immediately after continuous heel raises were performed to fatigue. The results of the balance tests showed no significant group × time interaction, whether subjects stood barefoot on one foot or stood on a soft mat with eyes open or closed (p > 0.05). Only the sway distance and sway velocity of the center of pressure (COP) when subjects stood barefoot on one foot with eyes open were significantly higher in the inhibition taping group than in the placebo taping group (p < 0.05). In addition, significant differences were noted in the sway area and sway distance of the COP before taping, after taping, and after exercise to fatigue when the participants stood on the soft mat with their eyes open (p < 0.05). When the participants stood on the soft mat on one foot with their eyes closed, no significant differences were noted among the groups. When subjects stood on a soft mat on one foot with eyes open, significant improvements were noted after fatiguing exercise versus before taping for all three groups (p < 0.05). The results of the superficial sensory test showed no significant group × time interaction and no difference among the three taping conditions or before/after taping and after fatiguing exercise. Only in the two-point discrimination test was a sensory difference observed, with the facilitation taping group having a significantly shorter discrimination distance than the placebo taping and inhibition taping groups (p < 0.05). The present study showed that KT application for a simple balance task (e.g., barefoot on a hard floor with eyes open) may slightly influence postural control, especially when the inhibition method is used. However, more difficult balance tasks (e.g., barefoot on a soft mat with eyes closed) show no effect of KT application—either the facilitation method or the inhibition method—on posture control. [ABSTRACT FROM AUTHOR]