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Heritability of stroke is assumed not to be low, especially in the young-age stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population.We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGV) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next-generation sequencing panel.Among 1,033 patients, 131 (12.7%) had 28 CRGV, most frequently in RNF213 (n=59), followed by ABCC6 (n=53) and NOTCH3 (n=15). The frequency of CRGV differed by ischemic stroke subtypes (p0.01)-highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51-55 years (17.1% vs. 9.3%, p=0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUS) were found in 15.4% patients.CRGV in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGV did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGV or VUS should be explored. This article is protected by copyright. All rights reserved.

The phytohormone abscisic acid (ABA) plays a prominent role in various abiotic stress responses of plants. In the ABA-dependent osmotic stress response, SnRK2.6, one of the subclass III SnRK2 kinases, has been identified as playing a key role by phosphorylating and activating downstream genes. Although several modulatory proteins have been reported to be phosphorylated by SnRK2.6, the identities of the full spectrum of downstream targets have yet to be sufficiently established. In this study, we identified CaSAP14, a stress-associated protein in pepper (Capsicum annuum), as a downstream target of CaSnRK2.6. We elucidated the physical interaction between SnRK2.6 and CaSAP14, both in vitro and in vivo, and accordingly identified a C-terminal C2H2-type zinc finger domain of CaSAP14 as being important for their interaction. CaSAP14-silenced pepper plants showed dehydration- and high salt-sensitive phenotypes, whereas overexpression of CaSAP14 in Arabidopsis conferred tolerance to dehydration, high salinity, and mannitol treatment, with plants showing ABA-hypersensitive phenotypes. Furthermore, an in-gel kinase assay revealed that CaSnRK2.6 phosphorylates CaSAP14 in response to exogenous ABA, dehydration, and high-salinity stress. Collectively, these findings suggest that CaSAP14 is a direct substrate of CaSnRK2.6 and positively modulates dehydration- and high salinity-induced osmotic stress responses.

The phase reconstruction process in digital holographic microscopy involves a trade-off between the phase error and the high-spatial-frequency components. In this reconstruction process, if the narrow region of the sideband is windowed in the Fourier domain, the phase error from the DC component will be reduced, but the high-spatial-frequency components will be lost. However, if the wide region is windowed, the 3D profile will include the high-spatial-frequency components, but the phase error will increase. To solve this trade-off, we propose the high-variance pixel averaging method, which uses the variance map of the reconstructed depth profiles of the windowed sidebands of different sizes in the Fourier domain to classify the phase error and the high-spatial-frequency components. Our proposed method calculates the average of the high-variance pixels because they include the noise from the DC component. In addition, for the nonaveraged pixels, the reconstructed phase data created by the spatial frequency components of the widest window are used to include the high-spatial-frequency components. We explain the mathematical algorithm of our proposed method and compare it with conventional methods to verify its advantages.

OBJECTIVE We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score

This study investigates the dermatological as well as the esthetic potential of light-emitting diodes (LEDs) by performing a systematic review and meta-analysis. From the electronic databases, 554 articles were assessed; however, only 31 studies were selected after manually screening and eliminating unnecessary studies. The potential effectiveness of LEDs for skin therapies was assessed by evaluating the standardized mean differences (SMDs) and funnel plots of this meta-analysis. It was discovered that both red and blue LED lights play an important role in the treatment of acne vulgaris with an overall statistically significant SMD of -2.42 [-2.64, -2.15] and I

Background and aim We aimed to develop a convolutional neural network (CNN)-based object detection model for the discrimination of gastric subepithelial tumors (SETs), such as gastrointestinal stromal tumors (GISTs) and leiomyomas, in endoscopic ultrasound (EUS) images. Methods We used 376 images from 114 patients with histologically confirmed gastric GIST or leiomyoma to train the EUS-CNN. We constructed the EUS-CNN using an EfficientNet CNN model for feature extraction and a weighted bi-directional feature pyramid network for object detection. We assessed the performance of our EUS-CNN by calculating its accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC) using a validation set of 170 images from 54 patients. Four EUS experts and 15 EUS trainees were asked to judge the same validation dataset, and the diagnostic yields were compared between the EUS-CNN and human assessments. Results In the per-image analysis, the sensitivity, specificity, accuracy, and AUC of our EUS-CNN were 95.6%, 82.1%, 91.2%, and 0.9234, respectively. In the per-patient analysis, the sensitivity, specificity, accuracy, and AUC for our object detection model were 100.0%, 85.7%, 96.3%, and 0.9929, respectively. The EUS-CNN outperformed human assessment in terms of accuracy, sensitivity, and negative predictive value. Conclusions We developed the EUS-CNN system, which demonstrated high diagnostic ability for gastric GIST prediction. This EUS-CNN system can be helpful not only for less-experienced endoscopists but also for experienced ones. Additional EUS image accumulation and prospective studies are required alongside validation in a large multicenter trial.

BACKGROUND Although perioperative hypothermia was found to be associated with gastrointestinal anastomotic leakage in preclinical studies, its association with postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy was never evaluated. We investigated the association between intraoperative hypothermia and clinically relevant (CR)-POPF following pancreaticoduodenectomy. METHODS We retrospectively reviewed 2163 consecutive patients who underwent pancreaticoduodenectomy during 2007-2019. Based on intraoperative time-weighted average core temperature, patients were grouped into normothermia (36.0-37.5°C), mild hypothermia (35.0

Induction of the abscisic acid (ABA) signalling network is associated with various stress conditions, including cold, high salinity and drought. As core ABA signalling components, group A type 2C protein phosphatases (PP2Cs) interact with and inhibit snf1-related protein kinase2s. Here, we isolated and characterised the pepper mitogen-activated protein kinase kinase kinase CaADIK1, which interacts with the group A PP2C CaADIP1. CaADIK1 transcripts were induced by abiotic stresses, and CaADIK1 localised in the nucleus and cytoplasm. We verified that CaADIP1 inhibits the autokinase activity of CaADIK1; moreover, the kinase activity of CaADIK1 is enhanced by drought stress. We performed genetic analysis using CaADIK1-silenced pepper and CaADIK1-overexpressing (OX) Arabidopsis plants. CaADIK1-silenced pepper plants showed drought-sensitive phenotypes, whereas CaADIK1-OX Arabidopsis plants showed ABA-sensitive and drought-tolerant phenotypes. In CaADIK1K32N -OX Arabidopsis plants mutated at the ATP-binding site, the ABA-insensitive and drought-sensitive phenotypes were restored. Taken together, our findings show that CaADIK1 positively regulates the ABA-dependent drought stress response and is inhibited by CaADIP1.

Abscisic acid (ABA) is a plant hormone that activates adaptive mechanisms to environmental stress conditions. Plant adaptive mechanisms are complex and highly modulated processes induced by stress-responsive proteins; however, the precise mechanisms by which these processes function under adverse conditions remain unclear. Here, we isolated CaUBP12 (Capsicum annuum ubiquitin-specific protease 12) from pepper (C. annuum) leaves. We show that CaUBP12 expression is significantly induced after exposure to abiotic stress treatments. We conducted loss-of-function and gain-of-function genetic studies to elucidate the biological functions of CaUBP12 in response to ABA and dehydration stress. CaUBP12-silenced pepper plants and CaUBP12-overexpressing Arabidopsis plants displayed dehydration-sensitive and dehydration-tolerant phenotypes, respectively; these phenotypes were characterized by regulation of transpirational water loss and stomatal aperture. Under dehydration stress conditions, CaUBP12-silenced pepper plants and CaUBP12-overexpressing Arabidopsis plants exhibited lower and higher expression levels of stress-related genes, respectively, than the control plants. We isolated a CaUBP12 interaction protein, CaSnRK2.6, which is a homolog of Arabidopsis OST1; degradation of this protein was partially inhibited by CaUBP12. Similar to CaUBP12-silenced pepper plants and CaUBP12-overexpressing Arabidopsis plants, CaSnRK2.6-silenced pepper plants and CaSnRK2.6-overexpressing Arabidopsis displayed dehydration-sensitive and dehydration-tolerant phenotypes, respectively. Our findings suggest that CaUBP12 positively modulates the dehydration stress response by suppressing CaSnRK2.6 protein degradation.

Electromagnetic fields (EMFs) are widely used in a number of cell therapies and bone disorder treatments, and nanomagnetic particles (NMPs) also promote cell activity. In this study, we investigated the synergistic effects of EMFs and NMPs on the osteogenesis of the human Saos‐2 osteoblast cell line and in a rat calvarial defect model. The Saos‐2 cells and critical‐size calvarial defects of the rats were exposed to EMF (1 mT, 45 Hz, 8 h/day) with or without Fe3O4 NMPs. Biocompatibility was evaluated with MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays. This analysis showed that NMP and EMF did not induce cell toxicity. Quantitative reverse‐transcription polymerase chain reaction indicated that the osteogenesis‐related markers were highly expressed in the NMP‐incorporated Saos‐2 cells after exposure to EMF. Also, the expression of gene‐encoding proteins involved in calcium channels was activated and the calcium concentration of the NMP‐incorporated + EMF‐exposed group was increased compared with the control group. In particular, in the NMP‐incorporated + EMF‐exposed group, all osteogenic proteins were more abundantly expressed than in the control group. This indicated that the NMP incorporation + EMF exposure induced a signaling pathway through activation of p‐ERK and calcium channels. Also, in vivo evaluation revealed that rat calvarial defects treated with EMFs and NMPs had good regeneration results with new bone formation and increased mineral density after 6 weeks. Altogether, these results suggest that NMP treatment or EMF exposure of Saos‐2 cells can increase osteogenic activity and NMP incorporation following EMF exposure which is synergistically efficient for osteogenesis.

Background Prostate-specific membrane antigen (PSMA) is increasingly recognized as an excellent target for prostate cancer imaging and therapy. Finding compounds with a high target-to-nontarget ratio are an important challenge in the development of positron emission tomography (PET) imaging agents. In this study, we attempted to find a suitable compound from a simply-synthesized compound library. Method 18 F-labeling was achieved in a two-step synthesis consisting of [18 F]fluorination of azido sulfonates followed by copper(I)-catalyzed click ligation. In vitro binding experiment and in vivo studies were carried out using isogenic PSMA+ PC3-PIP and PSMA- PC3-flu cells and 22RV1 cells. [125 I]MIP-1095 was used to measure the binding affinities of compounds through a competitive binding assay, and [18 F]DCFPyL was used for a comparative assessment of compounds. Radiation dosimetry data were obtained using OLINDA/EXM software. Results Nine novel PSMA ligands were synthesized by the combination of three azido compounds and three terminal acetylene-containing Glu-urea-Lys compounds. Among them, compound 6f having a pyridine moiety showed a high binding affinity of 6.51 ± 0.19 nM (Ki ). 18 F-labeled compounds were obtained at moderate yields within 70 to 75 minutes (including high-performance liquid chromatography purification). Compound [18 F]6c had the lowest log P of -2.693. MicroPET/computed tomography (CT) images were acquired from 22RV1 cell xenograft mice after injecting [18 F]6c, [18 F]6f, and [18 F]6i. Additional microPET/CT experiments of [18 F]6c and [18 F]6f were performed using PSMA+ PC3-PIP and PSMA- PC3-flu cell-bearing mice. [18 F]6c was selected for further studies because it was found to have high uptake in tumors and rapid renal clearance, resulting in great tumor-to-nontumor ratios and distinct tumor images with very low background activity. Human dosimetry estimation of [18 F]6c using OLINDA/EXM software was calculated, resulting in an effective dose of 4.35 × 10-3 mSv/MBq. Conclusions [18 F]6c showed significant tumor uptake, a high tumor-to-nontumor ratio, and good radiation dosimetry results, suggesting further development as a potential diagnostic PET agent for prostate cancer.

Background/purpose Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. Methods A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. Results The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. Conclusion This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Since heat shock protein (HSP27) is a prognostic marker in cervical cancer, in the present study, the apoptotic mechanism of lambertianic acid (LA) was investigated in human cervical cancers in association with HSP27/STAT3/AKT signaling axis. LA exerted significant cytotoxicity, induced sub-G1 population, and increased the cleavage of Poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase3) in HeLa and Caski cancer cells. Consistently, LA downregulated anti-apopotic genes such as B-cell lymphoma 2 (Bcl-2) and inhibitors of apoptosis proteins (c-IAP) in HeLa and Caski cells. Furthermore, LA-inhibited phosphorylation of HSP27, signal transducer, and activator of transcription 3 (STAT3) and Protein kinase B (AKT) through disturbing the binding of HSP27 with STAT3 or AKT in HeLa cells. Notably, LA upregulated the level of miR216b in HeLa and Caski cells. Consistently, miR216b mimic suppressed phosphorylation of HSP27 and reduced the expression of pro-PARP, while miR216b inhibitor reversed the ability of LA to attenuate phosphorylation of AKT, HSP27, and STAT3 and to reduce the expression of pro-PARP in HeLa cells. Overall, our findings suggest that miRNA216b mediated inhibition of HSP27/STAT3/ AKT signaling axis is critically involved in LA-induced apoptosis in cervical cancers.

The immunoglobulin G (IgG) molecule has a long circulating serum half-life (~3 weeks) through pH- dependent FcRn binding-mediated recycling. To hijack the intracellular trafficking and recycling mechanism of IgG as a way to extend serum persistence of non-antibody therapeutic proteins, we have evolved the ectodomain of a low-affinity human FcγRIIa for enhanced binding to the lower hinge and upper CH2 region of IgG, which is very far from the FcRn binding site (CH2-CH3 interface). High-throughput library screening enabled isolation of an FcγRIIa variant (2A45.1) with 32-fold increased binding affinity to human IgG1 Fc (equilibrium dissociation constant: 9.04 × 10-7 M for wild type FcγRIIa and 2.82 × 10-8 M for 2A45.1) and significantly improved affinity to mouse serum IgG compared to wild type human FcγRIIa. The in vivo pharmacokinetic profile of PD-L1 fused with engineered FcγRIIa (PD-L1-2A45.1) was compared with that of PD-L1 fused with wild type FcγRIIa (PD-L1-wild type FcγRIIa) and human PD-L1 in mice. PD-L1-2A45.1 showed 11.7- and 9.7-fold prolonged circulating half-life (t1/2 ) compared to PD-L1 when administered intravenously and intraperitoneally, respectively. In addition, the AUCinf of PD-L1-2A45.1 was two-fold higher compared to that of PD-L1-wild type FcγRIIa. These results demonstrate that engineered FcγRIIa fusion offers a novel and successful strategy for prolonging serum half-life of therapeutic proteins.

BACKGROUND Although the use of radial endobronchial ultrasound (R-EBUS) with a guide sheath has shown improved diagnostic capability in peripheral pulmonary lesions, its utility is still low due to variable performance. To overcome its limitation, we evaluated the feasibility and efficacy of R-EBUS combined with transbronchial biopsy (TBB) under fluoroscopic guidance. METHODS We retrospectively reviewed medical records of 74 patients with non-small cell lung cancer (NSCLC) who underwent R-EBUS combined with TBB or TBB alone as a diagnostic technique. Subjects were grouped according to the diagnostic modality used (R-EBUS combined with TBB vs. TBB alone). Each group was matched for age, sex, and location of the biopsy. The chi-square test and paired t-test were used to compare characteristics and identify factors that affected the diagnostic yield. RESULTS The mean age of the study cohort was 67.4 ± 12.8 years, with 21 (56.8%) men and 16 (43.2%) women in each group. The lesion size was significantly smaller in the R-EBUS group (23.6 vs. 33.9, P

Background Picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element (DOE) generates micro-injury zones in the epidermis and upper dermis. Objective To investigate interactive tissue reactions between MLA-type picosecond laser pulses and cohesive polydensified matrix hyaluronic acid (CPMHA) filler in the dermis. Methods In vivo rats with or without CPMHA pretreatment were treated with a 1064-nm picosecond-domain neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using an MLA or DOE. Skin samples were obtained at post-treatment days 1, 10, and 21 and histologically and immunohistochemically analyzed. Results Picosecond-domain Nd:YAG laser treatment with an MLA-type or a DOE-type handpiece generated fractionated zones of pseudo-cystic cavitation along the lower epidermis and/or upper papillary dermis at Day 1. At Day 21, epidermal thickness, dermal fibroblasts, and collagen fibers had increased. Compared to CPMHA-untreated rats, rats pretreated with CPMHA showed marked increases in fibroblasts and collagen fibers in the papillary dermis. Immunohistochemical staining for the hyaluronic acid receptor CD44 revealed that MLA-type picosecond laser treatment upregulated CD44 expression in the basilar epidermis and dermal fibroblasts. Conclusions We suggest that the hyaluronic acid-rich environment associated with CPMHA treatment may enhance MLA-type picosecond-domain laser-induced tissue reactions in the epidermis and upper dermis.

This study aimed to evaluate growth factor concentration in platelet-rich plasma (PRP) (leukocyte-rich PRP) based on storage temperature, duration of storage, and method of activation. PRP samples were stored at 24℃ (room temperature group), 4℃ (refrigerator group), and -70℃ (deep-freezer group). In each temperature, four aliquots were prepared based on the time of analysis (immediately, 1, 3, and 7 days after preparation). After storage, concentrations of platelet-derived growth factor-AA (PDGF-AA), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor-basic (FGF-B) were assessed with/without activation using Quantikine colorimetric sandwich immunoassay kits. PRP was activated with 10% Triton-X for PDGF-AA, VEGF, FGF-B, IGF-1 measurement and sonication for TGF-β1 measurement. Without activation, PDGF-AA concentration was highest on day 7 in the room temperature group. With activation, the concentration of PDGF-AA was constant over the observation period at all temperatures. Without activation, the TGF-β1 concentration remained negligible over the observation period at all temperatures. However, with activation, TGF-β1 gradually increased to its highest concentration on day 7 at all temperatures. Over the observation period, VEGF and IGF-1 concentrations were constant with and without activation at all temperatures. Without activation, FGF-B concentration increased, with the highest concentration observed on day 7 in the deep-freezer group. With activation, FGF-B concentration decreased after day 1 in the room temperature group. Growth factor concentration in PRP differed significantly based on storage temperature, duration of storage, and method of activation. Appropriate storage conditions and activation are important to optimize its effects on desired clinical outcomes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:777-784, 2020.

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of β-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.

Ubiquitination is a eukaryotic protein modulation system for identifying and affecting proteins that are no longer needed in the cell. In a previous study, we elucidated the biological function of CaASRF1, which contains a RING finger domain and functions as an E3 ligase. We showed that CaASRF1 positively modulates abscisic acid (ABA) signalling and drought stress tolerance by modulating the stability of subgroup D bZIP transcription factor CaAIBZ1. We performed yeast two-hybrid (Y2H) screening to identify an additional target protein of CaASRF1. In this study, we identified pepper CaATBZ1 (Capsicum annuum ASRF1 target bZIP transcription factor 1), which belongs to the subgroup A bZIP transcription factors. We investigated the biological function of this protein using virus-induced gene silencing (VIGS) in pepper plants and by generating overexpressing transgenic Arabidopsis plants. Our loss-of-function and gain-of-function studies revealed that CaATBZ1 negatively modulates ABA signalling and drought stress response. Consistent with CaATBZ1-silenced pepper plants, CaASRF1/CaATBZ1-silenced pepper plants displayed drought-tolerant phenotypes via ABA-mediated signalling. Our results demonstrated that CaASRF1-mediated ubiquitination plays a crucial role in regulating the stability of CaATBZ1. These findings provide valuable insight into the post-translational regulation of transcriptional factors.

The 52-week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient-reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double-blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.

Although MgO-Al2 O3 is well known as having a spinel structure, the inversion of which occurs by exchange of the trivalent (Al3+ ) and divalent (Mg2+ ) cations, little analytical study of the degree of inversion has been carried out. This study concerns a simple methodology to identify the inversion by solid-state NMR spectroscopy, whereby its correlation with the CO2 capture capacity of MgO-rich MgO@MgO-Al2 O3 spinel structures is verified. Through 27 Al and 25 Mg NMR spectroscopy, temperature-programmed CO2 desorption, and thermogravimetric analysis, higher inversion is found to occur at low Mg/Al ratios and the inversion is found to decrease as the Mg/Al ratio increases. Moreover, the degree of inversion correlates with CO2 sorption, which is associated with the medium-strength basic sites induced by formation of the unsaturated O2- species. These results will open new pathways to exploit defects in complex oxides beyond spinels and their derivatives for desired applications. This demonstration of MgO-Al2 O3 for CO2 sorption can contribute to the design of future CO2 sorbents.

The effect of a small ionic surfactant, cetyltrimethylammonium bromide (CTAB), on the self-assembly of a β-peptide has been systematically studied by using scanning electron microscopy, X-ray diffraction, selected area electron diffraction, and molecular dynamics (MD) simulations. The latter study suggested that the formation of asymmetric microcrystals may be due to the preferential adsorption of CTAB on {011} and (001) crystal faces. This work provides a plausible rationale for the characteristic 3D morphogenesis of foldectures and elucidates the interaction between the surfactant and organic building block molecules.

The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)‐chelated 89Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO‐trastuzumab‐PTX) showed excellent radiolabeling efficiency with 89Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO‐trastuzumab‐PTX displayed comparable cytotoxicity with PTX and 89Zr‐DFO‐trastuzumab‐PTX exhibited HER2 receptor‐mediated binding on HER2‐positive MDA‐MB‐231 breast cancer cells. The results of our in vitro study indicate high potential of 89Zr‐DFO‐trastuzumab‐PTX to be utilized in the theranostic application against HER2‐postive breast cancers.