Understanding the local cation order in the crystal structure and its correlation with electrochemical performances has advanced the development of high‐energy Mn‐rich cathode materials for Li‐ion ...batteries, notably Li‐ and Mn‐rich layered cathodes (LMR, e.g., Li1.2Ni0.13Mn0.54Co0.13O2) that are considered as nanocomposite layered materials with C2/m Li2MnO3‐type medium‐range order (MRO). Moreover, the Li‐transport rate in high‐capacity Mn‐based disordered rock‐salt (DRX) cathodes (e.g., Li1.2Mn0.4Ti0.4O2) is found to be influenced by the short‐range order of cations, underlining the importance of engineering the local cation order in designing high‐energy materials. Herein, the nanocomposite is revealed, with a heterogeneous nature (like MRO found in LMR) of ultrahigh‐capacity partially ordered cathodes (e.g., Li1.68Mn1.6O3.7F0.3) made of distinct domains of spinel‐, DRX‐ and layered‐like phases, contrary to conventional single‐phase DRX cathodes. This multi‐scale understanding of ordering informs engineering the nanocomposite material via Ti doping, altering the intra‐particle characteristics to increase the content of the rock‐salt phase and heterogeneity within a particle. This strategy markedly improves the reversibility of both Mn‐ and O‐redox processes to enhance the cycling stability of the partially ordered DRX cathodes (nearly ≈30% improvement of capacity retention). This work sheds light on the importance of nanocomposite engineering to develop ultrahigh‐performance, low‐cost Li‐ion cathode materials.
The multi‐phase heterogeneous nature of ultrahigh‐energy Mn‐based partially disordered cathodes is revealed by combined experimental and computational studies. This fundamental understanding enables the novel nanocomposite design, which controls a phase fraction within a single particle. Consequently, T30 cathode via a nanocomposite engineering shows more reversible redox properties and a superior cycle retention, showing new insights into developing advanced Mn‐based cathodes.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder that manifests as chronic inflammation and joint tissue destruction. However, the etiology and pathogenesis of RA have not been fully ...elucidated. Here, we explored the role of the hypoxia-inducible factors (HIFs), HIF-1α (encoded by HIF1A) and HIF-2α (encoded by EPAS1). HIF-2α was markedly up-regulated in the intimal lining of RA synovium, whereas HIF-1α was detected in a few cells in the sublining and deep layer of RA synovium. Overexpression of HIF-2α in joint tissues caused an RA-like phenotype, whereas HIF-1α did not affect joint architecture. Moreover, a HIF-2α deficiency in mice blunted the development of experimental RA. HIF-2α was expressed mainly in fibroblast-like synoviocytes (FLS) of RA synovium and regulated their proliferation, expression of RANKL (receptor activator of nuclear factor-κB ligand) and various catabolic factors, and osteoclastogenic potential. Moreover, HIF-2α-dependent up-regulation of interleukin (IL)-6 in FLS stimulated differentiation of TH17 cells-crucial effectors of RA pathogenesis. Additionally, in the absence of IL-6 (Il6-/- mice), overexpression of HIF-2α in joint tissues did not cause an RA phenotype. Thus, our results collectively suggest that HIF-2α plays a pivotal role in the pathogenesis of RA by regulating FLS functions, independent of HIF-1α.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers ...patients' quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients' quality of life. Further research will help understand the mechanisms and develop new strategies in the future.
It is known that DNA hypomethylation of aryl hydrocarbon receptor repressor (AhRR), one of the epigenetic markers of environmental pollutants, causes skin diseases. However, the function and ...mechanisms are still unknown. We aimed to determine whether AhRR is hypomethylated in PBMC of psoriasis patients, as well as to examine the expression of psoriasis-related inflammatory cytokines and antimicrobial peptides after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in HaCaT cells overexpressing or silencing AhRR. AhRR was determined by qPCR, Western blot, immunohistochemistry, and immunocytochemistry in skin tissue and HaCaT cells. DNA methylation of AhRR was performed by Infinium Human Methylation450 BeadChip in PBMC of psoriasis patients and methylation-specific PCR (MSP) in HaCaT cells. NF-κB pp50 translocation and activity were performed by immunocytochemistry and luciferase reporter assay, respectively. We verified
gene expression in the epidermis from psoriasis patients and healthy controls.
hypomethylation in PBMC of psoriasis patients and pAhRR-HaCaT cells was confirmed. The expression level of AhRR was increased in both TCDD-treated HaCaT cells and pAhRR-HaCaT cells. NF-κB pp50 translocation and activity increased with TCDD. Our results showed that
was hypomethylated and overexpressed in the lesional skin of patients with psoriasis, thereby increasing AhRR gene expression and regulating pro-inflammatory cytokines through the NF-κB signaling pathway in TCDD-treated HaCaT cells.
Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue ...from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy.
•Isolated and characterized three types of human dental MSCs from a single donor.•MSCs of dental follicle, pulp and papilla had largely similar biological properties.•All MSCs were capable of transdifferentiating into functional hepatocyte-like cells.•2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs.•Similar proteomic profiles suggest interchangeable applications of dental MSCs.
Glycosylated hemoglobin (HbA1c) is an established marker associated with cardiovascular risk, even if it is below the diagnostic threshold for diabetes mellitus (DM). However, whether or not ...prediabetic and controlled diabetic levels of HbA1c are associated with increased major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains unclear. This observational study included a total of 9128 patients who underwent PCI in the COACT registry from eight centers in Korea. A total of 2517 non-DM patients were divided into three groups (Groups I, II, III) according to their HbA1c levels and compared with 965 controlled DM patients (HbA1c < 7.0%, Group IV). During 22 months of median follow-up, there was no significant differences in MACE (p = 0.294) and cardiac death (p = 0.105) among the four groups. In addition, there were also no significant differences in MACE (p = 0.058) between Group III and Group IV. Although patients were diagnosed as DM, they had a similar prognosis in the same range of newly diagnosed DM patients in HbA1c, if they were treated well. The results of this study suggest that intensive treatment is required to reach the Hba1c target in diabetic patients with PCI in order to have a similar prognosis to patients not previously diagnosed with diabetes.
Purpose:
The purpose of this study was to develop a dual‐modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the ...human brain.
Methods:
The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger‐mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom‐made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold‐plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh‐type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array‐embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3‐T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom‐made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired.
Results:
No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal‐to‐noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired.
Conclusions:
Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.
As interest in skin increases, the cosmetic market is also growing. It is difficult to choose between the numerous types of basic cosmetics on the market. This article aims to provide advice and ...guidance on which products to recommend according to a patient’s skin condition. Appropriate application of a moisturizer attempts not only to improve the dryness, but also improve the skin’s natural barrier function to protect the skin from internal and external irritants to keep the skin healthy. Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants, lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to provide readers with the background they need to choose the right moisturizer for themselves. As moisturizers play an important role as adjuvant in the treatment of common skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be recommended in consideration of the ingredients, effectiveness and safety of each product, and the skin condition of each patient.
To evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation for long coronary lesions, we performed a randomized multicenter prospective study comparing ...triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol; triple group, n = 250) and dual antiplatelet therapy (aspirin and clopidogrel; standard group, n = 250) for 6 months in patients with long lesions (≥25 mm) requiring a long DES (≥32 mm). The primary end point was in-stent late loss at 6-month angiography. The 2 groups had similar baseline clinical and angiographic characteristics. In-stent late loss (0.22 ± 0.48 mm vs 0.32 ± 0.51 mm, p = 0.031) and in-segment late loss (0.34 ± 0.49 mm vs 0.51 ± 0.49 mm, p = 0.001) at 6-month follow-up angiography were significantly lower in the triple group versus the standard group. There was a trend toward lower rates of in-segment restenosis in the triple group versus the standard group (6.7% vs 11.2%, p = 0.104). Target lesion revascularization (TLR; 2.8% vs 6.8%, p = 0.036) and major adverse cardiac events (2.8% vs 7.6%, p = 0.016), including death, myocardial infarction, and TLR at 9 months were significantly lower in the triple group than in the standard group. At 9 months, the 2 groups had similar rates of stent thrombosis (0.4% vs 0.4%, p = 0.999), death (0% vs 0.8%, p = 0.499), and myocardial infarction (0.4% vs 0.4%, p = 0.999). In conclusion, cilostazol significantly reduced late loss at 6 months after DES implantation and the occurrence of TLR and major adverse cardiac events in patients with long coronary lesions.
In the field of natural language processing, artificial intelligence (AI) technology has been utilized to solve various problems, such as text classification, similarity measurement, chatbots, ...machine translation, and machine reading comprehension. Significant advancements have been made in complex and rule-intensive natural language processing through deep learning, in which machines directly learn patterns. Machine reading comprehension, a natural language processing task, involves machines understanding questions and paragraphs to find answers within paragraphs. In 2019, bidirectional encoder representations from transformers (BERT) and a robust optimized BERT pretraining approach (RoBERTa) were introduced. They were then optimized for pretraining and fine-tuning, resulting in significant advancements. RoBERTa outperformed BERT in terms of training speed and performance by increasing the pretraining data and batch sizes, employing dynamic masking, and eliminating the next sentence prediction task. In RoBERTa, machine reading comprehension involves simultaneously inputting questions and paragraphs. However, this simultaneous input method suffers from the attention separate representation (ASP) problem, in which the attention distribution between the question and the paragraph spreads widely across keywords. This study proposed two methods to address the ASP problem. The existing input format, question-paragraph, was changed to three independent inputs: question, paragraph, and concatenated RoBERTa outputs. The concatenated matrix was then transformed into two matrices, and a machine reading comprehension algorithm using co-attention was proposed. An ablation study was conducted to evaluate and analyze the model's performance, comprehension, and design efficiency. According to the experimental results, the proposed method improved the EM by 0.9% and F1 by 1.0% compared to the existing methods. Consequently, the learning performance was enhanced through attention concentration and co-attention, and it could demonstrate much better performance compared to the existing models.