Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising epigenetic target for disease treatment. Several LSD1 inhibitors have advanced into clinical trials. Following our last annual ...review on LSD1 inhibitors in 2020 (Eur. J. Med. Chem. 2021, 214, 113254), in this review we aim to update LSD1 inhibitors including natural products, synthetic compounds and cyclic peptides reported during 2021. Design strategies, structure-activity relationships, binding model analysis and modes of action are highlighted. In particular, two FDA-approved antihypertensive drugs raloxifene and fenoldopam were repurposed as reversible LSD1 inhibitors. The clinical candidate TAK-418 for treating neurodevelopmental disorders and PET imaging agent 18F30 for LSD1 were identified. Moreover, dual inhibitors targeting both LSD1 and HDAC6 or tubulin displayed enhanced anti-cancer effects than single agents. These compounds further enrich the structural types of LSD1 inhibitors.
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•LSD1 is a promising epigenetic target for disease treatment.•Compounds with novel scaffolds enrich the structural diversity of LSD1 inhibitors.•Clinical candidate TAK-418 shows therapeutic potential for neurodevelopmental disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tourism eco-efficiency is an important indicator to measure the sustainable development of tourism with the core objective of "minimum resource input and environmental damage, maximum economic and ...social output". This paper explores the spatial and temporal evolution characteristics of tourism eco-efficiency and its influencing factors in Fujian Province from 2011 to 2020 by combining the unexpected output Super-SBM model, gravity center model, standard deviation ellipse, and optimal parameters-based geographical detector model. The results are as follows. Tourism eco-efficiency in Fujian Province showed an overall fluctuating growth trend with an increase of 160.065% during the study period. The coefficient of variation of tourism eco-efficiency tends to fluctuate and decrease, and regional differences narrow. The spatial differentiation is remarkable, and it presents the spatial distribution characteristics of "Xiamen > Nanping > Quanzhou > Fuzhou > Longyan > Ningde > Sanming > Zhangzhou > Putian". The spatial pattern of tourism eco-efficiency is obvious in the direction of "northeast-southwest", and the trajectory of the center of gravity is "southwest-northeast-northwest", with spatial characteristics tending towards agglomeration. Tourism industry structure has the greatest impact on tourism eco-efficiency, followed by education level, urbanization level, technology innovation level, infrastructure investment, and economic development level. This study provides reference suggestions for improving tourism eco-efficiency which helps to promote adequate, balanced, and sustainable development of the regional tourism industry.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recently, deep neural networks have shown great potential for solving dipole inversion of quantitative susceptibility mapping (QSM) with improved results. However, these studies utilized their ...limited dataset for network training and inference, which may lead to untrustworthy conclusions. Thus, a common dataset is needed for a fair comparison between different QSM reconstruction networks. Additionally, finding an in vivo reference susceptibility map that matches acquired single-orientation phase data remains an open problem. Susceptibility tensor imaging (STI) χ33 and Calculation of Susceptibility through Multiple Orientation Sampling (COSMOS) are considered reference susceptibility candidates. However, a large number of multi-orientation GRE data for both STI and COSMOS reconstruction are now unavailable for training supervised neural networks for QSM. In this study, we reported the largest multi-orientation dataset, to the best of our knowledge in the QSM research field, with a total of 144 scans from 8 healthy subjects collected using a 3D GRE sequence from the same MR scanner. In addition, the parcellation of deep gray matter is also provided for automatically extracting susceptibility values. Five recently developed deep neural networks, i.e., xQSM, QSMnet, autoQSM, LPCNN, and MoDL-QSM were performed on this dataset. This potential data source could provide a common framework and labels to test the accuracy and robustness of deep neural networks for QSM reconstruction. This dataset has the potential to provide a benchmark of reference susceptibility for the deep learning-based QSM methods. Additionally, the trained COSMOS-labeled and χ33-labeled networks were tested on the pathological data to explore their potential applications. The data together with deep gray matter parcellation maps are now publicly available via an open repository at https://osf.io/yfms7/, and the raw multi-orientation GRE data are also available at https://osf.io/y6rc3/.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aerobic granular sludge (AGS) process and microalgal-bacterial granular sludge (MBGS) process were comparably applied for municipal wastewater treatment in sequencing batch reactors with a height ...to diameter ratio of eight. For morphological appearances, the yellow aerobic granules were strip-shaped (4.0 mm × 0.62 mm) while the green microalgal-bacterial granules were elliptical-shaped (2.0 mm × 0.75 mm). The dominated rod-shaped bacteria (e.g.,
Acidobacteria
and
Bacteroidetes
) and the slender configuration might be associated with the strip shape of aerobic granules under weak acid conditions. The nutrients removal performances by MBGS process were generally slightly better than AGS process. In addition, nutrients removal mechanisms were identified to elucidate how organics, ammonia, and phosphorus were removed by AGS process and MBGS process, respectively. Mass balance calculation estimated that MBGS process appeared to achieve much less CO
2
emission (5.8%) compared with AGS process (44.4%). Overall, it proved that MBGS process, with the merits of potentially low energy cost, limited CO
2
emission, and excellent performance, showed more prospects in municipal wastewater treatment than AGS process.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Neutrophil extracellular traps (NETs) could entrap tumour cells and promote their dissemination and metastasis. Further analysis of NETs-related molecules is expected to provide a new strategy for ...prognosis prediction and treatment of lung adenocarcinoma (LUAD) patients.
The model construction was established through co-expression analysis, Lasso Cox regression, univariate and multivariate COX regression, Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway. The potential drugs and analysed drug sensitivity were screened by pRRophetic packages.
In this study, we constructed a 15 NETs-related long non-coding RNAs (lncRNAs) prognostic prediction model (AC091057.1, SPART-AS1, AC023796.2, AL031600.2, AC084781.1, AC032011.1, FAM66C, C026355.2, AL096870.2, AC092718.5, PELATON, AC008635.1, AL162632.3, AC087501.4 and AC123768.3) for patients with early-stage LUAD based on public databases and datasets. The signature is associated with immune cell functions, tumour mutation burden and treatment sensitivity in LUAD patients. Additionally, we found that FAM66C is highly expressed in lung cancer patients for the first time, which is associated with poor prognosis. FAM66C knockdown significantly inhibited the proliferation and migration ability of the tumour cells.
In conclusion, this model is a new and effective prognostic and efficacy predictive biomarker, FAM66C plays an oncogene role in the process of LUAD development. It may provide a new theoretical basis for the clinical diagnosis and treatment in LUAD patients in early stage.
The family, which is the basic unit of Chinese society, serves as the micro foundation of individual charitable behavior. This study examines the intergenerational effects on individual charitable ...donations in China based on China’s unique social structure, traditional culture, and philanthropic history. The study identifies the mutual influence of children’s charitable donation and parent’s charitable donation through both downward and upward intergenerational transmission. The effect of upward transmission is stronger than that of downward inheritance, especially among families with children born in the 1980s and 1990s. The findings reflect the “family-oriented” culture of Chinese society and highlight the necessity and urgency of developing a charitable donation theory rooted in Chinese experiences.
Quantitative susceptibility mapping (QSM) has demonstrated great potential in quantifying tissue susceptibility in various brain diseases. However, the intrinsic ill-posed inverse problem relating ...the tissue phase to the underlying susceptibility distribution affects the accuracy for quantifying tissue susceptibility. Recently, deep learning has shown promising results to improve accuracy by reducing the streaking artifacts. However, there exists a mismatch between the observed phase and the theoretical forward phase estimated by the susceptibility label. In this study, we proposed a model-based deep learning architecture that followed the STI (susceptibility tensor imaging) physical model, referred to as MoDL-QSM. Specifically, MoDL-QSM accounts for the relationship between STI-derived phase contrast induced by the susceptibility tensor terms (χ13, χ23 and χ33) and the acquired single-orientation phase. The convolutional neural networks are embedded into the physical model to learn a regularization term containing prior information. χ33 and phase induced by χ13 and χ23 terms were used as the labels for network training. Quantitative evaluation metrics were compared with recently developed deep learning QSM methods. The results showed that MoDL-QSM achieved superior performance, demonstrating its potential for future applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Herein, a sensitive photo-electrochemical sensor based on C3N4 and reduced graphene oxide nanosheets modified glassy carbon electrode (C3N4-RGO/GCE) has been fabricated for the ...detection of rutin under UV light illumination. In C3N4-RGO catalyst, RGO not only works as a template but also promotes electron transfer, meanwhile, C3N4 acts as a photocatalyst. Benefiting from the superior electron transfer capacity and efficient UV light effect of the C3N4-RGO catalyst, we get a photo-electrochemical sensor for the rutin detecting with a low detection limit of 1.78×10−9molL−1 and an excellent linear range of 5×10−9–1.4×10−4molL−1. Meanwhile, the achieved C3N4-RGO/GCE demonstrated nice selectivity, good reproducibility as well as reliable stability. Moreover, compared with the electrochemical determination, the C3N4-RGO electrode provides a new way for rutin detection by photo-electrochemical method with a promising UV light responsive result.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Silicon does not emit light efficiently, therefore the integration of other light‐emitting materials is highly demanded for silicon photonic integrated circuits. A number of integration approaches ...have been extensively explored in the past decade. Here, the most recent progress in this field is reviewed, covering the integration approaches of III‐V‐to‐silicon bonding, transfer printing, epitaxial growth and the use of colloidal quantum dots. The basic approaches to create waveguide‐coupled on‐chip light sources for different application scenarios are discussed, both for silicon and silicon nitride based waveguides. A selection of recent representative device demonstrations is presented, including high speed DFB lasers, ultra‐dense comb lasers, short (850nm) and long (2.3μm) wavelength lasers, wide‐band LEDs, monolithic O‐band lasers and micro‐disk lasers operating in the visible. The challenges and opportunities of these approaches are discussed.
This article reviews the most recent progress of the field of silicon integrated light sources. Novel integration approaches of III‐V‐to‐silicon bonding, transfer printing, epitaxial growth and the use of colloidal quantum dots are discussed and recent representative demonstrations are presented. The challenges and perspectives of these approaches are also discussed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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