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1. CLOSE: Curriculum Learning On the Sharing Extent Towards Better One-shot NAS

Author

Zhou, Zixuan, Ning, Xuefei, Cai, Yi, Han, Jiashu, Deng, Yiping, Dong, Yuhan, Yang, Huazhong, and Wang, Yu

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

One-shot Neural Architecture Search (NAS) has been widely used to discover architectures due to its efficiency. However, previous studies reveal that one-shot performance estimations of architectures might not be well correlated with their performances in stand-alone training because of the excessive sharing of operation parameters (i.e., large sharing extent) between architectures. Thus, recent methods construct even more over-parameterized supernets to reduce the sharing extent. But these improved methods introduce a large number of extra parameters and thus cause an undesirable trade-off between the training costs and the ranking quality. To alleviate the above issues, we propose to apply Curriculum Learning On Sharing Extent (CLOSE) to train the supernet both efficiently and effectively. Specifically, we train the supernet with a large sharing extent (an easier curriculum) at the beginning and gradually decrease the sharing extent of the supernet (a harder curriculum). To support this training strategy, we design a novel supernet (CLOSENet) that decouples the parameters from operations to realize a flexible sharing scheme and adjustable sharing extent. Extensive experiments demonstrate that CLOSE can obtain a better ranking quality across different computational budget constraints than other one-shot supernets, and is able to discover superior architectures when combined with various search strategies. Code is available at https://github.com/walkerning/aw_nas., Comment: accepted by ECCV 2022 (14 pages main texts)

Published
2022

5. Greedy Network Enlarging

Author

Liu, Chuanjian, Han, Kai, Xiao, An, Deng, Yiping, Zhang, Wei, Xu, Chunjing, and Wang, Yunhe

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Recent studies on deep convolutional neural networks present a simple paradigm of architecture design, i.e., models with more MACs typically achieve better accuracy, such as EfficientNet and RegNet. These works try to enlarge all the stages in the model with one unified rule by sampling and statistical methods. However, we observe that some network architectures have similar MACs and accuracies, but their allocations on computations for different stages are quite different. In this paper, we propose to enlarge the capacity of CNN models by improving their width, depth and resolution on stage level. Under the assumption that the top-performing smaller CNNs are a proper subcomponent of the top-performing larger CNNs, we propose an greedy network enlarging method based on the reallocation of computations. With step-by-step modifying the computations on different stages, the enlarged network will be equipped with optimal allocation and utilization of MACs. On EfficientNet, our method consistently outperforms the performance of the original scaling method. In particular, with application of our method on GhostNet, we achieve state-of-the-art 80.9% and 84.3% ImageNet top-1 accuracies under the setting of 600M and 4.4B MACs, respectively.

Published
2021

6. Augmented Shortcuts for Vision Transformers

Author

Tang, Yehui, Han, Kai, Xu, Chang, Xiao, An, Deng, Yiping, Xu, Chao, and Wang, Yunhe

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Transformer models have achieved great progress on computer vision tasks recently. The rapid development of vision transformers is mainly contributed by their high representation ability for extracting informative features from input images. However, the mainstream transformer models are designed with deep architectures, and the feature diversity will be continuously reduced as the depth increases, i.e., feature collapse. In this paper, we theoretically analyze the feature collapse phenomenon and study the relationship between shortcuts and feature diversity in these transformer models. Then, we present an augmented shortcut scheme, which inserts additional paths with learnable parameters in parallel on the original shortcuts. To save the computational costs, we further explore an efficient approach that uses the block-circulant projection to implement augmented shortcuts. Extensive experiments conducted on benchmark datasets demonstrate the effectiveness of the proposed method, which brings about 1% accuracy increase of the state-of-the-art visual transformers without obviously increasing their parameters and FLOPs.

Published
2021

7. Federated Learning with Positive and Unlabeled Data

Author

Lin, Xinyang, Chen, Hanting, Xu, Yixing, Xu, Chao, Gui, Xiaolin, Deng, Yiping, and Wang, Yunhe

Subjects
Computer Science - Machine Learning
Abstract

We study the problem of learning from positive and unlabeled (PU) data in the federated setting, where each client only labels a little part of their dataset due to the limitation of resources and time. Different from the settings in traditional PU learning where the negative class consists of a single class, the negative samples which cannot be identified by a client in the federated setting may come from multiple classes which are unknown to the client. Therefore, existing PU learning methods can be hardly applied in this situation. To address this problem, we propose a novel framework, namely Federated learning with Positive and Unlabeled data (FedPU), to minimize the expected risk of multiple negative classes by leveraging the labeled data in other clients. We theoretically analyze the generalization bound of the proposed FedPU. Empirical experiments show that the FedPU can achieve much better performance than conventional supervised and semi-supervised federated learning methods. Code is available at https://github.com/littleSunlxy/FedPU-torch

Published
2021

8. Manifold Regularized Dynamic Network Pruning

Author

Tang, Yehui, Wang, Yunhe, Xu, Yixing, Deng, Yiping, Xu, Chao, Tao, Dacheng, and Xu, Chang

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Neural network pruning is an essential approach for reducing the computational complexity of deep models so that they can be well deployed on resource-limited devices. Compared with conventional methods, the recently developed dynamic pruning methods determine redundant filters variant to each input instance which achieves higher acceleration. Most of the existing methods discover effective sub-networks for each instance independently and do not utilize the relationship between different inputs. To maximally excavate redundancy in the given network architecture, this paper proposes a new paradigm that dynamically removes redundant filters by embedding the manifold information of all instances into the space of pruned networks (dubbed as ManiDP). We first investigate the recognition complexity and feature similarity between images in the training set. Then, the manifold relationship between instances and the pruned sub-networks will be aligned in the training procedure. The effectiveness of the proposed method is verified on several benchmarks, which shows better performance in terms of both accuracy and computational cost compared to the state-of-the-art methods. For example, our method can reduce 55.3% FLOPs of ResNet-34 with only 0.57% top-1 accuracy degradation on ImageNet., Comment: This paper is accepted by CVPR 2021. Key words: Filter pruning, Dynamic network, Network compression, Manifold regularization

Published
2021

9. Pre-Trained Image Processing Transformer

Author

Chen, Hanting, Wang, Yunhe, Guo, Tianyu, Xu, Chang, Deng, Yiping, Liu, Zhenhua, Ma, Siwei, Xu, Chunjing, Xu, Chao, and Gao, Wen

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

As the computing power of modern hardware is increasing strongly, pre-trained deep learning models (e.g., BERT, GPT-3) learned on large-scale datasets have shown their effectiveness over conventional methods. The big progress is mainly contributed to the representation ability of transformer and its variant architectures. In this paper, we study the low-level computer vision task (e.g., denoising, super-resolution and deraining) and develop a new pre-trained model, namely, image processing transformer (IPT). To maximally excavate the capability of transformer, we present to utilize the well-known ImageNet benchmark for generating a large amount of corrupted image pairs. The IPT model is trained on these images with multi-heads and multi-tails. In addition, the contrastive learning is introduced for well adapting to different image processing tasks. The pre-trained model can therefore efficiently employed on desired task after fine-tuning. With only one pre-trained model, IPT outperforms the current state-of-the-art methods on various low-level benchmarks. Code is available at https://github.com/huawei-noah/Pretrained-IPT and https://gitee.com/mindspore/mindspore/tree/master/model_zoo/research/cv/IPT, Comment: CVPR 2021

Published
2020

10. Triglyceride-rich lipoprotein binding and uptake by heparan sulfate proteoglycan receptors in a CRISPR/Cas9 library of Hep3B mutants.

Author

Anower-E-Khuda, Ferdous, Singh, Gagandeep, Deng, Yiping, Esko, Jeffrey, and Gordts, Philip

Subjects
heparan sulfate 6-O-sulfotransferases, lipoprotein receptors, syndecan-1, triglyceride-rich lipoprotein remnants, CRISPR-Cas Systems, Cell Line, Tumor, Cells, Cultured, Hepatocytes, Humans, Lipoproteins, Loss of Function Mutation, N-Acetylglucosaminyltransferases, Protein Binding, Sulfotransferases, Syndecan-1, Triglycerides
Abstract

Binding and uptake of triglyceride-rich lipoproteins (TRLs) in mice depend on heparan sulfate and the hepatic proteoglycan, syndecan-1 (SDC1). Alteration of glucosamine N-sulfation by deletion of glucosamine N-deacetylase-N-sulfotransferase 1 (Ndst1) and 2-O-sulfation of uronic acids by deletion of uronyl 2-O-sulfotransferase (Hs2st) led to diminished lipoprotein metabolism, whereas inactivation of glucosaminyl 6-O-sulfotransferase 1 (Hs6st1), which encodes one of the three 6-O-sulfotransferases, had little effect on lipoprotein binding. However, other studies have suggested that 6-O-sulfation may be important for TRL binding and uptake. In order to explain these discrepant findings, we used CRISPR/Cas9 gene editing to create a library of mutants in the human hepatoma cell line, Hep3B. Inactivation of EXT1 encoding the heparan sulfate copolymerase, NDST1 and HS2ST dramatically reduced binding of TRLs. Inactivation of HS6ST1 had no effect, but deletion of HS6ST2 reduced TRL binding. Compounding mutations in HS6ST1 and HS6ST2 did not exacerbate this effect indicating that HS6ST2 is the dominant 6-O-sulfotransferase and that binding of TRLs indeed depends on 6-O-sulfation of glucosamine residues. Uptake studies showed that TRL internalization was also affected in 6-O-sulfation deficient cells. Interestingly, genetic deletion of SDC1 only marginally impacted binding of TRLs but reduced TRL uptake to the same extent as treating the cells with heparin lyases. These findings confirm that SDC1 is the dominant endocytic proteoglycan receptor for TRLs in human Hep3B cells and that binding and uptake of TRLs depend on SDC1 and N- and 2-O-sulfation as well as 6-O-sulfation of heparan sulfate chains catalyzed by HS6ST2.

Published
2019

13. The original scores of traditional Chinese medicine constitutions are risk and diagnostic factors in middle‐aged and older adults with sarcopenia.

Author

Nie, Xin, Wang, Chi, Zhang, He, Liu, Qianhui, Hou, Lisha, Deng, Yiping, Ye, Wenbin, Yue, Jirong, and He, Yong

Subjects
RISK assessment, CHINESE medicine, CROSS-sectional method, LIFESTYLES, SELF-evaluation, MEDICAL history taking, PREDICTIVE tests, RESEARCH funding, RECEIVER operating characteristic curves, T-test (Statistics), QUESTIONNAIRES, FUNCTIONAL status, DESCRIPTIVE statistics, MULTIVARIATE analysis, MANN Whitney U Test, CHI-squared test, HUMAN constitution, CLINICAL pathology, ENERGY metabolism, STATISTICS, SOCIODEMOGRAPHIC factors, SARCOPENIA, REGRESSION analysis, OLD age, MIDDLE age
Abstract

Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self‐reported medical history of individuals diagnosed with sarcopenia through a self‐administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi‐deficiency, Yang‐deficiency, Yin‐deficiency, Blood‐stagnation, and Qi‐stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi‐deficiency (in males, OR = 1.126), Yang‐deficiency (OR = 1.062), Phlegm‐dampness (in males, OR = 0.833), and Blood‐stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang‐deficiency and blood‐stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross‐sectional study of older people with higher original Qi‐deficiency, Yin deficiency, Yang‐deficiency, Blood‐stagnation, and Qi‐stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy.

Author

Wang, Chenglong, Li, Tao, Wang, Zhen, Li, Yao, Liu, Yan, Xu, Maochang, Zhang, Zongquan, Deng, Yiping, Cai, Liang, Zhang, Chunxiang, and Li, Chunhong

Abstract

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Sustained Remission and Decreased Severity of CAR T-Cell Related Adverse Events: A Pivotal Study Report of CNCT19 (inaticabtagene autoleucel) Treatment in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-Cell ALL) in China

Author

Wang, Ying, primary, Wei, Xudong, additional, Yan, Dongmei, additional, Zhang, Cheng, additional, Zhou, Hongsheng, additional, Tong, Chunrong, additional, Mei, Heng, additional, Jin, Jie, additional, Niu, Ting, additional, Liang, Aibin, additional, Ren, Jienan, additional, Deng, Yiping, additional, Jin, Wei, additional, Feng, Yi, additional, Shi, Lin, additional, Wang, Yongzeng, additional, Haudenschild, Changting, additional, Lv, Lulu, additional, and Wang, Jianxiang, additional

Published
2022
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19. Investigating Surface Oxide Composition and Formation on Metallic Vibenite® Alloys

Author

Monie, Emil, Säfström, Nils, Deng, Yiping, Möllerberg, Axel, Monie, Emil, Säfström, Nils, Deng, Yiping, and Möllerberg, Axel

Abstract

Oxide formation on metallic surfaces is a common phenomenon which occursnaturally or intently. Depending on the metallic oxide, they can be viewed as either nuisances or conveniences depending on the effects of the oxide. Formed oxides may also potentially smooth surfaces of metallic alloys since a portion of the surface in contact with the oxygen will be converted into the oxide via the metal-oxygeninteraction, leading to a smoother surface underneath the formed oxide. It was found that oxide formation was most significant when metallic Vibenite® alloys were treated at 1000°C for a minimum of 3 hours with an oxygen flow into the oven of 10 L/min. This signifies the importance of a minimum temperature limit as well as an increased oxygen pressure within the oven the samples are being treated in, which concurs with various studies referred to in the report. The oxides were also somewhat successfully identified using analysis methods such as XPS, XRD and Raman spectroscopy with supporting evidence from simulated Thermo-Calc approximations. Thepost-treatment surfaces of the samples, after having their oxide layers removed, were confirmed to have undergone surface smoothing using the optical analysis method of VSI. The results of this report indicate validity in the use of the oxide formation technique for surface smoothing and strongly suggests further study in material optimised heat-treatments for different metallic alloys with the purpose of surface refinement

Published
2022

22. Prognostic characteristics of T-cell mediated cell killing-related genes in lung adenocarcinoma.

Author

Bi, Lei, Ai, Cheng, Zhang, Hong, Chen, Zhengyu, Deng, Yiping, Xiong, Jing, and Lv, Zhongzhu

Subjects
DISEASE risk factors, T cells, PROGNOSTIC models, PROGNOSIS, GENE ontology, REGRESSION analysis, BIOLOGICAL crosstalk
Abstract

Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive crosstalk. The pivotal factor influencing the survival time of patients and their response to immunotherapy lies in the intratumoral immune environment. We obtained 112 differential genes related to T cell-mediated tumor killing in LUAD by employing bioinformatics analysis on the basis of the TCGA and TISIDB databases. Then the 6-gene prognostic risk score model (CA9, OIP5, TIMP1, SEC11C, FURIN, and TLR10) was constructed by conducting univariate LASSO as well as multivariate Cox regression analyses. The median risk score was taken as the threshold to classify the samples into two groups. Survival analysis revealed that the low-risk group exhibited a more favorable prognosis. Subsequently, the Cox regression analysis combined with clinical information (age, gender, and pathological stage) and the risk score of LUAD patients demonstrated the potential of this model as an independent prognostic factor. The nomogram established based on clinical information and a risk score in combination with the calibration curve indicated that this model had good predictive ability. Notable enrichment of the differential genes from the high- and low-risk groups was discovered in immune-associated processes or pathways, as shown by the GO and KEGG enrichment analyses. The combined use of single-sample gene enrichment analysis (ssGSEA) and immunophenoscore (IPS) demonstrated heightened immune infiltration and IPS scores in the low-risk group, indicating that immunotherapy was likely to show good efficacy in patients from this group. To sum up, the prognostic model of LUAD constructed based on T-cell-mediated cell killing-related genes was not only capable of screening the prognosis of LUAD patients but was also used for screening those LUAD patients with high sensitivity to immunotherapy. Our study offered novel insights into the clinical treatment and prognostic prediction of LUAD patients. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Liquid antisolvent precipitation: an effective method for ocular targeting of lutein esters

Author

Wu,Mingfang, Feng,Ziqi, Deng,Yiping, Zhong,Chen, Liu,Yanjie, Liu,Jiaying, Zhao,Xiuhua, Fu,Yujie, Wu,Mingfang, Feng,Ziqi, Deng,Yiping, Zhong,Chen, Liu,Yanjie, Liu,Jiaying, Zhao,Xiuhua, and Fu,Yujie

Abstract

Mingfang Wu,1,* Ziqi Feng,1,* Yiping Deng,1 Chen Zhong,2 Yanjie Liu,1 Jiaying Liu,1 Xiuhua Zhao,1 Yujie Fu1 1Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, Heilongjiang, China; 2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China *These authors contributed equally to this work Background: Lutein ester (LE) is an important carotenoid fatty acid ester. It is a form in which lutein is present in nature and is produced by free non-esterification and fatty acid esterification. LE is one of the safe sources of lutein. Increasing lutein intake can prevent and treat age-related macular degeneration. In addition, it can effectively inhibit gastric cancer, breast cancer, and esophageal cancer. However, the poor aqueous solubility of LE has impeded its clinical applications.Objective: The objective of this study was to prepare lutein ester nanoparticles (LE-NPs) by liquid antisolvent precipitation techniques to improve the bioavailability of LE in vivo and improve eye delivery efficiency.Materials and methods: The physical characterization of LE-NPs was performed, and their in vitro dissolution rate, in vitro antioxidant capacity, in vivo bioavailability, tissue distribution, and ocular pharmacokinetics were studied and evaluated.Results: The LE freeze-dried powder obtained under the optimal conditions possessed a particle size of ~164.1±4.3 nm. The physical characterization analysis indicated the amorphous form of LE-NPs. In addition, the solubility and dissolution rate of LE-NPs in artificial gastric juice were 12.75 and 9.65 times that of the raw LE, respectively. The bioavailability of LE-NPs increased by 1.41 times compared with that of the raw LE. The antioxidant capacity of LE-NPs was also superior to the raw LE. The concentration of lutein in the main organs of rats treated with the LE-NPs was higher than that in rats treated with the raw

Published
2019

29. Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability.

Author

Wu, Mingfang, Zhong, Chen, Deng, Yiping, Zhang, Qian, Zhang, Xiaoxue, and Zhao, Xiuhua

Subjects
SERUM albumin, RESVERATROL, HIGH performance liquid chromatography, BIOAVAILABILITY, PHARMACOKINETICS
Abstract

There are many kinds of biological activities of resveratrol itself, but its clinical application is limited by its poor solubility in water and low bioavailability. Therefore, we have prepared glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles (GL-HSA-RESNPs). The purpose of this study was to investigate the bioavailability, pharmacokinetics and tissue distribution of resveratrol in rats after single-dose tail vein injection administration of GL-HSA-RESNPs. A sensitive and reliable high performance liquid chromatography (HPLC) method was established to verify the content of resveratrol in rat plasma and organs. The Cmax value after GL-HSA-RESNPs administration was significantly higher than that of resveratrol suspension (933 ± 76.64 ng/mL vs. 618 ± 42.54 ng/mL, p <.01). The Tmax value obtained after GL-HSA-RESNPs administration was significantly shorter than that after resveratrol suspension administration (0.17 ± 0.01 h vs. 0.25 ± 0.01 h, p <.001). The bioavailability of GL-HSA-RESNPs was 4.25 times higher than that of the pure resveratrol. The concentration of resveratrol in the main organs of rats treated with the GL-HSA-RESNPs was higher than that in rats treated with the pure resveratrol. Rats treated with GL-HSA-RESNPs had the highest concentration of resveratrol in their liver. It is indicated that GL-HSA-RESNPs is a promising liver-targeted delivery system that improves the in vivo bioavailability of resveratrol. [ABSTRACT FROM AUTHOR]

Published
2020
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30. Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s–PPARα axis signalling

Author

Shao, Mengle, primary, Shan, Bo, additional, Liu, Yang, additional, Deng, Yiping, additional, Yan, Cheng, additional, Wu, Ying, additional, Mao, Ting, additional, Qiu, Yifu, additional, Zhou, Yubo, additional, Jiang, Shan, additional, Jia, Weiping, additional, Li, Jingya, additional, Li, Jia, additional, Rui, Liangyou, additional, Yang, Liu, additional, and Liu, Yong, additional

Published
2014
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31. Preparation of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles for hepatocellular carcinoma-targeted drug delivery

Author

Zu,Yuangang, Meng,Li, Zhao,Xiuhua, Ge,Yunlong, Yu,Xinyang, Zhang,Yin, Deng,Yiping, Zu,Yuangang, Meng,Li, Zhao,Xiuhua, Ge,Yunlong, Yu,Xinyang, Zhang,Yin, and Deng,Yiping

Abstract

Yuangang Zu, Li Meng, Xiuhua Zhao, Yunlong Ge, Xinyang Yu, Yin Zhang, Yiping Deng Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, People’s Republic of China Introduction: The livertaxis of glycyrrhizic acid-conjugated bovine serum albumin (GL-BSA) has been reported in the literature. Now, in this paper, we describe a novel type of drug-targeted delivery system containing 10-hydroxycamptothecin (HCPT) with liver tumor targeting. Methods: First, GL was coupled to BSA then HCPT was encapsulated in GL-BSA by high-pressure homogenization emulsification. In the experimental design, the influencing variables on particle size and drug loading efficiency were determined to be BSA concentration, volume ratio of water to organic phase, and speed and speed duration of homogenization as well as homogenization pressure and the number of times homogenized at certain pressures. Particle size plays an important role in screening optimal conditions of nanoparticles preparation. Characteristics of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles (GL-BSA-HCPT-NPs), such as the drug encapsulation efficiency, drug loading efficiency, and GL-BSA content were studied. In addition, the morphology of the nanoparticles (NPs) and weight loss rate were determined and Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy, and thermal analysis performed. Results: The average particle size of the sample NPs prepared under optimal conditions was 157.5 nm and the zeta potential was −22.51 ± 0.78 mV; the drug encapsulation efficiency and drug loading efficiency were 93.7% and 10.9%, respectively. The amount of GL coupling to BSA was 98.26 µg/mg. Through physical property study of the samples, we determined that the HCPT had been successfully wrapped in GL-BSA. In vitro drug-release study showed that the nanoparticles could release the drug slowl

Published
2013

33. Traditional Chinese medicine constitution and sarcopenia: a cross-sectional study.

Author

Wang C, Zhang H, Nie X, Ding F, Liu Q, Hou L, Deng Y, Ye W, Yue J, and He Y

Subjects
Humans, Cross-Sectional Studies, Female, Male, Aged, Middle Aged, Yin Deficiency diagnosis, ROC Curve, Aged, 80 and over, Sarcopenia diagnosis, Medicine, Chinese Traditional
Abstract

Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution., Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis., Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707., Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Nie, Ding, Liu, Hou, Deng, Ye, Yue and He.)

Published
2024
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34. Enhanced Solubility and Bioavailability of Apigenin via Preparation of Solid Dispersions of Mesoporous Silica Nanoparticles.

Author

Huang Y, Zhao X, Zu Y, Wang L, Deng Y, Wu M, and Wang H

Abstract

In this study, a novel mesoporous silica nanoparticles drug carrier contributes to improving the solubility, dissolution, and the oral bioavailability of apigenin (AP). The apigenin of solid dispersion of mesoporous silica nanoparticles (AP-MSN) was prepared by physical absorption method and also, in-vitro drug release and in-vivo bioavailability performance were evaluated. Based on its solubility, the AP-MSN solid dispersion was prepared at the weight ratio of 1:1 to obtain the optimum solubility. The loading efficiency (LE), encapsulation efficiency (EE), and solubility of AP-MSN solid dispersion were 29.71%, 42.27%, and 25.11 µg/mL, respectively. SEM, TEM, BET, FTIR, XRD, DSC, and TG were also carried out. These results demonstrated that AP was good absorbed into the pores of MSN through physical absorption effect of MSN. The DMF residues of AP-MSN solid dispersion meet the ICH requirements. It was vital that the AP-MSN solid dispersion behaved well in-vitro and the accumulative release of AP-MSN solid dispersion was 2.37 times higher than that of raw AP. In-vivo study, the AP area under curve 0-t was 8.32 times higher for the AP-MSN solid dispersion than that of raw AP, which indicated that the bioavailability of AP-MSN solid dispersion was greatly improved. Therefore, the prepared AP-MSN solid dispersion presents potential as a novel oral therapeutic agent formulation for clinical application.

Published
2019

35. Preparation of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles for hepatocellular carcinoma-targeted drug delivery.

Author

Zu Y, Meng L, Zhao X, Ge Y, Yu X, Zhang Y, and Deng Y

Subjects
Animals, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacokinetics, Camptothecin administration & dosage, Camptothecin chemistry, Camptothecin pharmacokinetics, Carcinoma, Hepatocellular drug therapy, Cattle, Cell Line, Tumor, Drug Carriers administration & dosage, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Glycyrrhizic Acid administration & dosage, Hemolysis drug effects, Humans, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Nanoparticles administration & dosage, Particle Size, Rabbits, Serum Albumin, Bovine administration & dosage, Camptothecin analogs & derivatives, Carcinoma, Hepatocellular metabolism, Glycyrrhizic Acid chemistry, Nanoparticles chemistry, Serum Albumin, Bovine chemistry
Abstract

Introduction: The livertaxis of glycyrrhizic acid-conjugated bovine serum albumin (GL-BSA) has been reported in the literature. Now, in this paper, we describe a novel type of drug-targeted delivery system containing 10-hydroxycamptothecin (HCPT) with liver tumor targeting., Methods: First, GL was coupled to BSA then HCPT was encapsulated in GL-BSA by high-pressure homogenization emulsification. In the experimental design, the influencing variables on particle size and drug loading efficiency were determined to be BSA concentration, volume ratio of water to organic phase, and speed and speed duration of homogenization as well as homogenization pressure and the number of times homogenized at certain pressures. Particle size plays an important role in screening optimal conditions of nanoparticles preparation. Characteristics of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles (GL-BSA-HCPT-NPs), such as the drug encapsulation efficiency, drug loading efficiency, and GL-BSA content were studied. In addition, the morphology of the nanoparticles (NPs) and weight loss rate were determined and Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy, and thermal analysis performed., Results: The average particle size of the sample NPs prepared under optimal conditions was 157.5 nm and the zeta potential was -22.51 ± 0.78 mV; the drug encapsulation efficiency and drug loading efficiency were 93.7% and 10.9%, respectively. The amount of GL coupling to BSA was 98.26 μg/mg. Through physical property study of the samples, we determined that the HCPT had been successfully wrapped in GL-BSA. In vitro drug-release study showed that the nanoparticles could release the drug slowly and continuously. Hemolysis testing showed the safety of GL-BSA as a novel drug delivery system. The targeting properties of GL-BSA-HCPT-NPs were studied in an in vitro cell uptake study and cell proliferation assay. Cells incubated with GL-BSA-HCPT-NPs and labeled with fluorescein isothiocyanate showed more extensive fluorescence spots and stronger fluorescence intensity than samples without GL conjugation. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the inhibitory rate of the samples. It was found that the inhibitory rate of GL-BSA-HCPT-NPs develops as concentration rises. Further, the inhibitory rate of GL-BSA-HCPT-NPs was higher at the same concentration and had a lower half maximal inhibitory concentration value than the other samples. The half maximal inhibitory concentration values of GL-BSA-HCPT-NPs, BSA-HCPT-NPs, and HCPT sodium were 0.78 ± 0.015, 1.62 ± 0.039, and 7.93 ± 0.255 μg/mL, respectively., Conclusion: The results of this study show GL-BSA-HCPT to be a promising new vehicle for hepatocellular carcinoma-targeting therapy.

Published
2013
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