Publications by authors named "Xiao Dong"

600 Publications

Cell-penetrating Mitochondria-targeting Ligands for Universal Delivery of Small Molecules, Proteins and Nanomaterials.

Chemistry 2021 Jun 11. Epub 2021 Jun 11.

National University of Singapore, Department of Chemistry, 3 Science Dr., 117543, Singapore, SINGAPORE.

Mitochondria are key organelles that perform vital cellular functions such as cell survival and death. Targeted delivery of different types of cargos to mitochondria is a well-established strategy to study mitochondrial biology and diseases. Of various existing mitochondria-transporting vehicles, most of them suffered from poor cytosolic entry, low delivery efficiency, limited cargo types, and cumbersome preparation protocols, and none was known to be universally applicable for mitochondrial delivery of different types of cargos (small molecules, proteins and nanomaterials). Herein, we disclose two new cell-penetrating mitochondria-targeting ligands (named MitoLigand), as well as their corresponding chemoselective conjugation chemistry, that are capable of effectively "tagging" small- molecule drugs, native proteins and nanomaterials. Upon successful cellular delivery and rapid endosome escape, the released native cargos were found to be predominantly localized inside mitochondria. Finally, by successfully delivering doxorubicin, a well-known anticancer drug, to the mitochondria of HeLa cells, we showed the released drug possessed potent cell cytotoxicity, caused disruption of mitochondrial membrane potential and finally led to cell apoptosis. Our strategy thus paves the way for future mitochondria-targeted therapy with a variety of biologically active agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202101989DOI Listing
June 2021

Self-Training Enhanced: Network Embedding and Overlapping Community Detection With Adversarial Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Network embedding (NE) aims to encode the relations of vertices into a low-dimensional space. After NE, we can obtain the learned vectors of vertices that preserve the proximity of network structures for subsequent applications, e.g., vertex classification and link prediction. In existing NE models, they usually exploit the skip-gram with a negative sampling method to optimize their objective functions. Generally, this method learns the vertex representation only from the local connectivity of vertices (i.e., neighbors). However, there is a larger scope of vertex connectivity in real-world scenarios: a vertex may have multifaceted aspects and should belong to overlapping communities. Taking a social network as the overlapping example, a user may subscribe to the channels of politics, economy, and sports simultaneously, but the politics share more common attributes with the economy and less with the sports. In this article, we propose an adversarial learning approach (ACNE) for modeling overlapping communities of vertices. Specifically, we map the association between communities and vertices into an embedding space. Moreover, we take further research on enhancing our ACNE with the following two operations. First, in the initialization stage, we adopt a walking strategy with perception to obtain paths containing more possible boundary vertices to improve overlapping community detection. Then, after representation learning with ACNE, we use soft community assignments from a simple classifier as supervision to update the weights of ACNE. This self-training mechanism referred to as ACNE-ST can help ACNE to achieve better performance. Experimental results demonstrate that the proposed methods, including ACNE and ACNE-ST, can outperform the state-of-the-art models on the subsequent tasks of vertex classification and overlapping community detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNNLS.2021.3083318DOI Listing
June 2021

Output-Related and -Unrelated Fault Monitoring with an Improvement Prototype Knockoff Filter and Feature Selection Based on Laplacian Eigen Maps and Sparse Regression.

ACS Omega 2021 Apr 19;6(16):10828-10839. Epub 2021 Apr 19.

College of Information Science and Engineering and Liaoning Key Laboratory of Intelligent Diagnosis and Safety for Metallurgical Industry, Northeastern University, Shenyang 110819, China.

In the process industry, fault monitoring related to output is an important step to ensure product quality and improve economic benefits. In order to distinguish the influence of input variables on the output more accurately, this paper introduces a subalgorithm of fault-unrelated block partition into the prototype knockoff filter (PKF) algorithm for its improvement. The improved PKF algorithm can divide the input data into three blocks: fault-unrelated block, output-related block, and output-unrelated block. Removing the data of fault-unrelated blocks can greatly reduce the difficulty of fault monitoring. This paper proposes a feature selection based on the Laplacian Eigen maps and sparse regression algorithm for output-unrelated blocks. The algorithm has the ability to detect faults caused by variables with small contribution to variance and proves the descent of the algorithm from a theoretical point of view. The output relation block is monitored by the Broyden-Fletcher-Goldfarb-Shanno method. Finally, the effectiveness of the proposed fault detection method is verified by the recognized Eastman process data in Tennessee.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c00506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153765PMC
April 2021

Endoscopic Endonasal Transclival Approach to Ventral Pontine Cavernous Malformation: Case Report.

Front Surg 2021 12;8:654837. Epub 2021 May 12.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Ventral medial pontine cavernous malformations are challenging due to the location in eloquent tissue, surrounding critical anatomy, and potential symptomatic bleeding. Conventional approaches, such as anterolateral, lateral and dorsal approach, are associated with high risk of deleterious consequences due to excessive traction and damage to the surrounding tissues. The authors present an endoscopic endonasal approach for the resection of midline ventral pontine cavernous malformations, which follows principles of optimal access to brainstem cavernous malformations as the "two-point method." No CSF leak or any other complications are obtained. The successful outcomes indicate that an individualized approach should be chosen before the surgery for brainstem cavernous malformations. With the advance of techniques, endoscopic endonasal approach could provide the most direct route to ventral pontine lesions with safety and efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fsurg.2021.654837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149788PMC
May 2021

S-nitrosated proteomic analysis reveals the regulatory roles of protein S-nitrosation and S-nitrosoglutathione reductase during Al-induced PCD in peanut root tips.

Plant Sci 2021 Jul 29;308:110931. Epub 2021 Apr 29.

College of Agronomy, Guangxi University, Nanning, China; Guangxi Key Laboratory for Agro-Environment and Agro-Product Safety, Nanning, China. Electronic address:

Nitric oxide-mediated S-nitrosation through S-nitrosoglutathione reductase (GSNOR) plays important roles in cellular processes and signaling of plants; however, the regulatory mechanism of programmed cell death (PCD) by S-nitrosation remains unclear. In this study, the S-nitrosated proteomic and functions of GSNOR during Al-induced PCD in peanut were investigated. Al stress induced an increase of S-nitrosothiol (SNO) content and GSNOR activity in Al-induced PCD. There was significant positive correlation between SNO content and hydrogen peroxide content. The S-nitrosated proteomic analysis identified 402 S-nitrosated proteins containing 551 S-nitrosated sites during Al-induced PCD in the root tips of peanut. These S-nitrosated proteins were involved in regulation of various biological processes including energy metabolism, maintenance of cell wall function and organic acid secretion. Among them, 128 S-nitrosated proteins were up-regulated and one was down-regulated after Al stress. Experiments with recombinant AhGSNOR revealed that activity of the enzyme was inhibited by its S-nitrosation, with a moderate decrease of 17.9 % after 100 μM GSNO incubation. These data provide novel insights to understanding the functional mechanism of NO-mediated S-nitrosation during plant PCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plantsci.2021.110931DOI Listing
July 2021

Age-related telomere attrition causes aberrant gene expression in sub-telomeric regions.

Aging Cell 2021 May 21:e13357. Epub 2021 May 21.

Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.

Telomere attrition has been proposed as a biomarker and causal factor in aging. In addition to causing cellular senescence and apoptosis, telomere shortening has been found to affect gene expression in subtelomeric regions. Here, we analyzed the distribution of age-related differentially expressed genes from the GTEx RNA sequencing database of 54 tissue types from 979 human subjects and found significantly more upregulated than downregulated genes in subtelomeric regions as compared to the genome-wide average. Our data demonstrate spatial relationships between telomeres and gene expression in aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13357DOI Listing
May 2021

Normalizing Clinical Document Titles to LOINC Document Ontology: an Initial Study.

AMIA Annu Symp Proc 2020 25;2020:1441-1450. Epub 2021 Jan 25.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.

The normalization of clinical documents is essential for health information management with the enormous amount of clinical documentation generated each year. The LOINC Document Ontology (DO) is a universal clinical document standard in a hierarchical structure. The objective of this study is to investigate the feasibility and generalizability of LOINC DO by mapping from clinical note titles across five institutions to five DO axes. We first developed an annotation framework based on the definition of LOINC DO axes and manually mapped 4,000 titles. Then we introduced a pre-trained deep learning model named Bidirectional Encoder Representations from Transformers (BERT) to enable automatic mapping from titles to LOINC DO axes. The results showed that the BERT-based automatic mapping achieved improved performance compared with the baseline model. By analyzing both manual annotations and predicted results, ambiguities in LOINC DO axes definition were discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075502PMC
January 2021

Molecular identification of common hard ticks (Acari: Ixodidae) in Xinjiang, China.

Zootaxa 2021 Mar 29;4950(1):zootaxa.4950.1.2. Epub 2021 Mar 29.

Department of Emergency Response and Plague Control, Xinjiang Center for Disease Control and Prevention, Urumqi 830002, China.

We provide data on the cytochrome c oxidase subunit I (COI) and 16S rDNA genes for eight species of common hard ticks in Xinjiang: Dermacentor montanus, D. niveus, Haemaphysalis sulcate, Hyalomma asiaticum asiaticum, Hya. detritum, Hya. scupense, Rhipicephalus sanguineus and R. pumilio. Genetic distances, calculated based on the Kimura two-parameter (K2P) distance model, found the same trend of intraspecies level≤interspecies levelintragenus level. Phylogenetic trees, constructed with the neighbor-joining (NJ) and minimum-evolution (ME) methods, demonstrated that each species clustered into separate clades, thus confirming the usefulness of CO1 and 16S rDNA genes for tick species identification. The genera Dermacentor, Haemaphysalis and Rhipicephalus were all recovered in the phylogenetic analysis, as was the subfamily Rhipicephalinae, but a monophyletic Hyalomma was not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11646/zootaxa.4950.1.2DOI Listing
March 2021

Non-in Situ Technique of Heart-lung Transplantation: Case Series and Technique Description.

Ann Thorac Surg 2021 Apr 23. Epub 2021 Apr 23.

Department of Thoracic Surgery/Oncology, State Key Laboratory and National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address:

Purpose: Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively.

Description: Between September 2015 and September 2020, twelve patients without previous heart surgery, underwent a traditional HLTx, were divided into a control group. Three patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the length of intensive care unit (ICU) and hospital stay were assessed between traditional surgery and non-in situ HLTx.

Evaluation: The innovative non-in situ HLTx was successfully performed in the three cases. We found that the length of ICU and hospital stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the three cases compared with the traditional surgery.

Conclusion: Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2021.03.101DOI Listing
April 2021

Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy.

Adv Sci (Weinh) 2021 04 1;8(8):2003679. Epub 2021 Mar 1.

Hongqiao International Institute of Medicine Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of Medicine Shanghai 200025 China.

Photodynamic therapy (PDT) of cancer is limited by tumor hypoxia. Platinum nanoparticles (nano-Pt) as a catalase-like nanoenzyme can enhance PDT through catalytic oxygen supply. However, the cytotoxic activity of nano-Pt is not comprehensively considered in the existing methods to exert their multifunctional antitumor effects. Here, nano-Pt are loaded into liposomes via reverse phase evaporation. The clinical photosensitizer verteporfin (VP) is loaded in the lipid bilayer to confer PDT activity. Murine macrophage cell membranes are hybridized into the liposomal membrane to confer biomimetic and targeting features. The resulting liposomal system, termed "nano-Pt/[email protected]," is investigated for chemophototherapy in vitro and in vivo in mouse tumor models. At the tumor site, oxygen produced by nano-Pt catalyzation improves the VP-mediated PDT, which in turn triggers the release of nano-Pt via membrane permeabilization. The ultrasmall 3-5 nm nano-Pt enables better penetration in tumors, which is also facilitated by the generated oxygen gas, for enhanced chemotherapy. Chemophototherapy with a single injection of nano-Pt/[email protected] and light irradiation inhibits the growth of aggressive 4T1 tumors and their lung metastasis, and prolongs animal survival without overt toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202003679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061387PMC
April 2021

LncRNA MNX1-AS1 drives aggressive laryngeal squamous cell carcinoma progression and serves as a ceRNA to target FoxM1 by sponging microRNA-370.

Aging (Albany NY) 2021 03 19;13(7):9900-9910. Epub 2021 Mar 19.

Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun 130021, China.

Long non-coding RNA (LncRNA) MNX1 antisense RNA 1(MNX1-AS1) is associated with the pathology of numerous cancers. But, the role and underlying pathways of MNX1-AS1 in the regulation of laryngeal squamous cell carcinoma (LSCC) is not known. We demonstrated remarkably elevated levels of MNX1-AS1 in the LSCC tissues, which was correlated with poor disease prognosis. Moreover, MNX1-AS1-silencing strongly suppressed LSCC cell proliferation, migration, and invasion. We also demonstrated that MNX1-AS1 sequesters that activity of miR-370, thereby releasing Forkhead Box ml (FoxM1) from the inhibitory actions of MNX1-AS1. Furthermore, the positive correlation of MNX1-AS1 and FoxM1 as well as the converse correlation between miR-370 and MNX1-AS1 (or FoxM1) were revealed in LSCC tissues using experiments. Based on rescue assays, FoxM1 overexpression or miR-370 downregulation partially recovered the inhibitory effect of MNX1-AS1 silencing on LSCC cells. Moreover, knockdown of MNX1-AS1 retarded tumor growth in nude mice model. In summary, these findings verified that MNX1-AS1 modulated LSCC progression by competitively binding with miR-370 to regulate FoxM1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064170PMC
March 2021

LINC01303 promotes the proliferation and migration of laryngeal carcinoma by regulating miR-200c/TIMP2 axis.

Am J Transl Res 2021 15;13(3):1643-1656. Epub 2021 Mar 15.

Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University Changchun 130021, People's Republic of China.

Background: It is reported that long non-coding RNA is crucial in many cancer progressions. But the function and regulatory mechanism of LINC01303 in human laryngeal squamous cell carcinoma (LSCC) remains unclear. Hence, this research aims at investigating the biological function and potential mechanism of LINC01303 in LSCC.

Methods: Real-time quantitative PCR (qRT-PCR) was applied for the determination of LINC01303, miR-200c and TIMP metallopeptidase inhibitor 2 (TIMP2) expression in LSCC tissues and cell lines. Corresponding experiments were carried out to determine the impacts of LINC01303 on LSCC cell proliferation, apoptosis, migration and invasion. The interaction between LINC01303 and miR-200c was analyzed with bioinformatics analysis and luciferase activity analysis.

Results: LINC01303 expression in LSCC tissues was notably higher than that in adjacent normal tissues. High LINC01303 expression was bound up with lymphatic metastasis and advanced clinical stage. In addition, inhibition of LINC01303 by siRNA could evidently block LSCC cell proliferation, induce apoptosis, and inhibit invasion and migration. Mechanically, LINC01303 acted as carcinogenic lncRNA in LSCC by regulating miR-200c/TIMP2 axis.

Conclusion: LINC01303 plays a carcinogenic part in LSCC carcinogenesis through regulating miR-200c/TIMP2 axis, which may become a promising target of LSCC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014399PMC
March 2021

Early enteral feeding versus traditional feeding in neonatal congenital gastrointestinal malformation undergoing intestinal anastomosis: A randomized multicenter controlled trial of an enhanced recovery after surgery (ERAS) component.

J Pediatr Surg 2021 Mar 18. Epub 2021 Mar 18.

Department of Neonatal Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China. Electronic address:

Purpose: the aim of this clinical trial was to evaluate the safety and efficacy of early enteral feeding (EEN) following intestinal anastomosis in neonates with congenital gastrointestinal malformation.

Methods: a multicenter, prospective, randomized controlled trial (registered under chictr.org.cn Identifier no.ChiCTR-INR-17014179) was conducted between 2018 and 2019. Four centers in China analyzed 156 newborns of congenital gastrointestinal malformation undergoing intestinal anastomosis to EEN group (n = 78) or control (C) group (n = 78). The primary outcomes of this study were length of postoperative stay (LOPS) and time to full feeds. Secondary outcomes included morbidity of complications, parenteral nutrition (PN) duration, feeding intolerance, 30 day mortality rate and 30 day readmission rate.

Results: the mean time to full feeds and LOPS in the EEN group were 15.0 (9.8-22.8) days and 17.6 (12.0-29.8) days, while that were 18.0 (12.0-24.0) days and 20.0 (15.0-30.3) days in C groups respectively. There was no significant difference between two groups(P >0.05). No significant intergroup difference was found with respect to postoperative morbidity, PN duration or feeding intolerance(P >0.05).

Conclusions: early enteral feeding following intestinal anastomosis in neonates with congenital gastrointestinal malformation is safe. Post-operative outcomes demonstrated a trend toward improvement.

Level Of Evidence: Level Ⅰ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2021.02.067DOI Listing
March 2021

Tumor suppressor DCAF15 inhibits epithelial-mesenchymal transition by targeting ZEB1 for proteasomal degradation in hepatocellular carcinoma.

Aging (Albany NY) 2021 04 4;13(7):10603-10618. Epub 2021 Apr 4.

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Epithelial-mesenchymal transition (EMT) is an evolutionarily conserved developmental program that has been implicated in tumorigenesis and confers metastatic properties upon cancer cells. ZEB1 is a master transcription factor that activates the EMT process in various cancers. ZEB1 is reportedly degraded through the ubiquitin proteasome pathway, but the underlying molecular mechanism of this process remains largely unknown in hepatocellular carcinoma (HCC). Here, we identified ZEB1 as a substrate of the CRL4-DCAF15 (DDB1 and CUL4 associated factor 15) E3 ubiquitin ligase complex. DCAF15 acts as an adaptor that specifically recognizes the N-terminal zinc finger domain of ZEB1, then triggers its degradation via the ubiquitin-proteasome pathway. DCAF15 knockdown led to upregulation of ZEB1 and activation of EMT, whereas overexpression of DCAF15 suppressed ZEB1 and inhibited EMT. DCAF15 knockdown also promoted HCC cell proliferation and invasion in a ZEB1-dependent manner. In HCC patients, low DCAF15 expression was predictive of an unfavorable prognosis. These findings reveal the distinct molecular mechanism by which DCAF15 suppresses HCC malignancy and provides insight into the relationship between the CUL4-DCAF15 E3 ubiquitin ligase complex and ZEB1 in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064142PMC
April 2021

Endothelial Wnts control mammary epithelial patterning via fibroblast signaling.

Cell Rep 2021 Mar;34(13):108897

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:

Endothelial and fibroblast niches are crucial for epithelial organs. How these heterotypic cells interact is of great interest. In this study, we reveal an axis of signaling in which fibroblasts relay Wnt signals from the endothelial niche to organize epithelial patterning. We generate an Axin2-membrane GFP (mGFP) reporter mouse and observe robust Wnt/β-catenin signaling activities in fibroblasts surrounding the mammary epithelium. To enable cell-type-specific gene manipulation in vitro, we establish an organoid system via coculture of endothelial cells (ECs), fibroblasts, and mammary epithelial cells. Deletion of β-catenin in fibroblasts impedes epithelium branching, and ECs are responsible for the activation of Wnt/β-catenin signaling in fibroblasts. In vivo, EC deletion of Wntless inhibits Wnt/β-catenin signaling activity in fibroblasts, rendering a reduction in epithelial branches. These findings highlight the significance of the endothelial niche in tissue patterning, shedding light on the interactive mechanisms in which distinct niche components orchestrate epithelial organogenesis and tissue homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.108897DOI Listing
March 2021

Recent Advances in Polymeric Nanoparticles for Enhanced Fluorescence and Photoacoustic Imaging.

Angew Chem Int Ed Engl 2021 Mar 11. Epub 2021 Mar 11.

Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544, Singapore.

In recent years, polymeric nanoparticles (NPs) have become increasingly popular for in vitro and in vivo bioimaging because of their excellent versatility and exceptional optical properties. Following a brief introduction on fluorescence and photoacoustic imaging, as well as the merits of using polymeric NPs over other types of fluorescent probes, this Minireview gives a concise summary of key advances made in recent years (2017-2020) in the use of polymeric NPs for fluorescence and photoacoustic imaging. A particular focus is placed on various strategies used for enhanced bioimaging applications, including polymeric NPs that encapsulate near-infrared dyes, aggregation-induced-emission fluorogens, cationic dyes doped with bulky hydrophobic counterions, and semiconducting polymers. Next, the current limitations in some of these polymeric NP systems are summarized and potential solutions offered to overcome them. Finally, some critical considerations in regard to the design of polymeric NPs are given for future bioimaging and sensing applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202101964DOI Listing
March 2021

An updated review of autophagy in ischemic stroke: From mechanisms to therapies.

Exp Neurol 2021 Jun 5;340:113684. Epub 2021 Mar 5.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, China; Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Stroke is a leading cause of mortality and morbidity worldwide. Understanding the underlying mechanisms is important for developing effective therapies for treating stroke. Autophagy is a self-eating cellular catabolic pathway, which plays a crucial homeostatic role in the regulation of cell survival. Increasing evidence shows that autophagy, observed in various cell types, plays a critical role in brain pathology after ischemic stroke. Therefore, the regulation of autophagy can be a potential target for ischemic stroke treatment. In the present review, we summarize the recent progress that research has made regarding autophagy and ischemic stroke, including common signaling pathways, the role of autophagic subtypes (e.g. mitophagy, pexophagy, aggrephagy, endoplasmic reticulum-phagy, and lipophagy) in ischemic stroke, as well as the current methods for autophagy detection and potential therapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2021.113684DOI Listing
June 2021

Direct Arylation of Azoles Enabled by Pd/Cu Dual Catalysis.

Org Lett 2021 03 5;23(6):1996-2001. Epub 2021 Mar 5.

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

A practical approach toward the synthesis of 2-arylazoles via direct arylation is described. The transformation relies on a Pd/Cu cocatalyst system that operates with low catalyst loadings. The reaction conditions were found to be tolerant of a wide range of functional groups and nitrogen-containing heterocycles commonly employed in a drug discovery setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00100DOI Listing
March 2021

IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.

Mol Ther Oncolytics 2021 Mar 19;20:187-198. Epub 2020 Dec 19.

Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both and . We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889451PMC
March 2021

Transcriptome analysis reveals significant difference in gene expression and pathways between two peanut cultivars under Al stress.

Gene 2021 May 23;781:145535. Epub 2021 Feb 23.

National Demonstration Center for Experimental Plant Science Education, College of Agriculture, Guangxi University, Nanning 530004, PR China; Guangxi Key Laboratory for Agro-Environment and Agro-Product Safety, Nanning 530004, PR China. Electronic address:

Aluminum (Al) toxicity is an important factor in limiting peanut growth on acidic soil. The molecular mechanisms underlying peanut responses to Al stress are largely unknown. In this study, we performed transcriptome analysis of the root tips (0-1 cm) of peanut cultivar ZH2 (Al-sensitive) and 99-1507 (Al-tolerant) respectively. Root tips of peanuts that treated with 100 μM Al for 8 h and 24 h were analyzed by RNA-Seq, and a total of 8,587 differentially expressed genes (DEGs) were identified. GO and KEGG pathway analysis excavated a group of important Al-responsive genes related to organic acid transport, metal cation transport, transcription regulation and programmed cell death (PCD). These homologs were promising targets to modulate Al tolerance in peanuts. It was found that the rapid transcriptomic response to Al stress in 99-1507 helped to activate effective Al tolerance mechanisms. Protein and protein interaction analysis indicated that MAPK signal transduction played important roles in the early response to Al stress in peanuts. Moreover, weighted correlation network analysis (WGCNA) identified a predicted EIL (EIN3-like) gene with greatly increased expression as an Al-associated gene, and revealed a link between ethylene signaling transduction and Al resistance related genes in peanut, which suggested the enhanced signal transduction mediated the rapid transcriptomic responses. Our results revealed key pathways and genes associated with Al stress, and improved the understanding of Al response in peanut.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145535DOI Listing
May 2021

A fully automated rib fracture detection system on chest CT images and its impact on radiologist performance.

Skeletal Radiol 2021 Feb 18. Epub 2021 Feb 18.

Shanghai United Imaging Intelligence Co.,Ltd., Shanghai, 201210, China.

Objective: To compare rib fracture detection and classification by radiologists using CT images with and without a deep learning model.

Materials And Methods: A total of 8529 chest CT images were collected from multiple hospitals for training the deep learning model. The test dataset included 300 chest CT images acquired using a single CT scanner. The rib fractures were marked in the bone window on each CT slice by experienced radiologists, and the ground truth included 861 rib fractures. We proposed a heterogeneous neural network for rib fracture detection and classification consisting of a cascaded feature pyramid network and a classification network. The deep learning-based model was evaluated based on the external testing data. The precision rate, recall rate, F1-score, and diagnostic time of two junior radiologists with and without the deep learning model were computed, and the Chi-square, one-way analysis of variance, and least significant difference tests were used to analyze the results.

Results: The use of the deep learning model increased detection recall and classification accuracy (0.922 and 0.863) compared with the radiologists alone (0.812 vs. 0.850). The radiologists achieved a higher precision rate, recall rate, and F1-score for fracture detection when using the deep learning model, at 0.943, 0.978, and 0.960, respectively. When using the deep learning model, the radiologist's reading time was decreased from 158.3 ± 35.7 s to 42.3 ± 6.8 s.

Conclusion: Radiologists achieved the highest performance in diagnosing and classifying rib fractures on CT images when assisted by the deep learning model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-021-03709-8DOI Listing
February 2021

Brassica carinata genome characterization clarifies U's triangle model of evolution and polyploidy in Brassica.

Plant Physiol 2021 Feb 4. Epub 2021 Feb 4.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, China.

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U's triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U's triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U's triangle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plphys/kiab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154070PMC
February 2021

A workflow for simultaneous DNA copy number and methylome analysis of inner cell mass and trophectoderm cells from human blastocysts.

Fertil Steril 2021 Jun 12;115(6):1533-1540. Epub 2021 Feb 12.

Department of Genetics, Albert Einstein College of Medicine, Bronx, New York; Center for Single-Cell Omics in Aging and Disease, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Objective: To establish a workflow for isolating single trophectoderm (TE) and inner cell mass (ICM) cells and to simultaneously evaluate these cells for copy number variation (CNV) as well as methylome development.

Design: Experimental.

Setting: Academic medical center.

Patient(s): Donated genetically abnormal blastocysts.

Intervention(s): Single cells were isolated, followed by bisulfite conversion and sequencing to identify CNV and methylome profiles.

Main Outcome Measure(s): CNV and methylation profiling.

Result(s): Two embryos were dissociated, isolating 46 single cells, with 17 ICM and 12 TE cells selected for further downstream analysis. Chromosome ploidies and embryo sex were concordant with the results from conventional aneuploidy testing. In 3 of the 29 cells, additional aneuploidies were discovered, indicating possible mosaicism undetected by routine preimplantation genetic testing for aneuploidy. CpG methylation frequency was higher in ICM cells compared with TE cells (44.3% vs. 32.4%), respectively, while non-CpG methylation frequency was similar among both cell types. CpG methylation levels accurately distinguished ICM from TE cells epigenetically.

Conclusion(s): We describe an effective workflow for isolating and sequencing single ICM and TE cells from human blastocysts. The use of methylation profiling can help distinguish these two cell populations better then morphologic identification alone. TE cells had significantly lower levels of DNA methylation, which may be explained in part by the fact that these cells have begun the process of differentiation and are transcriptionally more active than ICM. This approach may be used to explore the genetic complexities within human embryos, specifically among the two primary cell types seen at this stage of development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.11.007DOI Listing
June 2021

Screening for obstructive sleep apnea using a contact-free system compared with polysomnography.

J Clin Sleep Med 2021 May;17(5):1075-1082

Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, China.

Study Objectives: To evaluate the utility of a contact-free device in screening for obstructive sleep apnea.

Methods: Three hundred fifty-nine participants (mean age 46 ± 13 years, body mass index 26.1 ± 4.2 kg/m², 67.7% male) underwent overnight monitoring using a contact-free device, the OrbSense, and polysomnography (PSG) in the sleep laboratory simultaneously. The OrbSense recordings were analyzed automatically, and PSG was scored based on recommended guidelines.

Results: The respiratory event index from the OrbSense was lower than the apnea-hypopnea index (AHI) from PSG (25.5 ± 20.7 vs 27.0 ± 25.2 events/h; P = .007) and was significantly correlated with AHI (Pearson coefficient, 0.92; P < .0001). Bland-Altman analysis showed a mean difference of 1.5 events/h, and the limit of agreement was -18.6 to 21.5 events/h. Use of the OrbSense resulted in larger underestimates of AHI and lower negative predictive values at higher AHI values (especially when AHI ≥ 30 events/h). When we used a PSG diagnostic criterion of AHI > 5 events/h, the optimal diagnostic cutoff value from the OrbSense was 8 events/h, with a sensitivity of 90.4%, a specificity of 77.6%, a 94.6% positive predictive value, and a 65% negative predictive value. For patients with moderate to severe obstructive sleep apnea whose AHI was > 15 events/h, the OrbSense cutoff was 16.6 events/h, with a sensitivity of 87.1% and a specificity of 89.7%. Among the 359 participants, 250 patients (69.6%) had the same obstructive sleep apnea severity division classified by both PSG and the OrbSense.

Conclusions: The contact-free device OrbSense can detect respiratory events during sleep and has close agreement with in-laboratory PSG in screening for obstructive sleep apnea. Further studies are warranted to test its utility in community-based settings and at home.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.9138DOI Listing
May 2021

CRL: Collaborative Representation Learning by Coordinating Topic Modeling and Network Embeddings.

IEEE Trans Neural Netw Learn Syst 2021 Feb 10;PP. Epub 2021 Feb 10.

Network representation learning (NRL) has shown its effectiveness in many tasks, such as vertex classification, link prediction, and community detection. In many applications, vertices of social networks contain textual information, e.g., citation networks, which form a text corpus and can be applied to the typical representation learning methods. The global context in the text corpus can be utilized by topic models to discover the topic structures of vertices. Nevertheless, most existing NRL approaches focus on learning representations from the local neighbors of vertices and ignore the global structure of the associated textual information in networks. In this article, we propose a unified model based on matrix factorization (MF), named collaborative representation learning (CRL), which: 1) considers complementary global and local information simultaneously and 2) models topics and learns network embeddings collaboratively. Moreover, we incorporate the Fletcher-Reeves (FR) MF, a conjugate gradient method, to optimize the embedding matrices in an alternative mode. We call this parameter learning method as AFR in our work that can achieve convergence after a few numbers of iterations. Also, by evaluating CRL on topic coherence and vertex classification using several real-world data sets, our experimental study shows that this collaborative model not only can improve the performance of topic discovery over the baseline topic models but also can learn better network representations than the state-of-the-art context-aware NRL models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNNLS.2021.3054422DOI Listing
February 2021

Response of activity and community composition of nitrite-oxidizing bacteria to partial substitution of chemical fertilizer by organic fertilizer.

Environ Sci Pollut Res Int 2021 Feb 8. Epub 2021 Feb 8.

College of Agronomy, Anhui Agricultural University, Hefei, 230036, China.

Nitrite oxidation as the second step of nitrification can become the determining step in disturbed soil systems. As a beneficial fertilization practice to maintain high crop yield and soil fertility, partial substitution of chemical fertilizer (CF) by organic fertilizer (OF) may exert a notable disturbance to soil systems. However, how nitrite oxidation responds to different proportions of CF to OF is still unclear. We sampled soils from a 4-year field experiment subject to a gradient of increasing proportions of OF to CF application. Activity, size, and structure of Nitrospira-like and Nitrobacter-like nitrite-oxidizing bacteria (NOB) community were measured. The results revealed that with increasing proportion of OF to CF application, potential nitrite oxidation activity (PNO) showed a marked decreasing trend. PNO was significantly correlated with the abundance of Nitrobacter-like but not Nitrospira-like NOB. The abundance of Nitrobacter-like was significantly influenced by soil organic matter, organic nitrogen (N), and available N. In addition, PNO was also affected by the structure of Nitrobacter-like NOB. The relative abundance of Nitrobacter hamburgensis, alkalicus, winogradskyi, and vulgaris responded differently to the proportions of OF to CF application. Organic N, organic matter, and available N were the main factor shaping their community structure. Overall, Nitrobacter-like NOB is more sensitive and plays a more important role than Nitrospira-like NOB in responding to different proportions of OF to CF application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-12038-7DOI Listing
February 2021

Genome Assembly and Analyses of the Macrofungus .

Biomed Res Int 2021 18;2021:6656365. Epub 2021 Jan 18.

College of Biological Big Data, Yunnan Agricultural University, Kunming 650201, China.

() is a macrofungus genus that contains a big number of fairly fleshy gilled mushrooms with white spores. This macrofungus produces diverse bioactive compounds, antioxidants, and water-soluble polysaccharides. However, the genomic resources of this species remain unknown. Here, we assembled the genome of (41.23 Mb) into 336 scaffolds with a N50 size of 374,455 bp and compared it with the genomes of eleven other macrofungi. Comparative genomics study confirmed that belonged to the genus, a stand-alone genus different from the genus. In addition, we found that glycosyl hydrolase family 28 (GH28) in shared conserved motifs that were significantly different from their counterparts in . The genomic resource uncovered by this study will enhance our understanding of fungi biology, especially the differences in their growth rates and energy metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6656365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841450PMC
January 2021

Long non-coding RNA LINC02446 suppresses the proliferation and metastasis of bladder cancer cells by binding with EIF3G and regulating the mTOR signalling pathway.

Cancer Gene Ther 2021 Feb 2. Epub 2021 Feb 2.

Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, China.

Accumulating evidence has been obtained to understand the mechanisms of long non-coding RNAs (lncRNAs) in bladder cancer (BC). However, due to the recurrence and metastasis of BC, searching for lncRNAs that are related to prognosis and metastasis and exploring the pathogenesis of BC might provide new insights for the treatment of BC. In the present study, we used the TCGA and GEO databases and identified LINC02446 as associated with prognosis and differentially expressed in bladder cancer tissues and para-cancer tissues. Then, we found that LINC02446 could affect the proliferation, migration and invasion of BC cells. Additionally, we found that LINC02446 could bind to the EIF3G protein and regulate the protein stability of EIF3G and then inhibit the mTOR signalling pathway. In summary, all these findings show that LINC02446 might serve as a promising therapeutic target for BC intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41417-020-00285-2DOI Listing
February 2021

A Method of Mining Truck Loading Volume Detection Based on Deep Learning and Image Recognition.

Sensors (Basel) 2021 Jan 18;21(2). Epub 2021 Jan 18.

School of Resources and Civil Engineering, Northeastern University, Shenyang 110004, China.

Detection of the loading volume of mining trucks is an important task in open pit mining. Aiming at the addressing the current problems of low accuracy and high cost of the detection of the loading volume of mining trucks, this paper proposes a mining truck loading volume detection model based on deep learning and image recognition. The training and test data of the model consists of 6000 sets of images taken in a laboratory environment. After image preprocessing, the VGG16 network model is used to pre classify the ore images. The classification results are displayed and the possibility of each category is determined. Then, the loading volume of mining trucks is calculated by using the classification results and the least squares algorithm. By using the labeled image data of five kinds of mining truck loading volume, the arbitrary loading volume detection of mining trucks is realized, which effectively solves the problem of a lack of labeled data types caused by the difficulty in obtaining mine data. Root mean square error (RMSE) and mean absolute error (MAE) are used to evaluate the fitting effect of the model. The experimental results show that the model has high prediction accuracy. The average absolute error is 17.85 cm3. In addition, this paper uses 400 real mining truck images of open-pit mines to verify the model and the average absolute error is 2.53 m3. The experimental results show that the model has good generality and can be applied well to the actual production of open-pit mines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21020635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831092PMC
January 2021

Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma.

Cell Death Discov 2021 Jan 18;7(1):14. Epub 2021 Jan 18.

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell proliferation and inhibits cell apoptosis by accelerating cell glycolysis. Taken together, our work identifies the heterogeneity of HCC subclones, and suggests MLXIPL might be a promising therapeutic target for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41420-021-00403-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814056PMC
January 2021