Publications by authors named "Yang Su"

517 Publications

An Early Stage Researcher's Primer on Systems Medicine Terminology.

Netw Syst Med 2021 Feb 25;4(1):2-50. Epub 2021 Feb 25.

Faculty of Health, Medicine & Life Science, Maastricht University, Maastricht, The Netherlands.

Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of applications, and lists of relevant references. This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic.
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http://dx.doi.org/10.1089/nsm.2020.0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919422PMC
February 2021

TRPM2-AS Promotes Bladder Cancer by Targeting miR-22-3p and Regulating GINS2 mRNA Expression.

Onco Targets Ther 2021 23;14:1219-1237. Epub 2021 Feb 23.

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China.

Background: Bladder cancer (BLCA) refers to the malignancy growth that spreads from the bladder linings to the bladder muscles. However, the impact of miR-22-3p and lncRNA TRPM2-AS on this tumor has generated divergent views in the literature. This research aimed to study the effects of lncRNA TRPM2-AS on BLCA and its interaction with miR-22-3p and GINS2 mRNA.

Methods: qRT-PCR was employed to measure the expression of TRPM2-AS, miR-22-3p and GINS2 mRNA in bladder tissues and cells. The subcellular localization of TRPM2-AS in T24 and 5637 cell lines was identified using a cell fractionation system. Luciferase assay, RIP assay and RNA pull-down assay were later performed to validate the direct binding relationship between TRPM2-AS, miR-22-3p and GINS2 mRNA. Several experiments were conducted to determine the viability, proliferation, colony formation and apoptosis of the cell lines.

Results: Findings indicated that TRPM2-AS was significantly upregulated in BLCA tissues and cell lines. Apart from that, it was observed that TRPM2-AS knockdown significantly inhibited the viability, proliferation and colony formation of BCLA cells, but it promoted the apoptosis of the BCLA cells. A significant downstream target of TRPM2-AS, miR-22-3p was found to show a lower expression level in BLCA tissues and cell lines. However, the inhibition of miR-22-3p considerably enhanced BLCA cell phenotypes. As well as discovering that GINS2 mRNA was a downstream target of miR-22-3p and was significantly upregulated in BLCA, experimental results also indicated that the knockdown of GINS2 suppressed BLCA cell phenotypes.

Conclusion: This research confirmed that TRPM2-AS could promote BCLA by binding to miR-22-3p to increase GINS2 expression. This novel interactome in BLCA cell lines might provide more insights into BLCA therapy.
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http://dx.doi.org/10.2147/OTT.S282151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914110PMC
February 2021

The Top 100 Most Cited Articles on Anterior Cruciate Ligament Reconstruction: A Bibliometric Analysis.

Orthop J Sports Med 2021 Feb 8;9(2):2325967120976372. Epub 2021 Feb 8.

Department of Orthopaedic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: The concept of anterior cruciate ligament (ACL) reconstruction (ACLR) has become widely accepted, gaining increased attention in recent years and resulting in many research achievements in this field.

Purpose: The aim of this study was to determine which original articles on ACLR have been most influential in this field by identifying and analyzing the characteristics of the 100 most cited articles.

Study Design: Cross-sectional study.

Methods: Articles on ACLR were identified via the Thomson ISI Web of Science database on November 30, 2019. The 100 most cited articles were identified based on inclusion and exclusion criteria. The data extracted from each article for the subsequent analysis included title, date of publication, total citations, average citations per year (ACY), journal name, first author, institutions, themes, level of evidence, and keywords.

Results: The total number of citations was 29,629. The date of publication ranged from 1975 to 2015. A majority of the articles originated from the United States (58%) and were published in the 1990s (32%) and 2000s (48%). The mean ACY was 18.43 ± 9.51. Of the selected articles, nearly one-half were published in the (42%). The most prolific co-author and first author were Freddie H. Fu (n = 13) and K. Donald Shelbourne (n = 5), respectively. The most productive institution was the University of Pittsburgh (14%). Material comparison (19%) and technique comparison (16%) were the 2 most popular themes. More than one-quarter of articles were level 4 evidence (37%). Moreover, the keywords , , , , , and showed the highest degree of centrality.

Conclusion: By analyzing the characteristics of articles, this study demonstrated that ACLR is a growing and popular area of research, with the focus of research varying through timeline trends. Studies on anatomic reconstruction and biomechanics might be areas of future trends.
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http://dx.doi.org/10.1177/2325967120976372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876772PMC
February 2021

Epigallocatechin-3-gallate inhibits proliferation and triggers apoptosis in colon cancer via the hedgehog/phosphoinositide 3-kinase pathways.

Authors:
Feng Ding Su Yang

Can J Physiol Pharmacol 2021 Feb 22. Epub 2021 Feb 22.

First Affiliated Hospital of Jinzhou Medical University, 457651, No.40.Section 3, Songpo Road, Jinzhou, China, 121002;

The present study evaluated whether EGCG effectively attenuates tumor growth in colon cancer cells and in the xenografts of nude mice and to investigated the underlying mechanisms by focusing on the Shh and PI3K pathways. Three kinds of colon cancer cells and BALB/c nude mice were used to evaluate the antiproliferative effect of EGCG.The results showed that EGCG exhibited an antiproliferative effect against colon cancer cells in a dose-dependent manner with low toxicity against normal colon epithelial cells. Administration of EGCG caused significant apoptosis and inhibited the migration and invasion of colon cancer cells. The toxic effect of EGCG was accompanied by downregulation of the Shh and PI3K/Akt pathways. In addition, EGCG reduced tumor weight without affecting the body weight of nude mice and inhibited the activation of the Shh and PI3K/Akt pathways in tumor tissue. Purmorphamine (Shh agonist) or IGF-1 (PI3K agonist) partly abolished the effect of EGCG on cell proliferation, migration and apoptosis. Cyclopamine (Shh inhibitor) and LY294002 (PI3K inhibitor) showed the similar toxic effects as EGCG on colon cancer cells. In conclusion, EGCG inhibited colon tumor growth via downregulation of the Shh and PI3K pathways and may be a potential chemotherapeutic agent against colon cancer.
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http://dx.doi.org/10.1139/cjpp-2020-0588DOI Listing
February 2021

High probability of yield gain through conservation agriculture in dry regions for major staple crops.

Sci Rep 2021 Feb 8;11(1):3344. Epub 2021 Feb 8.

UMR Agronomie, INRAE AgroParisTech, Université Paris-Saclay, 78850, Thiverval-Grignon, France.

Conservation agriculture (CA) has been promoted to mitigate climate change, reduce soil erosion, and provide a variety of ecosystem services. Yet, its impacts on crop yields remains controversial. To gain further insight, we mapped the probability of yield gain when switching from conventional tillage systems (CT) to CA worldwide. Relative yield changes were estimated with machine learning algorithms trained by 4403 paired yield observations on 8 crop species extracted from 413 publications. CA has better productive performance than no-till system (NT), and it stands a more than 50% chance to outperform CT in dryer regions of the world, especially with proper agricultural management practices. Residue retention has the largest positive impact on CA productivity comparing to other management practices. The variations in the productivity of CA and NT across geographical and climatical regions were illustrated on global maps. CA appears as a sustainable agricultural practice if targeted at specific climatic regions and crop species.
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http://dx.doi.org/10.1038/s41598-021-82375-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870656PMC
February 2021

Harvesting More Energetic Photoexcited Electrons from Closely Packed Gold Nanoparticles.

J Am Soc Mass Spectrom 2021 Mar 8;32(3):815-824. Epub 2021 Feb 8.

Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong S.A.R., P. R. China.

The characterization of photoexcited electrons on the surface of nanomaterial remains challenging. Herein, laser excitation mass spectrometry combined with a chemical thermometer and electron acceptor has been developed to characterize the energetics and population density of photoexcited electrons transferred from gold nanoparticles (AuNPs). In contrast to laser fluence and bias voltage, the hot spots of closely packed AuNPs play a more significant role in enhancing the average energetics of photoexcited electrons, which can be harvested effectively by the electron acceptor. By harvesting more energetic photoexcited electrons for the desorption and ionization process, it is anticipated that the sensitive detection of biomarkers can be achieved, which is beneficial to metabolomic studies and early disease diagnosis.
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http://dx.doi.org/10.1021/jasms.0c00480DOI Listing
March 2021

The Top 100 Most Cited Articles on Arthroscopy: Most Popular Topic is Rotator Cuff Rather Than Cartilage in the Recent 5 Years.

Arthroscopy 2021 Feb 1. Epub 2021 Feb 1.

Orthopaedic department, The Second Xiangya hospital of Central South University, Changsha, Hunan province, China. Electronic address:

Purpose: To highlight the characteristics of the 100 most-cited articles on arthroscopy and provide the variation trend of citation rate among the top 25 articles in the past nine years. We further analyzed the topics of interest in the past or currently.

Methods: The Thomson ISI Web of Science database was used to identify arthroscopy related articles that were published from 1950 to March 31, 2020. The 100 most-cited articles were selected for further analysis. In addition, author keywords of the articles that published in the recent 5 years were further analyzed.

Results: Mean of citations was 433.59±400.73. The publication year ranged from 1980 to 2013. Most articles were focused on cartilage lesions and treatments (26%). A large proportion of articles were published in the 2000's (61%). Arthroscopy - the Journal of Arthroscopic and Related Surgery (23%) was the most popular journal. One half of the articles originated from the United States. The most prolific institution and first author was the Steadman Philippon Research Institute (5%) and Marc J Philippon (4%). Most of the articles were level IV evidence (33%). The citation rate has increased by 131% from the previous top 25 articles published in 2011. A growth trend can be seen in the citation density over time. "Shoulder" (occurrences=535) is the most used joint keywords and "Rotator Cuff" (342) is the most used keywords of research objective in the last 5 years, while the occurrences of "Cartilage" only occurs 262 times.

Conclusion: Based on bibliometric analysis of the 100 most cited articles on arthroscopy combined with network analysis of the whole articles that published in the recent 5 years, the topic of most interest in the recent 5 years is rotator cuff rather than cartilage. The number of citations among the 25 most-cited articles is growing rapidly and at least doubles in size on average in the past nine years. Citation density among the 100 most-cited articles on arthroscopy have a growth trend.

Clinical Relevance: This article clarifies the characteristics of the 100 most cited papers and provides guidance on the topics of interest in the past or currently as a roadmap for future research on arthroscopy.
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http://dx.doi.org/10.1016/j.arthro.2021.01.039DOI Listing
February 2021

High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming.

Nat Commun 2021 02 3;12(1):773. Epub 2021 Feb 3.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation.
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http://dx.doi.org/10.1038/s41467-021-21066-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858590PMC
February 2021

Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells.

Front Cell Dev Biol 2020 12;8:585565. Epub 2021 Jan 12.

Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.

Accumulating evidence shows that exosomal circRNAs reflect the physiological status of donor cells, and various cell reactions are induced after exosomal circRNAs are captured by recipient cells. In this study, qRT-PCR was performed to detect circ-0004277 expression in hepatocellular carcinoma (HCC) cell lines, tissues, and plasma exosomes. The effects of circ-0004277 on the proliferation and migration of HCC cells were assessed by cell counting, 5-ethynyl-2'-deoxyuridine assays, Transwell migration assays, and tumor formation in nude mice. We found that circ-0004277 was significantly upregulated in HCC cells, tissues, and plasma exosomes compared to that in normal controls. Overexpression of circ-0004277 enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of HCC cells and . Furthermore, exosomes from HCC cells enhanced circ-0004277 expression in surrounding normal cells and stimulated EMT progression. ZO-1, a tight junction adapter protein, was downregulated in HCC tissues. In conclusion, our findings suggest that circ-0004277 promotes the malignant phenotype of HCC cells via inhibition of and promotion of EMT progression. In addition, exosomal circ-0004277 from HCC cells stimulates EMT of peripheral cells through cellular communication to further promote the invasion of HCC into normal surrounding tissues.
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http://dx.doi.org/10.3389/fcell.2020.585565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835424PMC
January 2021

A global dataset for crop production under conventional tillage and no tillage systems.

Sci Data 2021 01 28;8(1):33. Epub 2021 Jan 28.

UMR Agronomie, INRAE AgroParisTech, Université Paris-Saclay, 78850, Thiverval-Grignon, France.

No tillage (NT) is often presented as a means to grow crops with positive environmental externalities, such as enhanced carbon sequestration, improved soil quality, reduced soil erosion, and increased biodiversity. However, whether NT systems are as productive as those relying on conventional tillage (CT) is a controversial issue, fraught by a high variability over time and space. Here, we expand existing datasets to include the results of the most recent field experiments, and we produce a global dataset comparing the crop yields obtained under CT and NT systems. In addition to crop yield, our dataset also reports information on crop growing season, management practices, soil characteristics and key climate parameters throughout the experimental year. The final dataset contains 4403 paired yield observations between 1980 and 2017 for eight major staple crops in 50 countries. This dataset can help to gain insight into the main drivers explaining the variability of the productivity of NT and the consequence of its adoption on crop yields.
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http://dx.doi.org/10.1038/s41597-021-00817-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844240PMC
January 2021

Expansion and Functional Diversification of TFIIB-Like Factors in Plants.

Int J Mol Sci 2021 Jan 23;22(3). Epub 2021 Jan 23.

College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou 310018, China.

As sessile organisms, plants have evolved unique patterns of growth and development, elaborate metabolism and special perception and signaling mechanisms to environmental cues. Likewise, plants have complex and highly special programs for transcriptional control of gene expression. A case study for the special transcription control in plants is the expansion of general transcription factors, particularly the family of Transcription Factor IIB (TFIIB)-like factors with 15 members in Arabidopsis. For more than a decade, molecular and genetic analysis has revealed important functions of these TFIIB-like factors in specific biological processes including gametogenesis, pollen tube growth guidance, embryogenesis, endosperm development, and plant-microbe interactions. The redundant, specialized, and diversified roles of these TFIIB-like factors challenge the traditional definition of general transcription factors established in other eukaryotes. In this review, we discuss general transcription factors in plants with a focus on the expansion and functional analysis of plant TFIIB-like proteins to highlight unique aspects of plant transcription programs that can be highly valuable for understanding the molecular basis of plant growth, development and responses to stress conditions.
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http://dx.doi.org/10.3390/ijms22031078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865254PMC
January 2021

Improved effect of a mitochondria-targeted antioxidant on hydrogen peroxide-induced oxidative stress in human retinal pigment epithelium cells.

BMC Pharmacol Toxicol 2021 Jan 20;22(1). Epub 2021 Jan 20.

Inha Research Institute for Aerospace Medicine, Inha University, Incheon, 22212, South Korea.

Background: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (HO)-induced oxidative stress in RPE cells.

Methods: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with HO or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR).

Results: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in HO-treated ARPE-19 cells. Mitochondrial dysfunction from the HO-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).

Conclusion: We verified the protective effect of TPP-Niacin against HO-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.
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http://dx.doi.org/10.1186/s40360-020-00471-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819191PMC
January 2021

Sea Voyage Training and Motion Sickness Effects on Working Ability and Life Quality After Landing.

Aerosp Med Hum Perform 2021 Feb;92(2):92-98

The effects of seasickness on working performance during motion exposure have been reported, while the aftereffects on working ability and life quality decline (WLD) still remain unclarified. Two cohorts of healthy male Chinese subjects received either a single (SSV) or repeated (RSV) sea voyage training program on different vessels. A seasickness incidence (SSI) questionnaire was administered to assess the prevalence of seasickness symptoms (vomiting, nausea, other, or no symptoms). A WLD questionnaire was used to survey the general feeling of WLD (severe, moderate, slight, and none) by a 4-point score as well as the incidence rate (IR) of specific WLD items within 24 h after landing. The RSV cohort had lower overall IR of WLD than the SSV cohort (54.64% vs. 63.78%, 657 for both cohorts). The landing ship trainees in both cohorts showed higher general WLD score and higher IRs of physical fatigue, sleep disorder, and spontaneous locomotion decrement than those trained on the small vessels. Subjects with vomiting or nausea had higher general WLD score and higher IRs of concentration distraction, physical fatigue, anorexia, and spontaneous locomotion decrement than those with no symptoms. Higher IRs of firing accuracy decline (SSV: 21.35% vs. 7.13%, 9.14%; RSV: 22.11% vs. 9.28%, 5.27%), equipment operation disturbance (SSV: 16.85% vs. 3.57%, 6.85%; RSV: 20.47% vs. 7.85%, 7.03%) were also observed in the vomiting subjects than those with other symptoms and no symptoms. Significant WLD after landing was associated with transportation types, seasickness severity, and habituation during sea voyage training.
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http://dx.doi.org/10.3357/AMHP.5614.2021DOI Listing
February 2021

A disease-relevant mutation of SPOP highlights functional significance of ATM-mediated DNA damage response.

Signal Transduct Target Ther 2021 Jan 15;6(1):17. Epub 2021 Jan 15.

Department of Biochemistry and Molecular Biology, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

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http://dx.doi.org/10.1038/s41392-020-00381-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809020PMC
January 2021

Rescue effects of Se-enriched rice on physiological and biochemical characteristics in cadmium poisoning mice.

Environ Sci Pollut Res Int 2021 Jan 6. Epub 2021 Jan 6.

Rice Research Institute, Sichuan Agricultural University, 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, China.

Cadmium (Cd) is an element injurious for human health and is possibly toxic to organisms at minor concentrations. While some of other trace metallic elements have antagonistic features to it. One of them is the interaction between selenium (Se) and Cd in plant different organs. Literature review disclosed that the intake of Se to some extent can reduce the accumulation of Cd in plants, while the research on of trace metallic elements (Cd) and Se-enriched food (rice) in the living body has rarely been reported. This study intended to explore whether there was a mitigating effect of Se-enriched rice on mice poisoned with Cd. A mouse model of low-dose and high-dose Cd poisoning was established (supplemented with cadmium chloride(CdCl·2½H0)), followed by feeding two groups (1) Se-enriched rice and (2) setting an equal amount of inorganic Se group. After that, the impact of Se-enriched rice on the antioxidant activity was evaluated. The Se-enriched diet enhanced the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and enzyme activities of GSH peroxidase (GSH-Px) in mice livers and kidney whereas significantly decreased the malondialdehyde (MDA) contents. Moreover, the degree of physiological damage in mice with low cadmium poisoning was significantly alleviated, and the expression of antioxidant genes (Nrf-2, GPX1, TrxR2, TNF-2) was increased. In conclusion, the Se-enriched diet has a positive effect on the biological effects in mice, and it can be used as a daily diet to resist damage to the body's low Cd state and support enzymatic antioxidant systems by eliminating oxidative injury.
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http://dx.doi.org/10.1007/s11356-020-11854-1DOI Listing
January 2021

A Hardware Pseudo-Random Number Generator Using Stochastic Computing and Logistic Map.

Micromachines (Basel) 2020 Dec 30;12(1). Epub 2020 Dec 30.

School of Computing and Engineering, University of West London, London W5 5RF, UK.

Recent research showed that the chaotic maps are considered as alternative methods for generating pseudo-random numbers, and various approaches have been proposed for the corresponding hardware implementations. In this work, an efficient hardware pseudo-random number generator (PRNG) is proposed, where the one-dimensional logistic map is optimised by using the perturbation operation which effectively reduces the degradation of digital chaos. By employing stochastic computing, a hardware PRNG is designed with relatively low hardware utilisation. The proposed hardware PRNG is implemented by using a Field Programmable Gate Array device. Results show that the chaotic map achieves good security performance by using the perturbation operations and the generated pseudo-random numbers pass the TestU01 test and the NIST SP 800-22 test. Most importantly, it also saves 89% of hardware resources compared to conventional approaches.
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http://dx.doi.org/10.3390/mi12010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824605PMC
December 2020

DOCK2 contributes to endotoxemia-induced acute lung injury in mice by activating proinflammatory macrophages.

Biochem Pharmacol 2021 Feb 28;184:114399. Epub 2020 Dec 28.

Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. Electronic address:

Dedicator of cytokinesis 2 (DOCK2), an atypical Rac activator, has important anti-inflammatory properties in blepharitis, enteric bacterial infection and colitis. However, the roles of DOCK2 in macrophage activation and acute lung injury (ALI) are still poorly elucidated. In vitro studies demonstrated that DOCK2 was essential for the nucleotide-sensing Toll-like receptor (TLR) 4-mediated inflammatory response in macrophages. We also confirmed that exposure of macrophages to LPS induced Rac activation through a TLR4-independent, DOCK2-dependent mechanism. Phosphorylation of IκB kinase (IKK) β and nuclear translocation of transcription factor nuclear factor kappa B (NF-κB) were impaired in Ad-shDOCK2-expressing macrophages, resulting in a decreased inflammatory response. Similar results were obtained when EHop-016 (a Rac inhibitor) was used to treat uninfected macrophages. In summary, these data indicate that the DOCK2-Rac signaling pathway acts in parallel with TLR4 engagement to control IKKβ activation for inflammatory cytokine release. Next, we investigated whether pharmacological inhibition of DOCK2 protects against endotoxemia-induced lung injury in mice. Treatment with 4-[3'-(2″-chlorophenyl)-2'-propen-1'-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP), a small-molecule inhibitor of DOCK2, reduced the severity of lung injury, as indicated by decreases in the lung injury score and myeloperoxidase (MPO) activity. Moreover, CPYPP attenuated LPS-induced proinflammatory cytokine release in mice. Our studies suggest that inhibition of DOCK2 may suppress LPS-induced macrophage activation and that DOCK2 may be a novel target for treating endotoxemia-related ALI.
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http://dx.doi.org/10.1016/j.bcp.2020.114399DOI Listing
February 2021

Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China.

Cancer Med 2021 Feb 31;10(3):999-1011. Epub 2020 Dec 31.

Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.

Background: Despite numerous chimeric antigen receptor T-cell (CAR-T) trials conducted in China, no CAR-T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR-T manufacture abroad. Relma-cel (JWCAR029), an anti-CD19 product produced with a commercial-ready process in China, was evaluated in the first prospective, single-arm, multicenter, pivotal study of CAR-T therapy conducted under Chinese IND to support an NMPA-accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215).

Methods: Patients were randomized to receive either 100 × 10 (low dose, n = 27) or 150 × 10 (high dose, n = 32) CAR+ T-cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25 mg/m and cyclophosphamide 250 mg/m daily × 3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3 months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics.

Results: As of the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy-evaluable patients, the primary endpoint of 3 month ORR was 60.3% (95% CI, 46.6-73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%.

Conclusions: Relma-cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR-T-associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China.
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http://dx.doi.org/10.1002/cam4.3686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897944PMC
February 2021

Long-term and short-term outcomes of robot- versus video-assisted anatomic lung resection in lung cancer: a systematic review and meta-analysis.

Eur J Cardiothorac Surg 2020 Dec 23. Epub 2020 Dec 23.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: Minimally invasive thoracic surgery has evolved with the introduction of robotic platforms. This study aimed to compare the long-term and short-term outcomes of the robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for anatomic lung resection.

Methods: We searched published studies that investigated RATS and VATS in anatomic lung resection. Long-term outcomes (disease-free survival and overall survival) and short-term outcomes (30-day mortality, postoperative complications, conversion rate to open surgery and lymph node upstaging) were extracted. The features were compared and tested as hazard ratios (HRs) and odds ratios (ORs) at a 95% confidence interval (CI).

Results: Twenty-five studies with 50 404 patients (7135 for RATS and 43 269 for VATS) were included. The RATS group had a longer disease-free survival than the VATS group (HR: 0.76; 95% CI: 0.59-0.97; P = 0.03), and the overall survival showed a similar trend but was not statistically significant (HR: 0.77; 95% CI: 0.57-1.05; P = 0.10). The RATS group showed a significantly lower 30-day mortality (OR: 0.55; 95% CI: 0.38-0.81; P = 0.002). No significant difference was found in postoperative complications (OR: 1.01; 95% CI: 0.87-1.16; P = 0.94), the conversion rate to open surgery (OR: 0.92; 95% CI: 0.56-1.52; P = 0.75) and lymph node upstaging (OR: 0.89; 95% CI: 0.52-1.54; P = 0.68).

Conclusions: RATS has comparable short-term outcomes and potential long-term survival benefits for anatomic lung resection compared with VATS.
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http://dx.doi.org/10.1093/ejcts/ezaa426DOI Listing
December 2020

Active components of Bupleurum chinense and Angelica biserrata showed analgesic effects in formalin induced pain by acting on Nav1.7.

J Ethnopharmacol 2021 Apr 25;269:113736. Epub 2020 Dec 25.

School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China. Electronic address:

Ethnopharmacology Relevance: Pain is an unpleasant sensory and emotional experience, often accompanied by the occurrence of a variety of diseases. More than 800 kinds of traditional Chinese medicines (TCM) has now been reported for pain relief and several monomers have been developed into novel analgesic drugs. Bupleurum chinense and Angelica biserrata were representatives of the TCM that are currently available for the treatment of pain.

Aim Of The Study: The study aims to detect the potential analgesic activity of each monomer of Bupleurum chinense and Angelica biserrata and to explore whether Nav1.7 is one of the targets for its analgesic activity.

Materials And Methods: In this study, five monomers from Bupleurum chinense (Saikosaponin A, Saikosaponin B1, Saikosaponin B2, Saikosaponin C, Saikosaponin D) and five monomers from the Angelica biserrata (Osthole, Xanthotoxin, Imperatorin, Isoimperatorin, Psoralen) were examined by whole-cell patch-clamp on Nav1.7, which was closely associated with pain. Classical mouse pain models were also used to further verify the analgesic activity in vivo.

Results: The results showed that monomers of Saikosaponins and Angelica biserrata all inhibited the peak currents of Nav1.7, indicating that Nav1.7 might be involved in the analgesic mechanism of Saikosaponins and Angelica biserrata. Among them, Saikosaponin A and Imperatorin showed the strongest inhibitory effect on Nav1.7. Furthermore, both Saikosaponin A and Imperatorin showed inhibitory effects on thermal pain and formalin-induced pain in phase II in vivo.

Conclusion: The results provide valuable information for future studies on the potential of TCM in alleviating pain.
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http://dx.doi.org/10.1016/j.jep.2020.113736DOI Listing
April 2021

Profiling of cybersickness and balance disturbance induced by virtual ship motion immersion combined with galvanic vestibular stimulation.

Appl Ergon 2021 Apr 16;92:103312. Epub 2020 Dec 16.

Department of Nautical Injury Prevention, Faculty of Navy Medicine, Naval Medical University, Shanghai, China. Electronic address:

Profile of cybersickness and balance disturbance induced by virtual ship motion alone and in combination with galvanic vestibular stimulation (GVS) remained unclear. Subjects were exposed to a ship deck vision scene under simulated Degree 5 or 3 sea condition using a head-mounted virtual reality display with or without GVS. Virtual ship motion at Degree 5 induced significant cybersickness with symptom profile: nausea syndrome > central (headache and dizziness) > peripheral (cold sweating) > increased salivation. During a single session of virtual ship motion exposure, GVS aggravated balance disturbance but did not affect most cybersickness symptoms except cold sweating. Repeated exposure induced cybersickness habituation which was delayed by GVS, while the temporal change of balance disturbance was unaffected. These results suggested that vestibular inputs play different roles in cybersickness and balance disturbance during virtual reality exposure. GVS might not serve as a potential countermeasure against cybersickness induced by virtual ship motion.
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http://dx.doi.org/10.1016/j.apergo.2020.103312DOI Listing
April 2021

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia.

Front Neurol 2020 23;11:577927. Epub 2020 Nov 23.

Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Ischemia/reperfusion (I/R) injury is a significant cause of mortality and long-term disability worldwide. Recent evidence has proved that pyroptosis, a novel cell death form, contributes to inflammation-induced neuron death and neurological function impairment following ischemic stroke. Gasdermin D (GSDMD) is a newly discovered key molecule of cell pyroptosis, but its biological function and precise role in ischemic stroke are still unclear. The present study investigates the cleavage activity of GSDMD, localization of pyroptotic cells, and global neuroinflammation in mice after I/R. The level of cell pyroptosis around the infarcted area was significantly increased in the acute phase of cerebral I/R injury. The ablation of GSDMD reduced the infraction volume and improved neurological function against cerebral I/R injury. Furthermore, we confirmed I/R injury induced cell pyroptosis mainly in microglia. Knockdown of GSDMD effectively inhibited the secretion of mature IL-1β and IL-18 from microglia cells but did not affect the expression of caspase-1/11 and . In summary, blocking GSDMD expression might serve as a potential therapeutic strategy for ischemic stroke.
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http://dx.doi.org/10.3389/fneur.2020.577927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719685PMC
November 2020

Acetylation of PhoP K88 Is Involved in Regulating Virulence.

Infect Immun 2021 Feb 16;89(3). Epub 2021 Feb 16.

Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China

The PhoP-PhoQ two-component regulation system of serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of Typhimurium. Here, we demonstrate that a conserved lysine residue, K88, is crucial for the function of PhoP and its acetylation-downregulated PhoP activities. K88 could be specifically acetylated by acetyl phosphate (AcP), and the acetylation level of K88 decreased significantly after phagocytosis of Typhimurium by macrophages. Acetylation of K88 inhibited PhoP dimerization and DNA-binding abilities. In addition, mutation of K88 to glutamine, mimicking the acetylated form, dramatically attenuated intestinal inflammation and systemic infection of Typhimurium in the mouse model. These findings indicate that nonenzymatic acetylation of PhoP by AcP is a fine-tuned mechanism for the virulence of Typhimurium and highlights that virulence and metabolism in the host are closely linked.
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http://dx.doi.org/10.1128/IAI.00588-20DOI Listing
February 2021

Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.

Nat Commun 2020 12 10;11(1):6322. Epub 2020 Dec 10.

Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4 macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3 T cells with high proportion of TIGIT cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.
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http://dx.doi.org/10.1038/s41467-020-20059-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730477PMC
December 2020

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Clin Cancer Res 2021 Mar 8;27(5):1305-1315. Epub 2020 Dec 8.

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia.

Purpose: We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models.

Experimental Design: [Zr]DFO-YS5 was prepared and its binding affinity for CD46 was measured. ImmunoPET imaging was conducted in male athymic nu/nu mice bearing DU145 [AR, CD46, prostate-specific membrane antigen-negative (PSMA)] or 22Rv1 (AR, CD46, PSMA) tumors, and in NOD/SCID gamma mice bearing patient-derived adenocarcinoma xenograft, LTL-331, and neuroendocrine prostate cancers, LTL-331R and LTL-545.

Results: [Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [Zr]DFO-YS5 was 13.3 ± 3.9 and 11.2 ± 2.5 %ID/g, respectively, in DU145 and 22Rv1 xenografts, 4 days postinjection. Notably, [Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [Zr]DFO-YS5 also showed uptake in the patient-derived LTL-331 and -331R models, with particularly high uptake in the LTL-545 neuroendocrine prostate cancer tumors (18.8 ± 5.3, 12.5 ± 1.8, and 32 ± 5.3 %ID/g in LTL-331, LTL-331R, and LTL-545, respectively, at 4 days postinjection).

Conclusions: [Zr]DFO-YS5 is an excellent PET imaging agent across a panel of prostate cancer models, including in both adenocarcinoma and neuroendocrine prostate cancer, both cell line- and patient-derived xenografts, and both PSMA-positive and -negative tumors. It demonstrates potential for clinical translation as an imaging agent, theranostic platform, and companion biomarker in prostate cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925362PMC
March 2021

MiR-582-5p Inhibits Bladder Cancer-Genesis by Suppressing TTK Expression.

Cancer Manag Res 2020 20;12:11933-11944. Epub 2020 Nov 20.

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, People's Republic of China.

Background: Bladder cancer (BC) refers to the malignant growth found in the cells and tissues of the urinary bladder. While many studies have researched the progression of BC, scientists are yet to fully understand the mechanism of BC. This research aimed to explore the role of miR-582-5p and its target gene TTK in BC pathogenesis.

Methods: The evaluation of miR-582-5p and TTK mRNA expression in BC tissues or cells was performed using qRT-PCR. TargetScan was then used to predict the binding site of miR-582-5p on TTK mRNA. Subsequently, dual-luciferase reporter and RNA pull-down assays were employed to validate the binding relationship between miR-582-5p and TTK mRNA. CCK-8, BrdU, flow cytometry, and caspase-3 activity assays were later conducted to evaluate the viability, proliferation, cell cycle, and apoptosis of BC cells.

Results: Investigations revealed that miR-582-5p was downregulated in BC tissues and cells. Meanwhile, miR-582-5p inhibited the viability and proliferation of BC cells while stimulating the apoptosis and cycle arrest of the cells. TTK, the target gene of miR-582-5p, was later found to be over-expressed in BC tissues and cells. TTK, however, was observed to exhibit an opposite effect on miR-582-5p. Simply put, it stimulated BC cell malignant phenotypes, and this stimulation could be directly reversed by miR-582-5p.

Conclusion: This research confirmed that miR-582-5p could restrain bladder carcinogenesis by inhibiting TTK expression.
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http://dx.doi.org/10.2147/CMAR.S274835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685364PMC
November 2020

A Single-Stranded DNA-Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks.

Adv Sci (Weinh) 2020 Nov 14;7(22):2001970. Epub 2020 Oct 14.

Department of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 Switzerland.

A versatile and Lipinski-compliant DNA-encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB-DEL library, constructed in single-stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single-stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self-assembled selectable chemical structures, leading to the identification of affinity-matured compounds.
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http://dx.doi.org/10.1002/advs.202001970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675038PMC
November 2020

Author Correction: Truncation of mutant huntingtin in knock-in mice demonstrates exon1 huntingtin is a key pathogenic form.

Nat Commun 2020 Nov 19;11(1):5989. Epub 2020 Nov 19.

Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, 510632, Guangzhou, China.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19873-9.
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http://dx.doi.org/10.1038/s41467-020-19873-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677395PMC
November 2020

Size-dependent strong metal-support interaction in TiO supported Au nanocatalysts.

Nat Commun 2020 Nov 16;11(1):5811. Epub 2020 Nov 16.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

The strong metal-support interaction (SMSI) has long been studied in heterogonous catalysis on account of its importance in stabilizing active metals and tuning catalytic performance. As a dynamic process taking place at the metal-support interface, the SMSI is closely related to the metal surface properties which are usually affected by the size of metal nanoparticles (NPs). In this work we report the discovery of a size effect on classical SMSI in Au/TiO catalyst where larger Au particles are more prone to be encapsulated than smaller ones. A thermodynamic equilibrium model was established to describe this phenomenon. According to this finding, the catalytic performance of Au/TiO catalyst with uneven size distribution can be improved by selectively encapsulating the large Au NPs in a hydrogenation reaction. This work not only brings in-depth understanding of the SMSI phenomenon and its formation mechanism, but also provides an alternative approach to refine catalyst performance.
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http://dx.doi.org/10.1038/s41467-020-19484-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669859PMC
November 2020