Publications by authors named "Mingyu Li"

139 Publications

Variations in Env at amino acids 328 and 330 affect HIV-1 replicative fitness and entry inhibitor sensitivity.

Virus Res 2021 Jul 18;299:198424. Epub 2021 Apr 18.

Unit of HIV Molecular Epidemiology and Virology, State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. Electronic address:

While the variations in the HIV-1 Env V3 loop have been the focus of much research to explore its functional effect, how specific mutations of certain amino acids in the V3 loop affect viral fitness remains unclear. In this study, we evaluated a series of natural polymorphisms at positions 328 and 330 with different combinations of adjacent glycosylation sites in the HIV-1 subtype B backbone to address their role in replicative fitness and sensitivity to entry inhibitors based on analysis of env sequence frequency at the population level. Pairwise growth competition experiment showed that wild-type virus with major consensus amino acids obviously had higher replicative fitness (P < 0.001). A change at position 328 to a less frequently occurring amino acid, K, together with a mutated N332 glycosylation site harbored lower fitness and became more sensitive to coreceptor antagonists (AMD3100), fusion inhibitors (T20) and sCD4. A change at position 330 to a less frequently occurring amino acid, Y, together with a mutated N332 glycosylation site resulted in higher fitness and less sensitivity to entry inhibitors (T20, AMD3100, and sCD4), and viruses containing both changes showed intermediate activity. It seems that the H330Y mutation compensated for the reduced replicative capacity caused by the Q328 K mutation. Moreover, viruses that showed lower replicative fitness also exhibited slower entry kinetics, lower levels of replication intermediates and protein packaging, and a lower ability to replicate in primary peripheral blood mononuclear cells (PBMCs). The findings highlight the functional effect of variations at 328 and 330 in the V3 loop on replicative fitness and may benefit HIV-1 treatment by helping predict the sensitivity to entry inhibitors.
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http://dx.doi.org/10.1016/j.virusres.2021.198424DOI Listing
July 2021

The Peculiar Clinical Symptoms and Treatment of Limbic Encephalitis Associated with AMPA Receptor Antibody.

Eur Neurol 2021 Apr 15:1-6. Epub 2021 Apr 15.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-related diseases are very rare in autoimmune neurological diseases. We collected and analyzed the data of 3 patients with peculiar clinical manifestation positive for AMPA2-R antibody in the Department of Neurology, Xuanwu Hospital, Capital Medical University. In our reported case series, 2 patients were male and 1 was female. The initial clinical features of 3 patients were all consistent with an encephalopathy predominantly involving the limbic system. Interestingly, as the disease continues to advance, case 1 presented with limb paralysis, case 2 developed typical cerebellar ataxia, and case 3 had symptoms of autonomic instability. These 3 types of clinical features were very rare in patients with AMPAR-Ab. After immunotherapy, cases 1 and 3 responded well and case 2 was not responsive. During the follow-up, residual memory loss of cases 1 and 3 improved gradually, and they returned to work. To eliminate the influence of the presence of other pathogenic antibodies, we analyzed the available individual clinical information of 37 patients with the single AMPAR-Ab by systematic literature review. A majority of patients had sudden short-term memory loss as the initial symptom and developed limbic encephalitis. Residual memory deficit was the most common symptom after discharge. The combination of at least 2 types of immunotherapy was recommended as the first-line treatment, and patients would benefit from the tumor screening. In addition, compared with the patients positive for single AMPAR-Ab, the patients with both AMPAR-Ab and other antibodies had a higher risk of malignant tumor and might have a poor therapeutic response, which led to a poor prognosis.
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http://dx.doi.org/10.1159/000515592DOI Listing
April 2021

Sustainable Performance Evaluation: Evidence from Listed Chinese Mining Corporations.

Entropy (Basel) 2021 Mar 15;23(3). Epub 2021 Mar 15.

College of Economics and Management, Shandong University of Science and Technology, Qingdao 266590, China.

Rapid industrial development has caused a series of environmental problems, which is not conducive to sustainable development of society as a whole. It is necessary to build a sustainable development evaluation system. Most of the existing literature has evaluated corporate sustainable performance from the economy, environment and society on the basis of triple bottom lines. Considering the research gap and the practice need, an evaluation system is established from four dimensions, referred to as economy, society, environment and responsibility management, and 29 indicators are designed to measure these four dimensions. Twenty seven listed Chinese mining corporations are selected as research samples, and the entropy-weight-based Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is applied to calculate indicators' weights. Results show that the four dimensions of sustainable performance weights from high to low are society, environment, economy, and management process.
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http://dx.doi.org/10.3390/e23030349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002129PMC
March 2021

Mechanistic insights into the effect of phosphorylation on Ras conformational dynamics and its interactions with cell signaling proteins.

Comput Struct Biotechnol J 2021 9;19:1184-1199. Epub 2021 Feb 9.

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.

Ras undergoes interconversion between the active GTP-bound state and the inactive GDP-bound state. This GTPase cycle, which controls the activities of Ras, is accelerated by Ras GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (SOS). Oncogenic Ras mutations could affect the GTPase cycle and impair Ras functions. Additionally, Src-induced K-Ras Y32/64 dual phosphorylation has been reported to disrupt GTPase cycle and hinder Ras downstream signaling. However, the underlying mechanisms remain unclear. To address this, we performed molecular dynamics simulations (~30 μs in total) on unphosphorylated and phosphorylated K-Ras4B in GTP- and GDP-bound states, and on their complexes with GTPase cycle regulators (GAP and SOS) and the effector protein Raf. We found that K-Ras4B dual phosphorylation mainly alters the conformation at the nucleotide binding site and creates disorder at the catalytic site, resulting in the enlargement of GDP binding pocket and the retard of Ras-GTP intrinsic hydrolysis. We observed phosphorylation-induced shift in the distribution of Ras-GTP inactive-active sub-states and recognized potential druggable pockets in the phosphorylated Ras-GTP. Moreover, decreased catalytic competence or signal delivery abilities due to reduced binding affinities and/or distorted catalytic conformations of GAP, SOS and Raf were observed. In addition, the allosteric pathway from Ras/Raf interface to the distal Raf L4 loop was compromised by Ras phosphorylation. These results reveal the mechanisms by which phosphorylation influences the intrinsic or GAP/SOS catalyzed transformations between GTP- and GDP-bound states of Ras and its signal transduction to Raf. Our findings project Ras phosphorylation as a target for cancer drug discovery.
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http://dx.doi.org/10.1016/j.csbj.2021.01.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902900PMC
February 2021

Dual roles of ATP-binding site in protein kinases: Orthosteric inhibition and allosteric regulation.

Adv Protein Chem Struct Biol 2021 13;124:87-119. Epub 2021 Feb 13.

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; Medicinal Chemistry and Bioinformatics Centre, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address:

Protein kinases use ATP to phosphorylate other proteins. Phosphorylation (p) universally orchestrates a fine-tuned network modulating a multitude of biological processes. Moreover, the start of networks, ATP-binding site, has been recognized dual roles to impact protein kinases function: (i) orthosteric inhibition, via being blocked to interference ATP occupying and (ii) allosteric regulation, via being altered first to induce further conformational changes. The above two terminologies are widely used in drug design, which has acquired quite a significant progress in the protein kinases field over the past 2 decades. Most small molecular inhibitors directly compete with ATP to implement orthosteric inhibition, still exhibiting irreplaceable and promising therapeutic effects. Additionally, numerous inhibitors can paradoxically lead protein kinases to hyperphosphorylation, even activation, indicative of the allosteric regulation role of the ATP-binding site. Here, we review the quintessential examples that apply for the dual roles in diverse ways. Our work provides an insight into the molecular mechanisms under the dual roles and will be promisingly instructive for future drug development.
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http://dx.doi.org/10.1016/bs.apcsb.2020.09.005DOI Listing
May 2021

Integrated Metabolomics and Lipidomics Analysis Reveal Remodeling of Lipid Metabolism and Amino Acid Metabolism in Glucagon Receptor-Deficient Zebrafish.

Front Cell Dev Biol 2020 14;8:605979. Epub 2021 Jan 14.

Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.

The glucagon receptor (GCGR) is activated by glucagon and is essential for glucose, amino acid, and lipid metabolism of animals. GCGR blockade has been demonstrated to induce hypoglycemia, hyperaminoacidemia, hyperglucagonemia, decreased adiposity, hepatosteatosis, and pancreatic α cells hyperplasia in organisms. However, the mechanism of how GCGR regulates these physiological functions is not yet very clear. In our previous study, we revealed that GCGR regulated metabolic network at transcriptional level by RNA-seq using GCGR mutant zebrafish (). Here, we further performed whole-organism metabolomics and lipidomics profiling on wild-type and zebrafish to study the changes of metabolites. We found 107 significantly different metabolites from metabolomics analysis and 87 significantly different lipids from lipidomics analysis. Chemical substance classification and pathway analysis integrated with transcriptomics data both revealed that amino acid metabolism and lipid metabolism were remodeled in -deficient zebrafish. Similar to other studies, our study showed that zebrafish exhibited decreased ureagenesis and impaired cholesterol metabolism. More interestingly, we found that the glycerophospholipid metabolism was disrupted, the arachidonic acid metabolism was up-regulated, and the tryptophan metabolism pathway was down-regulated in zebrafish. Based on the omics data, we further validated our findings by revealing that zebrafish exhibited dampened melatonin diel rhythmicity and increased locomotor activity. These global omics data provide us a better understanding about the role of GCGR in regulating metabolic network and new insight into GCGR physiological functions.
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http://dx.doi.org/10.3389/fcell.2020.605979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841139PMC
January 2021

A general Fc engineering platform for the next generation of antibody therapeutics.

Theranostics 2021 1;11(4):1901-1917. Epub 2021 Jan 1.

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.

Fc engineering has become the focus of antibody drug development. The current mutagenesis and protein design methods are confined by the limited throughput and high cost, while the high-throughput phage display and yeast display technologies are not suitable for screening glycosylated Fc variants. Here we developed a mammalian cell display-based Fc engineering platform. By using mammalian cell display and next generation sequencing, we screened millions of Fc variants for optimized affinity and specificity for FcγRIIIa or FcγRIIb. The identified Fc variants with improved binding to FcγRIIIa were substituted into trastuzumab and rituximab and the effector function of antibodies were examined in the PBMC-based assay. On the other hand, the identified Fc variants with selectively enhanced FcγRIIb binding were applied to CD40 agonist antibody and the activities of the antibodies were measured on different cell assays. The immunostimulatory activity of CD40 antibodies was also evaluated by OVA-specific CD8 T cell response model in FcγR/CD40-humanized mice. Using this approach, we screened millions of Fc variant and successfully identified several novel Fc variants with enhanced FcγRIIIa or FcγRIIb binding. These identified Fc variants displayed a dramatic increase in antibody-dependent cellular cytotoxicity in PBMC-based assay. Novel variants with selectively enhanced FcγRIIb binding were also identified. CD40 agonist antibodies substituted with these Fc variants displayed activity more potent than the parental antibody in the and models This approach increased the throughput of Fc variant screening from thousands to millions magnitude, enabled screening variants containing multiple mutations and could be integrated with glycoengineering technology, represents an ideal platform for Fc engineering. The initial efforts demonstrated the capability of the platform and the novel Fc variants could be substituted into nearly any antibody for the next generation of antibody therapeutics.
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http://dx.doi.org/10.7150/thno.51299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778609PMC
January 2021

Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis.

Cell 2021 01 14;184(1):184-193.e10. Epub 2020 Nov 14.

MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China. Electronic address:

Transcription of SARS-CoV-2 mRNA requires sequential reactions facilitated by the replication and transcription complex (RTC). Here, we present a structural snapshot of SARS-CoV-2 RTC as it transitions toward cap structure synthesis. We determine the atomic cryo-EM structure of an extended RTC assembled by nsp7-nsp8-nsp12-nsp13-RNA and a single RNA-binding protein, nsp9. Nsp9 binds tightly to nsp12 (RdRp) NiRAN, allowing nsp9 N terminus inserting into the catalytic center of nsp12 NiRAN, which then inhibits activity. We also show that nsp12 NiRAN possesses guanylyltransferase activity, catalyzing the formation of cap core structure (GpppA). The orientation of nsp13 that anchors the 5' extension of template RNA shows a remarkable conformational shift, resulting in zinc finger 3 of its ZBD inserting into a minor groove of paired template-primer RNA. These results reason an intermediate state of RTC toward mRNA synthesis, pave a way to understand the RTC architecture, and provide a target for antiviral development.
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http://dx.doi.org/10.1016/j.cell.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666536PMC
January 2021

Architecture of a SARS-CoV-2 mini replication and transcription complex.

Nat Commun 2020 11 18;11(1):5874. Epub 2020 Nov 18.

MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.

Non-structural proteins (nsp) constitute the SARS-CoV-2 replication and transcription complex (RTC) to play a pivotal role in the virus life cycle. Here we determine the atomic structure of a SARS-CoV-2 mini RTC, assembled by viral RNA-dependent RNA polymerase (RdRp, nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2), by cryo-electron microscopy. Two groups of mini RTCs with different conformations of nsp13-1 are identified. In both of them, nsp13-1 stabilizes overall architecture of the mini RTC by contacting with nsp13-2, which anchors the 5'-extension of RNA template, as well as interacting with nsp7-nsp8-nsp12-RNA. Orientation shifts of nsp13-1 results in its variable interactions with other components in two forms of mini RTC. The mutations on nsp13-1:nsp12 and nsp13-1:nsp13-2 interfaces prohibit the enhancement of helicase activity achieved by mini RTCs. These results provide an insight into how helicase couples with polymerase to facilitate its function in virus replication and transcription.
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http://dx.doi.org/10.1038/s41467-020-19770-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675986PMC
November 2020

A circular RNA from NFIX facilitates oxidative stress-induced H9c2 cells apoptosis.

In Vitro Cell Dev Biol Anim 2020 Oct 16;56(9):715-722. Epub 2020 Oct 16.

Department of Inspection, The Medical Faculty, Qingdao University, Qingdao, 266003, China.

Myocardial infarction is the leading cause of death worldwide, and cardiomyocyte apoptosis during myocardial infarction and reperfusion is a significant factor of poor prognosis. As important regulatory molecules, biofunctions of circRNAs in the pathogenesis of myocardial infarction remain elusive. To confirm the expression level and biological function of circNFIX in cardiomyocytes upon oxidative stress. Divergent polymerase chain reaction and Sanger sequencing were performed to verify the circular structure. The stability of circNFIX was confirmed by RNase R treatment and actinomycin D assay. In order to simulate oxidative stress during myocardial infarction, H9c2 cells were subjected to hydrogen peroxide and hypoxia stimulation. In vivo, mouse models of myocardial ischemia were established. The biological function of circNFIX in cardiomyocytes was investigated through loss- and gain-of-function assays, and cardiomyocyte apoptosis level was detected by the terminal deoxyribonucleotidyl transferase-mediated TdT-mediated dUTP nick end labeling assay and Western blot. CircNFIX is abundant, conserved, and stable in H9c2 cells. The expression of circNFIX was significantly downregulated in cardiomyocytes subjected to oxidative stress. Enforced CircNFIX promotes H9c2 cells apoptosis induced by hydrogen peroxide, in sharp contrast to circNFIX knockdown. In this study, we found that circNFIX served as a pro-apoptosis factor in cardiomyocyte apoptosis. CircNFIX possesses potential to be the biomarker and therapeutic target in myocardial infarction.
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http://dx.doi.org/10.1007/s11626-020-00476-zDOI Listing
October 2020

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

J Nat Prod 2020 10 23;83(10):2996-3003. Epub 2020 Sep 23.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus as a promising candidate. After fermentation and extraction of , we isolated five new prenylated xanthones, namely, staprexanthones A-E (-), with staprexanthone A () being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Compounds , , and significantly increased β-cell numbers in a zebrafish model. Further analysis revealed that and promoted β-cell mass expansion by increasing proliferation of existing β-cells though promotion of cell-cycle progression at the G1/S transition. These findings indicate that prenylated xanthones are potential new drug leads for antidiabetes therapy by stimulating β-cell regeneration.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00535DOI Listing
October 2020

IDDB: a comprehensive resource featuring genes, variants and characteristics associated with infertility.

Nucleic Acids Res 2021 01;49(D1):D1218-D1224

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200011, China.

Infertility is a complex multifactorial disease that affects up to 10% of couples across the world. However, many mechanisms of infertility remain unclear due to the lack of studies based on systematic knowledge, leading to ineffective treatment and/or transmission of genetic defects to offspring. Here, we developed an infertility disease database to provide a comprehensive resource featuring various factors involved in infertility. Features in the current IDDB version were manually curated as follows: (i) a total of 307 infertility-associated genes in human and 1348 genes associated with reproductive disorder in 9 model organisms; (ii) a total of 202 chromosomal abnormalities leading to human infertility, including aneuploidies and structural variants; and (iii) a total of 2078 pathogenic variants from infertility patients' samples across 60 different diseases causing infertility. Additionally, the characteristics of clinically diagnosed infertility patients (i.e. causative variants, laboratory indexes and clinical manifestations) were collected. To the best of our knowledge, the IDDB is the first infertility database serving as a systematic resource for biologists to decipher infertility mechanisms and for clinicians to achieve better diagnosis/treatment of patients from disease phenotype to genetic factors. The IDDB is freely available at http://mdl.shsmu.edu.cn/IDDB/.
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http://dx.doi.org/10.1093/nar/gkaa753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779019PMC
January 2021

Thermo-Optical Tuning Cascaded Double Ring Sensor with Large Measurement Range.

Sensors (Basel) 2020 Sep 9;20(18). Epub 2020 Sep 9.

Department of Optical Engineering, School of Opto-Electronic Engineering, Changchun University of Science and Technology, Changchun 130022, China.

In this paper, a thermo-optic tuning optical waveguide sensor system based on a cascaded double micro-ring resonator is investigated. The system consists of a micro-ring resonator with the microheater as a reference ring and a micro-ring resonator with removing the upper cladding layers as a sensing ring, combined with a microfluidic control. The refractive index change of the sample is measured by the electric power change of the microheater. The experimental results show that the sensitivity of the thermo-optic tuning is 34.231 W/RIU (refractive index units), and the measurement range is 4.325 × 10 RIU, almost eight times larger than that of the cascaded double micro-ring resonator without thermo-optic tuning for the intensity interrogation.
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http://dx.doi.org/10.3390/s20185149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570838PMC
September 2020

Wearable Circuits Sintered at Room Temperature Directly on the Skin Surface for Health Monitoring.

ACS Appl Mater Interfaces 2020 Oct 27;12(40):45504-45515. Epub 2020 Sep 27.

Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

A soft body area sensor network presents a promising direction in wearable devices to integrate on-body sensors for physiological signal monitoring and flexible printed circuit boards (FPCBs) for signal conditioning/readout and wireless transmission. However, its realization currently relies on various sophisticated fabrication approaches such as lithography or direct printing on a carrier substrate before attaching to the body. Here, we report a universal fabrication scheme to enable printing and room-temperature sintering of the metal nanoparticle on paper/fabric for FPCBs and directly on the human skin for on-body sensors with a novel sintering aid layer. Consisting of polyvinyl alcohol (PVA) paste and nanoadditives in the water, the sintering aid layer reduces the sintering temperature. Together with the significantly decreased surface roughness, it allows for the integration of a submicron-thick conductive pattern with enhanced electromechanical performance. Various on-body sensors integrated with an FPCB to detect health conditions illustrate a system-level example.
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http://dx.doi.org/10.1021/acsami.0c11479DOI Listing
October 2020

Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix.

J Clin Invest 2020 09;130(9):4704-4709

Division of Hematology and Oncology, Department of Medicine and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, USA.

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti-lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.
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http://dx.doi.org/10.1172/JCI136760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456216PMC
September 2020

Impact-Induced Removal of a Deposited Droplet: Implications for Self-Cleaning Properties.

J Phys Chem Lett 2020 Aug 27;11(15):6396-6403. Epub 2020 Jul 27.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, People's Republic of China.

The ability to remove a deposited drop on a substrate is crucial for self-cleaning materials. Here, an approach to achieve the removal of a deposited droplet by employing the impact of a smaller droplet as remover is reported. The results give visible evidence that with the increase of the impact velocity and the size of the impacting droplet, a deposition-to-rebound transition of droplets could occur. Correspondingly, a map showing the relationship between the states of the impacted droplet and the impacting conditions is depicted. More importantly, the proposed model suggests that this novel deposition-to-rebound transition induced by the impact is ascribed to the production of positive excess energy during the process from maximum spreading to complete retraction, which provides the critical value of spreading factor (β) and equilibrium contact angle (θ) for determining whether the transition occurs.
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http://dx.doi.org/10.1021/acs.jpclett.0c01718DOI Listing
August 2020

Role of salt ions and molecular weights on the formation of Mesona chinensis polysaccharide-chitosan polyelectrolyte complex hydrogel.

Food Chem 2020 Dec 6;333:127493. Epub 2020 Jul 6.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; School of Food Science and Technology, Nanchang University, Nanchang 330047, China. Electronic address:

The effects of the addition of salt ions and molecular weights (Mw) of CH on Mesona chinensis polysaccharide (MCP)-chitosan (CH) hydrogel were investigated. Result indicated both low concentration of monovalent salt ions (Na and K), divalent cations (Ca) and oxoanions (SO) could promote the gel properties of MCP-CH hydrogel. The Mw of CH has huge impact on the formation and properties of hydrogel. Combining the relationship between rheology and structural, monovalent salt ions such as Na and K affect gel formation and its properties by influencing electrostatic interaction and chain conformation. Both divalent cations (Ca) and oxoanions (SO) facilitated the formation of gel networks via electrostatic interaction, coordination bonds and hydrogen bonds. Moreover, Mw of CH influenced formation and texture of MCP-CH hydrogel via affecting the conformation of CH molecular chain. These findings will provide a few theoretical bases to understand the formation mechanism of MCP-CH hydrogel.
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http://dx.doi.org/10.1016/j.foodchem.2020.127493DOI Listing
December 2020

The Expression and Clinical Significance of MicroRNA-409-3p in Acute Myeloid Leukemia.

Clin Lab 2020 Jun;66(6)

Background: MicroRNA-409-3p, is down-regulated in a variety of malignant diseases. However, the expression level and clinical value of microRNA-409-3p in acute myeloid leukemia has not yet been systematically studied.

Methods: We collected 88 bone marrow samples derived from 73 patients with acute myeloid leukemia and 15 healthy controls. Then we evaluated the expression of microRNA-409-3p by quantitative real-time PCR.

Results: The results revealed that compared with the healthy controls, microRNA-409-3p expression in a newly diagnosed group was significantly lower (p < 0.001). In addition, the microRNA-409-3p expression in the complete remission group was strikingly higher compared to that of the newly diagnosed group (p < 0.001). There was a correlation between microRNA-409-3p expression and white blood cells (p = 0.021). Most importantly, the micro-RNA-409-3p low expression group indicated a shorter event-free survival compared with microRNA-409-3p high expression group by using Kaplan-Meier analysis (p < 0.0438).

Conclusions: The microRNA-409-3p expression level could be a novel potential biomarker for acute myeloid leukemia diagnosis and prognosis, providing a new therapeutic strategy for acute myeloid leukemia treatment.
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http://dx.doi.org/10.7754/Clin.Lab.2019.191107DOI Listing
June 2020

Structure of African swine fever virus p15 reveals its dual role for membrane-association and DNA binding.

Protein Cell 2020 08;11(8):606-612

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, People's Republic of China.

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http://dx.doi.org/10.1007/s13238-020-00731-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381529PMC
August 2020

Ag-Sn bimetallic nanoparticles paste for high temperature service in power devices.

Nanotechnology 2020 Aug 13;31(34):345204. Epub 2020 May 13.

Department of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, People's Republic of China.

In this paper, high strength Cu-Cu interconnections were achieved by sintering the paste of Ag-Sn bimetallic nanoparticles at low temperature. Compared with nano-Ag paste, the outer Sn coatings of the nano-Ag particles were found to be favorable for the densification of the bondline. The microstructures of Ag-Sn bimetallic nanoparticles and the bondlines under different sintereing conditions were studied in detail by x-ray photoelectron spectroscopy (XPS), x-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The Ag-Sn bimetallic nanoparticles bondline exhibit a high shear strength of 35.3 MPa and a low resistivity of 9.5 μΩ cm, when sintered at 260 °C for 20 min under a pressure of 0.5 MPa. The electrochemical migration time of this sintered Ag-Sn bimetallic nanoparticles was prolonged to be ten times of that of sintered nano-Ag. This bonding technology based on Ag-Sn bimetallic nanoparticles was a promising die attach method for high temperature power device packaging.
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http://dx.doi.org/10.1088/1361-6528/ab92cdDOI Listing
August 2020

Characterization of Insulin and Glucagon Genes and Their Producing Endocrine Cells From Pygmy Sperm Whale ().

Front Endocrinol (Lausanne) 2020 31;11:174. Epub 2020 Mar 31.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, China.

Insulin and glucagon are hormones secreted by pancreatic β and α cells, respectively, which together regulate glucose homeostasis. Dysregulation of insulin or glucagon can result in loss of blood glucose control, characterized by hyperglycemia or hypoglycemia. To better understand the endocrine physiology of cetaceans, we cloned and characterized the and genes from pygmy sperm whale (. We obtained the complete coding sequences of the and genes, which encodes the preproinsulin protein of 110 amino acid (aa) residues and encodes the preproglucagon protein of 179 aa residues, respectively. Sequence comparison and phylogenetic analyses demonstrate that protein structures were similar to other mammalian orthologs. Immunohistochemistry and immunofluorescence staining using insulin, glucagon, and somatostatin antibodies allowed analysis of pygmy sperm whale islet distribution, architecture, and composition. Our results showed the pygmy sperm whale islet was irregularly shaped and randomly distributed throughout the pancreas. The architecture of α, β, and δ cells of the pygmy sperm whale was similar to that of artiodactyls species. This is the first report about and genes in cetaceans, which provides new information about the structural conservation of the insulin and glucagon genes. Furthermore, offers novel information on the properties of endocrine cells in cetacean for further studies.
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http://dx.doi.org/10.3389/fendo.2020.00174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137828PMC
March 2021

Ultrasonic-accelerated metallurgical reaction of Sn/Ni composite solder: Principle, kinetics, microstructure, and joint properties.

Ultrason Sonochem 2020 Sep 25;66:105090. Epub 2020 Mar 25.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology at Shenzhen, Shenzhen 518055, Guangdong, China; Flexible Printing Electronic Technology Center, Harbin Institute of Technology at Shenzhen, Shenzhen 518055, China. Electronic address:

The high-melting-point joints by transient-liquid-phase are increasingly playing a crucial role in the die bonding for the high temperature electronic components. In this study, three kinds of Sn/Ni composite solder pastes composed of different sizes of Ni particles were synthesized to accelerate metallurgical reaction among Sn/Ni interfaces under the ultrasonic-assisted transient liquid phase (U-TLP) soldering. The temperature evolution, microstructure and mechanical property in joints composed by these composite solder pastes with or without ultrasonic energy were systemically investigated. The intermetallic joint consisted of high-melting-point sole NiSn intermetallic compound with a little residual Ni was obtained under the conditions of no pressure and lower power (200 W) in a high-temperature duration of only 10 s, its shear strength was up to 45.3 MPa. Ultrasonic effects significantly accelerated the reaction among the interfaces of liquid Sn and solid Ni, which attributed to the temperature rise caused by acoustic cavitation because of large number of liquid/solid interfaces during U-TLP, resulting in accelerated solid/liquid interfacial diffusion and growth of intermetallic compounds. This intermetallic joint formed by U-TLP soldering has a promising potential for applications in high-power device packaging.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105090DOI Listing
September 2020

Predictive modelling of the distribution of sect. . . under climate change reveals a range expansion during the Last Glacial Maximum.

PeerJ 2020 9;8:e8729. Epub 2020 Mar 9.

Beijing Forestry University, Beijing, China.

Background: The knowledge of distributional dynamics of living organisms is a prerequisite for protecting biodiversity and for the sustainable use of biotic resources. sect. . . is a small group of shrubby, yellow-flowered species distributed mainly in arid and semi-arid areas of China. Plants in this section are both horticulturally and ecologically important.

Methods: Using past, present, and future environmental variables and data with Maximum Entropy (Maxent) modeling, we evaluated the importance of the environmental variables on the section's estimated distributions, thus simulating its distributional dynamics over time. The contractions and expansions of suitable habitat between the past and future scenarios and the present were then compared.

Results And Discussion: The models revealed that the areas with high and moderate suitability currently encompass about 725,110 km. The distribution centroid location varies between points in Ningxia and Inner Mongolia during the different scenarios. Elevation, Mean UV-B of Lowest Month, Precipitation of Coldest Quarter, and Mean Temperature of Driest Quarter were major factors determining the section's distribution. Our modeling indicated that sect. underwent a significant range contraction during the last interglacial period, and then expanded during the last glacial maximum (LGM) to amounts like those of the present. Cold, dry, and relatively stable climate, as well as steppe or desert steppe environments may have facilitated range expansion of this cold-adapted, drought-resistant plant taxon during the LGM. Predicted future scenarios show little change in the amounts of suitable habitat for sect. . This study aids understanding of the distributional dynamics of sect. , and the results will help the conservation and sustainable use of these important woody plants in Chinese arid and semiarid areas.
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http://dx.doi.org/10.7717/peerj.8729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067196PMC
March 2020

What ultimately drives the wrapping, deprivation, and transfer of graphene nanosheets.

Phys Chem Chem Phys 2020 Mar 13;22(12):6553-6559. Epub 2020 Mar 13.

School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, Manchester, M13-9PL, UK.

This study was devoted to investigating the interactions between graphene sheets (GNSs) and metal nanowires via molecular dynamics simulations. The simulation results indicated that the element type, shape, and size of the nanowires would affect their adhering behavior and help achieve the interesting wrapping, deprivation, and transfer phenomenon of a GNS. An appropriate length-width ratio of the GNS and nanowire contributed to the formation of a helical configuration of GNS out of nanowires under the action of van der Waals interactions. Importantly, some of the GNSs could spontaneously peel off from one nanowire and re-assemble a new spiral core-shell structure on another nanowire. This deprivation and re-assembly was associated with the definite elemental selectivity, which was determined by the adsorption energy of the GNSs on the nanowires. The adsorption energy difference drove the full or partial transfer of the GNSs. This study provides deep insights into the interactions between GNSs and nanowires.
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http://dx.doi.org/10.1039/c9cp06909gDOI Listing
March 2020

Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network.

Int J Mol Sci 2020 Jan 22;21(3). Epub 2020 Jan 22.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China.

The glucagon receptor (GCGR) is a G-protein-coupled receptor (GPCR) that mediates the activity of glucagon. Disruption of GCGR results in many metabolic alterations, including increased glucose tolerance, decreased adiposity, hypoglycemia, and pancreatic α-cell hyperplasia. To better understand the global transcriptomic changes resulting from GCGR deficiency, we performed whole-organism RNA sequencing analysis in wild type and -deficient zebrafish. We found that the expression of 1645 genes changes more than two-fold among mutants. Most of these genes are related to metabolism of carbohydrates, lipids, and amino acids. Genes related to fatty acid β-oxidation, amino acid catabolism, and ureagenesis are often downregulated. Among -deficient zebrafish, we experimentally confirmed increases in lipid accumulation in the liver and whole-body glucose uptake, as well as a modest decrease in total amino acid content. These results provide new information about the global metabolic network that GCGR signaling regulates in addition to a better understanding of the receptor's physiological functions.
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http://dx.doi.org/10.3390/ijms21030724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037442PMC
January 2020

Multi-layer silver nanowire/polyethylene terephthalate mesh structure for highly efficient transparent electromagnetic interference shielding.

Nanotechnology 2020 May 20;31(18):185303. Epub 2020 Jan 20.

Electromagnetic interference protection in optoelectronic devices is challenging because of the dual requirements of optical transmittance and high shielding effectiveness (SE). Herein, we propose a novel silver nanowire (AgNW)/polyethylene terephthalate (PET) multi-layer mesh pattern structure for transparent electromagnetic shielding obtained via laser marking and transfer printing. A three-layer composite shielding film with an optical transmittance of 67.8% exhibits a SE of 44 dB at 10 GHz, which is superior to most of the reported transparent shielding films composed of AgNWs to date. The newly designed multi-layer composite structure can enhance the transparent shielding properties of the shielding film via optimization of the AgNW distribution and the shielding film structure. It is expected that this multi-layer mesh composite structure will have splendid application prospects in electromagnetic shielding films, which require both light transmittance and high SE.
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http://dx.doi.org/10.1088/1361-6528/ab6d9dDOI Listing
May 2020

MicroRNAs: pivotal regulators in acute myeloid leukemia.

Ann Hematol 2020 Mar 13;99(3):399-412. Epub 2020 Jan 13.

Department of Clinical Hematology, Medical College of Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.

MicroRNAs are a class of small non-coding RNAs that are 19-22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level. MicroRNA dysregulation disrupts normal biological processes, resulting in tumorigenesis. Acute myeloid leukemia is an invasive hematological malignancy characterized by the abnormal proliferation and differentiation of immature myeloid cells. Due to the low 5-year survival rate, there is an urgent need to discover novel diagnostic markers and therapeutic targets. In recent years, microRNAs have been shown to play important roles in hematological malignancies by acting as tumor suppressors and oncogenes. MicroRNAs have the potential to be a breakthrough in the diagnosis and treatment of acute myeloid leukemia. In this review, we summarize the biology of microRNAs and discuss the relationships between microRNA dysregulation and acute myeloid leukemia in the following aspects: signaling pathways, the abnormal biological behavior of acute myeloid leukemia cells, the clinical application of microRNAs and competing endogenous RNA regulatory networks.
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http://dx.doi.org/10.1007/s00277-019-03887-5DOI Listing
March 2020

Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment.

Mater Sci Eng C Mater Biol Appl 2020 Mar 5;108:110386. Epub 2019 Nov 5.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang'an South Road, Xiamen, Fujian, 361102, China. Electronic address:

Therapeutic peptide, NuBCP-9 (N9) as a Bcl-2 functional converter, has been demonstrated to have the remarkable anticancer efficiency in Bcl-2-abundant cancer. However, it faced technical challenges in clinical use, such as the low bioavailability, the easily-destroyed bio-stability, and the insusceptibility to cellular interior. With the potential of mesoporous silica nanoparticles (MSNs) as the promising delivery vehicle of therapeutic macromolecules, we developed a kind of MSNs with the surface coating of folic acid (FA) for cancer cell targeting and with the macropore loading of N9 peptide for cancer therapy. Our results showed that the functional MSNs had the relatively greater biosafety than the naked MSNs in zebrafish models, leading to less than 30% embryo of death at 200 μg/ml, which could further specifically target the folate receptor (FR)-overexpressed cervical cancer HeLa cells instead of FR-negative normal embryonic kidney HEK 293T cells in a FA-competitive manner. N9 peptide with the delivery of functional MSNs could be internalized by HeLa cells, and co-localized with mitochondria in a Bcl-2-dependent manner. Moreover, N9 peptide delivered by FA-modified MSNs displayed the excellent anticancer efficiency with great selectivity, inducing approximately 52% HeLa cells into apoptosis. In summary, our results illustrated the potential of functional MSNs with large pore size as an efficient nanocarrier for the intracellular delivery of peptide drugs with targeting proteins to realize cancer therapy.
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http://dx.doi.org/10.1016/j.msec.2019.110386DOI Listing
March 2020

Characteristic Microbiomes Correlate with Polyphosphate Accumulation of Marine Sponges in South China Sea Areas.

Microorganisms 2019 Dec 30;8(1). Epub 2019 Dec 30.

College of Ocean and Earth Science of Xiamen University, Xiamen 361005, China.

Some sponges have been shown to accumulate abundant phosphorus in the form of polyphosphate (polyP) granules even in waters where phosphorus is present at low concentrations. But the polyP accumulation occurring in sponges and their symbiotic bacteria have been little studied. The amounts of polyP exhibited significant differences in twelve sponges from marine environments with high or low dissolved inorganic phosphorus (DIP) concentrations which were quantified by spectral analysis, even though in the same sponge genus, e.g., sp. or sp. PolyP enrichment rates of sponges in oligotrophic environments were far higher than those in eutrophic environments. Massive polyP granules were observed under confocal microscopy in samples from very low DIP environments. The composition of sponge symbiotic microbes was analyzed by high-throughput sequencing and the corresponding polyphosphate kinase () genes were detected. Sequence analysis revealed that in the low DIP environment, those sponges with higher polyP content and enrichment rates had relatively higher abundances of cyanobacteria. Mantel tests and canonical correspondence analysis (CCA) examined that the polyP enrichment rate was most strongly correlated with the structure of microbial communities, including genera , , and . About 50% of genes obtained from the total DNA of sponge holobionts, had above 80% amino acid sequence similarities to those sequences from . In general, it suggested that sponges employed differentiated strategies towards the use of phosphorus in different nutrient environments and the symbiotic could play a key role in accumulating polyP.
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http://dx.doi.org/10.3390/microorganisms8010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022310PMC
December 2019