Publications by authors named "Yihan Liu"

75 Publications

The first mitochondrial genome of a fern sawfly, Stephens, 1835 (Hymenoptera: Tenthredinidae).

Mitochondrial DNA B Resour 2021 Mar 15;6(3):902-904. Epub 2021 Mar 15.

College of Life Sciences, Jiangxi Normal University, Nanchang, China.

The first mitochondrial genome of a fern sawfly, Stephens, 1835 was determined. The sequence is 15,210 bp in length, including 37 typical mitochondrial genes. Four tRNA gene arrangements were observed. This mitochondrial genome provided an essential resource for addressing taxonomic issues and studying molecular evolution.
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http://dx.doi.org/10.1080/23802359.2021.1886019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971261PMC
March 2021

Emerging roles of extracellular vesicles in COVID-19, a double-edged sword?

Immunology 2021 Mar 19. Epub 2021 Mar 19.

Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, 200072, China.

The sudden outbreak of SARS-CoV-2 infected disease (COVID-19), initiated from Wuhan, China, has rapidly grown into a global pandemic. Emerging evidence has implicated extracellular vesicles (EVs), a key intercellular communicator, in the pathogenesis and treatment of COVID-19. In the pathogenesis of COVID-19, cells that express ACE2 and CD9 can transfer these viral receptors to other cells via EVs, making recipient cells more susceptible for SARS-CoV-2 infection. Once infected, cells release EVs packaged with viral particles that further facilitate viral spreading and immune evasion, aggravating COVID-19 and its complications. In contrast, EVs derived from stem cells, especially mesenchymal stromal/stem cells, alleviate severe inflammation (cytokine storm) and repair damaged lung cells in COVID-19 by delivery of anti-inflammatory molecules. These therapeutic beneficial EVs can also be engineered to function as a drug delivery platform or vaccine to fight against COVID-19. Therefore, EVs from diverse sources exhibit distinct effects in regulating viral infection, immune response, and tissue damage/repair, functioning as a double-edged sword in COVID-19. Here, we summarize the recent progress in understanding the pathological roles of EVs in COVID-19. A comprehensive discussion of the therapeutic effects/potentials of EVs is also provided.
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http://dx.doi.org/10.1111/imm.13329DOI Listing
March 2021

Mechanical heart valve thrombosis during pregnancy under nonwarfarin anticoagulation therapy: Twocase report and literature review.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Feb;46(2):207-211

Xiangya School of Medicine, Central South University, Changsha 410013, China.

Anticoagulation drugs should be used for patients with mechanical heart valve (MHV) in case of potential risk of thrombosis. Pregnant women with MHV have to change therapies due to teratogenic effect of some anti-coagulation drugs. European Society of Cardiology clinical guidelines for the management of cardiovascular diseases during pregnancy gives specific suggestions for anticoagulation therapy.We have treated 2 patients with mechanical heart valve thrombosis (MVT) during pregnancy: One received low molecular weight heparin (LMWH) throughout the pregnancy and developed MVT at the third trimester of pregnancy; one developed MVT at the first trimester when replacing vitamin K antagonists (VKA) with LMWH. These patients raised secondary reflection on the balance between clinical guideline and personalized medicine. During LMWH therapy, we should dynamically monitor patients' anti-activated factor X (anti-Xa) level to evaluate coagulation function during pregnancy. When a pregnant woman with MHV develops symptoms of acute heart failure, stuck mechanical valve should be paid attention to and surgery should be promptly performed if necessary.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200645DOI Listing
February 2021

Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma.

Theranostics 2021 26;11(8):3676-3693. Epub 2021 Jan 26.

Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Methyltransferase-like 14 (METTL14) participates in tumorigenesis in several malignancies, but how METTL14 mediates the metastasis of renal cell carcinoma (RCC) has never been reported. Western blotting, quantitative real-time PCR, and immunohistochemistry were used to determine the mRNA and protein levels of relevant genes. Methylated RNA immunoprecipitation sequencing and RNA sequencing were utilized to screen potential targets of METTL14. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing were performed to investigate epigenetic alterations. The biological roles and mechanisms of METTL14/BPTF in promoting lung metastasis were confirmed and using cell lines, patient samples, xenograft models, and organoids. Utilizing the TCGA-KIRC and Ruijin-RCC datasets, we found low expression of METTL14 in mRCC samples, which predicted poor prognosis. METTL14 deficiency promoted RCC metastasis and . Mechanistically, METTL14-mediated mA modification negatively regulated the mRNA stability of bromodomain PHD finger transcription factor (BPTF) and depended on BPTF to drive lung metastasis. Accumulated BPTF in METTL14-deficient cells remodeled the enhancer landscape to reinforce several oncogenic crosstalk. Particularly, BPTF constituted super-enhancers that activate downstream targets like enolase 2 and SRC proto-oncogene nonreceptor tyrosine kinase, leading to glycolytic reprogramming of METTL14 cells. Finally, we determined the efficacy of the BPTF inhibitor AU1 in suppressing mRCC of patient-derived cells, mRCC-derived organoids (MDOs), and orthotopic xenograft models. Our study is the first to investigate the essential role of mA modification and the METTL14/BPTF axis in the epigenetic and metabolic remodeling of mRCC, highlighting AU1 as a vital therapeutic candidate.
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http://dx.doi.org/10.7150/thno.55424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914369PMC
January 2021

Epigenome screening highlights that JMJD6 confers an epigenetic vulnerability and mediates sunitinib sensitivity in renal cell carcinoma.

Clin Transl Med 2021 Feb;11(2):e328

Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high-throughput sequencing data revealed that JMJD6 could assemble super-enhancers to drive a list of identity genes in kidney cancer, including VEGFA, β-catenin, and SRC. Moreover, this JMJD6-mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient-derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients.
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http://dx.doi.org/10.1002/ctm2.328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882098PMC
February 2021

Cerebral venous sinus thrombosis secondary to tonsillectomy.

Auris Nasus Larynx 2021 Feb 23. Epub 2021 Feb 23.

Department of ENT, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Cerebral venous sinus thrombosis(CVST) is considered to be a rare, high-risk, easily misdiagnosed disease with a mortality rate of 9.4%. Early diagnosis and timely anticoagulant thrombolytic therapy can reduce the mortality and disability rate and improve the prognosis of patients. This report describes the situation of a young male patient with bilateral tonsillectomy who, after going under low temperature plasma and general anesthesia surgery, presented with headache on the 4th day after the operation, and was diagnosed to be CVST by computed tomography(CT) and Magnetic Resonance Imaging(MRI). Due to severe pharynx swallowing pain after the surgery, his total daily intake was less than 2000 ml. After treatment, his prognosis was optimistic. The rarity and high risk of CVST after tonsillectomy suggest that we should pay attention to the related problems in the perioperative management of tonsillectomy include Bacterial infections, high condensation state of dehydration, using hemostatic drugs sparingly, etc.
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http://dx.doi.org/10.1016/j.anl.2020.11.017DOI Listing
February 2021

Biochemical characterization of a tyrosinase from Bacillus aryabhattai and its application.

Int J Biol Macromol 2021 Apr 8;176:37-46. Epub 2021 Feb 8.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

Although lots of tyrosinases have been isolated from bacteria, few studies are focused on tyrosinases from Bacillus sp.. In this study, a tyrosinase from B. aryabhattai TCCC 111983 (TYR) was functionally expressed, purified, and then biochemically characterized. The recombinant tyrosinase (rTYR) presented a good catalytic activity in a broad temperature and pH range, retaining over 60% of the relative activity at 30 °C-90 °C and 45% at pH 3.0 to 10.0. Especially, rTYR exhibited 20% of its maximum activity at 0 °C, and it also showed a variable stability towards different effectors. It presented high tolerance towards salinity and chloride, retaining 81% of its original activity in 2 M NaCl. Kinetic parameters indicated that rTYR displayed a relatively good affinity for both l-tyrosine and l-DOPA. Additionally, rTYR demonstrated remarkable advantages on efficient decolorizing azo and anthraquinonic food dyes (carmine and erythrosin), and more five industrial dyes with or without mediators in acidic, neutral, and alkaline conditions. As the first report on the tyrosinase from B. aryabhattai, the aforementioned results indicated that rTYR would be potential for food industrial applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.042DOI Listing
April 2021

Enhancing the functional characteristics of soy protein isolate via cross-linking catalyzed by Bacillus subtilis transglutaminase.

J Sci Food Agric 2020 Dec 26. Epub 2020 Dec 26.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin, P. R. China.

Background: Although Streptomyces mobaraense transglutaminase (MTG) has been extensively applied to enhance the functional characteristics of soy protein isolate (SPI) through cross-linking, various transglutaminases (TGs) in nature may provide more choice in the food industry. Previous research reported that TG derived from Bacillus subtilis (BTG) exhibited better pH stability and thermostability than MTG.

Results: An attempt was made to study the influence of BTG induced cross-linking on the properties of SPI. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that almost all protein constituents (α', α, β, AS, and BS) in SPI could be cross-linked with BTG treatment. The BTG treatment also resulted in a significant increase (*P < 0.05) in SPI mean particle size. Emulsifying activity and stability were improved from 0.11535 m g and 48.3% for native SPI to 0.13252 m g and 83.9% for SPI treated with BTG at 6 h. Similarly, the modified SPI showed better foam activity (1.32 mL) and stability (87.6%) than the original SPI (0.93 mL and 56.8%). The water-holding capacity of SPI gel was found to increase with time, with a value of 95.43% at 6 h. Furthermore, SPI gel's texture profiles were greatly improved by adding BTG (*P < 0.05).

Conclusion: The results of the present study indicated that BTG could be a promising cross-linking agent for improving the functional characteristics of SPI. As a substitute for MTG, BTG could thus potentially be used for food structure engineering to enhance the functional characteristics of multiple proteins to advance the development of food chemistry. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11052DOI Listing
December 2020

Efficient secretion expression of phospholipase D in Bacillus subtilis and its application in synthesis of phosphatidylserine by enzyme immobilization.

Int J Biol Macromol 2021 Feb 15;169:282-289. Epub 2020 Dec 15.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, State Key Laboratory of Food Nutrition and Safety, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

Transphosphatidylation catalyzed by phospholipase D has gained increasing attention for producing phosphatidylserine (PS), which can be used in functional food and medicine. In this study, we investigated the effects of six signal peptides on the secretion of PLD (PLD) from Streptomyces antibioticus TCCC 21059 in the food-grade GRAS bacterium Bacillus subtilis. It indicated that the optimal signal peptide DacB with an Ala-X-Ala sequence motif at the C-terminus showed the highest secretory expression ability, resulting in increased production of 2.84 U/mL PLD. Then PLD was immobilized on the epoxy-based carriers, and one of these carriers allowed PLD loading of up to 2.7 mg/g. The immobilized PLD was more stable over a wide range of pH value (4.5-7.5) and temperature (16 °C-60 °C) than free PLD. Subsequently, the synthesis of PS from soybean phosphatidylcholine (PC) was carried out in purely aqueous solution using immobilized PLD, leading to a high yield of 65%. The immobilized PLD catalyst maintained a relative PS production of 60% after 5 recycles. Notably, the use of toxic solvent was completely eliminated in the whole process, which would be more profitable for the application of PS.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.103DOI Listing
February 2021

A Genome-Wide Analysis of Long Noncoding RNAs in Circulating Leukocytes and Their Differential Expression in Type 1 Diabetes Patients.

J Diabetes Res 2020 25;2020:9010314. Epub 2020 Nov 25.

School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Long noncoding RNAs (lncRNAs) regulate gene expression at different levels in various diseases, including type 1 diabetes (T1D). However, the expression of circulating lncRNAs in leukocytes in T1D has not been well documented. To identify differentially expressed lncRNAs between T1D patients and healthy controls, RNA sequencing was performed on samples of leukocytes collected from both healthy persons and T1D patients. The categories, enriched pathways, coexpression networks, and the characteristics of novel lncRNAs were analyzed to provide an extensive profile. qPCR was adopted to validate the differential expression of lncRNAs in the validation cohort. A total of 14,930 lncRNAs and 16,063 mRNAs were identified in the peripheral blood leukocyte of T1D patients. After optimization using an adjusted value (threshold of <0.05), 393 circulating lncRNAs were identified, of which 69 were downregulated and 324 were upregulated in T1D patients. Gene Ontology analysis indicated that these lncRNAs and mRNAs were enriched in the immune system category. Further analysis showed that 61.28% of the novel lncRNAs were conserved in humans. A set of 12 lncRNAs were selected for qPCR validation, and 9 of 12 lncRNAs were confirmed to show significant differential expression between the T1D and control validation cohorts. Among the 9 confirmed lncRNAs, lncRNA MSTRG.128697 and lncRNA MSTRG.128958 were novel and human-specific; however, further validation is required. lncRNA MSTRG.63013 has orthologous sequences in the mouse genome and was identified as a key node for etiology and pathophysiology in animal studies, which will help understand the epigenetic mechanisms of T1D complications.
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http://dx.doi.org/10.1155/2020/9010314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710437PMC
November 2020

Reducing the cell lysis to enhance yield of acid-stable alpha amylase by deletion of multiple peptidoglycan hydrolase-related genes in Bacillus amyloliquefaciens.

Int J Biol Macromol 2021 Jan 2;167:777-786. Epub 2020 Dec 2.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

Bacillus amyloliquefaciens is a major industrial host for extracellular protein production, with great potential in the enzyme industry. However, the strain has accelerated the autolysis drawback in the process of secreting extracellular enzymes, which can significantly lower the density of cells and decrease the product yield. To identify target genes, we employed comparative transcriptome sequencing and KEGG analysis to indicate the increased expression of peptidoglycan hydrolase-regulated genes from the exponential phase to the apoptotic phase of growth; this was further confirmed by quantitative RT-PCR. By deleting lytD, lytE, and sigD genes, cell lysis was reduced and the production of acid-stable Bacillus licheniformis alpha-amylase was enhanced. After 36 h of culture, multiple deletion mutant BA ΔSDE had significantly more viable cells compared to the control strain BA Δupp, and flow cytometry analysis indicated that 48.43% and 64.03% of the cells were lysed in cultures of BA ΔSDE and BA Δupp, respectively. In a 2-L fed-batch fermenter, viable cell number of the triple deletion mutant BA ΔSDE increased by 2.79 Log/cfu/mL, and the activity of acid-stable alpha-amylase increased by 48.4%, compared to BA Δupp. Systematic multiple peptidoglycan hydrolases deletion relieved the autolysis and increased the production of industrial enzymes, and provided a useful strategy for guiding efforts to manipulate the genomes of other B. amyloliquefaciens used for chassis host.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.193DOI Listing
January 2021

Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung cancer through cancer-derived exosomes.

Aging (Albany NY) 2020 11 21;12(24):25981-25999. Epub 2020 Nov 21.

School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.

Small cell lung cancer (SCLC) is highly aggressive and prone to hypervascular metastases. Recently, we found profilin 2 (PFN2) expression in SCLC but not in normal tissues. Furthermore, PFN2 expression had been shown to promote angiogenesis through exosomes. However, it remains unclear whether PFN2 contributes to the progression and metastasis of SCLC through angiogenesis. We report here that overexpression (OE) of PFN2 increased, whereas its knockdown (KD) decreased the proliferation, migration, and invasion of SCLC cell H446. The exosomes from OE-H446 (SCLC-OE-exo) exhibited similar effects on H446 properties. Culturing of endothelial cells (ECs) in SCLC-OE conditioned medium (CM) or SCLC-OE-exo increased the migration and tube formation ability of ECs, whereas SCLC-KD-CM and SCLC-KD-exo had inhibitory effects. Interestingly, both SCLC- and EC-derived exosomes were internalized in H446 more rapidly than in ECs. More importantly, OE-PFN2 dramatically elevated SCLC growth and vasculature formation as well as lung metastasis in tumor xenograft models. Finally, we found that PFN2 activated Smad2/3 in H446 and pERK in ECs, respectively. Taken together, our study revealed the role of PFN2 in SCLC development and metastasis, as well as tumor angiogenesis through exosomes, providing a new molecular target for SCLC treatment.
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http://dx.doi.org/10.18632/aging.202213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803489PMC
November 2020

Enzymatic characterization, molecular dynamics simulation, and application of a novel Bacillus licheniformis laccase.

Int J Biol Macromol 2021 Jan 14;167:1393-1405. Epub 2020 Nov 14.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economic and Technological Development Area, Tianjin 300457, PR China. Electronic address:

A new laccase gene from newly isolated Bacillus licheniformis TCCC 111219 was actively expressed in Escherichia coli. This recombinant laccase (rLAC) exhibited a high stability towards a wide pH range and high temperatures. 170% of the initial activity was detected at pH 10.0 after 10-d incubation, and 60% of the initial activity was even kept after 2-h incubation at 70 °C. It indicated that only single type of extreme environment, such as strong alkaline environment (300 K, pH 12) or high temperature (370 K, pH 7), did not show obvious impact on the structural stability of rLAC during molecular dynamics simulation process. But the four loop regions of rLAC where the active site is situated were seriously destroyed when strong alkaline and high temperature environment existed simultaneously (370 K, pH 12) because of the damage of hydrogen bonds and salt bridges. Moreover, this thermo- and alkaline-stable enzyme could efficiently decolorize the structurally differing azo, triphenylmethane, and anthraquinone dyes with appropriate mediator at pH 3.0, 7.0, and 9.0 at 60 °C. These rare characteristics suggested its high potential in industrial applications to decolorize textile dyeing effluent.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.093DOI Listing
January 2021

Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

medRxiv 2020 Nov 4. Epub 2020 Nov 4.

We aimed to summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% : 1.90-4.29) or high ( : 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 ( = 0.0004 and = 0.0003, respectively) and day 28/35 ( < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All < 0.001). In conclusion, our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.
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http://dx.doi.org/10.1101/2020.11.03.20224998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654888PMC
November 2020

On-Mask Chemical Modulation of Respiratory Droplets.

Matter 2020 Nov 29;3(5):1791-1810. Epub 2020 Oct 29.

Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.

Transmission of infectious respiratory diseases starts from pathogen-laden respiratory droplets released during coughing, sneezing, or speaking. Here we report an on-mask chemical modulation strategy, whereby droplets escaping a masking layer are chemically contaminated with antipathogen molecules (e.g., mineral acids or copper salts) preloaded on polyaniline-coated fabrics. A colorimetric method based on the color change of polyaniline and a fluorometric method utilizing fluorescence quenching microscopy are developed for visualizing the degree of modification of the escaped droplets by H and Cu, respectively. It is found that even fabrics with low fiber-packing densities (e.g., 19%) can readily modify 49% of the escaped droplets by number, which accounts for about 82% by volume. The chemical modulation strategy could offer additional public health benefits to the use of face covering to make the sources less infectious, helping to strengthen the response to the current pandemic or future outbreaks of infectious respiratory diseases.
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http://dx.doi.org/10.1016/j.matt.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598905PMC
November 2020

Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of triple negative breast cancer cells.

Breast Cancer 2021 Mar 12;28(2):368-378. Epub 2020 Oct 12.

School of Basic Medical Sciences, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, 100069, China.

Background: Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC.

Methods: PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-β/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice.

Results: PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial‑to‑mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo.

Conclusions: Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.
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http://dx.doi.org/10.1007/s12282-020-01169-xDOI Listing
March 2021

Enhancing the thermostability of phospholipase D from Streptomyces halstedii by directed evolution and elucidating the mechanism of a key amino acid residue using molecular dynamics simulation.

Int J Biol Macromol 2020 Dec 26;164:3065-3074. Epub 2020 Aug 26.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

To enhance the thermostability of phospholipase D (PLD), error-prone polymerase chain reaction method was used to create mutants of PLD (PLD) from Streptomyces halstedii. One desirable mutant (S163F) with Ser to Phe substitution at position 163 was screened with high-throughput assay. S163F exhibited a 10 °C higher optimum temperature than wild-type (WT). Although WT exhibited almost no activity after incubating at 50 °C for 40 min, S163F still displayed 27% of its highest activity after incubating at 50 °C for 60 min. Furthermore, the half-life of S163F at 50 °C was 3.04-fold higher than that of WT. The analysis of molecular dynamics simulation suggested that the Ser163Phe mutation led to the formation of salt bridge between Lys300 and Glu314 and a stronger hydrophobic interaction of Phe163 with Pro341, Leu342, and Trp460, resulting in an increased structural rigidity and overall enhanced stability at high temperature. This study provides novel insights on PLD tolerance to high temperature by investigating the structure-activity relationship. In addition, it provides strong theoretical foundation and preliminary information on the engineering of PLD with improved characteristics to meet industrial demand.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.160DOI Listing
December 2020

Correlation of A-Kinase Interacting Protein 1 With Clinical Features, Treatment Response, and Survival Profiles in Patients With Multiple Myeloma.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820935856

Department of Hematology, 159397Huashan Hospital, Fudan University, Shanghai, China.

Objective: The present study aimed to detect A-kinase interacting protein 1 expression and further explore the association of A-kinase interacting protein 1 with clinical features and prognosis in patients with multiple myeloma.

Methods: Totally, 152 symptomatic patients with multiple myeloma and 30 healthy donors were enrolled. Bone marrow mononuclear cells derived plasma cells were collected from patients with multiple myeloma before initial treatment and from healthy donors on the enrollment, respectively, and then A-kinase interacting protein 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction. Treatment response (complete response and overall response rate) was assessed, and survival profiles (progression-free survival and overall survival) were calculated in patients with multiple myeloma.

Results: A-kinase interacting protein 1 protein/messenger RNA expressions were elevated in patients with multiple myeloma compared to healthy donors, and A-kinase interacting protein 1 (area under the curve: 0.809, 95% confidence interval: 0.726-0.891)/messenger RNA (area under the curve: 0.839, 95% confidence interval: 0.764-0.914) presented good value in differentiating patients with multiple myeloma from healthy donors. In patients with multiple myeloma, A-kinase interacting protein 1 /messenger RNA expressions negatively correlated with albumin while positively correlated with Beta-2-microglobulin, lactate dehydrogenase, International Staging System stage, and t (4;14). Meanwhile, there were 39 (25.7%) complete response patients, 113 (74.3%) noncomplete response patients, 112 (73.7%) overall response rate patients, and 40 (26.3%) nonoverall response rate patients. Complete response and overall response rates were decreased in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. Additionally, progression-free survival and overall survival were reduced in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1.

Conclusion: A-kinase interacting protein 1 exhibits the potency as a biomarker for multiple myeloma progression and prognosis, which implies the clinical application of A-kinase interacting protein 1 in multiple myeloma management.
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http://dx.doi.org/10.1177/1533033820935856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436786PMC
August 2020

Purification, characterization and in vitro antioxidant activity of a polysaccharide AAP-3-1 from Auricularia auricula.

Int J Biol Macromol 2020 Nov 8;162:1453-1464. Epub 2020 Aug 8.

College of Food Science and Biotechnology, Tianjin Agricultural University, Tianjin 300384, China. Electronic address:

The objective was to investigate the in vitro antioxidant activity of a novel polysaccharide AAP-3-1 from Auricularia auricula. AAP-3-1 was isolated from the fruiting bodies of A. auricula by hot water extraction and ethanol precipitation and was purified by DEAE FF ion exchange chromatography and Superdex 200 gel filtration chromatography. The molecular weight and monosaccharide composition were determined by high performance gel permeation chromatography and high-performance liquid chromatography, respectively. Ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy were used for structural characterization. The results showed that AAP-3-1 is a heteropolysaccharide and is mainly composed of mannose and glucose in a molar ratio of 1.4:1 with a molecular weight of 320.9 kDa. AAP-3-1 exhibited antioxidant activity in a concentration-dependent manner and the scavenging rates at 1.6 mg/mL on superoxide anions and hydroxyl and 1,1-diphenyl-2-picrylhydrazyl radicals were 88.13%, 93.03% and 68.31%, respectively. AAP-3-1 effectively ameliorated 2,2'-azobis-2-methyl-propanimidamide-induced oxidative stress in HepG2 cells by inhibiting reactive oxygen species generation, decreasing the content of malondialdehyde, and increasing the activities of superoxide dismutase, glutathione peroxidase and catalase. The results indicated that the antioxidant mechanism of AAP-3-1 was associated with both non-enzymatic and enzymatic defense systems.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.314DOI Listing
November 2020

Enhanced moisture resistance of Cu/Ce catalysts for CO oxidation via Plasma-Catalyst interactions.

Chemosphere 2020 Dec 22;261:127739. Epub 2020 Jul 22.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China; Quanzhou Institute for Environmental Protection Industry, Nanjing University, Beifeng Road, Quanzhou, 362000, China. Electronic address:

Copper/cerium bimetallic catalyst is an efficient material for the removal of carbon monoxide, while the rapid deactivation under moisture-rich conditions in the conventional thermal-catalysis limited its wide application. Here, we investigated the plasma-assisted catalytic oxidation of CO over Cu/Ce oxides supported on γ-Alumina in comparison with the conventional thermal catalytic oxidation. The TOF values of the Cu/Ce catalysts showed that the plasma catalysis was the better catalytic system for CO oxidation (2.96 s for thermal catalysis, 5.13 s for plasma catalysis). Importantly, the energy barriers for plasma catalysis were much lower than that for thermal catalysis, especially under moisture-rich conditions (e.g. 130.3 kJ/mol versus 246.1 kJ/mol under 9.8 vol% water vapor). The loss of activity caused by water was reversible for the plasma process, but not for the thermal process. The Cu/Ce catalyst remained good stability within 60 h in the presence of 6.1% water for plasma oxidation, while the thermal catalytic activity declines gradually. Also, water could inhibit the formation of gas byproducts (O and NO). The promoting role of plasma could be mainly ascribed to the enhanced strength of oxygen mobility and plasma-assisted decomposition of surface carbonate in the presence of water, as revealed by the in-situ NTP-TPR, XPS, and the ex-situ DRIFTS analyses.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127739DOI Listing
December 2020

Single network double cross-linker (SNDCL) hydrogels with excellent stretchability, self-recovery, adhesion strength, and conductivity for human motion monitoring.

Soft Matter 2020 Aug;16(31):7323-7331

Yantai Institute of Materia Medica, Yantai, 264000, China.

Hydrogels, as a kind of soft materials, are good candidates for smart skin-like materials. A double network is usually fabricated to improve the mechanical properties of hydrogels, and involves two different kinds of networks. In this work, a novel strategy for preparing single network double cross-linker (SNDCL) hydrogels was proposed and the prepared hydrogels exhibited excellent mechanical properties, including stretchability, compressibility, self-recovery, adhesion, shape memory and mechanical strength. N,N'-Methylenebisacrylamide forms covalent bonds with the network, while citric acid can form multiple weak interactions due to the polycarboxylic structure. This improves the tensile properties (6564%) and compressive properties of the hydrogel, and the hydrogels also exhibit long-lasting self-adhesion ability on various substrates. In addition, the hydrogels with multiple properties can be used as flexible strain sensors, allowing the monitoring of body movements. The hydrogels can hopefully be used in wearable electronic sensor devices and for healthcare monitoring.
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http://dx.doi.org/10.1039/d0sm00375aDOI Listing
August 2020

Screening of the candidate inhibitory peptides of subtilisin by in vitro RNA display technique.

Int J Biol Macromol 2020 Nov 14;163:1162-1167. Epub 2020 Jul 14.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, National Engineering Laboratory for Industrial Enzymes, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

The application of inhibitors facilitates the stable preservation of enzyme in liquid detergent by mitigating the proteolytic activity of subtilisin. The conventionally used subtilisin inhibitors such as boric acid pose a threat to the environment and human health. Thus, the formulation of novel subtilisin inhibitors demands immediate attention. In the current study, we have screened the peptide inhibitors for subtilisin by employing the in vitro mRNA display technique. It is a sensitive screening technique with a high library capacity. The affinity screening was performed between the biotin-modified subtilisin immobilized on the streptavidin magnetic beads and the cDNA-mRNA-peptide fusion molecular library acquired from the in vitro translation and reverse transcription. The candidate peptides with high affinity were obtained after multiple rounds of screening. Furthermore, the inhibitory effect was evaluated, showing that some candidate peptides had inhibitory effects, but the isothermal titration calorimetry and time dependent experiments ultimately proved that these candidate peptides were not stable inhibitors. However, the in vitro mRNA display method explored in this study can be used as a preliminary screening method to provide candidate peptides for the screening of subtilisin inhibitors.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.115DOI Listing
November 2020

Composition of Phenolic Acids and Antioxidant Properties of Selected Pulses Cooked with Different Heating Conditions.

Foods 2020 Jul 10;9(7). Epub 2020 Jul 10.

Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON N1G 5C9, Canada.

Pulses are recommended for healthy eating due to their high content of nutrients and bioactive compounds that can undergo changes during cooking. This study investigated the effects of four cooking methods (boiling, pressure, microwave, slow) and three heating solutions (water, salt, sugar) on the phenolic acids and antioxidant properties of three pulses (faba beans, lentils, peas). The composition of phenolic acids differed among the three pulses with -coumaric and ferulic being the dominant acids. Cooking increased free phenolic acids and lessened bound phenolic acids in faba beans and peas, while decreased both free and bound phenolic acids in lentils. Cooking resulted in reductions in total phenol content (TPC) in faba bean methanol and bound extracts. Pressure and microwave cooking increased TPC in lentil methanol extracts, while pot boiling and slow cooking reduced TPC. Microwave cooking resulted in increases in TPC in bound phenolic extracts from lentils. For peas, cooking increased TPC in both methanol and bound phenolic extracts. Significant changes were also observed in the antioxidant capacity of cooked pulses based on the scavenging ability of DPPH, ABTS and peroxyl radicals subject to the type of pulse, polyphenol and antioxidant assay. Despite the significant reduction in antioxidants, high amounts of phenolics with potent antioxidant activities are still found in cooked pulses.
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http://dx.doi.org/10.3390/foods9070908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404658PMC
July 2020

Tunable physical and mechanical properties of gelatin hydrogel after transglutaminase crosslinking on two gelatin types.

Int J Biol Macromol 2020 Nov 20;162:405-413. Epub 2020 Jun 20.

State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

The crosslinking and related gel properties of 3 wt% gelatin (type-A and type-B) catalyzed by microbial transglutaminase (MTG, dose of 0-20 U/g gelatin) have been investigated. A MTG-depended increase in the molecular weight and mean diameter of both gelatins was observed, where type-A presented a higher crosslinking efficiency than type-B due to more acyl donors of the former. As MTG concentration increased, the surface hydrophobicity and thermal stability of type-A gelatin increased. Textural profile analysis (TPA) of type-A gelatin hydrogel showed a decrease in hardness and slight increase in springiness, while type-B gelatin gel was not affected generally. Rheological measurements confirmed the melting point of type-A gelatin hydrogel continually increased until the disappearance of gel thermo-reversibility at higher MTG levels (≥12 U/g gelatin), while type-B gelatin hydrogel always showed a sol-gel transition, suggesting that the gel performance was depended on the dominance of whether physical crosslinking or chemical crosslinking. Scanning electron microscope (SEM) results showed that the network structure of the type-A gelatin became more irregular as MTG increasing which indicated that introducing additional covalent cross-links within or between gelatin chains had a profound influence on gel's network structure, closely associated with the gel properties mentioned above. In summary, the superiority of type-A in MTG-crosslinking efficiency than type-B, can be used to modulate the physical and mechanical properties of gelatin hydrogel, governing by the combing of weak physical crosslinking and strong covalent crosslinking, which will be suitable for numerous industrial applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.185DOI Listing
November 2020

Pulmonary light chain deposition disease: a case series and literature review.

Ann Transl Med 2020 May;8(9):588

Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200082, China.

Background: Light chain deposition disease (LCDD) is a systemic disorder typically characterized by non-amyloid monoclonal immunoglobulin light chain deposition in tissues. LCDD is recognized as a multisystem disease, in which the kidneys and liver are often affected. However, it is rarely encountered as a localized pulmonary disease. This study set out to characterize the clinical manifestations and features of pulmonary light-chain deposition disease (PLCDD) by conducting a retrospective analysis of clinical data obtained from patients, with the aim of improving clinical understanding of PLCDD.

Methods: Data from inpatients diagnosed with PLCDD at Shanghai Pulmonary Hospital (Shanghai, China) between January 2010 and December 2018 were retrospectively collected and analyzed.

Results: A total of 4 PLCDD patients confirmed with PLCDD by pulmonary tissue biopsy were analyzed. All of the patients were female and were found by physical examination. Chest images of each patient's lungs showed multiple cystic cavities with nodules. A history of Sjogren's syndrome was present with 1 patient, 2 patients were diagnosed with Sjogren's syndrome after surgery (including 1 diagnosed with Sjogren's syndrome in the 8th year of follow up), and 3 patients had leukopenia. The longest follow-up period was 8 years. During the follow-up period, 2 patients developed pulmonary lesions (1 patient had an enlarged original cystic lesion in basal segment of right lower lobe 2 years after surgery, while the other developed new nodules 7 years after surgery).

Conclusions: PLCDD is characterized by multiple cystic changes with nodules in both lungs and can be easily complicated by lymphoid diseases such as Sjogren's syndrome. The clinical symptoms cannot be characterized, and the diagnosis depends on lung biopsy.
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http://dx.doi.org/10.21037/atm-20-2708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290530PMC
May 2020

Impact of age on N-methyl-N-nitrosourea induced microsatellite instability in young and old C57BL/6J mice.

Mutat Res 2020 05 27;853:503189. Epub 2020 Apr 27.

School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing 100069, China.

Age is an important factor in the evaluation of chemical toxicology. Chemical carcinogenic compounds can induce genomic mutations. However, few studies have been conducted on the association between genomic mutation frequency, such as microsatellite instability (MSI), and the age of mice treated with a nitrosourea mutagen. In the current work, we treated young (6 weeks) and old (10 months) mice with N-methyl-N-nitrosourea (MNU) for 4 months; the MSI frequency was then measured using polymerase chain reaction (PCR) and short tandem repeat (STR) scanning. The percentage of animals with MSI in the old group was significantly higher than that in the young group (100% and 75%). The frequency of MSI events was significantly different between the two groups as well (15.8% for old and 9.4% for young). The ratio of MSI loci displayed no obvious difference between the two groups. In addition, a few loci, including D15Mit5 and D8Mit14 exhibited the highest frequency of MSI events. Since specific loci showed increased MSI in the present study and a higher frequency in previous studies, these loci could be regarded as "hot spot". These results suggested that old mice would be more susceptible to this mutagen, and prone to accrue MSI. The hot spot microsatellite loci are potentially useful markers for genomic instability analysis.
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http://dx.doi.org/10.1016/j.mrgentox.2020.503189DOI Listing
May 2020

Author Correction: Jawbone microenvironment promotes periodontium regeneration by regulating the function of periodontal ligament stem cells.

Sci Rep 2020 May 27;10(1):8807. Epub 2020 May 27.

State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-65652-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253425PMC
May 2020

Multifunctional red carbon dots: a theranostic platform for magnetic resonance imaging and fluorescence imaging-guided chemodynamic therapy.

Analyst 2020 May;145(10):3592-3597

School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang 453003, China.

In recent years, carbon dots (CDs) with red-emitting wavelengths have received increasing attention in cancer therapy and imaging. Here, we reported a multi-functional CD based platform combining bimodal magnetic resonance/fluorescence (MR/FL) imaging and chemodynamic therapy (CDT) for in vivo imaging of tumor tissues and efficient anticancer treatment. The red-emitting CDs were synthesized via a one-step solvothermal method with p-phenylenediamine as the carbon source. Ethylenediaminetetraacetic acid (EDTA) was covalently coupled to the surface of CDs and then complexed with Fe2+ and Gd3+ to obtain functionalized red CDs (CDs@EDTA@Gd@Fe). CDs@EDTA@Gd@Fe exhibited bright and stable fluorescence and strong T1-weighted MR imaging (MRI) contrast. Moreover, the CDs@EDTA@Gd@Fe showed an excellent anticancer effect both in vitro and in vivo via a Fenton reaction-based CDT by releasing Fe2+ in the tumor. Our study offers a promising strategy for developing multi-functional CDs for cancer theranostics.
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http://dx.doi.org/10.1039/d0an00267dDOI Listing
May 2020

A new application of Krafft point concept: an ultraviolet-shielded surfactant switchable window.

Chem Commun (Camb) 2020 May 13;56(39):5315-5318. Epub 2020 Apr 13.

Key Laboratory of Colloid and Interface Chemistry (Ministry of Education), Shandong University, Jinan 250100, China.

We report thermo-responsive gels of polyacrylamide (PAAm) with ionic surfactants in mixed water and ethylene glycol (W-EG) solvents as smart windows to solubilize ultraviolet absorbents for UV shielding materials. The Krafft point (T) of the ionic surfactants determines the phase transition that switches the transparency and opacity of the gels. The T can be flexibly tuned within a wide temperature range (6-75 °C) with high predictability by changing the surfactant or adjusting the ratio of W-EG solvents.
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http://dx.doi.org/10.1039/d0cc01727bDOI Listing
May 2020

Exploiting Dual-Gate Ambipolar CNFETs for Scalable Machine Learning Classification.

Sci Rep 2020 03 31;10(1):5735. Epub 2020 Mar 31.

University of Illinois at Chicago, Chicago, 60607, Illinois, USA.

Ambipolar carbon nanotube based field-effect transistors (AP-CNFETs) exhibit unique electrical characteristics, such as tri-state operation and bi-directionality, enabling systems with complex and reconfigurable computing. In this paper, AP-CNFETs are used to design a mixed-signal machine learning logistic regression classifier. The classifier is designed in SPICE with feature size of 15 nm and operates at 250 MHz. The system is demonstrated in SPICE based on MNIST digit dataset, yielding 90% accuracy and no accuracy degradation as compared with the classification of this dataset in Python. The system also exhibits lower power consumption and smaller physical size as compared with the state-of-the-art CMOS and memristor based mixed-signal classifiers.
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http://dx.doi.org/10.1038/s41598-020-62718-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109128PMC
March 2020