Publications by authors named "Long Yu"

716 Publications

Zr(OH)4 Catalyzed Controllable Selective Oxidation of Anilines to Azoxybenzenes, Azobenzenes and Nitrosobenzenes.

Angew Chem Int Ed Engl 2021 Oct 13. Epub 2021 Oct 13.

Lanzhou university, Department of Chemistry and Chemical engineering, tianshui road 222#, 730000, Lanzhou, CHINA.

The selective oxidation of aniline to metastable and valuable azoxybenzene, azobenzene or nitrosobenzene has important practical significance in organic synthesis. However, uncontrollable selectivity and laborious synthesis of the expensive required catalysts severely hinder the uptake of these reactions in industrial settings. Herein, we have pioneered the discovery of Zr(OH) 4 as an efficient heterogeneous catalyst capable of the selective oxidation of aniline, using either peroxide or O 2 as oxidant, to selectively obtain various azoxybenzenes, symmetric/unsymmetric azobenzenes, as well as nitrosobenzenes, by simply regulating the reaction solvent, without the need for additives. Mechanistic experiments and DFT calculations demonstrate that the activation of H 2 O 2 and O 2 is primarily achieved by the bridging hydroxyl and terminal hydroxyl groups of Zr(OH) 4 respectively. The present work provides an economical and environmentally friendly strategy for the selective oxidation of aniline in industrial applications.
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http://dx.doi.org/10.1002/anie.202112907DOI Listing
October 2021

Auxin Treatment Enhances Anthocyanin Production in the Non-Climacteric Sweet Cherry ( L.).

Int J Mol Sci 2021 Oct 5;22(19). Epub 2021 Oct 5.

Commonwealth Scientific and Industrial Research Organisation (CSIRO), Waite Campus, Glen Osmond, SA 5064, Australia.

Abscisic acid (ABA) is a key signaling molecule promoting ripening of non-climacteric fruits such as sweet cherry ( L.). To shed light on the role of other hormones on fruit development, ripening and anthocyanin production, the synthetic auxin 1-naphthaleneacetic acid (NAA) was applied to sweet cherry trees during the straw-color stage of fruit development. NAA-treated fruits exhibited higher concentrations of 1-aminocyclopropane-1-carboxylic acid (ACC) and ABA-glucose ester (ABA-GE), which are a precursor of ethylene and a primary storage form of ABA, respectively. Consistent with these observations, transcript levels of genes encoding ACC synthase and ACC oxidase, both involved in ethylene biosynthesis, were increased after 6 days of NAA treatment, and both ABA concentration and expression of the regulator gene of ABA biosynthesis ( encoding 9-cis-epoxycarotenoid dioxygenase) were highest during early fruit ripening. In addition, transcript levels of key anthocyanin regulatory, biosynthetic and transport genes were significantly upregulated upon fruit exposure to NAA. This was accompanied by an increased anthocyanin concentration and fruit weight whilst fruit firmness and cracking index decreased. Altogether our data suggest that NAA treatment alters ethylene production, which in turn induces ripening in sweet cherry and enhanced anthocyanin production, possibly through ABA metabolism. The results from our study highlight the potential to use a single NAA treatment for manipulation of cherry ripening.
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http://dx.doi.org/10.3390/ijms221910760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509301PMC
October 2021

Anti-cancer Peptide Recognition Based on Grouped Sequence and Spatial Dimension Integrated Networks.

Interdiscip Sci 2021 Oct 12. Epub 2021 Oct 12.

People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.

The diversification of the characteristic sequences of anti-cancer peptides has imposed difficulties on research. To effectively predict new anti-cancer peptides, this paper proposes a more suitable feature grouping sequence and spatial dimension-integrated network algorithm for anti-cancer peptide sequence prediction called GRCI-Net. The main process is as follows: First, we implemented the fusion reduction of binary structure features and K-mer sparse matrix features through principal component analysis and generated a set of new features; second, we constructed a new bidirectional long- and short-term memory network. We used traditional convolution and dilated convolution to acquire features in the spatial dimension using the memory network's grouping sequence model, which is designed to better handle the diversification of anti-cancer peptide feature sequences and to fully learn the contextual information between features. Finally, we achieved the fusion of grouping sequence features and spatial dimensional integration features through two sets of dense network layers, achieved the prediction of anti-cancer peptides through the sigmoid function, and verified the approach with two public datasets, ACP740 (accuracy reached 0.8230) and ACP240 (accuracy reached 0.8750). The following is a link to the model code and datasets mentioned in this article: https://github.com/ YouHongfeng101/ACP-DL.
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http://dx.doi.org/10.1007/s12539-021-00481-0DOI Listing
October 2021

MYH9 is crucial for stem cell-like properties in non-small cell lung cancer by activating mTOR signaling.

Cell Death Discov 2021 Oct 11;7(1):282. Epub 2021 Oct 11.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The fatality rate of non-small cell lung cancer (NSCLC) has been high due to the existence of cancer stem cells (CSCs). Non-muscle myosin heavy chain 9 (MYH9) can promote the progression of various tumors, but its effect on the stem cell-like characteristics of lung cancer cells (LCCs) has not been clarified. Our research found that the stemness characteristics of LCCs were significantly enhanced by the overexpression of MYH9, and the knockout of MYH9 had the opposite effects. The in vivo with inhibitor blebbistatin further confirmed the effect of MYH9 on the stem cell-like behavior of LCCs. Furthermore, western blotting showed that the expression level of CSCs markers (CD44, SOX2, Nanog, CD133, and OCT4) was also regulated by MYH9. Mechanistic studies have shown that MYH9 regulates stem cell-like features of LCCs by regulating the mTOR signaling pathway, which was supported by sphere formation experiments after LCCs were treated with inhibitors Rapamycin and CHIR-99021. Importantly, high expression of MYH9 in lung cancer is positively correlated with poor clinical prognosis and is an independent risk factor for patients with NSCLC.
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http://dx.doi.org/10.1038/s41420-021-00681-zDOI Listing
October 2021

The Role of Osteocalcin in Placental Function in Gestational Diabetes Mellitus.

Reprod Biol 2021 Oct 6;21(4):100566. Epub 2021 Oct 6.

Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China; Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China. Electronic address:

Evidence for the role of osteocalcin in glucose metabolism is increasing. The aim of this study was to examine the associations between osteocalcin and gestational diabetes mellitus. Thirteen discovery study subjects and 76 reduplication study subjects were recruited from the Maternal and Child Health Hospital Guangxi Zhuang Autonomous Region from May 2018 to August 2018. Total osteocalcin and biochemical indices of maternal serum and umbilical vein serum were analyzed. Placental tissue samples were used for transcriptome sequencing. For the discovery study subjects, the total osteocalcin concentration in umbilical vein serum was significantly higher than that in maternal serum and umbilical artery serum (55.32 ng/mL ± 17.37 vs. 12.06 ng/mL ± 5.42 [P < 0.001] vs. 38.31 ng/mL ± 11.52 [P < 0.01]), suggesting that trophoblasts may synthesize osteocalcin. In a reduplication subject study, the gestational diabetes mellitus group had lower umbilical vein serum total osteocalcin (51.46 ng/mL ± 24.29 vs. 67.00 ng/mL ± 25.33, P = 0.008), lower adiponectin (1099.72 μg/L ± 102.65 vs. 1235.85 μg/L ± 94.63, P < 0.001). Spearman's correlation analysis showed that umbilical vein serum total osteocalcin levels were closely correlated with leptin (r = -0.456, P = 0.007). A coexpression model of the placental RNA sequence was constructed. Two modules were correlated with osteocalcin, and the Gene ontology pathways of these modules were rich in glucose and lipid metabolism. In conclusion, the placenta may synthesize osteocalcin by itself, and a lower osteocalcin level in umbilical vein serum is associated with gestational diabetes mellitus.
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http://dx.doi.org/10.1016/j.repbio.2021.100566DOI Listing
October 2021

Kinetic Characterization and Inhibitor Screening of Pyruvate Kinase I From .

Front Microbiol 2021 16;12:710678. Epub 2021 Sep 16.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

The apicomplexan is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of -cultured with IC values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti- drugs.
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http://dx.doi.org/10.3389/fmicb.2021.710678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481833PMC
September 2021

Reversible electrochemical oxidation of sulfur in ionic liquid for high-voltage Al-S batteries.

Nat Commun 2021 Sep 29;12(1):5714. Epub 2021 Sep 29.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia.

Sulfur is an important electrode material in metal-sulfur batteries. It is usually coupled with metal anodes and undergoes electrochemical reduction to form metal sulfides. Herein, we demonstrate, for the first time, the reversible sulfur oxidation process in AlCl/carbamide ionic liquid, where sulfur is electrochemically oxidized by AlCl to form AlSCl. The sulfur oxidation is: 1) highly reversible with an efficiency of ~94%; and 2) workable within a wide range of high potentials. As a result, the Al-S battery based on sulfur oxidation can be cycled steadily around ~1.8 V, which is the highest operation voltage in Al-S batteries. The study of sulfur oxidation process benefits the understanding of sulfur chemistry and provides a valuable inspiration for the design of other high-voltage metal-sulfur batteries, not limited to Al-S configurations.
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http://dx.doi.org/10.1038/s41467-021-26056-7DOI Listing
September 2021

The Failure Mechanisms of Precast Geopolymer after Water Immersion.

Materials (Basel) 2021 Sep 14;14(18). Epub 2021 Sep 14.

School of Materials Science and Engineering, Tongji University, 4800 Cao'an Road, Shanghai 201804, China.

Precast geopolymers with lower water/binder (0.14), which mainly consists of alkali solution, fly ash (FA) and steel slag (SS), were manufactured through molding pressing technology. The failure mechanisms of precast geopolymers after water immersion were studied by testing the loss of compressive strength, the pH of the leaching solution, the concentration of ions (Na, Ca, Si and Al), the evolution of phases, pore structure and morphology, and further discussion of the regulation evolution was performed. The results show that the harmful pores (>50 nm) of geopolymers progressively decrease from 70% to 50% after 28 days of water immersion when the content of steel slag increases from 0 to 80 wt.%. Compressive strength of geopolymers sharply reduces in the first 3 days and then increases during the water immersion process, but the phase composition varies slightly. Furthermore, increasing the content of steel slag could decrease the total porosity and further prevent the water resistance.
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http://dx.doi.org/10.3390/ma14185299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469394PMC
September 2021

Fluorescent probe visualization for selective detection of cuprous ion.

Anal Sci 2021 Sep 10. Epub 2021 Sep 10.

Guangdong Provincial Key Laboratory of Petrochemical Pollution Process and Control, School of Environmental Science and Engineering, Guangdong University of Petrochemical Technology.

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http://dx.doi.org/10.2116/analsci.21P218DOI Listing
September 2021

Biomarkers and Immune Repertoire Metrics Identified by Peripheral Blood Transcriptomic Sequencing Reveal the Pathogenesis of COVID-19.

Front Immunol 2021 24;12:677025. Epub 2021 Aug 24.

Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, , a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.
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http://dx.doi.org/10.3389/fimmu.2021.677025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421539PMC
September 2021

Moisture-induced autonomous surface potential oscillations for energy harvesting.

Nat Commun 2021 09 6;12(1):5287. Epub 2021 Sep 6.

Department of Mechanical Engineering, University of California Berkeley, Berkeley, CA, USA.

A variety of autonomous oscillations in nature such as heartbeats and some biochemical reactions have been widely studied and utilized for applications in the fields of bioscience and engineering. Here, we report a unique phenomenon of moisture-induced electrical potential oscillations on polymers, poly([2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide-co-acrylic acid), during the diffusion of water molecules. Chemical reactions are modeled by kinetic simulations while system dynamic equations and the stability matrix are analyzed to show the chaotic nature of the system which oscillates with hidden attractors to induce the autonomous surface potential oscillation. Using moisture in the ambient environment as the activation source, this self-excited chemoelectrical reaction could have broad influences and usages in surface-reaction based devices and systems. As a proof-of-concept demonstration, an energy harvester is constructed and achieved the continuous energy production for more than 15,000 seconds with an energy density of 16.8 mJ/cm. A 2-Volts output voltage has been produced to power a liquid crystal display toward practical applications with five energy harvesters connected in series.
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http://dx.doi.org/10.1038/s41467-021-25554-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421362PMC
September 2021

Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion.

Front Immunol 2021 17;12:724662. Epub 2021 Aug 17.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Previous studies have reported the involvement of γδ T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of γδ T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for γδ T cells by flow cytometry ( = 9-11 for each group). Moreover, the decidua from pregnant RSA patients and healthy controls (RSA-P and HC-P group, respectively) was simultaneously stained for γδ T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral γδ T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on Vδ2 cells was increased in pregnant patients. Furthermore, peripheral Vδ2 cells in RSA-P patients demonstrated significantly increased expression of CD107a, as compared to that in pregnant healthy controls. In addition, RSA-P patients had higher proportion of IL-17A-secreting but not IL-4-secreting Vδ2 cells compared to the control groups. In decidua, an inflammatory microenvironment was also evident in RSA-P patients, in which expression and the infiltration of certain immune cells were higher than that in the HC-P group, as revealed by transcriptional analysis. Finally, although the presence of γδ T cells in decidua could be detected during pregnancy in both RSA patients and healthy subjects by multicolor IHC analysis, the expression of CD107a on γδ T cells was markedly higher in the RSA-P group. Collectively, our results indicated that the increased activation, cytotoxicity, and inflammatory potential of peripheral and/or local γδ T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of γδ T cells in RSA and shed light on novel treatment strategies by targeting γδ T cells for RSA patients.
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http://dx.doi.org/10.3389/fimmu.2021.724662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416064PMC
August 2021

M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis.

Cell Biol Int 2021 Aug 25. Epub 2021 Aug 25.

Department of Spine Surgery, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China.

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management.
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http://dx.doi.org/10.1002/cbin.11690DOI Listing
August 2021

Thermomechanically processed chitosan:gelatin films being transparent, mechanically robust and less hygroscopic.

Carbohydr Polym 2021 Nov 4;272:118522. Epub 2021 Aug 4.

International Institute for Nanocomposites Manufacturing (IINM), WMG, University of Warwick, Coventry CV4 7AL, United Kingdom. Electronic address:

Chitosan and gelatin are attractive polymeric feedstocks for developing environmentally benign, bio-safe, and functional materials. However, cost-effective methods to achieve advantageous materials properties and tailor their functionality are still lacking, but interesting. Herein, we found that physically mixing chitosan and gelatin at 1:1 (w/w) ratio resulted in materials with properties (higher Young's modulus (603.8 MPa) and tensile strength (33.6 MPa), and reduced water uptake (45%) after 6 h of water soaking) better than those of the materials based on mainly chitosan or gelatin. We attribute this synergy to the ionic and hydrogen-bonding interactions between the two biopolymers enabled by high-viscosity thermomechanical processing. Despite the lowest hygroscopicity, the 1:1 chitosan:gelatin films displayed the highest surface hydrophilicity. Besides, addition of gelatin to chitosan led to films being brighter, more transparent and amorphous. Thus, this work has generated new understanding to enhance the application of biopolymers for e.g. packaging, coating, and biomedical applications.
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http://dx.doi.org/10.1016/j.carbpol.2021.118522DOI Listing
November 2021

Utilizing heterologously overexpressed endo-1,3-fucanase to investigate the structure of sulfated fucan from sea cucumber (Holothuria hilla).

Carbohydr Polym 2021 Nov 24;272:118480. Epub 2021 Jul 24.

College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

Sea cucumber sulfated fucan (SC-FUC) attracted increasing interests in the recent decades. Endo-1,3-fucanase has been employed in the structural clarification and structure-function relationship investigations of SC-FUC. Nevertheless, the preparation of wild-type endo-1,3-fucanase is costly and time-consuming, which hinders its further utilization. In this study, a heterologously overexpressed endo-1,3-fucanase (FunA) was introduced into structural identification of SC-FUC. FunA was efficiently prepared within one day and utilized in the investigation of sulfated fucan from sea cucumber Holothuria hilla (Hh-FUC). By using enzymatic degradation, glycomics and NMR analysis, the major structure of Hh-FUC was identified to be composed of a tetrasaccharide repeating unit →3-α-l-Fucp-1 → 3-α-l-Fucp2,4(OSO)-1 → 3-α-l-Fucp2(OSO)-1 → 3-α-l-Fucp2(OSO)-1→. Due to the efficient acquisition of enzyme and the superior oligosaccharide recovery, 0.6 mL of E. coli broth and 10 mg of Hh-FUC were sufficient for the structural identification. The results demonstrated the superiority of heterologously overexpressed fucanase over its wild-type enzyme in structural investigation of sulfated fucan.
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http://dx.doi.org/10.1016/j.carbpol.2021.118480DOI Listing
November 2021

Anchor and bridge functions of APTES layer on interface between hydrophilic starch films and hydrophobic soyabean oil coating.

Carbohydr Polym 2021 Nov 20;272:118450. Epub 2021 Jul 20.

Collage of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China; Sino-Singapore International Joint Research Institute, Knowledge City, Guangzhou 510663, China. Electronic address:

One of the well-recognized weaknesses of starch-based materials is their sensitivity to moisture, which limits their expanding applications. Natural materials, soyabean oils have been used as a coating for starch film, but the poor interface between hydrophilic starch and hydrophobic soyabean oil needs to be improved. In this work, (3-Aminopropyl) triethoxysilane (APTES) was used to reinforce the bonding between starch matrix and the coating of bio-based acrylated epoxidized soyabean oil (AESO). Study results show that APTES interacted effectively with both starch films via hydrogen bonding, and chemical bonds with AESO through the Michael addition reaction. Pull adhesion and cross-cutting tests demonstrated that the interfacial adhesion was significantly improved after treating their surface with APTES. The interfacial adhesion strength increased over 4 times after treating with 1.6 wt% APTES. The starch films treated with APTES and AESO coating were intact after soaking in water for more than 2 h.
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http://dx.doi.org/10.1016/j.carbpol.2021.118450DOI Listing
November 2021

Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies.

AAPS PharmSciTech 2021 Aug 18;22(7):222. Epub 2021 Aug 18.

Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, No.1688, Meiling Road, Wanli District, Nanchang, Jiangxi, ,330004, People's Republic of China.

Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration.
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http://dx.doi.org/10.1208/s12249-021-02093-9DOI Listing
August 2021

Presence of TSHR in NK Cells and Action of TSH on NK Cells.

Neuroimmunomodulation 2021 Aug 13:1-8. Epub 2021 Aug 13.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Introduction: Thyroid-stimulating hormone receptor (TSHR) is widely expressed in human tissues and cells. TSHR is not only involved in thyroid disease but also in the neuroendocrine-immune regulatory network. However, no study has exclusively focused on the expression and function of TSHR in natural killer (NK) cells.

Methods: We studied TSHR expression using reverse transcription PCR to verify TSHR mRNA transcripts in human and mouse NK cells. Human and mouse thyroid and liver tissues as well as peripheral blood mononuclear cells (PBMCs) or spleen lymphoid cells (SLCs) were used as controls. The TSHR protein levels in NK-92 cells were determined by immunofluorescence staining. The function of TSHR in NK cells was investigated by measuring the TSH-stimulated cAMP levels.

Results: TSHR mRNA was detected in human and mouse NK cells as well as in NK-92 cells and had the same sequence as that of thyroid-derived, PBMC-derived, and liver-derived mRNA. The TSHR protein was also expressed in the cell membrane of NK-92 cells. Furthermore, the cAMP levels in NK-92 cells were significantly higher after adding 102 mIU/mL of bovine TSH at p < 0.05, which stimulated cAMP production in NK-92 cells.

Conclusions: Our findings confirm that TSHR is present and functional in NK cells and provide key clues for the potential regulatory effects of TSH on TSHR in NK cells in the immune system.
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http://dx.doi.org/10.1159/000516925DOI Listing
August 2021

A Comprehensive Study on the Hardening Features and Performance of Self-Compacting Concrete with High-Volume Fly Ash and Slag.

Materials (Basel) 2021 Jul 31;14(15). Epub 2021 Jul 31.

Key Laboratory of Advanced Civil Engineering Materials, Tongji University, Ministry of Education, Shanghai 201804, China.

The main concern of this work is to evaluate the influences of supplementary cementitious materials (fly ash, slag) and a new type of polycarboxylate superplasticizer containing viscosity modifying agents (PCE-VMA) on the performance of self-compacting concrete (SCC). The workability, hydration process, mechanical property, chloride permeability, degree of hydration and pore structure of SCC were investigated. Results indicate that the addition of fly ash and slag slows down early hydration and decreases the hydration degree of SCC, and thus leads to a decline in compressive strengths, especially within the first 7 days. The addition of slag refines pore structure and contributes to lower porosity, and thus the chloride permeability of SCC is decreased during the late hydration stage. Additionally, a new factor of calculated water-binder ratio is put forward, which can directly reflect the free water content of concrete mixture after mixing, and guide the mix proportion design of SCC.
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http://dx.doi.org/10.3390/ma14154286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347473PMC
July 2021

Preparation and Characterization of Instant Casein Phosphopeptide by Supercritical Fluid Assisted Atomization.

Foods 2021 Jul 5;10(7). Epub 2021 Jul 5.

Collage of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.

Casein phosphopeptide (CPP) has been widely used as micronutrient supplementation for certain populations. However, its solubility performance is far from satisfying. In this work, instant CPP powders with micropore structures were fabricated by supercritical fluid-assisted atomization (SAA) using supercritical CO fluid (SC-CO) as an atomizing agent. The effects of the processing parameters (temperature, time, and pressure) on SC-CO absorption rate and dissolution rate were systematically evaluated and studied. The viscosity of the CPP solution increased with increased pressure of SC-CO as pressure increased its solubility. The processing conditions are optimized as follows: 40 °C, 40 min, and 8.27 MPa, with an SC-CO absorption rate of about 8 wt.%. The dissolution time of the SAA-CPP powders was significantly decreased from 1800 s to 54 s at room temperature, due to the micropore structures and almost 10 times increase in the specific surface area of SAA-CPP. The bioactivities of the instant SAA-CPP, especially the calcium-binding capacity, were also evaluated and showed no observable difference. Among the four CPPs prepared in different ways in this work, SAA-CPP had better dissolution performance. The results show that SAA technology is a promising way to prepare instant polypeptide powders.
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http://dx.doi.org/10.3390/foods10071555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304231PMC
July 2021

Corrigendum: Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Front Immunol 2021 16;12:731824. Epub 2021 Jul 16.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

[This corrects the article DOI: 10.3389/fimmu.2021.659150.].
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http://dx.doi.org/10.3389/fimmu.2021.731824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323518PMC
July 2021

Marginal frequent itemset mining for fault prevention of railway overhead contact system.

ISA Trans 2021 Jul 13. Epub 2021 Jul 13.

Department of Electrical Engineering, Southwest Jiaotong University, Chengdu, China. Electronic address:

The overhead contact system (OCS), as the power source of electrified railway, has a complex composition and various types of faults, so it places high requirements on its fault prevention. In recent years, with the establishment of railway OCS fault database, association analysis has been used to implement fault prevention from system-wise perspective and provide guidance for operation and maintenance. However, due to the hierarchical structure of fault database, the existing frequent itemset mining has a lot of redundancy in the results, and cannot locate the most precise faults, which affects the decision-making and makes troubleshooting lack of pertinence. To address this issue, this paper proposed a new concept, called marginal frequent itemset, which is an itemset composed of as precise items as possible in hierarchical database that meets the threshold, and an alternative mining task: mining marginal frequent itemsets instead of all the frequent itemsets. Two methods, path transform and descending depth of itemset, are proposed for achieving mining a set of marginal frequent itemsets. Two novel measures, margin degree and marginal information quantity, are proposed to evaluate the content of the mining results. An efficient algorithm, named MFIM, is developed for mining cross-level marginal frequent itemsets from railway OCS fault database. Our performance study shows that MFIM has high performance and can obtain more key information and reduce the number of results. Furthermore, marginal frequent itemset mining can simplify the fault relation network constructed by association rules and optimize the decision-making process for fault prevention of railway OCS.
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http://dx.doi.org/10.1016/j.isatra.2021.07.018DOI Listing
July 2021

Viscoelastic behaviour of rapid and slow self-healing hydrogels formed by densely branched arabinoxylans from Plantago ovata seed mucilage.

Carbohydr Polym 2021 Oct 9;269:118318. Epub 2021 Jun 9.

School of Chemical Engineering, University of Queensland, Brisbane, QLD 4076, Australia; School of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD, United Kingdom. Electronic address:

We report rheological characterisation of hydrogels formed by highly substituted brush-like arabinoxylans from Plantago ovata seed mucilage. Two arabinoxlyan fractions with similar molecular weight and linkage compositions are chosen to form gels with distinct rheological properties but a similar network structure. Small and large amplitude oscillatory shear rheology is used to characterise the sol-gel transition as a function of temperature and concentration. Differences in rheology and gelation of the two hydrogels are found to be associated with the different proportion of 'slow'- and 'fast'-dissociating junctions stabilised by hydrogen bonds, with the 'fast'-dissociating junctions playing an important role in rapid self-healing of the gel. Based on the temperature dependence of storage modulus and time-temperature superposition principle in combination with the Arrhenius equation, the activation energies of junction zone dissociation are estimated to be 402-480 kJ/mol and 97-144 kJ/mol for the 'slow' and 'fast' junction types, respectively.
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http://dx.doi.org/10.1016/j.carbpol.2021.118318DOI Listing
October 2021

Deciphering variation of 239 elite japonica rice genomes for whole genome sequences-enabled breeding.

Genomics 2021 Sep 6;113(5):3083-3091. Epub 2021 Jul 6.

Huazhi Biotech Co. Ltd., Changsha, Hunan 410125, China; China Southern Regional Collaborative Innovation Center for Cereal and Oil Crops, College of Agriculture, Hunan Agricultural University, Changsha, Hunan 410125, China. Electronic address:

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.
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http://dx.doi.org/10.1016/j.ygeno.2021.07.002DOI Listing
September 2021

Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis.

Sci Rep 2021 07 7;11(1):14024. Epub 2021 Jul 7.

Department of Breast Center, The Fourth Hospital of Hebei Medical University, 169 Tianshan Street, Shijiazhuang, 050000, People's Republic of China.

Mounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan-Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314-6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016-7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77-17.2, p = 0.003) and OS (HR 7.0395% CI 1.94-25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41-172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39-130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.
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http://dx.doi.org/10.1038/s41598-021-93428-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263554PMC
July 2021

MYB77 regulates high-affinity potassium uptake by promoting expression of HAK5.

New Phytol 2021 10 26;232(1):176-189. Epub 2021 Jul 26.

State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng, 475001, China.

In Arabidopsis, the high-affinity K transporter HAK5 is the major pathway for root K uptake when below 100 µM; HAK5 responds to Low-K (LK) stress by strongly and rapidly increasing its expression during K -deficiency. Therefore, positive regulators of HAK5 expression have the potential to improve K uptake under LK. Here, we show that mutants of the transcription factor MYB77 share a LK-induced leaf chlorosis phenotype, lower K content, and lower Rb uptake of the hak5 mutant, but not the shorter root growth, and that overexpression of MYB77 enhanced K uptake and improved tolerance to LK stress. Furthermore, we demonstrated that MYB77 positively regulates the expression of HAK5, by binding to the HAK5 promoter and enhances high-affinity K uptake of roots. As such, our results reveal a novel pathway for enhancing HAK5 expression under LK stress, and provides a candidate for increasing the tolerance of plants to LK.
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http://dx.doi.org/10.1111/nph.17589DOI Listing
October 2021

Multifunctional lanthanide metal-organic framework based ratiometric fluorescence visual detection platform for alkaline phosphatase activity.

Mikrochim Acta 2021 06 24;188(7):236. Epub 2021 Jun 24.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

A turn-on/off ratiometric fluorescence detection platform based on multifunctional lanthanide metal-organic framework (Ln-MOF) and an enzymatic cascade reaction is proposed for alkaline phosphatase (ALP) activity assay. L-phosphotyrosine is hydrolyzed to levodopa (L-dopa) by two steps of enzymatic reaction. L-dopa further reacts with naphthoresorcinol to produce carboxyazamonardine with strong emission at 490 nm. In this process, multifunctional Ln-MOF ([email protected], BTC is the 1,3,5-benzenetricarboxylic acid) acts not only as a nanozyme to catalyze the fluorogenic reaction between L-dopa and naphthoresorcinol but also as a fluorescence internal standard. The emission of [email protected] at 620 nm is quenched by phosphate anions, and the dual-response ratiometric fluorescence (F/F) can be achieved. A good linear relationship was obtained between Δ(F/F) and ALP activity in the range 0.3-24 U L with the detection limit of 0.02 U L. In addition, a portable assay tube was designed for visual and point-of-care testing of ALP activity by color variation (ratiometric chromaticity). Both the ratiometric fluorescence detection and the visual detection methods were successfully applied to monitor ALP activity in human serum samples with recovery between 95.5%-109.0% and 94.0%-110.1%, and relative standard deviation less than 8.1% and 9.5%, respectively. As far as we know, this is the first report of ALP activity assay assisted by multifunctional Ln-MOF.Graphical abstract.
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http://dx.doi.org/10.1007/s00604-021-04880-4DOI Listing
June 2021

BCAT1 Activates PI3K/AKT/mTOR Pathway and Contributes to the Angiogenesis and Tumorigenicity of Gastric Cancer.

Front Cell Dev Biol 2021 7;9:659260. Epub 2021 Jun 7.

Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Focusing on antiangiogenesis may provide promising choices for treatment of gastric cancer (GC). This study aimed to investigate the mechanistic role of BCAT1 in the pathogenesis of GC, particularly in angiogenesis.

Methods: Bioinformatics and clinical samples analysis were used to investigate the expression and potential mechanism of BCAT1 in GC. BGC823 cells with BCAT1 overexpression or silencing were induced by lentiviral transduction. Cell phenotypes and angiogenesis were evaluated. The relevant proteins were quantized by Western blotting, immunohistochemistry, or immunofluorescence. Xenograft models were constructed to confirm the role of BCAT1 .

Results: BCAT1 was overexpressed in GC patients and associated with lower survival. BCAT1 expression was correlated with proliferation-, invasion-, or angiogenesis-related markers expression and pathways. Silencing BCAT1 expression suppressed cell viability, colony formation, cycle progression, invasion, and angiogenesis of BGC823 cells, as well as the tumor growth of xenograft models, whereas overexpressing BCAT1 had the opposite results both and . Bioinformatics analysis and Western blotting demonstrated that BCAT1 activated the PI3K/AKT/mTOR pathway. The addition of LY294002 reversed the tumor growth induced by BCAT1 overexpression, further verifying this mechanism.

Conclusion: BCAT1 might act as an oncogene by facilitating proliferation, invasion, and angiogenesis through activation of the PI3K/AKT/mTOR pathway. This finding could aid the optimization of antiangiogenesis strategies.
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http://dx.doi.org/10.3389/fcell.2021.659260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215359PMC
June 2021

ULECGNet: An Ultra-Lightweight End-to-End ECG Classification Neural Network.

IEEE J Biomed Health Inform 2021 Jun 18;PP. Epub 2021 Jun 18.

ECG classification is a key technology in intelligent ECG monitoring. In the past, traditional machine learning methods such as SVM and KNN have been used for ECG classification, but with limited classification accuracy. Recently, the end-to-end neural network has been used for the ECG classification and shows high classification accuracy. However, the end-to-end neural network has large computational complexity including a large number of parameters and operations. Although dedicated hardware such as FPGA and ASIC can be developed to accelerate the neural network, they result in large power consumption, large design cost, or limited flexibility. In this work, we have proposed an ultra-lightweight end-to-end ECG classification neural network which has extremely low computational complexity (~8.2k parameters & ~227k MUL/ADD operations) and can be squeezed into a low-cost MCU (i.e. microcontroller) while achieving 99.1% overall classification accuracy. This outperforms the state-of-the-art ECG classification neural network. Implemented on a low-cost MCU (i.e. MSP432), the proposed design consumes only 0.4 mJ and 3.1 mJ per heartbeat classification for normal and abnormal heartbeats respectively for real-time ECG classification.
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http://dx.doi.org/10.1109/JBHI.2021.3090421DOI Listing
June 2021

Multifunctional nanoscale lanthanide metal-organic framework based ratiometric fluorescence paper microchip for visual dopamine assay.

Nanoscale 2021 Jul;13(25):11188-11196

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

Dopamine (DA) plays a significant role in the human body and cerebral nervous system, and the accurate and rapid assay of DA is essential for the diagnosis of related diseases. Herein, we proposed a turn-on ratiometric fluorescent DA assay strategy by integrating a specific DA-resorcinol chemical reaction with a multifunctional lanthanide metal-organic framework (Ln-MOF). First, Eu-BTC (1,3,5-benzenetricarboxylic acid) was synthesized and further modified to obtain [email protected], which simultaneously plays multiple roles such as fluorescence internal standard, nanoreactor, cooperative catalysis effect and color shift enhancement. The [email protected] dispersion-based method exhibits ultra-sensitive (limit of detection, LOD is 0.01 μM) and wide-range linear response (0.04-30 μM) to DA in real serum. More importantly, it has excellent selectivity for DA, even in the presence of epinephrine and norepinephrine analogs. Thus, this method realizes the accurate and precise quantification of DA in serum (recoveries: 98.1%-110.1%, relative standard deviation RSD < 4.6%). Next, [email protected] was prepared into paper microchip, which has good storage stability (RSD < 3.5%, n = 3) in four weeks and achieves point-of-care visual DA assay coupled with smartphone-assisted portable detection device. The MOF paper microchip-based method shows low sample consumption (30 μL), high accuracy and precision for the quantification of DA in serum (recovery of 92.9%-106.2%, RSD < 5.3%), and gets the same assay results as the MOF dispersion-based method (relative error ≤ 6.83%). To our knowledge, this is the first time to propose the catalytic fluorescence turn-on detection strategy of DA based on a MOF paper microchip.
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http://dx.doi.org/10.1039/d1nr02036fDOI Listing
July 2021
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