Publications by authors named "Zhiyong Wang"

697 Publications

Mitochondrial Breast Cancer Resistant Protein Sustains the Proliferation and Survival of Drug-Resistant Breast Cancer Cells by Regulating Intracellular Reactive Oxygen Species.

Front Cell Dev Biol 2021 28;9:719209. Epub 2021 Sep 28.

Public Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

ATP-binding cassette (ABC) transporter family are major contributors to the drug resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells and . RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.
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http://dx.doi.org/10.3389/fcell.2021.719209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505676PMC
September 2021

Dynamical and noninvasive monitoring of curcumin effect on the changes in the viscoelasticity of human breast cancer cells: A novel model to assess cell apoptosis.

Talanta 2022 Jan 22;236:122899. Epub 2021 Sep 22.

Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, PR China.

A real-time quartz crystal microbalance (QCM) cytosensor was first developed for dynamical and noninvasive monitoring of cell viscoelasticity for evaluation of apoptosis degree. In this work, human breast cancer cells MCF-7 and MDA-MB-231 were employed as cell model and respectively captured on the surface of QCM electrode modified with mercaptosuccinic acid and poly-l-lysine. Cell viscoelasticity was measured dynamically by real-time monitoring energy dissipation with QCM, and the dynamic diagram of the energy dissipation of MDA-MB-231 cells treated with curcumin was first obtained. The results displayed that the changes of energy dissipation in MDA-MB-231 cells and MCF-7 cells were 8.81 × 10 and 5.29 × 10, particularly due to the difference in cell viscoelasticity. Furthermore, curcumin was used to induce cell apoptosis and suppress energy dissipation of MDA-MB-231 cells. Combining apoptosis assay with QCM measurement, the results revealed good linear relationship between cell viscoelasticity inhibition and apoptosis rate with correlation coefficient R = 0.9908. The QCM cytosensor could rapidly, accurately, dynamically, and noninvasively monitor the changes of cell viscoelasticity for evaluation of apoptosis degree in MDA-MB-231 cells. The study established a new model for cell apoptosis assessment, facilitating understanding of the mechanisms of cell apoptosis on the aspect of mechanical properties.
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http://dx.doi.org/10.1016/j.talanta.2021.122899DOI Listing
January 2022

Comprehensive Analysis of Splicing Factor and Alternative Splicing Event to Construct Subtype-Specific Prognosis-Predicting Models for Breast Cancer.

Front Genet 2021 24;12:736423. Epub 2021 Sep 24.

Public Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Recent evidence suggests that splicing factors (SFs) and alternative splicing (AS) play important roles in cancer progression. We constructed four SF-risk-models using 12 survival-related SFs. In Luminal-A, Luminal-B, Her-2, and Basal-Like BRCA, SF-risk-models for three genes (, , and ), four genes (, , , and ), three genes (, , and ), and three genes (, , and ) were constructed. These models have a promising prognosis-predicting power. The co-expression and protein-protein interaction analysis suggest that the 12 SFs are highly functional-connected. Pathway analysis and gene set enrichment analysis suggests that the functional role of the selected 12 SFs is highly context-dependent among different BRCA subtypes. We further constructed four AS-risk-models with good prognosis predicting ability in four BRCA subtypes by integrating the four SF-risk-models and 21 survival-related AS-events. This study proposed that SFs and ASs were potential multidimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA.
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http://dx.doi.org/10.3389/fgene.2021.736423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497829PMC
September 2021

Viologen-Immobilized 2D Polymer Film Enabling Highly Efficient Electrochromic Device for Solar-Powered Smart Window.

Adv Mater 2021 Oct 6:e2106073. Epub 2021 Oct 6.

Center for Advancing Electronics Dresden (cfaed) and Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, 01062, Dresden, Germany.

Electrochromic devices (ECDs) have emerged as a unique class of optoelectronic devices for the development of smart windows. However, current ECDs typically suffer from low coloration efficiency (CE) and high energy consumption, which have thus hindered their practical applications, especially as components in solar-powered EC windows. Here, the high-performance ECDs with a fully crystalline viologen-immobilized 2D polymer (V2DP) thin film as the color-switching layer is demonstrated. The high density of vertically oriented pore channels (pore size ≈ 4.5 nm; pore density ≈ 5.8 × 10 m ) in the synthetic V2DP film enables high utilization of redox-active viologen moieties and benefits for Li ion diffusion/transport. As a result, the as-fabricated ECDs achieve a rapid switching speed (coloration, 2.8 s; bleaching, 1.2 s), and a high CE (989 cm C ), and low energy consumption (21.1 µW cm ). Moreover, it is managed to fabricate transmission-tunable, self-sustainable EC window prototypes by vertically integrating the V2DP ECDs with transparent solar cells. This work sheds light on designing electroactive 2D polymers with molecular precision for optoelectronics and paves a practical route toward developing self-powered EC windows to offset the electricity consumption of buildings.
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http://dx.doi.org/10.1002/adma.202106073DOI Listing
October 2021

Genome-wide identification and transcriptome-based expression profiling of the Sox gene family in the spinyhead croaker (Collichthys lucidus).

J Fish Biol 2021 Sep 23. Epub 2021 Sep 23.

Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen, China.

Sox genes encode transcription factors with a high-mobility group (HMG) box, playing critical roles in the initiation and maintenance of a variety of developmental processes, such as sex determination and differentiation. In the present study, we identified 26 Sox genes in the genome of spinyhead croaker Collichthys lucidus (Richardson, 1844) with homology-based analysis of the HMG box. The transcriptome-based expression profiles revealed that the expression of the Sox gene in gonads began to differ between sexes when the body length was 2.74 ± 0.24 cm. At that time, three Sox genes (Sox11b, Sox8a and Sox19) were significantly upregulated, accompanied by the downregulation of 12 Sox genes in the ovary, and six Sox genes were temporarily significantly upregulated in the testis. Afterwards, the expression profile of Sox genes changed only with a small amplitude in both the ovary and testis. For adult tissues, huge differences were observed in the expression profiles of Sox genes between ovaries and testes, as well as small differences in somatic tissues between sexes. These results provide clues to further decipher the role of Sox genes in the processes of sex determination and differentiation in spinyhead croaker and other teleosts.
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http://dx.doi.org/10.1111/jfb.14913DOI Listing
September 2021

Nanoporous bismuth for the electrocatalytic reduction of CO to formate.

Phys Chem Chem Phys 2021 Sep 15;23(35):19195-19201. Epub 2021 Sep 15.

College of Chemistry and Molecular Sciences, Hubei key laboratory of Electrochemical powder sources, Wuhan university, Wuhan, 430072, P. R. China.

Bi is an attractive catalyst towards the electrochemical reduction of CO to formate. In this work, nanoporous bismuth was prepared by dealloying MgBi with tartaric acid (TA) solution, and the size of the primary Bi nanoparticles was adjusted according to the concentration of TA. When the concentration of TA increased from 2 wt% to 20 wt%, the particle size of Bi increased from about 70 nm to 400 nm. The synthesized nanoporous Bi samples were investigated as electrocatalysts for the reduction of CO in KHCO electrolyte, and it was found that the smaller the particle size, the higher the catalytic activity. However, nanoporous Bi comprising 70 nm particles suffered from mass transfer difficulty and sintering during the reaction, whereas the 100 nm nanoporous Bi delivered both a high formate formation current and faradaic efficiency (FE) (16 mA cm, FE > 90% at -0.88 V RHE) and showed excellent durability.
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http://dx.doi.org/10.1039/d1cp02661eDOI Listing
September 2021

Signal Filtering Enabled by Spike Voltage-Dependent Plasticity in Metalloporphyrin-Based Memristors.

Adv Mater 2021 Oct 12;33(43):e2104370. Epub 2021 Sep 12.

Center for Molecular Systems & Organic Devices (CMSOD), Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.

Neural systems can selectively filter and memorize spatiotemporal information, thus enabling high-efficient information processing. Emulating such an exquisite biological process in electronic devices is of fundamental importance for developing neuromorphic architectures with efficient in situ edge/parallel computing, and probabilistic inference. Here a novel multifunctional memristor is proposed and demonstrated based on metalloporphyrin/oxide hybrid heterojunction, in which the metalloporphyrin layer allows for dual electronic/ionic transport. Benefiting from the coordination-assisted ionic diffusion, the device exhibits smooth, gradual conductive transitions. It is shown that the memristive characteristics of this hybrid system can be modulated by altering the metal center for desired metal-oxygen bonding energy and oxygen ions migration dynamics. The spike voltage-dependent plasticity stemming from the local/extended movement of oxygen ions under low/high voltage is identified, which permits potentiation and depression under unipolar different positive voltages. As a proof-of-concept demonstration, memristive arrays are further built to emulate the signal filtering function of the biological visual system. This work demonstrates the ionic intelligence feature of metalloporphyrin and paves the way for implementing efficient neural-signal analysis in neuromorphic hardware.
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http://dx.doi.org/10.1002/adma.202104370DOI Listing
October 2021

Graph Fusion Network-Based Multimodal Learning for Freezing of Gait Detection.

IEEE Trans Neural Netw Learn Syst 2021 Aug 31;PP. Epub 2021 Aug 31.

Freezing of gait (FoG) is identified as a sudden and brief episode of movement cessation despite the intention to continue walking. It is one of the most disabling symptoms of Parkinson's disease (PD) and often leads to falls and injuries. Many computer-aided FoG detection methods have been proposed to use data collected from unimodal sources, such as motion sensors, pressure sensors, and video cameras. However, there are limited efforts of multimodal-based methods to maximize the value of all the information collected from different modalities in clinical assessments and improve the FoG detection performance. Therefore, in this study, a novel end-to-end deep architecture, namely graph fusion neural network (GFN), is proposed for multimodal learning-based FoG detection by combining footstep pressure maps and video recordings. GFN constructs multimodal graphs by treating the encoded features of each modality as vertex-level inputs and measures their adjacency patterns to construct complementary FoG representations, thus reducing the representation redundancy among different modalities. In addition, since GFN is devised to process multimodal graphs of arbitrary structures, it is expected to achieve superior performance with inputs containing missing modalities, compared to the alternative unimodal methods. A multimodal FoG dataset was collected, which included clinical assessment videos and footstep pressure sequences of 340 trials from 20 PD patients. Our proposed GFN demonstrates a great promise of multimodal FoG detection with an area under the curve (AUC) of 0.882. To the best of our knowledge, this is one of the first studies to utilize multimodal learning for automated FoG detection, which offers significant opportunities for better patient assessments and clinical trials in the future.
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http://dx.doi.org/10.1109/TNNLS.2021.3105602DOI Listing
August 2021

Dopamine receptor 2 downregulation and brain-derived neurotrophic factor upregulation in the paraventricular nucleus are correlated with brown adipose tissue thermogenesis in rats with bilateral substantia nigra lesions.

J Chem Neuroanat 2021 Nov 26;117:102016. Epub 2021 Aug 26.

Department of Human Anatomy and Histoembrology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang 453003, China; Henan International Joint Laboratory of Noninvasive Neuromodulation, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:

The thermogenesis resulting from brown adipose tissue (BAT)-induced energy consumption is an important method of energy regulation. It has been reported that brain-derived neurotrophic factor (BDNF)-positive neurons in the paraventricular nucleus (PVN) can regulate adaptive thermogenesis in interscapular brown adipose tissue (IBAT), but the upstream regulatory mechanism is still unclear. Our previous studies have found that a large number of dopamine (DA) receptors (DRs) are expressed on BDNF-positive neurons in the PVN and that the substantia nigra (SN) can directly project to the PVN (forming the SN-PVN pathway). Therefore, we speculate that DA in the SN can regulate the expression of BDNF via DRs and then affect IBAT thermogenesis. In this study, bilateral SN lesions were induced in rats with 6-hydroxydopamine (6-OHDA), and the altered expression of DRs and BDNF in the PVN and the metabolic changes in IBAT were studied via double immunofluorescence and western blotting. The results showed that BDNF-positive neurons in the PVN expressed DR 1 (D1) and DR 2 (D2) and were surrounded by a large number of tyrosine hydroxylase (TH)-positive nerve fibers. Compared with the control group, the 6-OHDA group exhibited significantly fewer TH-positive neurons and significantly lower TH expression in the SN, but body weight, IBAT weight and food consumption did not differ between the groups. In the PVN, BDNF expression was upregulated in the 6-OHDA group, while D2 and TH expression was downregulated. In IBAT, the expression of uncoupling protein-1 (UCP-1), phosphorylated hormone-sensitive lipase (p-HSL), TH and β3-adrenergic receptor (β3-AR) was increased, while the expression of fatty acid synthase (FAS) was decreased. The IBAT cell diameter was also decreased in the 6-OHDA group. The results suggest that the SN-PVN pathway may be an upstream neural pathway that can affect BDNF expression in the PVN and that DRs may mediate its regulatory effects. This study expands our understanding of the relationship between DA and obesity.
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http://dx.doi.org/10.1016/j.jchemneu.2021.102016DOI Listing
November 2021

Transcriptome and Coexpression Network Analyses Reveal Hub Genes in Chinese Cabbage ( L. ssp. ) During Different Stages of Infection.

Front Plant Sci 2021 10;12:650252. Epub 2021 Aug 10.

Institute of Horticulture, Henan Academy of Agricultural Sciences, Graduate T&R Base of Zhengzhou University, Zhengzhou, China.

Clubroot, caused by the soil-borne protist , is one of the most destructive diseases of Chinese cabbage worldwide. However, the clubroot resistance mechanisms remain unclear. In this study, in both clubroot-resistant (DH40R) and clubroot-susceptible (DH199S) Chinese cabbage lines, the primary (root hair infection) and secondary (cortical infection) infection stages started 2 and 5 days after inoculation (dai), respectively. With the extension of the infection time, cortical infection was blocked and complete resistance was observed in DH40R, while disease scales of 1, 2, and 3 were observed at 8, 13, and 22 dai in DH199S. Transcriptome analysis at 0, 2, 5, 8, 13, and 22 dai identified 5,750 relative DEGs (rDEGs) between DH40R and DH199S. The results indicated that genes associated with auxin, PR, disease resistance proteins, oxidative stress, and and transcription factors were involved in clubroot resistance regulation. In addition, weighted gene coexpression network analysis (WGCNA) identified three of the modules whose functions were highly associated with clubroot-resistant, including ten hub genes related to clubroot resistance (, , , , , , two , , and ). These results provide valuable information for better understanding the molecular regulatory mechanism of Chinese cabbage clubroot resistance.
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http://dx.doi.org/10.3389/fpls.2021.650252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383047PMC
August 2021

Isotopically Dimethyl Labeling-Based Quantitative Proteomic Analysis of Phosphoproteomes of Soybean Cultivars.

Biomolecules 2021 08 16;11(8). Epub 2021 Aug 16.

Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.

Isotopically dimethyl labeling was applied in a quantitative post-translational modification (PTM) proteomic study of phosphoproteomic changes in the drought responses of two contrasting soybean cultivars. A total of 9457 phosphopeptides were identified subsequently, corresponding to 4571 phosphoprotein groups and 3889 leading phosphoproteins, which contained nine kinase families consisting of 279 kinases. These phosphoproteins contained a total of 8087 phosphosites, 6106 of which were newly identified and constituted 54% of the current soybean phosphosite repository. These phosphosites were converted into the highly conserved kinase docking sites by bioinformatics analysis, which predicted six kinase families that matched with those newly found nine kinase families. The overly post-translationally modified proteins (OPP) occupies 2.1% of these leading phosphoproteins. Most of these OPPs are photoreceptors, mRNA-, histone-, and phospholipid-binding proteins, as well as protein kinase/phosphatases. The subgroup population distribution of phosphoproteins over the number of phosphosites of phosphoproteins follows the exponential decay law, Y = 4.13e - 0.04. Out of 218 significantly regulated unique phosphopeptide groups, 188 phosphoproteins were regulated by the drought-tolerant cultivar under the water loss condition. These significantly regulated phosphoproteins (SRP) are mainly enriched in the biological functions of water transport and deprivation, methionine metabolic processes, photosynthesis/light reaction, and response to cadmium ion, osmotic stress, and ABA response. Seventeen and 15 SRPs are protein kinases/phosphatases and transcription factors, respectively. Bioinformatics analysis again revealed that three members of the calcium dependent protein kinase family (CAMK family), GmSRK2I, GmCIPK25, and GmAKINβ1 kinases, constitute a phosphor-relay-mediated signal transduction network, regulating ion channel activities and many nuclear events in this drought-tolerant cultivar, which presumably contributes to the development of the soybean drought tolerance under water deprivation process.
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http://dx.doi.org/10.3390/biom11081218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393417PMC
August 2021

Percutaneous coronary intervention for acute coronary syndrome in a patient with dextrocardia and situs inversus.

Asian J Surg 2021 Oct 14;44(10):1318-1319. Epub 2021 Aug 14.

Inner Mongolia Medical University, Department of Neonatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010050, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.06.064DOI Listing
October 2021

3D Printed Wesselsite Nanosheets Functionalized Scaffold Facilitates NIR-II Photothermal Therapy and Vascularized Bone Regeneration.

Adv Sci (Weinh) 2021 Oct 15;8(20):e2100894. Epub 2021 Aug 15.

Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor-initiated bone defects. Such scaffolds are usually composed of a near-infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long-term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR-I) with intrinsic poor tissue penetration depth. Also, most of these agents are non-bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR-II photothermal conversion agent (Wesselsite [SrCuSi O ] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as-designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR-II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor-induced bone defects.
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http://dx.doi.org/10.1002/advs.202100894DOI Listing
October 2021

Downregulation of long noncoding RNA SNHG7 protects against inflammation and apoptosis in Parkinson's disease model by targeting the miR-425-5p/TRAF5/NF-κB axis.

J Biochem Mol Toxicol 2021 Oct 8;35(10):e22867. Epub 2021 Aug 8.

Department of Neurosurgery, XiangYang Center Hospital, Xiangyang, China.

Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague-Dawley (SD) rats and SH-SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1β [IL-1β], IL-6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor-associated factor (TRAF5), I-κB, nuclear factor-κB (NF-κB), HO-1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p, and TRAF5. Dual-luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR-425-5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot-mediated rat model of PD.
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http://dx.doi.org/10.1002/jbt.22867DOI Listing
October 2021

Arthroscopic debridement combined with proximal fibular osteotomy in medial tibial articular genu osteoarthritis treatment: systematic review and meta-analysis.

Ann Palliat Med 2021 Jul;10(7):7894-7904

Orthopedics Department, Gansu Provincial Hospital of TCM, Lanzhou, China.

Background: We performed a systematic review and meta-analysis to evaluate the therapeutic effects of arthroscopic debridement and proximal fibular osteotomy (AD & PFO) on medial tibial articular genu osteoarthritis (MTAGO), so as to provide a theoretical reference for clinical surgical analgesia for patients.

Methods: We searched and screened randomized controlled trials (RCTs) focusing on AD & PFO on MTAGO surgical analgesia published before December 31, 2020 in English databases including PubMed, Embase, Medline, Ovid, Springer, and Web of Science. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was adopted for bias risk assessment, and Review Manager 5.3 was used to conduct the meta-analysis.

Results: Twelve eligible studies were included, involving 765 research subjects. The meta-analysis results indicated that, relative to control group, satisfaction was markedly increased [mean difference (MD) =3.10; 95% confidence interval (CI), (1.48 to 6.51); Z=3; P=0.003], adverse reactions were reduced [MD =0.33; 95% CI, (0.08 to 1.32); Z=1.56; P=0.12] the hospital special surgery (HSS) score was lower [MD =5.37; 95% CI, (3.18 to 7.55); Z=4.82; P<0.00001], the visual analogue scale (VAS) score decreased [MD =-1.68; 95% CI, (-2.22 to -1.13); Z=6.01; P<0.00001], and the Knee Society score (KSS) was reduced [MD =6.16; 95% CI, (3.85 to 8.47); Z=5.23; P<0.00001]. However, the difference in the femoro-tibial (FT) angle between the control and study groups was not statistically considerable [MD =0.14; 95% CI, (-6.22 to 6.49); Z=0.04; P=0.97].

Discussion: The combined adoption of AD & PFO for MTAGO surgical analgesia can reduce the HSS, KSS, and VAS scores of patients. The postoperative analgesia effect is good, and effectively reduces pain and adverse reactions in patients. Thus, it is suitable for analgesia in MTAGO.
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http://dx.doi.org/10.21037/apm-21-1381DOI Listing
July 2021

STAT3 mediated upregulation of C-MET signaling acts as a compensatory survival mechanism upon EGFR family inhibition in chemoresistant breast cancer cells.

Cancer Lett 2021 Oct 1;519:328-342. Epub 2021 Aug 1.

Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. Electronic address:

Chemotherapy remains the most common treatment for all types of breast cancer. Chemoresistance in tumors is still a major obstacle for treating late-stage breast cancer. In the process of acquiring resistance, tumor cells dynamically evolve to adapt to the challenge of anti-cancer drugs. Besides the upregulation of drug-pumps, signal pathways related to proliferation and survival undergo adaptive evolution. Thus, these drug-resistant cells are more conducive to proliferation, even in stressful conditions. Nevertheless, the detailed mechanism that drives cancer cells to sustain their proliferation ability is unclear. Herein, we reported that the upregulated C-MET signaling acts as a compensatory mechanism that sustains the proliferation of chemoresistant cells in which EGFR family signaling was attenuated. Both C-MET and EGFR family are essential for cell proliferation due to their activation of the STAT3 signaling. Different from other cell models in which C-MET interacts with and phosphorylates EGFR family members, our cell model showed no direct interaction between C-MET and EGFR family members. Therefore, C-MET and EGFR family signaling pathways function independently to sustain the proliferation of resistant cells. Moreover, chemoresistant cells have evolved a novel, STAT3-C-MET feed-forward loop that plays a vital role in sustaining cell proliferation. The activated STAT3 interacts with the MET gene promoter to upregulate its transcription. Most importantly, the combined inhibition of C-MET and EGFR family synergistically inhibits the proliferation of drug-resistant cells in vitro and in xenograft tumor models. This work provides a new strategy for treating drug-resistant breast cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.07.048DOI Listing
October 2021

Interfacial Synthesis of Layer-Oriented 2D Conjugated Metal-Organic Framework Films toward Directional Charge Transport.

J Am Chem Soc 2021 Sep 3;143(34):13624-13632. Epub 2021 Aug 3.

Center for Advancing Electronics Dresden (cfaed) and Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, 01062 Dresden, Germany.

The development of layer-oriented two-dimensional conjugated metal-organic frameworks (2D c-MOFs) enables access to direct charge transport, dial-in lateral/vertical electronic devices, and the unveiling of transport mechanisms but remains a significant synthetic challenge. Here we report the novel synthesis of metal-phthalocyanine-based p-type semiconducting 2D c-MOF films (Cu[PcM-O], M = Cu or Fe) with an unprecedented edge-on layer orientation at the air/water interface. The edge-on structure formation is guided by the preorganization of metal-phthalocyanine ligands, whose basal plane is perpendicular to the water surface due to their π-π interaction and hydrophobicity. Benefiting from the unique layer orientation, we are able to investigate the lateral and vertical conductivities by DC methods and thus demonstrate an anisotropic charge transport in the resulting Cu[PcCu-O] film. The directional conductivity studies combined with theoretical calculation identify that the intrinsic conductivity is dominated by charge transfer along the interlayer pathway. Moreover, a macroscopic (cm size) Hall-effect measurement reveals a Hall mobility of ∼4.4 cm V s for the obtained Cu[PcCu-O] film. The orientation control in semiconducting 2D c-MOFs will enable the development of various optoelectronic applications and the exploration of unique transport properties.
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http://dx.doi.org/10.1021/jacs.1c05051DOI Listing
September 2021

A calcium phosphate drug carrier loading with 5-fluorouracil achieving a synergistic effect for pancreatic cancer therapy.

J Colloid Interface Sci 2022 Jan 20;605:263-273. Epub 2021 Jul 20.

The Seventh Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH particles could be efficiently uptaken by cancer cells, and then decompose into Ca and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH drug delivery platform for enhanced 5Fu chemotherapeutic effect.
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http://dx.doi.org/10.1016/j.jcis.2021.07.080DOI Listing
January 2022

Characterization and functional study of a chimera galectin from yellow drum Nibea albiflora.

Int J Biol Macromol 2021 Sep 24;187:361-372. Epub 2021 Jul 24.

Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture, Fisheries College, Jimei University, Xiamen 361021, China. Electronic address:

Galectins are protein that participates in a variety of immune responses in the process of pathogenic infections. In the present study, a chimera galectin gene was screened from the transcriptome database of Nibea albiflora, which was named as YdGal-3. The results of qRT-PCR showed that the mRNA transcripts of YdGal-3 were ubiquitously distributed in all the detected tissues. After infection with Vibrio harveyi, the expression of YdGal-3 in liver, spleen, and head kidney increased significantly. Immunohistochemistry showed that YdGal-3 protein was widely expressed in the head kidney. The purified YdGal-3 protein by prokaryotic expression agglutinated red blood cells. Sugar inhibition assay showed that the agglutinating activity of YdGal-3 protein was inhibited by different sugars including lactose, D-galactose, and lipopolysaccharide. In addition, we mutated YdGal-3 His 294 into proline (P), alanine (A), glycine (G), and aspartic acid (D), it was further proved that the residue plays a key role in agglutination. YdGal-3 agglutinated some gram-negative bacteria including Pseudomonas plecoglossicida, Vibrio parahemolyticus, V. harveyi, and Aeromonas hydrophila, and exhibited antibacterial activity. These results suggested that YdGal-3 protein played an important role in the innate immunity of N. albiflora.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.118DOI Listing
September 2021

Multi-Modal Fusion Emotion Recognition Method of Speech Expression Based on Deep Learning.

Front Neurorobot 2021 9;15:697634. Epub 2021 Jul 9.

School of Information Engineering, Shandong Youth University of Political Science, Jinan, China.

The redundant information, noise data generated in the process of single-modal feature extraction, and traditional learning algorithms are difficult to obtain ideal recognition performance. A multi-modal fusion emotion recognition method for speech expressions based on deep learning is proposed. Firstly, the corresponding feature extraction methods are set up for different single modalities. Among them, the voice uses the convolutional neural network-long and short term memory (CNN-LSTM) network, and the facial expression in the video uses the Inception-Res Net-v2 network to extract the feature data. Then, long and short term memory (LSTM) is used to capture the correlation between different modalities and within the modalities. After the feature selection process of the chi-square test, the single modalities are spliced to obtain a unified fusion feature. Finally, the fusion data features output by LSTM are used as the input of the classifier LIBSVM to realize the final emotion recognition. The experimental results show that the recognition accuracy of the proposed method on the MOSI and MELD datasets are 87.56 and 90.06%, respectively, which are better than other comparison methods. It has laid a certain theoretical foundation for the application of multimodal fusion in emotion recognition.
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http://dx.doi.org/10.3389/fnbot.2021.697634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300695PMC
July 2021

Tunable Electrosynthesis of Anthranilic Acid Derivatives via a C-C Bond Cleavage of Isatins.

J Org Chem 2021 Jul 14. Epub 2021 Jul 14.

Hefei National Laboratory for Physical Sciences at Microscale, Technology & School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.

A facile and direct electrocatalytic C-C bond cleavage/functionalization reaction of isatins was developed. With isatins as the amino-attached C1 sources, a variety of aminobenzoates, and aminobenzamides were synthesized in moderate to good yields under mild conditions.
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http://dx.doi.org/10.1021/acs.joc.1c01017DOI Listing
July 2021

3D printed hydrogel/PCL core/shell fiber scaffolds with NIR-triggered drug release for cancer therapy and wound healing.

Acta Biomater 2021 09 10;131:314-325. Epub 2021 Jul 10.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China. Electronic address:

Hydrogel based scaffolds with the ability of on-demand drug delivery gained increasing interests for localized cancer therapy and tissue engineering application. However, most drug-loaded hydrogels are generally not suitable for long-term drug delivery, because of the uncontrolled diffusion of drugs from the swollen hydrogels. Therefore, in this study, a core/shell fiber scaffold was fabricated by coating a homogeneous layer of polycaprolactone (PCL) on the 3D printed alginate-gelatin hydrogel scaffolds. The PCL coatings could reduce the free diffusion of drugs from the core gels. Subsequently, polydopamine (PDA) was coated on the Gel/PCL core/shell scaffolds, endowing the scaffolds with great photothermal effects. Thus, near-infrared (NIR) laser triggered on-demand drug release was realized in this system due to the thermally induced sol-gel transition of the core gels. The released drugs (doxorubicin) and photothermal therapy could effectively prohibit or ablate tumor in vitro and in vivo. Additionally, the Gel/PCL/PDA core/shell scaffold could serve as platform for promoting wound healing. Therefore, the reported Gel/PCL/PDA core/shell scaffolds have the potential for application in localized cancer therapy and tissue regeneration. Especially for those cancer patients suffering surgical resection, the scaffolds could be implanted in the resection site to kill the residual or recurrent cancer cells, as well as to repair the tissue defects caused by surgery. STATEMENT OF SIGNIFICANCE: This paper reported a facile strategy to realize stimuli-triggered on demand drug release in vitro and in vivo. Polycaprolactone (PCL) and polydopamine were sequentially deposited on the surface of 3D printed drug-loaded alginate/gelatin scaffold. PCL encapsulation could effectively reduce the free diffusion of drugs from the core hydrogel, achieving sustained drug release. Polydopamine with good photothermal effects endowed the scaffold with stimuli-triggered drug release in response to near-infrared (NIR) laser irradiation. This scaffold could be applied for localized cancer therapy and tissue regeneration. Especially for those cancer patients suffering surgical resection, the scaffolds could be implanted in the resection site to kill the residual or recurrent cancer cells, as well as to repair the tissue defects caused by surgery.
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http://dx.doi.org/10.1016/j.actbio.2021.07.011DOI Listing
September 2021

Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.

JCI Insight 2021 Sep 8;6(17). Epub 2021 Sep 8.

Division of Cancer Prevention and.

BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.
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http://dx.doi.org/10.1172/jci.insight.147096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492350PMC
September 2021

Reflections on the aconitine poisoning.

J Forensic Sci 2021 Sep 8;66(5):2035-2040. Epub 2021 Jul 8.

Shanghai Key Laboratory of Forensic Medicine (Academy of Forensic Science).

Aconitine is a natural toxic substance belonging to the family of aconitum alkaloids, which is used in small doses by Traditional Chinese practitioners. We present a case of accidental death due to acute aconitine poisoning. A 65-year-old Chinese man presented to a medical clinic with fever and shoulder pain. Soon after administration of intravenous ceftriaxone, a bottle of Chinese medicinal wine was administered. The man rapidly experienced headache, hearing loss and tinnitus, nausea, diarrhea, numbness of the lips, tongue, face, and the upper and lower extremities, cold sweat, fall of blood pressure, and discomfort of the entire body, and he died on the same day. Postmortem examination showed cyanosis of the nail beds, severe congestion in lungs and other organs, bilateral pleural effusions, and infiltration of basophils in the intestinal submucosa. No significant increase of IgE was found in the blood. Toxicological analysis detected aconitine in the medicinal wine, blood, and stomach contents by liquid chromatography-tandem mass spectrometry (LC-MS⁄MS). Aconitine was quantified in cardiac blood as 16.4 ng/ml, and in stomach contents (63.8 ng/ml) and wine sample (10.1 ug/ml). The cause of death was aconitine poisoning. This case report highlights the danger of aconitine. LC-MS⁄MS has the advantages of high analytic speed, sensitivity, and accuracy. It would be desirable for the government to control the use of aconitine-containing herbal extracts.
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http://dx.doi.org/10.1111/1556-4029.14766DOI Listing
September 2021

Agro-morphological and metabolomics analysis of low nitrogen stress response in .

AoB Plants 2021 Aug 7;13(4):plab022. Epub 2021 May 7.

Key Laboratory of Genetics and Germplasm Innovation of Tropical Special Forest Trees and Ornamental Plants, Ministry of Education, College of Forestry, Hainan University, Haikou, Hainan 570228, China.

also known as carpet grass is a robust, stoloniferous grass that can grow in minimal fertilization and resists well to abiotic and biotic stresses including low nitrogen (LN) stress. This study aimed at characterizing the agro-morphological and metabolome responses to LN in carpet grass leaves. Under LN stress, carpet grass increased yellowness of leaves and root dry matter while reduced turf quality and shoot dry weight. The metabolome comparison between samples from optimum and LN conditions indicated 304 differentially accumulated metabolites (DAMs), which could be classified into 12 major and 31 subclasses. The results revealed that the leaf tissues accumulated more anthocyanins and other flavonoid metabolites under LN stress. Conversely, amino acids, nucleic acids and their derivatives were reduced in response to LN stress. The overall evaluation of individual metabolites and pathways, and previous studies on metabolomes indicated that carpet grass reduced its energy consumption in leaves and increased the level of organic acid metabolism and secondary metabolism in order to resist LN stress conditions.
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http://dx.doi.org/10.1093/aobpla/plab022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256886PMC
August 2021

Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors.

Front Endocrinol (Lausanne) 2021 9;12:656641. Epub 2021 Jun 9.

Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Objective: A low concentration of plasma triiodothyronine (T3) indicates euthyroid sick syndrome (ESS), which could be associated with a poor outcome in patients in intensive care units (ICUs). This study evaluated the relationship between ESS and prognostic indicators in patients admitted to an ICU and examined the free T3 (FT3) cut-off points that could be associated with 28-day mortality.

Methods: This prospective observational study included patients admitted to the ICU of The Third Hospital of Hebei Medical University between February and November 2018. Baseline variables and data on the occurrence of low FT3 were collected. The patients were divided into ESS (FT3 < 3.28 pmol/L) and non-ESS groups. The relationship between ESS and prognostic indicators in patients admitted to the ICU was evaluated, and the FT3 cut-off points that could be associated with 28-day mortality were examined.

Results: Out of a total of 305 patients, 118 (38.7%) were in the ESS group. Levels of FT3 (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and hospitalization expenses in the ICU (P = 0.001) were higher in the ESS group. A univariable analysis identified ESS, FT3, free thyroxine (FT4)/FT3, the APACHE II score, the sequential organ failure (SOFA) score, the duration of mechanical ventilation, creatinine (CREA) levels, the oxygenation index (HGB), white blood cells, albumin (ALB) levels, age, and brain natriuretic peptide (BNP) levels as factors associated with 28-day mortality (all P < 0.05). The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L, and the 28-day mortality rate and hospitalization expenses in the ICU were higher in patients with ESS. The syndrome was confirmed to be independently associated with 28-day mortality.

Conclusion: This study determined the incidence of ESS in the comprehensive ICU to be 38.7%. APACHE II, SOFA, BNP, APTT, HGB, PLT, CREA, ALB, FT4, SBP, and DBP are closely related to ESS, while BNP, PLT, and ALB are independent risk factors for the syndrome.
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http://dx.doi.org/10.3389/fendo.2021.656641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220065PMC
June 2021

An SNP Mutation of Gene Converts Petal Color From Purple to White in Radish ( L.).

Front Plant Sci 2021 3;12:643579. Epub 2021 Jun 3.

Institute of Horticulture, Henan Academy of Agricultural Sciences, Zhengzhou, China.

Along with being important pigments that determining the flower color in many plants, anthocyanins also perform crucial functions that attract pollinators and reduce abiotic stresses. Purple and white are two different colors of radish petals. In this study, two cDNA libraries constructed with purple and white petal plants were sequenced for transcriptome profiling. Transcriptome results implied that the expression level of the genes participating in the anthocyanin biosynthetic pathway was commonly higher in the purple petals than that in the white petals. In particular, two genes, F3'H and DFR, had a significantly higher expression pattern in the purple petals, suggesting the important roles these genes playing in radish petal coloration. BSA-seq aided-Next Generation Sequencing of two DNA pools revealed that the radish purple petal gene () was located on chromosome 7. With additional genotyping of 617 F population plants, the was further confined within a region of 93.23 kb. Transcriptome and Sanger sequencing analysis further helped identify the target gene, . is a homologous gene to F3'H, a key gene in the anthocyanin biosynthetic pathway. These results will aid in elucidating the molecular mechanism of plant petal coloration and developing strategies to modify flower color through genetic transformation.
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http://dx.doi.org/10.3389/fpls.2021.643579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210830PMC
June 2021

Synthesis of MnO/C/CoO nanocomposites by a Mn-oxidizing bacterium as a biotemplate for lithium-ion batteries.

Sci Technol Adv Mater 2021 Jun 4;22(1):429-440. Epub 2021 Jun 4.

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

The biotemplate and bioconversion strategy represents a sustainable and environmentally friendly approach to material manufacturing. In the current study, biogenic manganese oxide aggregates of the Mn-oxidizing bacterium sp. T34 were used as a precursor to synthesize a biocomposite that incorporated Co (CMC-Co) under mild shake-flask conditions based on the biomineralization process of biogenic Mn oxides and the characteristics of metal ion subsidies. X-ray photoelectron spectroscopy, phase composition and fine structure analyses demonstrated that hollow MnO/C/CoO multiphase composites were fabricated after high-temperature annealing of the biocomposites at 800°C. The cycling and rate performance of the prepared anode materials for lithium-ion batteries were compared. Due to the unique hollow structure and multiphasic state, the reversible discharge capacity of CMC-Co remained at 650 mAh g after 50 cycles at a current density of 0.1 Ag, and the coulombic efficiency remained above 99% after the second cycle, indicating a good application potential as an anode material for lithium-ion batteries.
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http://dx.doi.org/10.1080/14686996.2021.1927175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183561PMC
June 2021

Exploring the Effect of Cyclization of Histamine H Receptor Antagonists on Ligand Binding Kinetics.

ACS Omega 2021 May 7;6(19):12755-12768. Epub 2021 May 7.

Amsterdam Institute of Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.

There is an increasing interest in guiding hit optimization by considering the target binding kinetics of ligands. However, compared to conventional structure-activity relationships, structure-kinetics relationships have not been as thoroughly explored, even for well-studied archetypical drug targets such as the histamine H receptor (HR), a member of the family A G-protein coupled receptor. In this study, we show that the binding kinetics of HR antagonists at the HR is dependent on the cyclicity of both the aromatic head group and the amine moiety of HR ligands, the chemotypes that are characteristic for the first-generation HR antagonists. Fusing the two aromatic rings of HR ligands into one tricyclic aromatic head group prolongs the HR residence time for benchmark HR ligands as well as for tailored synthetic analogues. The effect of constraining the aromatic rings and the basic amines is systematically explored, leading to a coherent series and detailed discussions of structure-kinetics relationships. This study shows that cyclicity has a pronounced effect on the binding kinetics.
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http://dx.doi.org/10.1021/acsomega.0c06358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154229PMC
May 2021
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