Publications by authors named "Chen Peng"

2,390 Publications

  • Page 1 of 1

Coordinating bioorthogonal reactions with two tumor-microenvironment-responsive nanovehicles for spatiotemporally controlled prodrug activation.

Chem Sci 2020 Jan 13;11(8):2155-2160. Epub 2020 Jan 13.

School of Life Science, Beijing Institute of Technology No. 5 South Zhong Guan Cun Street Beijing 100081 China

Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation through the IEDDA reaction. The hierarchically regulated and locally confined Dox liberation led to dramatically decreased side-effects that were much lower than those of the clinical Doxorubicin Hydrochloride Liposomal Injection (Doxil), while the antitumor therapeutic effect was potent.
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http://dx.doi.org/10.1039/c9sc05036aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150104PMC
January 2020

Gut Microbiota and Chemical-Induced Acute Liver Injury.

Front Physiol 2021 26;12:688780. Epub 2021 May 26.

Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Drug overdose or chemical exposures are the main causes of acute liver injury (ALI). Severe liver injury can develop into liver failure that is an important cause of liver-related mortality in intensive care units in most countries. Pharmacological studies have utilized a variety of comprehensive chemical induction models that recapitulate the natural pathogenesis of acute liver injury. Their mechanism is always based on redox imbalance-induced direct hepatotoxicity and massive hepatocyte cell death, which can trigger immune cell activation and recruitment to the liver. However, the pathogenesis of these models has not been fully stated. Many studies showed that gut microbiota plays a crucial role in chemical-induced liver injury. Hepatotoxicity is likely induced by imbalanced microbiota homeostasis, gut mucosal barrier damage, systemic immune activation, microbial-associated molecular patterns, and bacterial metabolites. Meanwhile, many preclinical studies have shown that supplementation with probiotics can improve chemical-induced liver injury. In this review, we highlight the pathogenesis of gut microorganisms in chemical-induced acute liver injury animal models and explore the protective mechanism of exogenous microbial supplements on acute liver injury.
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http://dx.doi.org/10.3389/fphys.2021.688780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187901PMC
May 2021

A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors.

Front Oncol 2021 25;11:692136. Epub 2021 May 25.

Department of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Background: Understanding common and unique mechanisms driving oncogenic processes in human tumors is indispensable to develop efficient therapies. Recent studies have proposed Twinfilin Actin Binding Protein 1 (TWF1) as a putative driver gene in lung cancer, pancreatic cancer and breast cancer, however a systematic pan-cancer analysis has not been carried out.

Methods: Here, we set out to explore the role of TWF1 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), and several bioinformatic tools.

Results: As part of our analysis, we have assessed expression across tumors. We found that over-expression of generally predicted poor OS for patients with tumors with high expression, such as mesothelioma, lung adenocarcinoma, cervical cancer and pancreatic adenocarcinoma. We also assessed the mutation burden of in cancer and the -associated survival of cancer patients, compared the phosphorylation of TWF1 between normal and primary tumor tissues and explored putative functional mechanisms in TWF1-mediated oncogenesis.

Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of TWF1 in multiple human cancers.
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http://dx.doi.org/10.3389/fonc.2021.692136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185641PMC
May 2021

A system review and meta-analysis of the treatment of acute angle-closure glaucoma under optical coherence tomography.

Ann Palliat Med 2021 May;10(5):5659-5670

Department of Ophthalmology, Affiliated Hospital of Hebei University, Baoding, China.

Background: A meta-analysis was conducted to investigate the value of treatment-related indicators of acute angle-closure glaucoma (AACG) based on optical coherence tomography (OCT) to evaluate the curative effect.

Methods: Articles on the treatment of AACG in clinical research of OCT published from January 2010 to June 2020 were retrieved from the PubMed, Web of Science, and Spring databases. RevMan 5.3 software was used for the meta-analysis of the relevant data. The angle opening distance (AOD), trabecular-iris space area (TISA), angle recess area (ARA), anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber area (ACA), anterior chamber volume (ACV), lens vault (LV), iris thickness 750 (IT750), intraocular pressure (IOP), and pupil diameter (PD) values were observed and compared before and after the treatment.

Results: A total of 12 articles were included in the meta-analysis. The results indicated that patients' ACD, I-Area, IOP, and PD values were lower after treatment than before treatment [mean deviation (MD): -0.32, 0.12, -0.04, 13.55, 0.30; 95% confidential interval (CI): -0.55 to -0.08, 0.04 to 0.1, -0.09 to 0.01, 4.71 to 22.39, 0.09 to 0.529; Z=2.66, 3.06, 1.39, 3, 2.75, and P=0.008, 0.002, 0.16, 0.003, 0.006, respectively]. The ACA, ACV, ARA, AOD750, and TISA500 values were higher after treatment than before treatment (MD: -3.22, -2.90, -0.03, -0.05, -0.01; 95% CI: -5.07 to -1.38, -5.44 to -0.36, -0.05 to -0.02, -0.08 to -0.03, -0.02 to -0.01; Z=3.42, 2.24, 4.10, 4.41, 7.77, and P=0.0006, 0.03, <0.0001, <0.0001, and <0.0001, respectively). The ACW, LV, I-Curve, IT750, AOD500, and TISA750 values showed little change (MD: 0.01, 0.05, 0.075, 0.05, -0.07, 0.02; 95% CI: -0.04 to 0.05, -0.01 to 0.11, 0 to 0.15, -0.08 to 0.17, -0.16 to 0.02, -0.03 to 0.07; Z=0.29, 1.65, 1.85, 0.72, 1.49, 0.79, and P=0.77, 0.10, 0.06, 0.47, 0.14, 0.43, respectively).

Discussion: The different indicators were not compared with the control group in this study, but it still could provide a reference for the selection of OCT diagnostic parameters before and after the treatment of AACG in the future.
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http://dx.doi.org/10.21037/apm-21-1054DOI Listing
May 2021

An Artificial Polyacrylonitrile Coating Layer Confining Zinc Dendrite Growth for Highly Reversible Aqueous Zinc-Based Batteries.

Adv Sci (Weinh) 2021 Jun 30;8(11):e2100309. Epub 2021 Mar 30.

Department of Chemistry, University of Venda, Thohoyandou, 0950, South Africa.

Aqueous rechargeable zinc-metal-based batteries are an attractive alternative to lithium-ion batteries for grid-scale energy-storage systems because of their high specific capacity, low cost, eco-friendliness, and nonflammability. However, uncontrollable zinc dendrite growth limits the cycle life by piercing the separator, resulting in low zinc utilization in both alkaline and mild/neutral electrolytes. Herein, a polyacrylonitrile coating layer on a zinc anode produced by a simple drop coating approach to address the dendrite issue is reported. The coating layer not only improves the hydrophilicity of the zinc anode but also regulates zinc-ion transport, consequently facilitating the uniform deposition of zinc ions to avoid dendrite formation. A symmetrical cell with the polymer-coating-layer-modified Zn anode displays dendrite-free plating/stripping with a long cycle lifespan (>1100 h), much better than that of the bare Zn anode. The modified zinc anode coupled with a Mn-doped V O cathode forms a stable rechargeable full battery. This method is a facile and feasible way to solve the zinc dendrite problem for rechargeable aqueous zinc-metal batteries, providing a solid basis for application of aqueous rechargeable Zn batteries.
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http://dx.doi.org/10.1002/advs.202100309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188195PMC
June 2021

Maintenance therapy for untreated diffuse large B-cell lymphoma: a systematic review and network meta-analysis.

Ther Adv Hematol 2021 29;12:20406207211018894. Epub 2021 May 29.

Epidemiology and Health Statistics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1, Wenhua Road West, Jinan, Shandong 250012, P.R. China.

Background: Several clinical trials have been conducted to evaluate the role of maintenance therapy in untreated diffuse large B-cell lymphoma (DLBCL) patients with complete response or partial response following standard immunochemotherapy; however, the effect of maintenance therapy remains uncertain, and a suitable maintenance strategy has not been determined because of the lack of direct/indirect comparisons.

Methods: We performed a systematic review and Bayesian network meta-analysis (NMA) to analyze and compare the effectiveness of different maintenance regimens in newly diagnosed DLBCL patients. We searched the , , , , and for relevant papers from inception to 18 March 2021. Our study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020168864). Data on overall survival (OS) were extracted and the treatments were ranked using the surface under the cumulative ranking (SUCRA) curve.

Results: Eight trials and seven treatments involving 3525 patients were analyzed. OS analysis indicated that none of the drugs showed any benefit compared with non-maintenance therapy. Maintenance therapy with lenalidomide (SUCRA 69.3%) was ranked first in terms of OS.

Conclusion: Based on the OS results observed in this NMA, we do not recommend maintenance therapy in patients with newly diagnosed DLBLC after first-line therapy.
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http://dx.doi.org/10.1177/20406207211018894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165531PMC
May 2021

A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau.

Cell Res 2021 Jun 7. Epub 2021 Jun 7.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

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http://dx.doi.org/10.1038/s41422-021-00517-6DOI Listing
June 2021

Clinical Analysis of Bilateral Thalamic Infarction Caused by Percheron Artery Occlusion.

Neuropsychiatr Dis Treat 2021 28;17:1707-1712. Epub 2021 May 28.

Department of Neurology, The First Hospital of Yulin, Yulin, People's Republic of China.

The Percheron artery (artery of Percheron, AOP) is a rare variant vessel. Its acute occlusion can cause a bilateral symmetrical thalamic stroke; typical symptoms of bilateral paramedian thalamic infarcts due to occlusion of AOP are vertical gaze palsy, memory impairment, confusion, drowsiness, hypersomnolence, or coma. We present the MR imaging findings in two cases with cerebral infarction caused by Percheron artery occlusion. Due to the difficulty in the diagnosis of acute Percheron arterial infarction, early conservative treatment is used. The prognosis of the disease is poor, with few patients completely rehabilitating. Therefore, clinicians must understand the characteristics of the disease, provide early diagnosis and administer timely and effective treatment to reduce the patient's disability rate and fatality rate and therefore improve the quality of life of patients. The patient's prognosis has extraordinary significance.
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http://dx.doi.org/10.2147/NDT.S296685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169551PMC
May 2021

A mutation in CsHY2 encoding a phytochromobilin (PΦB) synthase leads to an elongated hypocotyl 1(elh1) phenotype in cucumber (Cucumis sativus L.).

Theor Appl Genet 2021 Jun 6. Epub 2021 Jun 6.

College of Horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Key Message: The elongated hypocotyl1 (elh1) mutant in cucumber is due to a mutation in CsHY2, which is a homolog of the Arabidopsis HY2 encoding the phytochromobilin (PΦB) synthase for phytochrome biosynthesis Hypocotyl length is a critical determinant in establishing high quality seedlings for successful cucumber production, but knowledge on the molecular regulation of hypocotyl growth in cucumber is very limited. Here, we reported identification and characterization of a cucumber elongated hypocotyl 1 (elh1) mutant. We found that the longer hypocotyl in elh1 was due to longitudinal growth of hypocotyl cells. With fine mapping, the elh1 locus was delimited to a 20.9-kb region containing three annotated genes; only one polymorphism was identified in this region between two parental lines, which was a non-synonymous SNP (G28153633A) in the third exon of CsHY2 (CsGy1G030000) that encodes a phytochromobilin (PΦB) synthase. Uniqueness of the mutant allele at CsHY2 was verified in natural cucumber populations. Ectopic expression of CsHY2 in Arabidopsis hy2-1 long-hypocotyl mutant led to reduced hypocotyl length. The PΦB protein was targeted to the chloroplast. The expression levels of CsHY2 and five phytochrome genes CsPHYA1, CsPHYA2, CsPHYB, CsPHYC and CsPHYE were all significantly down-regulated while several cell elongation related genes were up-regulated in elh1 mutant compared to wild-type cucumber, which are correlated with dynamic hypocotyl elongation in the mutant. RNA-seq analysis in the WT and mutant revealed differentially expressed genes involved in porphyrin and chlorophyll metabolisms, cell elongation and plant hormone signal transduction pathways. This is the first report to characterize and clone the CsHY2 gene in cucumber. This work reveals the important of CsHY2 in regulating hypocotyl length and extends our understanding of the roles of CsHY2 in cucumber.
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http://dx.doi.org/10.1007/s00122-021-03849-4DOI Listing
June 2021

Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway.

Cell Biosci 2021 Jun 5;11(1):105. Epub 2021 Jun 5.

School of Life Science, Nanchang University, Nanchang, 330031, China.

Background: The neuromuscular junction (NMJ) is a peripheral synapse critical to muscle contraction. Like acetylcholine receptors (AChRs), many essential proteins of NMJ are extremely concentrated at the postjunctional membrane. However, the mechanisms of synapse-specific concentration are not well understood; furthermore, it is unclear whether signaling molecules critical to NMJ formation and maintenance are also locally transcribed.

Results: We studied the β-gal activity encoded by a lacZ cassette driven by the promoter of the Lrp4 gene. As reported for Lrp4 mRNA, β-gal was in the central region in embryonic muscles and at the NMJ after its formation. However, β-gal was no longer in the central areas of muscle fibers in Lrp4 or MuSK mutant mice, indicating a requirement of Lrp4/MuSK signaling. This phenotype could be rescued by transgenic expression of LRP4 with a transmembrane domain but not soluble ECD in Lrp4 mutant mice. β-gal and AChR clusters were distributed in a broader region in lacZ/ECD than that of heterozygous lacZ/+ mice, indicating an important role of the transmembrane domain in Lrp4 signaling. Synaptic β-gal activity became diffused after denervation or treatment with µ-conotoxin, despite its mRNA was increased, indicating synaptic Lrp4 mRNA enrichment requires muscle activity. β-gal was also diffused in aged mice but became re-concentrated after muscle stimulation. Finally, Lrp4 mRNA was increased in C2C12 myotubes by Wnt ligands in a manner that could be inhibited by RKI-1447, an inhibitor of ROCK in Wnt non-canonical signaling. Injecting RKI-1447 into muscles of adult mice diminished Lrp4 synaptic expression.

Conclusions: This study demonstrates that synapse-specific enrichment of Lrp4 mRNA requires a coordinated interaction between Lrp4/MuSK signaling, muscle activity, and Wnt non-canonical signaling. Thus, the study provides a new mechanism for Lrp4 mRNA enrichment. It also provides a potential target for the treatment of NMJ aging and other NMJ-related diseases.
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http://dx.doi.org/10.1186/s13578-021-00619-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180081PMC
June 2021

Proteomic profile of human stem cells from dental pulp and periodontal ligament.

J Proteomics 2021 Jun 4;245:104280. Epub 2021 Jun 4.

Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China; 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. Electronic address:

Background The study of molecular profiling of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) contributes to understanding the high proliferation ability and multi-lineage differentiation potential. Objectives The aim of the study was to compare the protein abundance and specific markers of DPSCs and PDLSCs by protein profiles. Material and methods The DPSCs and PDLSCs extracted from the same tooth were lysed with 3 biological replicates and the protein was collected. Two-dimensional electrophoresis technology and TMT proteomics were used to separate and identify proteins. The data are available via ProteomeXchange with identifier PXD021997. The RT-qPCR detection of mRNA expression revealed a special marker for distinguishing two kinds of dental stem cells. Results Compared with PDLSCs, 962 differential proteins (DAPs) were up-regulated, and 127 were down-regulated in DPSCs. In the up-regulated DAPs, two high-scoring sub-networks were detected for neural-related molecules, which encode cell vesicle transport and mitochondrial energy transfer to regulate cell proliferation and secretion factors. A large number of cell adhesion molecules were distinguished among the highly expressed molecules of PDLSCs, supporting that stem cells provide cell attachment functions. It was interpreted ENPL, HS90A and HS90B were highly expressed in DPSCs, while CKB was highly abundant in PDLSCs. Another cell group confirmed that these molecules can be used as special biomarkers to identify and distinguish between DPSCs and PDLSCs. Conclusions This study can promote the basic research and clinical application of dental stem cells. Significance The high-throughput protein profiles were tested by combining two-dimensional gel proteomics and TMT-based proteomics. The proteomics of DPSCs and PDLSCs without individual difference demonstrated an accurate and comprehensive molecular expression profiles and interpretation of neural application potential, this study promotes the basic research of dental stem cells and clinical application.
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http://dx.doi.org/10.1016/j.jprot.2021.104280DOI Listing
June 2021

Association Between Polymorphisms in Gastric Cancer Related Genes and Risk of Gastric Cancer: A Case-Control Study.

Front Mol Biosci 2021 17;8:690665. Epub 2021 May 17.

School of Medicine, Southeast University, Nanjing, China.

Gastric cancer has the second highest incidence among all the malignancies in China, just below lung cancer. Gastric cancer is likewise one of the main sources of cancer related passings. Gastric cancer therefore remains a huge threat to human health. The primary reason is absence of high sensitivity and specificity for early detection while the pathogenesis of GC is stayed muddled. During the last few decades, a lot of GC related genes have been identified. To find candidate GC related variant in these GC related genes, we conducted this case-control study. 29 tagSNPs located in 7 GC related genes were included. 228 gastric cancer patients and 299 healthy controls were enrolled. Significant differences were found between the genotype frequencies of rs4971066 polymorphism between gastric cancer patients and healthy controls. The result indicated that ephrin-A1 tagSNP rs4971066 GT/TT genotypes was significantly associated with reduced susceptibility of gastric cancer development.
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http://dx.doi.org/10.3389/fmolb.2021.690665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166284PMC
May 2021

Feeding Preference of Altica deserticola (Coleoptera: Chrysomelidae: Alticinae) for Leaves of Glycyrrhiza inflata and G. uralensis.

An Acad Bras Cienc 2021 28;93(2):e20190267. Epub 2021 May 28.

Ministry of Education Key Laboratory of Xinjiang Phytomedicine Resource Utilization, College of Life Sciences, Shihezi University, Xinjiang 832003, the People's Republic of China.

A leaf-disc-test method was used under controlled laboratory conditions to determine the feeding preference of Altica deserticola Latreille (Coleoptera: Chrysomelidae) on leaves of two liquorice species, Glycyrrhiza inflata Batalin and G. uralensis Fisch. ex DC. Leaf hardness and thickness, cuticle thickness, and nitrogen and tannin contents were compared between the two liquorices to explore their feeding resistance to A. deserticola. The larvae ate only G. uralensis leaves, while the adults fed on the leaves of both species but preferred those of G. inflata. The leaf hardness and thickness and cuticle thickness, as well as the nitrogen, total tannins, tannin chemicals contents in leaves, were significantly greater in G. inflata than in G. uralensis. The larvae having smaller chewing mouthparts could not feed on hard leaves with thick cuticle on both sides. The thicker cuticle and harder texture of G. inflata blades may be important physical traits for effective defence against larval phytophagy, while the higher tannin content in its leaves may be an important chemical trait determining their feeding preference. The larger adults, having stronger mouthparts, could consume nitrogen-richer G. inflata leaves to obtain the energy needed for flight and reproduction.
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http://dx.doi.org/10.1590/0001-3765202120190267DOI Listing
June 2021

Advances in small molecule inhibitors for treatment of psoriasis.

Chin Med J (Engl) 2021 Jan 11;134(11):1364-1366. Epub 2021 Jan 11.

Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China.

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http://dx.doi.org/10.1097/CM9.0000000000001351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183699PMC
January 2021

A Matrix Metalloproteinase Mediates Tracheal Development in .

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China.

The trachea of insects is a tubular epithelia tissue that transports oxygen and other gases. It serves as a useful model for the studying of the cellular and molecular events involved in epithelial tube formation. Almost all of the extracellular matrix can be degraded by Matrix metalloproteinases (MMPs), which is closely related to the processes of development and regeneration. The regulation of trachea by MMPs is roughly known in previous studies, but the detailed regulation mechanism and involved gene function are not fully explored. In this article, we found MMP1 expressed highly during tracheal remodeling, and knocked out it makes the tracheal branch number reduced in . In trachea of transgenic BmMMP1-KO silkworm, the space expanding of taenidium and epidermal cells and the structure of apical membrane were abnormal. To explore the underlying mechanism, we detected that DE-cadherin and Integrin β1 were accumulated in trachea of transgenic BmMMP1-KO silkworm by immunohistochemistry. Moreover, 5-Bromo-2'-Deoxyuridine (BrdU) labeling showed that knockout of BmMMP1 in silkworm inhibited tracheal cell proliferation, and BmMMP1 also regulated the proliferation and migration of BmNS cells. All of the results demonstrated that BmMMP1 regulates the development of the tracheal tissue by expanding the space of tracheal cuticles and increases the number of tracheal branches by degrading DE-cadherin and Integrin β1.
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http://dx.doi.org/10.3390/ijms22115618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198827PMC
May 2021

Corilagin ameliorates atherosclerosis by regulating MMP-1, -2, and -9 expression in vitro and in vivo.

Eur J Pharmacol 2021 May 29;906:174200. Epub 2021 May 29.

School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 West Chunrong Road, Chenggong, Kunming, Yunnan, 650500, PR China. Electronic address:

Corilagin is a polyphenol has been identified anti-inflammatory properties. However, the anti-atherosclerotic effects of corilagin are not well understood. Here, we evaluated the anti-atherosclerotic effects and the underlying mechanisms of corilagin. We also verified whether corilagin can reverse atherosclerosis by regulating matrix metalloproteinase (MMP)-1, -2, and -9 in vitro and in vivo. An atherosclerosis model was established by feeding minipigs a high-fat diet combined with balloon injury, and the effects of different concentrations of corilagin on common carotid artery atherosclerosis in minipigs were monitored. Murine RAW264.7 macrophages were cultured and induced with oxidized low-density lipoprotein; fluorescence microscopy revealed the nuclear translocation of NF-κB. Furthermore, MMP-1, -2, and -9 expression in common carotid artery plaques and cellular models was detected by immunohistochemistry, western blotting, and RT-PCR. The pathological results suggested that the vascular intima of the model control group was significantly thickened, a large amount of collagen fibers was deposited, endothelial cells were damaged and detached, and plaque and foam cell formation occurred to varying degrees on the arterial wall, with lipid deposition. Corilagin treatment significantly reduced the degree of injury in the common carotid artery and decreased the number of lipid plaques and foam cells. Additionally, corilagin downregulated MMP-1, -2, and -9 expression in the common carotid artery plaques and cellular model. Moreover, corilagin significantly inhibited NF-κB nuclear translocation in vitro. Overall, corilagin exerted substantial therapeutic effects on experimental atherosclerotic minipigs via the downregulation of MMP-1, -2, and -9 expression.
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http://dx.doi.org/10.1016/j.ejphar.2021.174200DOI Listing
May 2021

PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway.

Cell Death Dis 2021 May 28;12(6):552. Epub 2021 May 28.

Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China.

Some studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.
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http://dx.doi.org/10.1038/s41419-021-03837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163843PMC
May 2021

Structural basis for zinc-induced activation of a zinc uptake transcriptional regulator.

Nucleic Acids Res 2021 May 28. Epub 2021 May 28.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi Key Laboratory for Sugarcane Biology, Guangxi University, Nanning 530004, China.

The zinc uptake regulator (Zur) is a member of the Fur (ferric uptake regulator) family transcriptional regulators that plays important roles in zinc homeostasis and virulence of bacteria. Upon zinc perception, Zur binds to the promoters of zinc responsive genes and controls their transcription. However, the mechanism underlying zinc-mediated Zur activation remains unclear. Here we report a 2.2-Å crystal structure of apo Zur from the phytopathogen Xanthomonas campestris pv. campestris (XcZur), which reveals the molecular mechanism that XcZur exists in a closed inactive state before regulatory zinc binding. Subsequently, we present a 1.9-Å crystal structure of holo XcZur, which, by contrast, adopts an open state that has enough capacity to bind DNA. Structural comparison and hydrogen deuterium exchange mass spectrometry (HDX-MS) analyses uncover that binding of a zinc atom in the regulatory site, formed by the hinge region, the dimerization domain and the DNA binding domain, drives a closed-to-open conformational change that is essential for XcZur activation. Moreover, key residues responsible for DNA recognition are identified by site-directed mutagenesis. This work provides important insights into zinc-induced XcZur activation and valuable discussions on the mechanism of DNA recognition.
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http://dx.doi.org/10.1093/nar/gkab432DOI Listing
May 2021

Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study.

Front Med 2021 May 28. Epub 2021 May 28.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10) after 10 000 times permutation test (P = 2.49 × 10). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.
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http://dx.doi.org/10.1007/s11684-020-0826-1DOI Listing
May 2021

CsKTN1 for a katanin p60 subunit is associated with the regulation of fruit elongation in cucumber (Cucumis sativus L.).

Theor Appl Genet 2021 May 27. Epub 2021 May 27.

College of Horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Key Message: We identified a short fruit3 (sf3) mutant in cucumber. Map-based cloning revealed that CsKTN1 gene encodes a katanin p60 subunit, which is associated with the regulation of fruit elongation. Fruit length is an important horticultural trait for both fruit yield and quality of cucumber (Cucumis sativus L.). Knowledge on the molecular regulation of fruit elongation in cucumber is very limited. In this study, we identified and characterized a cucumber short fruit3 (sf3) mutant. Histological examination indicated that the shorter fruit in the mutant was due to reduced cell numbers. Genetic analysis revealed that the phenotype of the sf3 mutant was controlled by a single gene with semi-dominant inheritance. By map-based cloning and Arabidopsis genetic transformation, we showed that Sf3 was a homolog of KTN1 (CsKTN1) encoding a katanin p60 subunit. A non-synonymous mutation in the fifth exon of CsKTN1 resulted in an amino acid substitution from Serine in the wild type to Phenylalanine in the sf3 mutant. CsKTN1 expressed in all tissues of both the wild type and the sf3 mutant. However, there was no significant difference in CsKTN1 expression levels between the wild type and the sf3 mutant. The hormone quantitation and RNA-seq analysis suggested that auxin and gibberellin contents are decreased in sf3 by changing the expression levels of genes related with auxin and gibberellin metabolism and signaling. This work helps understand the function of the katanin and the molecular mechanisms of fruit growth regulation in cucumber.
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http://dx.doi.org/10.1007/s00122-021-03833-yDOI Listing
May 2021

Variants Cause Aortic Dissection by Activating TGF-β-Signaling Pathway.

J Am Heart Assoc 2021 Jun 27;10(11):e019276. Epub 2021 May 27.

Division of Cardiology Departments of Internal Medicine and Genetic Diagnosis Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan China.

Background Aortic dissection (AD) is one of the most life-threatening cardiovascular diseases that exhibit high genetic heterogeneity. However, it is unclear whether variants within the gene can cause AD. Therefore, we intend to determine whether is a causative gene of AD. Methods and Results We performed targeted sequencing in 702 patients with unrelated sporadic AD and 163 matched healthy controls using a predesigned panel with 152 vessel matrix-related genes. As a result, we identified that 11 variants in caused AD in 11 out of the 702 patients with AD. Furthermore, knockout () rats were generated through the CRISPR/Cas9 system. Although there was no spontaneous AD, electron microscopy revealed a fracture of elastic fibers and disarray of collagenous fibers in 6-week-old rats, but not in WT rats (93.3% versus 0.0%, <0.001). Three-week-old rats were used to induce the AD phenotype with β-aminopropionitrile monofumarate for 4 weeks followed by angiotensin II for 72 hours. The β-aminopropionitrile monofumarate and angiotensin II-treated rat model confirmed that rats had considerably higher AD incidence than WT rats. Subsequent mechanism analyses demonstrated that the transforming growth factor-β-signaling pathway was significantly activated in rats. Conclusions Our findings, for the first time, revealed a relationship between variants in and AD via targeted sequencing in 1.57% patients with sporadic aortic dissection. The knockout rats exhibited AD after an intervention, indicating that is a causative gene of AD. Activation of the transforming growth factor-β-signaling pathway may be implicated in the pathogenesis of this kind of AD.
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http://dx.doi.org/10.1161/JAHA.120.019276DOI Listing
June 2021

Membraneless condensates by Rapsn phase separation as a platform for neuromuscular junction formation.

Neuron 2021 Jun 24;109(12):1963-1978.e5. Epub 2021 May 24.

Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Electronic address:

Our daily life depends on muscle contraction, a process that is controlled by the neuromuscular junction (NMJ). However, the mechanisms of NMJ assembly remain unclear. Here we show that Rapsn, a protein critical for NMJ formation, undergoes liquid-liquid phase separation (LLPS) and condensates into liquid-like assemblies. Such assemblies can recruit acetylcholine receptors (AChRs), cytoskeletal proteins, and signaling proteins for postsynaptic differentiation. Rapsn LLPS requires multivalent binding of tetratricopeptide repeats (TPRs) and is increased by Musk signaling. The capacity of Rapsn to condensate and co-condensate with interaction proteins is compromised by mutations of congenital myasthenic syndromes (CMSs). NMJ formation is impaired in mutant mice carrying a CMS-associated, LLPS-deficient mutation. These results reveal a critical role of Rapsn LLPS in forming a synaptic semi-membraneless compartment for NMJ formation.
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http://dx.doi.org/10.1016/j.neuron.2021.04.021DOI Listing
June 2021

Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis.

Open Med (Wars) 2021 11;16(1):728-736. Epub 2021 May 11.

Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30-90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13-3.37, = 0.016) for PFS and 2.70 (95% CI: 1.81-4.02, < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5-1.7) and 8.8 months (95% CI: 8.5-9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.
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http://dx.doi.org/10.1515/med-2021-0272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114955PMC
May 2021

Effect of Team Health Education on Radiodermatitis in Patients with Head and Neck Tumor Radiotherapy Under the Joint Committee International Standards.

Semin Oncol Nurs 2021 May 16:151148. Epub 2021 May 16.

Department of Oncology, Qingdao Municipal Hospitalchool of Medicine, Qingdao University, Qingdao, Shandong, China. Electronic address:

Objectives: This study aimed to investigate the impacts of team health education on radiodermatitis in patients undergoing head and neck radiotherapy.

Data Sources: A total of 118 patients undergoing radiotherapy at the Oncology Department of Qingdao Municipal Hospital under the Joint Committee International (JCI) accreditation standards of medical and health institutions were divided into two groups according to the order of the admission: the intervention group (n = 66) and the control group (n = 52). The patients in the control group were given routine nursing, while those in the intervention group received team health education based on the control group. The incidence and satisfaction of radiodermatitis were observed and compared between the groups, and the EORTC QLQ-C30 and General Quality of Life Inventory-74 were used to evaluate the patients' quality of life when after radiotherapy and when after 6 months post the radiotherapy, respectively.

Conclusion: The incidence of radiodermatitis was 100% in both groups, and the difference in the grade of radiodermatitis and quality of life was significant (P < .05) between them.

Implications For Nursing Practice: Team health education under the JCI standards team can reduce the degree of skin injury due to radiodermatitis and improve the quality of life.
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http://dx.doi.org/10.1016/j.soncn.2021.151148DOI Listing
May 2021

Stereospecific Iron-Catalyzed Carbon (sp)-Carbon (sp) Cross-Coupling of Aryllithium with Vinyl Halides.

Org Lett 2021 Jun 18;23(11):4385-4390. Epub 2021 May 18.

Department of Chemistry, and State Key Laboratory of Synthetic Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

We present herein an efficient synthetic protocol involving iron-catalyzed cross-coupling of organolithium compounds with vinyl halides as key coupling partners. More than 30 examples were obtained with moderate to good yields and high stereoselectivities. The practicality of this method is evidenced by a gram-scale synthesis. In addition, a preliminary mechanistic investigation was also performed.
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http://dx.doi.org/10.1021/acs.orglett.1c01318DOI Listing
June 2021

Tumor-associated macrophage-derived CCL5 promotes chemotherapy resistance and metastasis in prostatic cancer.

Cell Biol Int 2021 May 18. Epub 2021 May 18.

Urology Department, Xinjiang Medical University Affiliated Tumor Hospital, Xinjiang, China.

The crosstalk between tumor microenvironment and cancer cells is emerging as a critical determinant in tumor progression. However, the underlying mechanism of tumor microenvironment-induced cancer development remains controversial. Here, our study provides evidence to suggest that tumor-associated macrophage (TAM) enrichment is found in chemo-resistant prostatic tumor tissues. Those TAMs are demonstrated to promote chemo-resistance and distant metastasis in prostatic cancer through secretion of CCL5. Mechanistically, TAM co-culture or additional CCL5 can mediate the STAT3-dependent epithelial-mesenchymal transition (EMT) process, resulting in distant metastasis in prostatic cancer. Meanwhile, activation of STAT3 induced by CCL5 can mediate up-regulation of the transcription factor Nanog, leading to drug resistance. In vivo study further demonstrated that blockade of STAT3 signals significantly reverses chemo-resistance and suppresses lung metastasis in colorectal tumor-bearing mice, suggesting a novel strategy for clinical prostatic cancer treatment. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/cbin.11630DOI Listing
May 2021

Application of multimodal MRI and radiologic features for stereotactic brain biopsy: insights from a series of 208 patients.

Br J Neurosurg 2021 May 18:1-8. Epub 2021 May 18.

Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.

Objectives: We reviewed our institutional experience during a 10-year period for improvement of safety and efficacy of stereotactic biopsy procedures.

Methods: We performed a retrospective review of inpatient summaries, stereotactic worksheets and radiologic investigations of 208 consecutive patients, who underwent MRI-guided stereotactic biopsies between March 2010 and March 2020.

Results: The overall diagnostic yield was 96.2%. CT-confirmed intracranial hemorrhage occurred in 17 patients (8.2%), and the overall mortality rate was 0.5%. Combined MRS and PWI helped target selection in 27 cases (13.0%), the diagnostic yield was 100%. The results of the regression analysis revealed that non-diagnostic biopsy specimen significantly correlated with the cystic trait (<.01) and edema of lesions (<.05). Enhancement (<.01) is shown to be an important factor for obtaining a diagnostic biopsy. Furthermore, the edema trait of lesions (<.01) showed the important factors of hemorrhage.

Conclusions: The radiological features of lesions and use of the most suitable MRI sequences during biopsy planning are recommended ways to improve the diagnostic yield and safety of this technique.
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http://dx.doi.org/10.1080/02688697.2021.1926922DOI Listing
May 2021

Successful Radical Pneumonectomy for a Primitive Neuroendodermal Tumor in the Lung: A Case Report and Review of the Literature.

Front Surg 2021 28;8:667467. Epub 2021 Apr 28.

Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Peripheral primitive neuroendodermal tumors (PNETs) and Ewing's sarcoma belong to the Ewing family of tumors and are small round-cell malignancies originating from spinal cord cells. These tumors account for 5% of all small round-cell malignant neoplasms. PNETs that arise from the lung parenchyma without pleural or chest wall involvement are very rare. We report a case of an adult female with a large pulmonary PNET who had given birth just 1 month prior to the diagnosis. She had cough and expectoration for 6 months, and the preoperative examination showed no metastases. Thus, we performed radical pneumonectomy and lymph node dissection. The patient recovered well without surgical complications and was discharged 7 days after the surgery. Postoperative pathology confirmed that the tumor was a small round-cell malignancy, and the tumor cells were positive for CD99, Friend leukemia virus integration 1 (FLI-1), and neuron-specific enolase (NSE), which was consistent with the diagnosis of a PNET. For primary large pulmonary PNETs, radical pneumonectomy may be a safe surgical method, worthy of further application in clinical practice.
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http://dx.doi.org/10.3389/fsurg.2021.667467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113621PMC
April 2021

Chemical engineering of bacterial effectors for regulating cell signaling and responses.

Curr Opin Chem Biol 2021 May 13;64:48-56. Epub 2021 May 13.

College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing, 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. Electronic address:

Bacteria have evolved a variety of effector proteins to facilitate their survival and proliferation within the host environment. Continuous competition at the host-pathogen interface has empowered these effectors with unique mechanism and high specificity toward their host targets. The rich repertoire of bacterial effectors has thus provided us an attractive toolkit for investigating various cellular processes, such as signal transductions. With recent advances in protein chemistry and engineering, we now have the capability for on-demand control of protein activity with high precision. Herein, we review the development of chemically engineered bacterial effectors to control kinase-mediated signal transductions, inhibit protein translation, and direct genetic editing within host cells. We also highlight future opportunities for harnessing diverse prokaryotic effectors as powerful tools for mechanistic investigation and therapeutic intervention of eukaryotic systems.
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http://dx.doi.org/10.1016/j.cbpa.2021.04.003DOI Listing
May 2021

Critical Comparison between Large and Mini Vertical Flow Immunoassay Platforms for Detection.

Anal Chem 2021 May 14. Epub 2021 May 14.

Center for Applied NanoBioscience and Medicine, College of Medicine, University of Arizona, Phoenix, Arizona 85004, United States.

is a Gram-negative bacterium that is the causative agent of plague and is widely recognized as a potential biological weapon. Due to the high fatality rate of plague when diagnosis is delayed, the development of rapid, sensitive, specific, and cost-effective methods is needed for its diagnosis. The low calcium response V (LcrV) protein has been identified as a potential microbial biomarker for the diagnosis of plague. In this paper, we present a highly sensitive, paper-based, vertical flow immunoassay (VFI) prototype for the detection of LcrV and the diagnosis of plague. An antigen-capture assay using monoclonal antibodies is employed to capture and detect the LcrV protein, using a colorimetric approach. In addition, the effect of miniaturizing the VFI device is explored based on two different sizes of VFI platforms, denoted as "large VFI" and "mini VFI." Also, a comparative analysis is performed between the VFI platform and a lateral flow immunoassay (LFI) platform to exhibit the improved assay sensitivity suitable for point-of-care (POC) diagnostics. The analytical sensitivity or limit of detection (LOD) in the mini VFI is approximately 0.025 ng/mL, that is, 10 times better than that of the large VFI platform or 80 times over a standard lateral flow configuration. The low LOD of the LcrV VFI appears to be highly suitable for testing clinical samples and potentially diagnosing plague at earlier time points. In addition, optimization of the gold nanoparticle (AuNP) concentration, nanomaterial plasmonic properties, and flow velocity analysis could improve the performance of the VFI. Furthermore, we developed automated image analysis software that shows potential for integrating the diagnostic system into a smartphone. These methods and findings demonstrate that the VFI platform is a highly sensitive device for detecting the LcrV and potentially many other biomarkers.
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http://dx.doi.org/10.1021/acs.analchem.0c05278DOI Listing
May 2021