Publications by authors named "Bo Tang"

1,037 Publications

  • Page 1 of 1

Elucidating the Relationship between ROS and Protein Phosphorylation through Fluorescence Imaging in the Pneumonia Mice.

Anal Chem 2021 Jul 29. Epub 2021 Jul 29.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China.

Revealing the relationship between reactive oxygen species (ROS) and levels of protein phosphorylation is of great significance for understanding the pathogenesis of diseases. Although mass spectrometry is used as a classical method for protein phosphorylation analysis, there are still some challenges to realize protein phosphorylation recognition. Herein, we designed and prepared an metal-organic framework (MOF)-based fluorescent nanoprobe with Zr(IV) and boronate ester as an active center, which achieved simultaneous recognition of ROS and phosphorylation sites. The ROS unit was constructed by 1,8-naphthalimide and boronate ester as a fluorophore and a recognition group, respectively. The specific interaction between Zr(IV) and a phosphate group was used to realize fluorescence imaging of phosphorylation sites. Using the advantages of two-photon property of the ROS recognition unit, the nanoprobe can effectively reduce the background fluorescence and thus improve the imaging sensitivity. Finally, the MOF-based nanoprobe was successfully applied to reveal the relationship between ROS and levels of phosphorylation in pneumonia mice, which illustrated that the ROS and phosphorylation levels in the process of pulmonary inflammation were obviously higher than those of the normal mice. This work provides feasible fluorescence tools that have important significance for revealing pathogenesis of diseases.
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http://dx.doi.org/10.1021/acs.analchem.1c01690DOI Listing
July 2021

A light-activatable photosensitizer for photodynamic therapy based on a diarylethene derivative.

Chem Commun (Camb) 2021 Jul 28. Epub 2021 Jul 28.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.

Herein, a light-activatable photosensitizer based on a diarylethene derivative, DAE-TPE, was developed for photodynamic therapy. Upon UV exposure, the "opened" form (OF) of DAE-TPE NPs was converted to the "closed" form (CF), and photosensitization was activated. The CF of DAE-TPE NPs exhibited sufficient photodynamic therapy effects upon HeLa cells.
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http://dx.doi.org/10.1039/d1cc02102hDOI Listing
July 2021

Sputum-Based Tumor Fluid Biopsy: Isolation and High-Throughput Single-Cell Analysis of Exfoliated Tumor Cells for Lung Cancer Diagnosis.

Anal Chem 2021 Jul 22. Epub 2021 Jul 22.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

Timely and effective diagnosis is of great significance for improving the survival rate of lung cancer patients. Although histopathology is the main diagnostic tool among the existing methods for lung cancer diagnosis, it is not suitable for high-risk groups, early lung cancer patients, patients with advanced-stage disease, and other situations wherein tumor tissues cannot be obtained. In view of this, we proposed an innovative lung cancer diagnosis method employing for the first time a microfluidic technology for high-efficiency isolation and high-throughput single-cell analysis of exfoliated tumor cells (ETCs) in sputum. This method fully combines the advantages of traditional sputum cytology and microfluidic technology and realizes the diagnosis of lung cancer by using a small amount of repeatable ETCs instead of the tumor tissue. This method is expected to provide a practical strategy for the non-invasive detection of lung cancer patients and lung cancer screening for high-risk groups.
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http://dx.doi.org/10.1021/acs.analchem.1c00833DOI Listing
July 2021

Duplex-Specific Nuclease-Assisted CRISPR-Cas12a Strategy for MicroRNA Detection Using a Personal Glucose Meter.

Anal Chem 2021 Jul 19. Epub 2021 Jul 19.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

A CRISPR-Cas system holds great promise as a next-generation biosensing technology for molecular diagnostics. Nevertheless, the current CRISPR-Cas12a-based detection strategies always need bulky instruments or auxiliary devices to obtain a quantitative signal output, which restrains its point-of-care testing application. Herein, we proposed a duplex-specific nuclease-assisted CRISPR-Cas12a strategy to detect microRNA (miRNA) with a personal glucose meter. The target miRNA was first converted into an amplified initiator DNA via duplex-specific nuclease. Afterward, the initiator DNA activated the collateral cleavage activity of CRISPR-Cas12a to cleave the single-strand DNA (ssDNA) linker on sucrase-ssDNA-modified magnetic beads, which led to the release of sucrase. The released sucrase was collected and then utilized to catalyze sucrose to glucose, which could be quantitatively detected by a personal glucose meter. The change in the glucose signal directly reflected the concentration of miRNA, which avoided expensive equipment for signal quantification. Two different miRNAs (miRNA21 and miRNA205) could be detected by simply changing the sequence of the template strand (H strand). The developed strategy showed high sensitivity with a limit of detection (LOD) of 2.4 and 1.1 pM for miRNA21 and miRNA205, respectively. In addition, good selectivity and anti-interference ability were achieved using this method, which enabled it promising for miRNA detection at the point-of-care.
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http://dx.doi.org/10.1021/acs.analchem.1c02478DOI Listing
July 2021

LYG1 Deficiency Attenuates the Severity of Acute Graft-Versus-Host Disease Skewing Allogeneic T Cells Polarization Towards Treg Cells.

Front Immunol 2021 28;12:647894. Epub 2021 Jun 28.

Department of Hematology, Peking University First Hospital, Beijing, China.

Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation. The mechanism involves the recognition of host antigens by donor-derived T cells which induces augmented response of alloreactive T cells. In this study, we characterized the role of a previously identified novel classical secretory protein with antitumor function-LYG1 (Lysozyme G-like 1), in aGVHD. LYG1 deficiency reduced the activation of CD4 T cells and Th1 ratio, but increased Treg ratio by MLR assay. By using major MHC mismatched aGVHD model, LYG1 deficiency in donor T cells or CD4 T cells attenuated aGVHD severity, inhibited CD4 T cells activation and IFN-γ expression, promoted FoxP3 expression, suppressed CXCL9 and CXCL10 expression, restrained allogeneic CD4 T cells infiltrating in target organs. The function of LYG1 in aGVHD was also confirmed using haploidentical transplant model. Furthermore, administration of recombinant human LYG1 protein intraperitoneally aggravated aGVHD by promoting IFN-γ production and inhibiting FoxP3 expression. The effect of rhLYG1 could partially be abrogated with the absence of IFN-γ. Furthermore, LYG1 deficiency in donor T cells preserved graft-versus-tumor response. In summary, our results indicate LYG1 regulates aGVHD by the alloreactivity of CD4 T cells and the balance of Th1 and Treg differentiation of allogeneic CD4 T cells, targeting LYG1 maybe a novel therapeutic strategy for preventing aGVHD.
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http://dx.doi.org/10.3389/fimmu.2021.647894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273552PMC
June 2021

hsa-miR-199b-3p Prevents the Epithelial-Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E-cadherin through Targeting KDM6A in Diabetic Nephropathy.

Oxid Med Cell Longev 2021 27;2021:8814163. Epub 2021 Jun 27.

Department of Urology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, China.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The association between epithelial-mesenchymal transition (EMT) and fibrosis is quite ascertained, but its link to eventual tubule dysfunction is missing. Here, we show that human microRNA- (hsa-miR-) 199b-3p protects renal tubules from diabetic-induced injury by repressing KDM6A, a histone lysine demethylase regulating E-cadherin expression. Lower E-cadherin expression is related to a higher level of KDM6A, while E-cadherin is promoted upon treatment with the KDM6A inhibitor GSK-J4 in both high glucose- (HG-) induced HK2 cells and the kidneys from streptozotocin- (STZ-) induced type 1 diabetic mice. However, overexpression or RNA silencing of E-cadherin fails to alter KDM6A expression. We also show that the upregulation of KDM6A is associated with the increased methylation level of the E-cadherin promoter. Then, the target prediction results and a dual-luciferase assay show that hsa-miR-199b-3p is a new miRNA that targets KDM6A. Overexpression of hsa-miR-199b-3p increases E-cadherin expression and prevents EMT through repressing KDM6A expression in HG-induced HK2 cells. In contrast, inhibitor-induced hsa-miR-199b-3p knockdown has opposite effects, as it decreases E-cadherin level and worsens EMT, accompanied by increased levels of KDM6A. Besides, Mir199b-knockout mice without mmu-miR-119b-3p expression exhibit more renal tubule dysfunction and more serious kidney tissue damage upon treatment with STZ. These results demonstrate that hsa-miR-199b-3p improves E-cadherin expression and prevents the progression of DN through targeting KDM6A. miR-199b-3p could be a future biomarker or target for the diagnosis or treatment of DN.
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http://dx.doi.org/10.1155/2021/8814163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257373PMC
June 2021

Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma.

Cell Death Dis 2021 Jul 5;12(7):678. Epub 2021 Jul 5.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, PR China.

Oncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development.
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http://dx.doi.org/10.1038/s41419-021-03940-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257691PMC
July 2021

miR-144-3p inhibited the growth, metastasis and epithelial-mesenchymal transition of colorectal adenocarcinoma by targeting ZEB1/2.

Aging (Albany NY) 2021 07 5;13(13):17349-17369. Epub 2021 Jul 5.

Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. and assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.
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http://dx.doi.org/10.18632/aging.203225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312459PMC
July 2021

Hydrogels-based ophthalmic drug delivery systems for treatment of ocular diseases.

Mater Sci Eng C Mater Biol Appl 2021 Aug 29;127:112212. Epub 2021 May 29.

School of Pharmacy, Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China. Electronic address:

An increasing number of people worldwide are affected by eye diseases, eventually leading to visual impairment or complete blindness. Conventional treatment involves the use of eye drops. However, these formulations often confer low ocular bioavailability and frequent dosing is required. Therefore, there is an urgent need to develop more effective drug delivery systems to tackle the current limitations. Hydrogels are multifunctional ophthalmic drug delivery systems capable of extending drug residence time and sustaining release of drugs. In this review, common ocular diseases and corresponding therapeutic drugs are briefly introduced. In addition, various types of hydrogels reported for ophthalmic drug delivery, including in-situ gelling hydrogels, contact lenses, low molecular weight supramolecular hydrogels, cyclodextrin/poly (ethylene glycol)-based supramolecular hydrogels and hydrogel-forming microneedles, are summarized. Besides, marketed hydrogel-based opthalmic formulations and clinical trials are also highlighted. Finally, critical considerations regarding clinical translation of biologics-loaded hydrogels are discussed.
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http://dx.doi.org/10.1016/j.msec.2021.112212DOI Listing
August 2021

-Induced Heparanase Promotes Colonization and Gastritis.

Front Immunol 2021 17;12:675747. Epub 2021 Jun 17.

Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China.

Chronic gastritis caused by () infection has been widely recognized as the most important risk factor for gastric cancer. Analysis of the interaction between the key participants in gastric mucosal immunity and infection is expected to provide important insights for the treatment of chronic gastritis and the prevention of gastric cancer. Heparanase is an endoglycosidase that degrades heparan sulfate, resulting in remodeling of the extracellular matrix thereby facilitating the extravasation and migration of immune cells towards sites of inflammation. Heparanase also releases heparan sulfate-bound cytokines and chemokines that further promote directed motility and recruitment of immune cells. Heparanase is highly expressed in a variety of inflammatory conditions and diseases, but its role in chronic gastritis has not been sufficiently explored. In this study, we report that infection promotes up-regulation of heparanase in gastritis, which in turn facilitates the colonization of in the gastric mucosa, thereby aggravating gastritis. By sustaining continuous activation, polarization and recruitment of macrophages that supply pro-inflammatory and pro-tumorigenic cytokines (i.e., IL-1, IL-6, IL-1β, TNF-α, MIP-2, iNOS), heparanase participates in the generation of a vicious circle, driven by enhanced NFκB and p38-MAPK signaling, that supports the development and progression of gastric cancer. These results suggest that inhibition of heparanase may block this self-sustaining cycle, and thereby reduce the risk of gastritis and gastric cancer.
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http://dx.doi.org/10.3389/fimmu.2021.675747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248549PMC
June 2021

Molecularly Imprinted Magnetic Fluorescent Nanocomposite-Based Sensor for Selective Detection of Lysozyme.

Nanomaterials (Basel) 2021 Jun 15;11(6). Epub 2021 Jun 15.

School of Life Science and Agricultural Engineering, Nanyang Normal University, Nanyang 473061, China.

A new strategy for the design and construction of molecularly imprinted magnetic fluorescent nanocomposite-based-sensor is proposed. This multifunctional nanocomposite exhibits the necessary optics, magnetism and biocompatibility for use in the selective fluorescence detection of lysozyme. The magnetic fluorescent nanocomposites are prepared by combining carboxyl- functionalized FeO magnetic nanoparticles with -cysteine-modified zinc sulfide quantum dots (MNP/QDs). Surface molecular imprinting technology was employed to coat the lysozyme molecularly imprinted polymer (MIP) layer on the MNP/QDs to form a core-shell structure. The molecularly imprinted MNP/QDs (MNP/[email protected]) can rapidly separate the target protein and then use fluorescence sensing to detect the protein; this reduces the background interference, and the selectivity and sensitivity of the detection are improved. The molecularly imprinted MNP/QDs sensor presented good linearity over a lysozyme concentration range from 0.2 to 2.0 μM and a detection limit of 4.53 × 10 μM for lysozyme. The imprinting factor of the MNP/[email protected] was 4.12, and the selectivity coefficient ranged from 3.19 to 3.85. Furthermore, the MNP/[email protected] sensor was applied to detect of lysozyme in human urine and egg white samples with recoveries of 95.40-103.33%. Experimental results showed that the prepared MNP/[email protected] has potential for selective magnetic separation and fluorescence sensing of target proteins in biological samples.
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http://dx.doi.org/10.3390/nano11061575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232576PMC
June 2021

Delivery nanoplatforms based on dynamic covalent chemistry.

Chem Commun (Camb) 2021 Jul;57(58):7067-7082

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

As a paramount factor to restrict the potential action of drugs and biologics, nanoplatforms based on dynamic covalent chemistry have been demonstrated as promising candidates to fulfill the full requirements during the whole delivery process by the virtue of their remarkable features such as adaptiveness, stimuli-responsiveness, specificity, reversibility and feasibility. This contribution summarizes the latest progress in dynamic covalent bond-based nanoplatforms with improved delivery efficiency and therapeutic performance. In addition, major challenges and perspectives in this field are also discussed. We expect that this feature article will provide a valuable and systematic reference for the further development of dynamic covalent bond-based nanoplatforms.
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http://dx.doi.org/10.1039/d1cc02246fDOI Listing
July 2021

Exploring the Changes of Peroxisomal Polarity in the Liver of Mice with Nonalcoholic Fatty Liver Disease.

Anal Chem 2021 07 30;93(27):9609-9620. Epub 2021 Jun 30.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, People's Republic of China.

Peroxisome proliferator-activated receptor alpha (PPAR-a) is a crucial nuclear transcription regulator of lipid metabolism, which is closely associated with the initiation and development of nonalcoholic fatty liver disease (NAFLD). Because PPAR-a can directly decide the level of peroxisomal metabolic enzymes, its changes might directly cause variations in peroxisomal polarity. Therefore, we developed a new two-photon fluorescence imaging probe, PX-P, in which the triphenylamine and cyanide moieties can real-time sense peroxisomal polarity changes. Using PX-P, we observed a prominent decrease in the peroxisomal polarity in the liver of mice with NAFLD for the first time. More importantly, we discovered that intracellular excessive peroxynitrite (ONOO) and hydrogen peroxide (HO) underwent nitrification and oxidation, respectively, with various sites of PPAR-a. Interestingly, the key site of PPAR-a was nitrated by a low concentration of ONOO rather than being oxidized by the high level of HO. These drastically reduced the activity of PPAR-a, accelerating the occurrence of NAFLD. Moreover, through activating PPARs with pioglitazone, peroxisomal polarity markedly increased compared with that of NAFLD. Altogether, our work presents a new approach for the early diagnosis of NAFLD and identifies potential therapeutic targets.
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http://dx.doi.org/10.1021/acs.analchem.1c01776DOI Listing
July 2021

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

Adv Ther (Weinh) 2021 May 20:2100055. Epub 2021 May 20.

Centre for Safe Medication Practice and Research Department of Pharmacology and Pharmacy LKS Faculty of Medicine University of Hong Kong Hong Kong Special Administrative Region, 1/F, Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road Pokfulam Hong Kong SAR China.

Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies.
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http://dx.doi.org/10.1002/adtp.202100055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212091PMC
May 2021

Correction: A "double-locked" probe for the detection of hydrogen sulfide in a viscous system.

Chem Commun (Camb) 2021 Jul;57(54):6693

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.

Correction for 'A "double-locked" probe for the detection of hydrogen sulfide in a viscous system' by Fanpeng Kong et al., Chem. Commun., 2021, DOI: 10.1039/d1cc01819a.
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http://dx.doi.org/10.1039/d1cc90224eDOI Listing
July 2021

Intelligent stimuli-responsive nano immunomodulators for cancer immunotherapy.

Chem Sci 2021 Feb 10;12(9):3130-3145. Epub 2021 Feb 10.

College of Chemistry, Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Cancer immunotherapy is a revolutionary treatment method in oncology, which uses a human's own immune system against cancer. Many immunomodulators that trigger an immune response have been developed and applied in cancer immunotherapy. However, there is the risk of causing an excessive immune response upon directly injecting common immunomodulators into the human body to trigger an immune response. Therefore, the development of intelligent stimuli-responsive immunomodulators to elicit controlled immune responses in cancer immunotherapy is of great significance. Nanotechnology offers the possibility of designing smart nanomedicine to amplify the antitumor response in a safe and effective manner. Progress relating to intelligent stimuli-responsive nano immunomodulators for cancer immunotherapy is highlighted as a new creative direction in the field. Considering the clinical demand for cancer immunotherapy, we put forward some suggestions for constructing new intelligent stimuli-responsive nano immunomodulators, which will advance the development of cancer immunotherapy.
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http://dx.doi.org/10.1039/d0sc06557aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179382PMC
February 2021

Fluorescent probe for the imaging of superoxide and peroxynitrite during drug-induced liver injury.

Chem Sci 2021 Jan 4;12(11):3921-3928. Epub 2021 Jan 4.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China

Drug-induced liver injury (DILI) is an important cause of potentially fatal liver disease. Herein, we report the development of a molecular probe () for the detection and imaging of two biomarkers involved in DILI. Initially, primary reactive oxygen species (ROS) superoxide (O˙) selectively activates a near-infrared fluorescence (NIRF) output by generating fluorophore . The C[double bond, length as m-dash]C linker of this hemicyanine fluorophore is subsequently oxidized by reactive nitrogen species (RNS) peroxynitrite (ONOO), resulting in cleavage to release xanthene derivative , detected using two-photon excitation fluorescence (TPEF). An alternative fluorescence pathway can occur through cleavage of by ONOO to non-fluorescent , which can react further with the second analyte O˙ to produce the same fluorescent species. By combining NIRF and TPEF, is capable of differential and simultaneous detection of ROS and RNS in DILI using two optically orthogonal channels. Probe could be used to detect O˙ or O˙ and ONOO in lysosomes stimulated by 2-methoxyestradiol (2-ME) or 2-ME and SIN-1 respectively. In addition, we were able to monitor the chemoprotective effects of -butylhydroxyanisole (BHA) against acetaminophen (APAP) toxicity in living HL-7702 cells. More importantly, TPEF and NIRF imaging confirmed an increase in levels of both O˙ and ONOO in mouse livers during APAP-induced DILI (confirmed by hematoxylin and eosin (H&E) staining).
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http://dx.doi.org/10.1039/d0sc05937dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179478PMC
January 2021

Cholangiojejunostomy Using a Novel Magnamosis Device: Initial Clinical Results.

World J Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

Background: Cholangiojejunostomy (CJ) is a popular operation; however, no specific anastomotic device is available. A novel magnamosis device for CJ was developed in 2017; here, we evaluated the feasibility and safety of the device.

Methods: Between January 2017 and December 2019, 23 patients who underwent CJ using a novel magnamosis device were enrolled. For the CJ: the parent magnet was placed in the proximal duct, and the purse-string suture was tightened over the rod of the parent magnet. The magnamosis device was introduced into the jejunum, and the mandrel penetrated the jejunum at the anastomotic site, before insertion into the rod of the parent magnet. After rotating the knob, the distance between two magnets was shortened enough to achieve coupling.

Results: Sixteen patients (69.6%) underwent open CJ, while 7 (30.4%) underwent laparoscopic CJ; 21 patients (91.3%) underwent choledochojejunostomy, and 2 (8.7%) underwent right or left hepatic duct jejunostomy. The mean time for completion of CJ was 9.2±2.5 min; it was significantly shorter for open CJ than for the laparoscopic way (8±1.2 min vs. 11.8±2.5 min, P<0.05). Only one patient (4.3%) suffered bile leakage after operation and was cured by conservative treatment. The magnets were discharged with a postoperative duration of 66.7±47.2 days, with a 100% expulsion rate. After a median follow-up of 15 months, only one patient (4.3%) developed inflammatory anastomotic stricture.

Conclusion: The novel magnamosis device is a simple, safe, and effective modality for CJ.
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http://dx.doi.org/10.1007/s00268-021-06196-zDOI Listing
June 2021

MAP3K7-IKK inflammatory signaling modulates AR protein degradation and prostate cancer progression.

Cancer Res 2021 Jun 22. Epub 2021 Jun 22.

Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science

Androgen receptor (AR) is a major survival factor for prostate cancer (PCa). Inflammation is implicated in many cancer types including PCa. Activation of MAP3K7 (also termed TAK1) and downstream IκB kinase β (IKKβ) by pro-inflammatory cytokines such as TNFα stimulates NF-κB survival pathways. Paradoxically, MAP3K7 is often deleted in human PCa. Here we demonstrate that AR protein expression is lower in inflammatory tumor areas compared to non-inflammatory tissues in PCa patients. Map3k7 knockout increased AR protein levels and activity in the mouse prostate, and MAP3K7 and AR protein levels were inversely correlated in PCa patient specimens. TNFα treatment increased AR protein ubiquitination and proteasomal degradation. Mechanistically, activation of IKKβ by TNFα induced phosphorylation and TRCP1/2 E3 ligase-mediated polyubiquitination and degradation of AR protein. TNFα suppressed prostate cancer proliferation, which could be rescued by blockade of AR degradation. These findings reveal a previously unrecognized tumor suppressive function of the inflammation-activated MAP3K7-IKKβ axis in degrading AR protein. Moreover, they suggest that aberrant elevation of AR protein could be a prognostic biomarker and therapeutic target for MAP3K7-deficient PCa.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-4194DOI Listing
June 2021

Versatile Gold-Coupled Te-Carbon Dots for Quantitative Monitoring and Efficient Scavenging of Superoxide Anions.

Anal Chem 2021 07 22;93(26):9111-9118. Epub 2021 Jun 22.

College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, 250014 P. R. China.

The superoxide anion (O) is a reactive oxygen species (ROS) that functions as an important regulator of signal transduction in living systems. However, excess O can cause metabolic imbalances and oxidative damage inside cells. Quantitative detection and efficient scavenging of O are therefore critical for maintaining intracellular redox balance and homeostasis. In this work, a nanomaterial (Au-TeCD) composed of BSA-modified gold nanoparticles (AuNPs) complexed with tellurium-containing carbon dots (TeCDs) was constructed. The introduction of Au-TeCDs to solutions containing superoxide resulted in enhanced elimination of the anion, indicating that Au-TeCDs are able to scavenge O from the surrounding environment. Notably, the respective TeCD and AuNP components of the Au-TeCDs were found to emit fluorescence at 425 and 640 nm upon exposure to superoxide anions. This unique spectroscopic property of Au-TeCDs allowed levels of O in solution to be quantified using dual-fluorescence detection. The Au-TeCDs developed herein also exhibited low-cytotoxicity, versatile capabilities for fluorescence imaging, and effective scavenging of O in living cells. Taken together, these results suggest that Au-TeCDs act as effective tools for monitoring superoxide concentrations in complex mixtures and may be developed as possible therapeutics designed to scavenge excess ROS from diseased cells.
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http://dx.doi.org/10.1021/acs.analchem.1c00844DOI Listing
July 2021

A Mitochondrial-Targeting Near-Infrared Fluorescent Probe for Revealing the Effects of Hydrogen Peroxide And Heavy Metal Ions on Viscosity.

Anal Chem 2021 07 22;93(26):9244-9249. Epub 2021 Jun 22.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, P. R. China.

As an important cell organelle, the mitochondrion has special viscosities, while abnormal mitochondrial viscosity is closely related to many diseases. Hydrogen peroxide (HO) is an active molecule related to the cell microenvironment, and its influence on mitochondrial viscosity is still not clear, so further investigation is needed. In addition, since excessive accumulation of heavy metal ions would lead to cells' dysfunction, the study of effect of excessive heavy metal ions on mitochondrial viscosity has not been reported. Herein, we designed and synthesized a mitochondrial-targeting near-infrared fluorescent probe (Mito-NV) for real-time in situ imaging and analysis of mitochondrial viscosity. Furthermore, the probe revealed that HO can raise mitochondrial viscosity, while heavy metal ions reduce the viscosity. This work is of great significance for understanding the execution of mitochondrial functions and the occurrence and development of related diseases.
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http://dx.doi.org/10.1021/acs.analchem.1c01511DOI Listing
July 2021

Wide-range, ultra-compact, and high-sensitivity ring resonator biochemical sensor with CMOS-compatible hybrid plasmonic waveguide.

Opt Express 2021 Jun;29(12):19058-19067

A ring resonator-based biochemistry sensor with a wide range, ultra-compact footprint, and high sensitivity is proposed, which utilizes a suspended slot hybrid plasmonic (SSHP) waveguide. The waveguide consists of a suspended Si nanowire separated from a Cu metal surface by a nanoscale air gap. The hybridization of fundamental mode of a Si channel waveguide with the surface plasmon polariton (SPP) mode of Cu-Si interface achieves a strong light confinement, high waveguide sensitivity (Sw), and low optical loss, showing a great potential in integrated optical sensor. The sensitivity, the detection limit and the detection range of the SSHP waveguide-based biochemistry sensor with a miniaturized radius of 1 µm are numerically demonstrated as 458.1 nm/RIU, 3.7 × 10 RIU and 0.225 RIU, respectively. These superior performances as well as the fully CMOS compatibility enable the integrated optical sensing applications.
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http://dx.doi.org/10.1364/OE.428159DOI Listing
June 2021

Low-loss silicon nitride strip-slot mode converter based on MMI.

Opt Express 2021 Jun;29(12):19049-19057

Slot waveguide has attracted a lot of attention due to its ability to confine light in the low refractive index region, while strip waveguide acts as the basic component of guiding light due to its relatively low optical loss. In the multifunctional photonic integrated chips, it is critical to achieve the low loss transition between the strip waveguide and the slot waveguide. In this work, a silicon nitride strip-slot mode converter with high efficiency, large bandwidth, and large fabrication tolerance are proposed and demonstrated through the numerical investigation and experiments. The coupling efficiency of the mode converter is up to - 0.1 dB (97.7%), which enables the extremely low transition loss between the strip waveguide and the slot waveguide. Moreover, the fabrication process of silicon nitride photonic devices with high performance is introduced, which is fully compatible with the CMOS technology. Photonic devices based on silicon nitride with the characteristics of the low optical loss and the temperature insensitivity represent a new paradigm in realizing silicon-based photonic multifunctional chips.
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http://dx.doi.org/10.1364/OE.427802DOI Listing
June 2021

Ameliorative effects of miR-186 on cisplatin-triggered acute kidney injury via targeting ZEB1.

Am J Transl Res 2021 15;13(5):4296-4308. Epub 2021 May 15.

Department of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University Qingpu District, Shanghai 201700, P. R. China.

Cisplatin is a commonly used chemotherapy drug in cancers, which can lead to acute kidney injury (AKI). AKI can occur in almost one third of tumor patients, who receive cisplatin treatment. microRNAs (miRNAs) are significant tools in regulating the expression of crucial factors in multiple diseases, but little is known about their biological roles in AKI. As exhibited, miR-186 has been observed to be down-regulated in tumors. Our study concentrated on the function of miR-186 in cisplatin-triggered AKI. Here, we reported miR-186 was considerably decreased in the serum samples from AKI patients compared with those from the healthy controls. Additionally, we found in NRK-52E cells exposed to 6 mM cisplatin, miR-186 was greatly decreased time-dependently. Meanwhile, an AKI model in rats was successfully set in our study. Levels of serum creatinine and blood urea nitrogen were significantly induced by cisplatin exposure. In AKI rat models, miR-186 exhibited a rapid decrease in both the serum and the kidney tissues. Then, miR-186 overexpression improved NRK-52E cell proliferation and protected NRK-52E cells against cisplatin-triggered apoptosis. Furthermore, ZEB1 was identified and confirmed as a target gene of miR-186. It has been demonstrated that ZEB1 exerts crucial roles in the development of AKI. As evidenced in our current study, ZEB1 was remarkably elevated in AKI patients and AKI rat models. Moreover, ZEB1 was induced by indicated doses of cisplatin in different time periods in NRK-52E cells. ZEB1 inhibition rescued the reduced proliferation and increased apoptosis of NRK-52E cells. In conclusion, loss miR-186 expression contributed to cisplatin-induced AKI, partly through targeting ZEB1. miR-186 might be provided as an effective biomarker for AKI via targeting ZEB1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205703PMC
May 2021

Proximity-Induced Hybridization Chain Reaction-Based Photoacoustic Imaging System for Amplified Visualization Protein-Specific Glycosylation in Mice.

Anal Chem 2021 06 18;93(25):8915-8922. Epub 2021 Jun 18.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.

Glycosylation is a key cellular mechanism that regulates several physiological and pathological functions. Therefore, identification and characterization of specific-protein glycosylation in vivo are highly desirable for studying glycosylation-related pathology and developing personalized theranostic modalities. Herein, we demonstrated a photoacoustic (PA) nanoprobe based on the proximity-induced hybridization chain reaction (HCR) for amplified visual detection of protein-specific glycosylation in vivo. Two kinds of functional DNA probes were designed. A glycan probe (DBCO-GP) was attached to glycans through metabolic oligosaccharide engineering (MOE) and protein probe (PP)-targeted proteins by aptamer recognition. Proximity-induced hybridization of the complementary domain between the two kinds of probes promoted conformational changes in the protein probes and in situ release of the HCR initiator domain. Gold nanoparticles (AuNPs) modified by complementary sequences (Au-H1 and Au-H2) self-assembled into Au aggregates via the HCR, thereby converting DNA signals to photoacoustic signals. Due to the high contrast and deep penetration of photoacoustic imaging, this strategy enabled in situ detection of Mucin 1 (MUC1)-specific glycosylation in mice with breast cancer and successfully monitored its dynamic states during tunicamycin treatment. This imaging technique provides a powerful platform for studying the effects of glycosylation on the protein structure and function, which helps to elucidate its role in disease processes.
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http://dx.doi.org/10.1021/acs.analchem.1c01352DOI Listing
June 2021

Stimuli-activated molecular photothermal agents for cancer therapy.

Chem Commun (Camb) 2021 Jul;57(54):6584-6595

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

Taking advantage of activatable and imaging-guided properties, stimuli-activated molecular photothermal agents (MPTAs) have drawn great attention in photothermal therapy (PTT) over the past decades. In this review, the recent progress in the study of stimuli-activated MPTAs is summarized from different stimuli, including pH, bioactive small molecules, and enzymes. The features and challenges of stimuli-activated MPTAs are also discussed. This review aims to motivate readers to design and synthesise more efficient MPTAs.
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http://dx.doi.org/10.1039/d1cc02116hDOI Listing
July 2021

Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation.

Chem Sci 2020 Aug 10;11(33):8895-8900. Epub 2020 Aug 10.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy. Although considerable efforts have been directed at drug screening in living cells, performing repeated drug sensitivity analysis using patient-derived primary tumor cells at the single-cell level remains challenging. Here, we present an efficient approach to assess phenotype-related drug sensitivity at the single-cell level using patient-derived circulating tumor cells (CTCs) based on a drug sensitivity microfluidic chip (DS-Chip). The DS-Chip consists of a drug gradient generator and parallel cell traps, achieving continuous single CTC capture, drug gradient distributions, drug stimulation, fluorescent probe labeling and three-color fluorescence imaging. Based on the established DS-Chip, we investigated the drug sensitivity of single cells by simultaneously monitoring epithelial-mesenchymal transition (EMT) biomarkers and apoptosis in living cells, and verified the correlation between EMT gradients and drug sensitivity. Using the new approach, we further tested the optimal drug response dose in individual CTCs isolated from 5 cancer patients through fluorescence analysis of EMT and apoptosis. The DS-Chip allows noninvasive and real-time measurements of the drug sensitivity of a patient's tumor cells during therapy. This developed approach has practical significance and can effectively guide drug selection and therapeutic evaluation for personalized medicine.
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http://dx.doi.org/10.1039/c9sc05566eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163339PMC
August 2020

Dual-targeted photothermal agents for enhanced cancer therapy.

Chem Sci 2020 Jul 17;11(31):8055-8072. Epub 2020 Jul 17.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Centre of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Photothermal therapy, in which light is converted into heat and triggers local hyperthermia to ablate tumors, presents an inherently specific and noninvasive treatment for tumor tissues. In this area, the development of efficient photothermal agents (PTAs) has always been a central topic. Although many efforts have been made on the investigation of novel molecular architectures and photothermal materials over the past decades, PTAs can cause severe damage to normal tissues because of the poor tumor aggregate ability and high irradiation density. Recently, dual-targeted photothermal agents (DTPTAs) provide an attractive strategy to overcome these problems and enhance cancer therapy. DTPTAs are functionalized with two classes of targeting units, including tumor environment targeting sites, tumor targeting sites and organelle targeting sites. In this perspective, typical targeted ligands and representative examples of photothermal therapeutic agents with dual-targeted properties are systematically summarized and recent advances using DTPTAs in tumor therapy are highlighted.
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http://dx.doi.org/10.1039/d0sc03173aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163445PMC
July 2020

A tumor acidity activatable and Ca-assisted immuno-nanoagent enhances breast cancer therapy and suppresses cancer recurrence.

Chem Sci 2020 Jun 29;11(28):7429-7437. Epub 2020 Jun 29.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Breast cancer recurrence is the greatest contributor to patient death. As the immune system has a long-term immune memory effect, immunotherapy has great potential for preventing cancer recurrence. However, cancer immunotherapy is often limited due to T cell activation being blocked by insufficient tumor immunogenicity and the complex immunosuppressive tumor microenvironment. Here we show a tumor acidity activatable and Ca-assisted immuno-nanoagent to synergistically promote T cell activation and enhance cancer immunotherapy. When the immuno-nanoagent reaches the acidic tumor microenvironment, the CaCO matrix disintegrates to release immune stimulants (CpG ODNs and IDOi) and Ca. CpG ODNs are responsible for triggering dendritic cell maturation to increase the immunogenicity for activation of T cells. And IDOi can inhibit the oxidative catabolism of tryptophan to kynurenine for preventing T-cell anergy and apoptosis. Due to the complexity of the immunosuppressive microenvironment, it is difficult to restore T cell activation by inhibiting only one pathway. Fortunately, the released Ca can promote the activation and proliferation of T cells with the support of the immune stimulants. experiments demonstrate that our Ca-assisted immuno-nanoagent can significantly suppress tumor progression and protect mice from tumor rechallenge due to the long-term memory effect. This immunotherapeutic strategy may provide more possibilities for clinical applications such as treating cancer and preventing relapse.
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http://dx.doi.org/10.1039/d0sc00293cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159290PMC
June 2020

h-FBN assisted negative ion paper spray for the sensitive detection of small molecules.

Chem Commun (Camb) 2021 Jul;57(54):6612-6615

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China.

Negative ion mode paper spray mass spectrometry (PS-MS) suffers from intense background noise and unstable MS signal. For the first time, we reported fluorinated boron nitride nanosheet (h-FBN) assisted negative ion PS-MS for the detection of a series of molecules. We demonstrated that the introduction of h-FBN can greatly improve the detection sensitivity and signal stability in the negative ion mode.
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http://dx.doi.org/10.1039/d1cc02338aDOI Listing
July 2021
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