Publications by authors named "Xiaoping Yang"

450 Publications

The antidepressant potential of lactobacillus casei in the postpartum depression rat model mediated by the microbiota-gut-brain axis.

Neurosci Lett 2022 Jan 24:136474. Epub 2022 Jan 24.

Hebei University of Engineering, Handan city, Hebei Province 056038, China. Electronic address:

Lactobacillus casei, a kind of probiotic, was reported as antidepressant effects. However, little is known about the effect of Lactobacillus casei on postpartum depression (PPD). In this study, we investigated the effects of Lactobacillus casei in improving PPD and potential mechanisms. Four hours of daily maternal separation from postnatal day 2 to day 21 was performed to establish the PPD model in rats. From postnatal day 2 to day 28, rats were gavage-fed with an equal volume of normal saline, Lactobacillus casei (8×10 CFU/kg/day), or paroxetine (1.8mg/kg/day), respectively. Rat behaviors were measured using the sucrose preference test, the elevated plus maze, the forced swim test, and the tail suspension test. Changes in gut microbiota were detected by real-time fluorescence quantitative PCR. Administration of Lactobacillus casei improved depressive-like behaviors, intestinal microflora, and oxidative stress in PPD model rats. Western Blot or HPLC assays showed that Lactobacillus casei intervention reversed the changes of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartic acid receptor 1 (NR1), ERK1/2, and monoamines in the brain of PPD rats. These results suggest that Lactobacillus casei could improve PPD through altering gut microbiota composition, brain monoamines and oxidative stress, which may be associated with the regulation of the BDNF-ERK1/2 pathway.
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http://dx.doi.org/10.1016/j.neulet.2022.136474DOI Listing
January 2022

Novel dihydroartemisinin derivative Mito-DHA induces apoptosis associated with mitochondrial pathway in bladder cancer cells.

BMC Pharmacol Toxicol 2022 Jan 20;23(1):10. Epub 2022 Jan 20.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.

Background: Bladder cancer is the second most common genitourinary malignancy and the eleventh most common cancer worldwide. Dihydroartemisinin (DHA), a first-line antimalarial drug, has been found to have potent antitumor activity. In our previous study, a novel dihydroartemisinin derivative Mito-DHA synthesized in our laboratory has a stronger anti-tumor activity than DHA. In this study, we investigated the apoptotic effect of Mito-DHA on bladder cancer T24 cells and molecular mechanisms underlying.

Methods: Antitumor activity in vitro was evaluated by MTT, wound healing and cloning formation assays. Mitochondrial membrane potential (MMP) was detected by JC-1 probe and ROS levels were measured by specific kit. The expression of caspase-3, cleaved-caspase3, mitochondrial Cyt-C, Bcl-2, Bax and PARP in T24 cells was evaluated by Western blotting.

Results: The results showed that Mito-DHA reduced cell viability with an IC value of 3.2 µM and induced T24 cell apoptosis in a dose-dependent manner, increased the production of ROS and decreased MMP. Mito-DHA could down-regulate the expression of Bcl-2, mitochondrial Cyt-C, Caspase-3, PARP and up-regulate the expression of Bax and cleaved Caspase-3.

Conclusions: These data suggested that Mito-DHA had a potent inhibitory effect on T24 bladder cancer cell growth and induced these cells apoptosis associated with mitochondrial pathway.
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http://dx.doi.org/10.1186/s40360-021-00542-6DOI Listing
January 2022

NLRP3 promotes immune escape by regulating immune checkpoints: A pan-cancer analysis.

Int Immunopharmacol 2022 Jan 10;104:108512. Epub 2022 Jan 10.

Department of Hepatobiliary Pancreatic Surgery, the First Hospital of Ningbo City, Ningbo 315010, China. Electronic address:

NLRP3 plays a pathogenic role in tumorigenesis by regulating innate and acquired immunity, apoptosis, differentiation, and intestinal microbes in tumors. Our research aimed to investigate the role of NLRP3 in pan-cancers based on multi-omics data in the TCGA database. Most types of tumors showed increased expression of NLRP3. Among them, the overexpressed NLRP3 in liver hepatocellular carcinoma (LIHC) and ovarian cancer (OV) indicated worse overall survival (OS). Further analysis also confirmed overexpressed NLRP3 in colon cancer (COAD) indicated a high probability of microsatellite instability (MSI) and low tumor mutational burden (TMB), which indicated a better response to immune checkpoint inhibitors (ICIs). Interestingly, overexpression of NLRP3 was closely related to high infiltration of immune cells (T cells, B cells, etc.) and overexpressed immune checkpoints (PD-1, PD-L1, LAG3, etc.). These results demonstrated NLRP3 promoted immune escape in cancers. Finally, we investigated the expression of various immune checkpoints by treating NLRP3 inhibitor MCC950 during the co-culture of peripheral blood mononuclear cells (PBMC) and LIHC cell line Hep3B. MCC950 significantly repressed the expression of PD-L1 and LAG3, and promoted the apoptosis rate of Hep3B. In conclusion, our research demonstrated the role of NLRP3 in pan-cancer, especially in LIHC. Inhibition of NLRP3 promoted the killing effect of T cells to cancer cells by repressing the expression of immune checkpoints.
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http://dx.doi.org/10.1016/j.intimp.2021.108512DOI Listing
January 2022

Head and neck tumor segmentation in PET/CT: The HECKTOR challenge.

Med Image Anal 2021 Dec 25;77:102336. Epub 2021 Dec 25.

Institute of Information Systems, University of Applied Sciences Western Switzerland (HES-SO), Sierre, Switzerland; Department of Nuclear Medicine and Molecular Imaging, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge's task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs.
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http://dx.doi.org/10.1016/j.media.2021.102336DOI Listing
December 2021

Regulatable Detection of Antibiotics Based on a Near-IR-Luminescent Tubelike Zn(II)-Yb(III) Nanocluster.

Inorg Chem 2022 Jan 3;61(2):1011-1017. Epub 2022 Jan 3.

Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States.

A tubelike Zn(II)-Yb(III) cluster, [ZnYbL(HL)(NO)(DMF)(EtOH)(HO)] (; DMF = ,-dimethylformamide and EtOH = ethanol; molecular size 1.5 × 1.8 × 2.9 nm), was synthesized from a new long-chain Schiff base ligand. exhibits a regulatable near-IR-luminescent response to nitrofuran antibiotics (NFAs) and fluoroquinolones with high sensitivity, which is not influenced by other antibiotics. The quenching constants of NFAs and fluoroquinolones range from 0.55 × 10 to 8.8 × 10 M, and the detection limits of to them are from 4.2 × 10 to 2.6 × 10 M. It also shows a luminescent response to real antibiotic drugs containing NFAs and fluoroquinolones.
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http://dx.doi.org/10.1021/acs.inorgchem.1c03071DOI Listing
January 2022

Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.

Front Oncol 2021 17;11:785855. Epub 2021 Dec 17.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, China.

Chiral drugs usually contain chiral centers, which are present as single enantiomers or racemates. Compared with achiral drugs, they have significant advantages in safety and efficacy with high stereoselectivity. Of these drugs, chirality not only exerts influence on the solubility and pharmacokinetic characteristics but also has specific mechanistic characteristics on their targets. We noted that small molecules with unique chiral properties have emerged as novel components of antitumor drugs approved by the FDA in decade. Since approved, these drugs have been continuously explored for new indications, new mechanisms, and novel combinations. In this mini review, recent research progress of twenty-two FDA-approved chiral small molecular-targeted antitumor drugs from 2011 to 2019 is summarized with highlighting the potential and advantages of their applications. We believe that these updated achievements may provide theoretical foundation and stimulate research interests for optimizing drug efficacy, expanding clinical application, overcoming drug resistance, and advancing safety in future clinical administrations of these chiral targeted drugs.
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http://dx.doi.org/10.3389/fonc.2021.785855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718447PMC
December 2021

Recent progress of microfluidic technology for pharmaceutical analysis.

J Pharm Biomed Anal 2022 Feb 11;209:114534. Epub 2021 Dec 11.

Center for Synthetic and Systems Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, PR China. Electronic address:

In recent years, the progress of microfluidic technology has provided new tools for pharmaceutical analysis and the proposal of pharm-lab-on-a-chip is appealing for its great potential to integrate pharmaceutical test and pharmacological test in a single chip system. Here, we summarize and highlight recent advances of chip-based principles, techniques and devices for pharmaceutical test and pharmacological/toxicological test focusing on the separation and analysis of drug molecules on a chip and the construction of pharmacological models on a chip as well as their demonstrative applications in quality control, drug screening and precision medicine. The trend and challenge of microfluidic technology for pharmaceutical analysis are also discussed and prospected. We hope this review would update the insight and development of pharm-lab-on-a-chip.
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http://dx.doi.org/10.1016/j.jpba.2021.114534DOI Listing
February 2022

Self-Enhancing Gel Polymer Electrolyte by In Situ Construction for Enabling Safe Lithium Metal Battery.

Adv Sci (Weinh) 2021 Dec 11:e2103663. Epub 2021 Dec 11.

State Key Laboratory of Organic-Inorganic Composites, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.

Lithium metal battery (LMB) possessing a high theoretical capacity is a promising candidate of advanced energy storage devices. However, its safety and stability are challenged by lithium dendrites and the leakage of liquid electrolyte. Here, a self-enhancing gel polymer electrolyte (GPE) is created by in situ polymerizing 1,3-dioxolane (DOL) in the nanofibrous skeleton for enabling safe LMB. The nanofiber membrane possesses a better affinity with poly-DOL (PDOL) than commercial separator for constructing homogeneous GPE with enhanced ion conductivity. Furthermore, polydopamine is introduced on nanofiber membrane to form hydrogen bonding with PDOL and bis((trifluoromethyl)sulfonyl)imide anion, dramatically improving the mechanical strength, ionic conductivity, and transference number of GPE. Besides, molecular dynamic simulation is used to reveal the intrinsic factors of high ionic conductivity and reinforcing effect in the meantime. Consequently, the LiFePO //Li batteries using self-enhancing GPE show extraordinary cyclic stability over 800 cycles under high current density of 2 C, with a capacity decay of 0.021% per cycle, effectively suppressing the growth of lithium dendrites. This ingenious strategy is expected to manufacture advanced performance and high safety LMBs and compatible with the current battery production.
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http://dx.doi.org/10.1002/advs.202103663DOI Listing
December 2021

Constructing a Rigid-and-Flexible Twin-Stage Gradient Interphase through Starlike Copolymer Coating on Carbon Fibers: A Route for Enhancing Interfacial Properties of Composites.

ACS Appl Mater Interfaces 2021 Nov 15;13(46):55633-55647. Epub 2021 Nov 15.

State Key Laboratory of Organic-Inorganic Composites, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

A rigid-and-flexible interphase was established by a starlike copolymer (Pc-PGMA/Pc) consisting of one tetraaminophthalocyanine (TAPc) core with four TAPc-difunctionalized poly(glycidyl methacrylate) (PGMA) arms through the surface modification of carbon fibers (CFs) and compared with various interphases constructed by TAPc and TAPc-connected PGMA (Pc-PGMA). The increase in the content of N-C═O showed that PGMA/Pc branches were successfully attached onto the CF-(Pc-PGMA/Pc) surface, exhibiting concavo-convex microstructures with the highest roughness. Through adhesive force spectroscopy by atomic force microscopy (AFM) with peak force quantitative nanomechanical mapping (PF-QNM) mode and visualization of the relative distribution of TAPc/PGMA via a Raman spectrometer, a rigid interphase with highly cross-linked TAPc and a flexible layer from PGMA arms as the soft segment were separately detected in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. The rigid-and-flexible interphase in the CF-(Pc-PGMA/Pc)/EP composite provided excellent stress-transfer capability by the rigid inner modulus intermediate layer and energy absorption efficiency from the flexible outer layer, which contributed to 64.6 and 61.8% increment of transverse fiber bundle test (TFBT) strength, and 33.8 and 40.6% enhancement in interfacial shear strength (IFSS) in comparison with those of CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. Accordingly, schematic models of the interphase reinforcing mechanism were proposed. The interfacial failures in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites were derived from the rigid interphase without effective relaxation of interfacial stress and soft interphase with excessive fiber-matrix interface slippage, respectively. The cohesive failure in the CF-(Pc-PGMA/Pc)/EP composite was attributed to the crack deflection through the balance of the modulus and deformability from the twin-stage gradient intermediate layer.
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http://dx.doi.org/10.1021/acsami.1c14535DOI Listing
November 2021

Corrigendum to "Residual -Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study".

J Diabetes Res 2021 31;2021:9830928. Epub 2021 Oct 31.

Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

[This corrects the article DOI: 10.1155/2021/9946874.].
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http://dx.doi.org/10.1155/2021/9830928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572609PMC
October 2021

Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling.

Mol Med Rep 2022 01 9;25(1). Epub 2021 Nov 9.

State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P.R. China.

Oxidative stress‑induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element‑binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (HO) . PD inhibited the HO‑induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated HO‑induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against HO. The results indicated that PD protected neuronal cells from HO by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.
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http://dx.doi.org/10.3892/mmr.2021.12525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600421PMC
January 2022

Fast evolution of SARS-CoV-2 driven by deamination systems in hosts.

Future Virol 2021 Sep 10;16(9):587-590. Epub 2021 Sep 10.

Department of Respiratory Diseases, Qingdao Haici Hospital, Shandong, China.

As an RNA virus, the fast evolution of SARS-CoV-2 is driven by the extensive RNA deamination by the host cells.
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http://dx.doi.org/10.2217/fvl-2021-0181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547201PMC
September 2021

A Study of Hydrophobically Modified Pullulan Nanoparticles with Different Hydrophobic Densities on the Effect of Anti-Colon Cancer Cell Efficiency.

J Biomed Nanotechnol 2021 Oct;17(10):1972-1983

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine; Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, 410013, PR China.

To discuss the effect of hydrophobic groups of a polymer on the structural properties and function of polymer nanoparticles (NPs), we grafted chenodeoxycholic acid (CDCA) with pullulan (PU) to form hydrophobically modified PU (PUC). Three PUC polymers, namely, PUC-1, PUC-2, and PUC-3, with different degrees of substitution were designed by changing the feed ratio of CDCA and PU. H-NMR spectra showed that the PUC polymer was successfully synthesized, and the degrees of hydrophobic substitution for PUC-1, PUC-2, and PUC-3 were calculated to be 10.66%, 13.92%, and 16.94%, respectively. The PUC NPs were prepared by the dialysis method and were shown to be uniformly spherical by transmission electron microscopy (TEM). The average sizes were about (220±10) nm, (203±7) nm, and (163±6) nm under dynamic light scattering (DLS) for PUC-1 NPs, PUC-2 NPs, and PUC-3 NPs, respectively. Drug release experiments showed that the three PUC/DOX NPs exhibited good sustained release. At 48 h, the IC of doxorubicin in inhibiting colon cancer HCT116 cells was 0.0904 μg/mL. A cell study showed that PUC-3/DOX NPs had the highest uptake efficiency by HCT116 cells with the most cytotoxicity and inhibited the migration of HCT116 cells with the highest efficiency. The structural properties and function of polymer NPs were closely related to the hydrophobic groups in the polymer, and NPs with higher hydrophobicity showed a smaller size, higher drug capacity, and greater cell efficiency.
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http://dx.doi.org/10.1166/jbn.2021.3173DOI Listing
October 2021

Preparation of ICA-loaded mPEG-ICA nanoparticles and their application in the treatment of LPS-induced H9c2 cell damage.

Nanoscale Res Lett 2021 Oct 17;16(1):155. Epub 2021 Oct 17.

Department of Geriatrics and General Medicine (QZ) of Affiliated Taihe Hospital, Pharmaology Department (LZ, JW, XG, QZ), School of Basic Medical Science, Hubei University of Medicine, Shiyan, 442000, Hubei, China.

Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.
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http://dx.doi.org/10.1186/s11671-021-03609-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523016PMC
October 2021

SARS-CoV-2 competes with host mRNAs for efficient translation by maintaining the mutations favorable for translation initiation.

J Appl Genet 2022 Feb 16;63(1):159-167. Epub 2021 Oct 16.

Department of Respiratory Diseases, Qingdao Haici Hospital, Qingdao, China.

During SARS-CoV-2 proliferation, the translation of viral RNAs is usually the rate-limiting step. Understanding the molecular details of this step is beneficial for uncovering the origin and evolution of SARS-CoV-2 and even for controlling the pandemic. To date, it is unclear how SARS-CoV-2 competes with host mRNAs for ribosome binding and efficient translation. We retrieved the coding sequences of all human genes and SARS-CoV-2 genes. We systematically profiled the GC content and folding energy of each CDS. Considering that some fixed or polymorphic mutations exist in SARS-CoV-2 and human genomes, all algorithms and analyses were applied to both pre-mutate and post-mutate versions. In SARS-CoV-2 but not human, the 5-prime end of CDS had lower GC content and less RNA structure than the 3-prime part, which was favorable for ribosome binding and efficient translation initiation. Globally, the fixed and polymorphic mutations in SARS-CoV-2 had created an even lower GC content at the 5-prime end of CDS. In contrast, no similar patterns were observed for the fixed and polymorphic mutations in human genome. Compared with human RNAs, the SARS-CoV-2 RNAs have less RNA structure in the 5-prime end and thus are more favorable of fast translation initiation. The fixed and polymorphic mutations in SARS-CoV-2 are further amplifying this advantage. This might serve as a strategy for SARS-CoV-2 to adapt to the human host.
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http://dx.doi.org/10.1007/s13353-021-00665-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520108PMC
February 2022

1-n-heptyl-5-(3, 4-difluorophenyl) biguanide inhibits non-small cell lung cancer cell growth by downregulating the EGFR signaling pathways.

Am J Transl Res 2021 15;13(9):10193-10205. Epub 2021 Sep 15.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University Changsha 410013, Hunan, China.

Lung cancer is among the diseases with the highest rates of morbidity and mortality. Our previous study found that a novel biguanide derivative, 1-n-heptyl-5-(3, 4-difluorophenyl) biguanide (8e) shows excellent anti-proliferative activity in non-small cell lung cancer (NSCLC) cell line A549. However, the underlying mechanism remains elusive. In this research, we analyzed the effect of 8e on NSCLC cell lines and explored the cell death mechanism caused by 8e. From our data, we found that 8e significantly decreased the cell activity and inhibited the colony formation of A549 and H1299 cells in a dose-dependent manner. Interestingly, this inhibitory effect of 8e was significantly reduced after silencing EGFR with lentiviral vectors. In contrast, after overexpressing EGFR in A549 and H1299, the lethality of 8e to the tumor cells increased. Simultaneously, we observed that 8e inhibited the expression of EGFR and its two essential downstream signaling pathways, AKT/mTOR and c-Raf/ERK1/2, and significantly reduced the activation of the EGFR pathway induced by EGF. Therefore, the results showed that 8e inhibits the proliferation of NSCLC cells by down-regulating the expression of EGFR, thereby inhibiting the downstream signaling pathway AKT/mTOR and c-Raf/ERK1/2. In addition, 8e also markedly reduces migration and induces the apoptosis of A549 and H1299 cells. results based on a lung cancer cell transplanted xenograft mouse model have further shown that 8e blocks A549 tumor growth without any significant hepatotoxicity or nephrotoxicity. These results indicate the high potential value of 8e as a candidate for treating NSCLC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507003PMC
September 2021

Compelling Evidence Suggesting the Codon Usage of SARS-CoV-2 Adapts to Human After the Split From RaTG13.

Evol Bioinform Online 2021 8;17:11769343211052013. Epub 2021 Oct 8.

Department of Respiratory Diseases, Qingdao Haici Hospital, Qingdao, Shandong, China.

SARS-CoV-2 needs to efficiently make use of the resources from hosts in order to survive and propagate. Among the multiple layers of regulatory network, mRNA translation is the rate-limiting step in gene expression. Synonymous codon usage usually conforms with tRNA concentration to allow fast decoding during translation. It is acknowledged that SARS-CoV-2 has adapted to the codon usage of human lungs so that the virus could rapidly proliferate in the lung environment. While this notion seems to nicely explain the adaptation of SARS-CoV-2 to lungs, it is unable to tell why other viruses do not have this advantage. In this study, we retrieve the GTEx RNA-seq data for 30 tissues (belonging to over 17 000 individuals). We calculate the RSCU (relative synonymous codon usage) weighted by gene expression in each human sample, and investigate the correlation of RSCU between the human tissues and SARS-CoV-2 or RaTG13 (the closest coronavirus to SARS-CoV-2). Lung has the highest correlation of RSCU to SARS-CoV-2 among all tissues, suggesting that the lung environment is generally suitable for SARS-CoV-2. Interestingly, for most tissues, SARS-CoV-2 has higher correlations with the human samples compared with the RaTG13-human correlation. This difference is most significant for lungs. In conclusion, the codon usage of SARS-CoV-2 has adapted to human lungs to allow fast decoding and translation. This adaptation probably took place after SARS-CoV-2 split from RaTG13 because RaTG13 is less perfectly correlated with human. This finding depicts the trajectory of adaptive evolution from ancestral sequence to SARS-CoV-2, and also well explains why SARS-CoV-2 rather than other viruses could perfectly adapt to human lung environment.
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http://dx.doi.org/10.1177/11769343211052013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504689PMC
October 2021

Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length.

Molecules 2021 Sep 24;26(19). Epub 2021 Sep 24.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha 410205, China.

Among the known biguanide drugs, proguanil has the best antiproliferative activity. In contrast, newly synthesized biguanide derivatives containing fluorine atoms have excellent biological activity, among which trifluoromethoxy compounds show the strongest ability. Preliminary work in our laboratory exhibited that n-heptyl containing proguanil derivatives on one alkyl chain side have better biological activity than those with a shorter carbon chain. However, the relationship between the length of the carbon chain and the activity of the compounds is unknown. In this study, we synthesized 10 new trifluoromethoxy-containing proguanil derivatives with various carbon chain lengths. The phenyl side is fixed as the trifluoromethoxy group with change of carbon chain length in alkyl chain side. It was found that the anti-cancer abilities of - with n-pentyl to n-octyl groups was significantly better than that of proguanil in the five human cancer cell lines. The colony formation assay demonstrated that - at 0.5 to 1.0 μM significantly inhibited the colony formation of human cancer cell lines, much stronger than that of proguanil. Pharmacologically, activates AMPK, leading to inactivation of the mTOR/p70S6K/4EBP1 pathway. Thus, these novel compounds have a great potential for developing new anti-cancer candidates.
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http://dx.doi.org/10.3390/molecules26195775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510509PMC
September 2021

Papillary squamous cell carcinoma successfully treated with bronchoscopic intratumoral injections of cisplatin and Endostar: a case report.

J Int Med Res 2021 Sep;49(9):3000605211047077

Department of Respiratory Diseases, 155177Qingdao Haici Hospital, Qingdao Haici Hospital, Qingdao, China.

Squamous cell carcinoma (SCC) is a malignant epithelial tumor originating from the bronchial epithelium that shows keratosis and/or intercellular bridges. Papillary squamous cell carcinoma (PSCC) is an extremely rare subtype of SCC that manifests with a unique intrabronchial papillary growth pattern. Surgical resection is still the first recommendation for localized noninvasive SCC. However, some patients are not candidates for surgical resection. With the development of interventional pulmonology, bronchoscopic interventional therapy has played a key role in the treatment of central airway tumors. Here, we report a case of noninvasive PSCC in the airway treated with an electric snare, argon plasma coagulation (APC), and cryotherapy. After removing the tumor by electrotomy, cryotherapy, and APC, the tumor was injected with Endostar 15 mg (3 ml) and cisplatin 20 mg (diluted to 3 ml with 0.9% normal saline) in six separate sites, once every 21 days. The tumor was eliminated, and the treatment was stopped after four treatment cycles. During the 1-year follow-up, there was no recurrence of PSCC in the airway. In this case, submucosal injections of Endostar combined with cisplatin was a feasible and effective endoscopic method for treating a low-grade intratracheal malignant tumor.
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http://dx.doi.org/10.1177/03000605211047077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485288PMC
September 2021

Ratiometric fluorescent detection of dipicolinic acid as an anthrax biomarker based on a high-nuclearity Yb nanoring.

Dalton Trans 2021 Oct 5;50(38):13528-13532. Epub 2021 Oct 5.

The University of Texas at Austin, Department of Chemistry and Biochemistry, 1 University Station A5300, Austin, Texas, 78712, USA.

An 18-metal lanthanide nanoring [Yb(L)(HL)(OAc)(MeOH)(EtOH)(HO)] (1), which shows a ratiometric fluorescent response to DPA, was constructed through the strategy of using two types of polydentate organic ligands. The addition of DPA increases the visible ligand-centered emission, but decreases the NIR lanthanide luminescence of 1. The limit of luminescent detection of 1 for DPA is 1.5 μM. The high fluorescence sensitivity of 1 to DPA is not affected by the existence of interferents such as aromatic carboxylates and ions.
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http://dx.doi.org/10.1039/d1dt01731dDOI Listing
October 2021

Shape prior generation and geodesic active contour interactive iterating algorithm (SPACIAL): fully automatic segmentation for 3D lumen in intravascular optical coherence tomography images.

Med Phys 2021 Nov 13;48(11):7099-7111. Epub 2021 Sep 13.

Department of Mathematics, Nanjing University, Nanjing, Jiangsu, China.

Purpose: Fully automatic lumen segmentation in intravascular optical coherence tomography (OCT) images can assist physicians in quickly estimating the health status of vessels. However, OCT images are usually degraded by residual blood, catheter walls, guide wire artifacts, etc., which significantly reduce the quality of segmentation. To achieve accurate lumen segmentation in low-quality images, we propose a novel segmentation algorithm named SPACIAL: Shape Prior generation and geodesic Active Contour Interactive iterAting aLgorithm, which is guided by an adaptively generated shape prior.

Methods: In this framework, the active contour evolves under the guidance of shape prior, while the shape prior is automatically and adaptively generated based on the active contour. The active contour and the shape prior interactively iterate each other, which can generate the adaptive shape prior and consequently lead to accurate segmentation results. In addition, a fast algorithm is introduced to accelerate the segmentation in 3D images.

Results: The validity of the model is verified in 3240 images from 12 OCT pullbacks. The experimental results show satisfactory segmentation accuracy and time efficiency: the average Dice coefficient of SPACIAL is 93.6(2.4)%, and 5.7 times faster than that of the classical level set method.

Conclusion: The proposed SPACIAL can quickly and efficiently perform accurate lumen segmentation on low quality OCT images, which is of great importance to cardiovascular disease diagnosis . The SPACIAL method shows great potential in clinical applications.
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http://dx.doi.org/10.1002/mp.15201DOI Listing
November 2021

Genetic diversity and epidemiology of human rhinovirus among children with severe acute respiratory tract infection in Guangzhou, China.

Virol J 2021 08 23;18(1):174. Epub 2021 Aug 23.

The Key Laboratory for Virology of Guangzhou, Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.

Background: Human rhinovirus (HRV) is one of the major viruses of acute respiratory tract disease among infants and young children. This work aimed to understand the epidemiological and phylogenetic features of HRV in Guangzhou, China. In addition, the clinical characteristics of hospitalized children infected with different subtype of HRV was investigated.

Methods: Hospitalized children aged < 14 years old with acute respiratory tract infections were enrolled from August 2018 to December 2019. HRV was screened for by a real-time reverse-transcription PCR targeting the viral 5'UTR.

Results: HRV was detected in 6.41% of the 655 specimens. HRV infection was frequently observed in children under 2 years old (57.13%). HRV-A and HRV-C were detected in 18 (45%) and 22 (55%) specimens. All 40 HRV strains detected were classified into 29 genotypes. The molecular evolutionary rate of HRV-C was estimated to be 3.34 × 10 substitutions/site/year and was faster than HRV-A (7.79 × 10 substitutions/site/year). Children who experienced rhinorrhoea were more common in the HRV-C infection patients than HRV-A. The viral load was higher in HRV-C detection group than HRV-A detection group (p = 0.0148). The median peak symptom score was higher in patients with HRV-C infection as compared to HRV-A (p = 0.0543), even though the difference did not significance.

Conclusion: This study revealed the molecular epidemiological characteristics of HRV in patients with respiratory infections in southern China. Children infected with HRV-C caused more severe disease characteristics than HRV-A, which might be connected with higher viral load in patients infected with HRV-C. These findings will provide valuable information for the pathogenic mechanism and treatment of HRV infection.
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http://dx.doi.org/10.1186/s12985-021-01645-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382100PMC
August 2021

Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways.

Am J Transl Res 2021 15;13(7):7508-7523. Epub 2021 Jul 15.

Department of Oncology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University Zhuzhou 412000, Hunan, China.

Sorafenib is a first-line drug to treat advanced hepatocellular carcinoma (HCC), which can prolong the median overall survival of patients by approximately 3 months. Phenformin is a biguanide derivative that has been shown to exhibit antitumor activity superior to that of metformin. We herein explored the ability of phenformin to enhance the anti-cancer activity of sorafenib against HCC and the mechanisms underlying such synergy. The Hep-G2 and SMMC-7721 HCC cell lines were treated with sorafenib and/or phenformin, after which the proliferation of these cells was evaluated via MTT and colony formation assays, while invasion and apoptotic cell death were evaluated via Transwell and flow cytometry assays, respectively. In addition, protein levels were assessed by Western blotting, drug synergy was assessed with the CompuSyn software, and xenograft models were established by implanting Hep-G2 cells into nude mice and then assessing drug antitumor efficacy. Sorafenib and phenformin exhibited a synergistic ability to suppress HCC cell proliferation, migration, and survival. Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Strikingly, the combination of these two drugs achieved better efficacy in a murine model system, without causing significant weight loss or hepatorenal toxicity. Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340162PMC
July 2021

AbdomenCT-1K: Is Abdominal Organ Segmentation A Solved Problem.

IEEE Trans Pattern Anal Mach Intell 2021 Jul 27;PP. Epub 2021 Jul 27.

With the unprecedented developments in deep learning, automatic segmentation of main abdominal organs seems to be a solved problem as state-of-the-art (SOTA) methods have achieved comparable results with inter-rater variability on many benchmark datasets. However, most of the existing abdominal datasets only contain single-center, single-phase, single-vendor, or single-disease cases, and it is unclear whether the excellent performance can generalize on diverse datasets. This paper presents a large and diverse abdominal CT organ segmentation dataset, termed AbdomenCT-1K, with more than 1000 (1K) CT scans from 12 medical centers, including multi-phase, multi-vendor, and multi-disease cases. Furthermore, we conduct a large-scale study for liver, kidney, spleen, and pancreas segmentation and reveal the unsolved segmentation problems of the SOTA methods, such as the limited generalization ability on distinct medical centers, phases, and unseen diseases. To advance the unsolved problems, we further build four organ segmentation benchmarks for fully supervised, semi-supervised, weakly supervised, and continual learning, which are currently challenging and active research topics. Accordingly, we develop a simple and effective method for each benchmark, which can be used as out-of-the-box methods and strong baselines. We believe the AbdomenCT-1K dataset will promote future in-depth research towards clinical applicable abdominal organ segmentation methods.
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http://dx.doi.org/10.1109/TPAMI.2021.3100536DOI Listing
July 2021

Human Cytomegalovirus UL23 Attenuates Signal Transducer and Activator of Transcription 1 Phosphorylation and Type I Interferon Response.

Front Microbiol 2021 9;12:692515. Epub 2021 Jul 9.

Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, China.

Human cytomegalovirus (HCMV), the human beta-herpesvirus, can cause severe syndromes among both immunocompromised adult patients and newborns. Type I interferon (IFN-I) exerts an important effect to resist infections caused by viruses such as HCMV, while IFN evasion may serve as a key determining factor for viral dissemination and disease occurrence within hosts. In this study, UL23, a tegument protein of HCMV, was confirmed to be a key factor for negatively regulating the type I IFN immune response. A detailed analysis indicated that the viral UL23 protein increases the IFN-I antiviral resistance during HCMV infections. Furthermore, UL23 was shown to significantly reduce the levels of IFN-stimulated genes (ISGs) and promoter activity of IFN-I-stimulated response element. Mechanically, UL23 was discovered to impair the signal transducer and activator of transcription 1 (STAT1) phosphorylation, although it was not found to affect phosphorylation and expression of STAT2, Janus activated kinase 1, or tyrosine kinase 2, which are associated with IFN-I signal transduction pathway. Additionally, a significantly reduced nuclear expression of STAT1 but not of IFN regulatory factor 9 or STAT2 was observed. Findings of this study indicate that HCMV UL23 is a viral antagonist that acts against the cellular innate immunity and reveal a possible novel effect of UL23 on IFN-I signaling.
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http://dx.doi.org/10.3389/fmicb.2021.692515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301221PMC
July 2021

Designing Intrinsic Topological Insulators in Two-Dimensional Metal-Organic Frameworks.

J Phys Chem Lett 2021 Jul 20;12(29):6934-6940. Epub 2021 Jul 20.

Institute of High Performance Computing, Agency for Science, Technology and Research, 1 Fusionopolis Way, #16-16 Connexis, Singapore 138632, Singapore.

The connection between electronic structures of metal-organic frameworks (MOFs) and their building subunits is a key cornerstone for rational MOF material design. Some two-dimensional conjugated MOFs were reported to be topological insulators. However, many of them are not intrinsic as the Fermi levels are far from the topological gaps. The subunit-to-MOF electronic orbital correspondence should be established to bridge their chemical structure and physical properties, thus understanding the design rules toward intrinsic topological insulators. Herein we reveal the fundamental role of the subunit-to-MOF symmetry relation in determining their orbital interaction and hybridization and, consequently, topological characteristics. In particular, such honeycomb-kagome MOFs possess delocalized symmetry-enforced nonbonding electronic states with the topological spin-orbit gap. The nonbonding nature of these states allows tailored band structure modulation through molecular structure and strain engineering, with the potential realization of an intrinsic metal-organic topological insulator.
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http://dx.doi.org/10.1021/acs.jpclett.1c01731DOI Listing
July 2021

Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.

Nat Commun 2021 07 16;12(1):4375. Epub 2021 Jul 16.

Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
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http://dx.doi.org/10.1038/s41467-021-24495-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285493PMC
July 2021

Reduced stress-associated FKBP5 DNA methylation together with gut microbiota dysbiosis is linked with the progression of obese PCOS patients.

NPJ Biofilms Microbiomes 2021 07 15;7(1):60. Epub 2021 Jul 15.

Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.
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http://dx.doi.org/10.1038/s41522-021-00231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282850PMC
July 2021

Residual -Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study.

J Diabetes Res 2021 28;2021:9946874. Epub 2021 Jun 28.

Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

Objective: To investigate the natural history and related factors of the pancreatic -cell function in Chinese type 1 diabetic patients from 3C study Shantou center.

Method: Stimulated C-peptide levels from follow-up data of 201 individuals in 3C study Shantou subgroup starting in 2012 were used. Residual -cell function was defined as stimulated C - peptide level ≥ 0.2 pmol/mL, on the basis of cut-points derived from the Diabetes Control and Complications Trial (DCCT).

Results: 36.8% of patients had residual -cell function, and the percentage was 68.2% in newly diagnosed diabetic patients. COX regression analysis indicated that the age of diagnosis, HbA1C level, and duration were independent factors of residual -cell function in individuals with ≤5 years duration, but in those with duration ≥5 years, only the age of diagnosis was a predictor. The pancreatic -cell function mainly declined in the first 5 years of the duration, and the rate of decline was correlated negatively with the duration and age of diagnosis. Receiver operating characteristic (ROC) analysis indicated that the cut-off point of stimulated C-peptide was 0.615 pmol/mL in patients with <5 years duration to have 7% HbA1c.

Conclusion: Age at diagnosis was the strongest predictor for residual C-peptide. There was a more rapid decline of stimulated C-peptide in duration ≤5 years and younger patients. Therefore, intervention therapies of -cells should start from the early stage, and the recommended target goal of stimulated C-peptide is 0.615 pmol/mL or above.
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http://dx.doi.org/10.1155/2021/9946874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261175PMC
January 2022

One high-nuclearity Eu nanoring with rapid ratiometric fluorescence response to dipicolinic acid (an anthrax biomarker).

Chem Commun (Camb) 2021 Jul 5;57(59):7316-7319. Epub 2021 Jul 5.

College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China.

One 18-metal Eu(iii) nanoring (size: 1.0 × 2.7 × 2.7 nm) was constructed as a rapid ratiometric fluorescent probe for the detection of dipicolinic acid with high sensitivity and selectivity, by using two types of polydentate organic ligands.
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http://dx.doi.org/10.1039/d1cc01706cDOI Listing
July 2021
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