Publications by authors named "Fu Li"

890 Publications

Investigating the Underlying Mechanisms of Circular RNAs and Their Application in Clinical Research of Cervical Cancer.

Front Genet 2021 25;12:653051. Epub 2021 Mar 25.

Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, China.

Circular RNAs (circRNAs) are non-coding RNA molecules, and these are differentially expressed in various diseases, including cancer, suggesting that circRNAs can regulate certain diseases. CircRNAs can act as miRNAs sponges, RNA-binding protein (RBP) sponges, and translation regulators, and they can become an important part of the regulation of gene expression. Furthermore, because of their biomedical features in body fluids, such as high abundance, conservation, and stability, circRNAs are seen as potential biomarkers for various cancers. Cervical cancer (CC) is one of the main causes of cancer-related death in women, and there have been a large number of studies that analyze circRNAs as a new object to be evaluated in CC. Therefore, this review, by understanding the role of circRNAs in CC, may create innovative strategies in the future clinical diagnosis, treatment, and prognosis of CC and promote the development of personalized and highly accurate cancer therapy.
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http://dx.doi.org/10.3389/fgene.2021.653051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027469PMC
March 2021

Evaluation of patient-reported outcome measures in intermittent self-catheterization users: A systematic review.

Arch Phys Med Rehabil 2021 Apr 8. Epub 2021 Apr 8.

School of Nursing, Tianjin Medical University, Observatory Road, Heping District, Tianjin 300070, People's Republic of China. Electronic address:

Objective: To identify patient-reported outcome measurements (PROMs) for intermittent self-catheterization (ISC) users, critically assess and summarize the quality of the measurement properties, and describe the application scenarios on each instrument.

Data Sources: PubMed, EMBASE, Medline, PsycINFO and relevant reference lists were systematically searched until December 2019 (updated May 2020).

Study Selection: Two reviewers independently identified original English language publications that evaluated the psychometric properties of specific PROMs used in ISC patients.

Data Extraction: The following data were obtained: author and publication year, content of domains/subscales, number of items, response options, constructs measured, language and information on measurement properties.

Data Synthesis: Eleven publications were deemed eligible, including 6 PROMs for measuring patients' ISC-related quality of life, self-confidence, satisfaction, difficulties, acceptance and adherence to treatment. The Intermittent Self-Catheterization Questionnaire provided the most detail, and the Intermittent Catheterization Acceptance Test could be evaluated on the most COSMIN properties.

Conclusion: Several tools are available for ISC users, but at present there is no comprehensive, concise and robust instrument with good psychometric properties. Further research on psychometric properties is needed to verify the remaining properties of existing scales and to develop novel tools for clinicians, researchers and patients.
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http://dx.doi.org/10.1016/j.apmr.2021.03.020DOI Listing
April 2021

Comprehensive Analysis of the Functions and Prognostic Value of RNA-Binding Proteins in Thyroid Cancer.

Front Oncol 2021 17;11:625007. Epub 2021 Mar 17.

The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

RNA binding proteins (RBPs) have been proved to play pivotal roles in a variety types of tumors. However, there is no convincible evidence disclosing the functions of RBPs in thyroid cancer (THCA) thoroughly and systematically. Integrated analysis of the functional and prognostic effect of RBPs help better understanding tumorigenesis and development in thyroid and may provide a novel therapeutic method for THCA. In this study, we obtained a list of human RBPs from Gerstberger database, which covered 1,542 genes encoding RBPs. Gene expression data of THCA was downloaded from The Cancer Genome Atlas (TCGA, n = 567), from which we extracted 1,491 RBPs' gene expression data. We analyzed differentially expressed RBPs using R package "limma". Based on differentially expressed RBPs, we constructed protein-protein interaction network and the GO and KEGG pathway enrichment analyses were carried out. We found six RBPs (AZGP1, IGF2BP2, MEX3A, NUDT16, NUP153, USB1) independently associated with prognosis of patients with thyroid cancer according to univariate and multivariate Cox proportional hazards regression models. The survival analysis and risk score analysis achieved good performances from this six-gene prognostic model. Nomogram was constructed to guide clinical decision in practice. Finally, biological experiments disclosed that NUP153 and USB1 can significantly impact cancer cell proliferation and migration. In conclusion, our research provided a new insight of thyroid tumorigenesis and development based on analyses of RBPs. More importantly, the six-gene model may play an important role in clinical practice in the future.
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http://dx.doi.org/10.3389/fonc.2021.625007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010172PMC
March 2021

Steroidal alkaloids from the bulbs of Fritillaria pallidiflora Schrenk and their anti-inflammatory activity.

Bioorg Chem 2021 Mar 22;112:104845. Epub 2021 Mar 22.

Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China. Electronic address:

Steroidal alkaloids (1-11), including one new 24-hydroxylated cevanine-type steroidal alkaloid, named yibeinone F (1), were isolated from the bulbs of Fritillaria pallidiflora Schrenk. Their structures were elucidated by analyses of extensive spectroscopic data and comparison of the NMR data with those reported previously, and the structures of compounds 1, 7 and 11 were further confirmed by X-ray single crystal diffraction analyses. The anti-inflammatory effects of all the isolated alkaloids were evaluated in LPS-activated RAW264.7 macrophages. Among them, compounds 9 (stenanzine) and 10 (hapepunine) showed significant inhibitory effects against LPS-induced NO production with IC values of 8.04 μM and 20.85 μM, respectively. Furthermore, compound 9 effectively inhibited the release of cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE), and suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in LPS-stimulated RAW264.7 cells. Further experiments revealed the underlying mechanism that 9 blocked LPS-induced phosphorylation and degradation of inhibitor-α of nuclear transcription factor κB (IκBα) and c-Jun N-terminal kinase (JNK) in RAW264.7 cells. Taken together, compound 9 may be a valuable candidate for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.bioorg.2021.104845DOI Listing
March 2021

BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection.

Cell 2021 Apr 16;184(8):2167-2182.e22. Epub 2021 Mar 16.

QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia. Electronic address:

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory "cytokine-storm", a cocktail of interferon gamma, interleukin 1β, and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids (hCOs) and hearts of SARS-CoV-2-infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCOs and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression, and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the Food and Drug Administration (FDA) breakthrough designated drug, apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.
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http://dx.doi.org/10.1016/j.cell.2021.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962543PMC
April 2021

Inhibition of Phosphodiesterase 5 Promotes the Aromatase-Mediated Estrogen Biosynthesis in Osteoblastic Cells by Activation of cGMP/PKG/SHP2 Pathway.

Front Endocrinol (Lausanne) 2021 12;12:636784. Epub 2021 Mar 12.

Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

Mechanical stimulation induces bone growth and remodeling by the secondary messenger, cyclic guanosine 3', 5'-monophosphate (cGMP), in osteoblasts. However, the role of cGMP in the regulation of estrogen biosynthesis, whose deficiency is a major cause of osteoporosis, remains unclear. Here, we found that the prenylated flavonoids, 3--methoxymethyl-7--benzylicaritin (13), 7--benzylicaritin (14), and 4'--methyl-8-isopentylkaempferol (15), which were synthesized using icariin analogs, promoted estrogen biosynthesis in osteoblastic UMR106 cells, with calculated EC values of 1.53, 3.45, and 10.57 µM, respectively. 14 and 15 increased the expression level of the bone specific promoter I.4-driven aromatase, the only enzyme that catalyzes estrogen formation by using androgens as substrates, in osteoblastic cells. 14 inhibited phosphodiesterase 5 (PDE5), stimulated intracellular cGMP level and promoted osteoblast cell differentiation. Inhibition of cGMP dependent-protein kinase G (PKG) abolished the stimulatory effect of 14 on estrogen biosynthesis and osteoblast cell differentiation. Further, PKG activation by 14 stimulated the activity of SHP2 (Src homology 2 domain-containing tyrosine phosphatase 2), thereby activating Src and ERK (extracellular signal-regulated kinase) signaling and increasing ERK-dependent aromatase expression in osteoblasts. Our findings reveal a previously unknown role of cGMP in the regulation of estrogen biosynthesis in the bone. These results support the further development of 14 as a PKG-activating drug to mimic the anabolic effects of mechanical stimulation of bone in the treatment of osteoporosis.
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http://dx.doi.org/10.3389/fendo.2021.636784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995890PMC
March 2021

The role of myeloid-derived suppressor cells in gastrointestinal cancer.

Cancer Commun (Lond) 2021 Mar 27. Epub 2021 Mar 27.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Centre, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518055, P. R. China.

Gastrointestinal (GI) cancer encompasses a range of malignancies that originate in the digestive system, which together represent the most common form of cancer diagnosed worldwide. However, despite numerous advances in both diagnostics and treatment, the incidence and mortality rate of GI cancer are on the rise. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that increase in number under certain pathological conditions, such as infection and inflammation, and this expansion is of particular relevance to cancer. MDSCs are heavily involved in the regulation of the immune system and act to dampen its response to tumors, favoring the escape of tumor cells from immunosurveillance and increasing both metastasis and recurrence. Several recent studies have supported the use of MDSCs as a prognostic and predictive biomarker in patients with cancer, and potentially as a novel treatment target. In the present review, the mechanisms underlying the immunosuppressive functions of MDSCs are described, and recent researches concerning the involvement of MDSCs in the progression, prognosis, and therapies of GI cancer are reviewed. The aim of this work was to present the development of novel treatments targeting MDSCs in GI cancer in the hope of improving outcomes for patients with this condition.
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http://dx.doi.org/10.1002/cac2.12156DOI Listing
March 2021

Citrullinated vimentin mediates development and progression of lung fibrosis.

Sci Transl Med 2021 Mar;13(585)

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

The mechanisms by which environmental exposures contribute to the pathogenesis of lung fibrosis are unclear. Here, we demonstrate an increase in cadmium (Cd) and carbon black (CB), common components of cigarette smoke (CS) and environmental particulate matter (PM), in lung tissue from subjects with idiopathic pulmonary fibrosis (IPF). Cd concentrations were directly proportional to citrullinated vimentin (Cit-Vim) amounts in lung tissue of subjects with IPF. Cit-Vim amounts were higher in subjects with IPF, especially smokers, which correlated with lung function and were associated with disease manifestations. Cd/CB induced the secretion of Cit-Vim in an Akt1- and peptidylarginine deiminase 2 (PAD2)-dependent manner. Cit-Vim mediated fibroblast invasion in a 3D ex vivo model of human pulmospheres that resulted in higher expression of CD26, collagen, and α-SMA. Cit-Vim activated NF-κB in a TLR4-dependent fashion and induced the production of active TGF-β1, CTGF, and IL-8 along with higher surface expression of TLR4 in lung fibroblasts. To corroborate ex vivo findings, mice treated with Cit-Vim, but not Vim, independently developed a similar pattern of fibrotic tissue remodeling, which was TLR4 dependent. Moreover, wild-type mice, but not and TLR4 mutant (MUT) mice, exposed to Cd/CB generated high amounts of Cit-Vim, in both plasma and bronchoalveolar lavage fluid, and developed lung fibrosis in a stereotypic manner. Together, these studies support a role for Cit-Vim as a damage-associated molecular pattern molecule (DAMP) that is generated by lung macrophages in response to environmental Cd/CB exposure. Furthermore, PAD2 might represent a promising target to attenuate Cd/CB-induced fibrosis.
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http://dx.doi.org/10.1126/scitranslmed.aba2927DOI Listing
March 2021

The effectiveness of Du moxibustion for chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis of randomized clinical trials.

Medicine (Baltimore) 2021 Mar;100(11):e24935

Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Background: As a common respiratory disease, Chronic Obstructive Pulmonary Disease (COPD) develops progressively. Du moxibustion can effectively treat COPD, and no adverse reactions have been reported. This research mainly evaluated the efficacy and safety of Du moxibustion in the treatment of COPD.

Methods: Seven databases (PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literatures Database (CBM), Wanfang Database (WF), Chinese Scientific Journal Database (VIP)) will be searched for all relevant eligible randomized controlled trials (RCTs) from the date of establishment to January 6, 2021. No matter whether they were blind or not, and regardless of the language and type of publication, these experiments could be included. Two authors (YRZ, ARG) will search the database respectively, extract relevant data, and use the Cochrane bias risk tool to evaluate the quality of the literature. RevMan V5.3 software will be used for data processing.

Results: The results of this research are mainly used to evaluate the efficacy and safety of Du moxibustion in the treatment of COPD.

Conclusions: This systematical review is expected to provide evidence-based and valuable suggestions for Du moxibustion in the treatment of COPD.

Study Registration Number: INPLASY202110045.
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http://dx.doi.org/10.1097/MD.0000000000024935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982187PMC
March 2021

Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity.

Gut 2021 Mar 10. Epub 2021 Mar 10.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China

Objective: Solid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC).

Design: Anti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses.

Results: A negative correlation between WNT2 CAFs and active CD8 T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades.

Conclusions: CAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.
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http://dx.doi.org/10.1136/gutjnl-2020-322924DOI Listing
March 2021

Synthetic heparan sulfate standards and machine learning facilitate the development of solid-state nanopore analysis.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3590;

The application of solid-state (SS) nanopore devices to single-molecule nucleic acid sequencing has been challenging. Thus, the early successes in applying SS nanopore devices to the more difficult class of biopolymer, glycosaminoglycans (GAGs), have been surprising, motivating us to examine the potential use of an SS nanopore to analyze synthetic heparan sulfate GAG chains of controlled composition and sequence prepared through a promising, recently developed chemoenzymatic route. A minimal representation of the nanopore data, using only signal magnitude and duration, revealed, by eye and image recognition algorithms, clear differences between the signals generated by four synthetic GAGs. By subsequent machine learning, it was possible to determine disaccharide and even monosaccharide composition of these four synthetic GAGs using as few as 500 events, corresponding to a zeptomole of sample. These data suggest that ultrasensitive GAG analysis may be possible using SS nanopore detection and well-characterized molecular training sets.
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http://dx.doi.org/10.1073/pnas.2022806118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980385PMC
March 2021

Surface-Defect-Induced and Synergetic-Effect-Enhanced NIR-II Electrochemiluminescence of Au-Ag Bimetallic Nanoclusters and Its Spectral Sensing.

Anal Chem 2021 03 8;93(11):4909-4915. Epub 2021 Mar 8.

School of Chemistry and Chemical Engineering, Shandong University, Shanda South Road #27, Jinan 250100, China.

Aqueous electrochemiluminescence (ECL) in the second near-infrared biowindow (NIR-II, 900-1700 nm) was anticipated for ECL evolution and spectral multiplexing. Herein, aqueous and monochromatic ECL with a single emission peak beyond 900 nm was achieved by employing methionine (Met)-capped Au-Ag bimetallic nanoclusters (BNCs) as luminophores and triethanolamine (TEOA) as a coreactant. The Met-capped Au-Ag BNCs with surface-defect-induced PL around 756 nm were water-soluble and synthesized via doping Met-capped Au NCs with Ag in a doping-in-growth way. By extensively exploiting the red-shifting nature of surface-defect-induced ECL to PL and the synergetic-effect-enhanced ECL of BNCs, physically surface-confined Au-Ag BNCs exhibited efficient NIR-II ECL around 906 nm in aqueous medium. A spectrum-based NIR-II ECL immunoassay around 915 nm was also achieved by immobilizing the Au-Ag BNCs onto an electrode surface via forming a sandwich immunocomplex, which could selectively determine CA125 from 5 × 10 to 1 U/mL with a detection limit of 5 × 10 U/mL (/ = 3). The combined strategy of surface-defect-induced ECL and synergetic-effect-enhanced ECL would enable promising biorelated application of NIR-II ECL.
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http://dx.doi.org/10.1021/acs.analchem.0c05187DOI Listing
March 2021

Simultaneous determination of forsythin and its major metabolites in human plasma via liquid chromatography-tandem mass spectrometry.

J Pharm Biomed Anal 2021 May 26;198:113992. Epub 2021 Feb 26.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Forsythiae suspensa is widely used in China as a traditional Chinese medicine. Forsythin is extracted from Forsythiae Fructus and has undergone phase II clinical trials as an antipyretic drug in China. The main metabolites of forsythin in human plasma are aglycone sulfate (KD-2-SOH) and aglycone glucuronide (KD-2-Glc). In the present study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the simultaneous analysis of forsythin, KD-2-Glc, and KD-2-SOH, in human plasma. After precipitating proteins with methanol, these three analytes were separated on a Gemini-C18 column along with teniposide as an internal standard. Mass spectrometry detection, under multiple reaction monitoring, was then carried out in negative mode using the Triple Quad™ 6500 LC-MS/MS system coupled with an electrospray ionization (ESI) ion source. The transitions of m/z 371.1→356.1 for forsythin, m/z 547.2→356.0 for KD-2-Glc and m/z 451.2→356.2 for KD-2-SOH were chosen to effectively maintain the balance between selectivity and sensitivity. The developed method was linear over the following concentrations in human plasma samples: 1.00-1000 ng/mL for forsythin, 2.50-2500 ng/mL for KD-2-Glc, and 5.00-5000 ng/mL for KD-2-SOH. Assays were validated and satisfied the acceptance criteria recommended by the CFDA guidance. Furthermore, this LC-MS/MS method was successfully implemented in a Phase I, first-in-human, dose-escalation pharmacokinetic study among Chinese healthy participants after single oral administration of forsythin tablets.
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http://dx.doi.org/10.1016/j.jpba.2021.113992DOI Listing
May 2021

Third-generation EGFR inhibitor HS-10296 in combination with famitinib, a multi-targeted tyrosine kinase inhibitor, exerts synergistic antitumor effects through enhanced inhibition of downstream signaling in EGFR-mutant non-small cell lung cancer cells.

Thorac Cancer 2021 Apr 3;12(8):1210-1218. Epub 2021 Mar 3.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Background: As a highly heterogeneous disease, lung cancer has a multitude of cellular components and patterns of gene expression which are not dependent on a single mutation or signaling pathway. Thus, using combined drugs to treat lung cancer may be a practical strategy.

Methods: The combined antitumor effects of HS-10296, a third-generation EGFR inhibitor targeting EGFR T790M mutation, with the multitargeted tyrosine kinase inhibitor (TKI) famitinib in non-small cell lung cancer (NSCLC) were evaluated by in vitro methods such as cell proliferation, apoptosis, angiogenesis assays, and in vivo animal efficacy studies.

Results: Famitinib strengthened the effects of HS-10296 on inhibiting proliferation and inducing apoptosis of NSCLC cells, possibly by synergistic inhibition of AKT and ERK phosphorylation. Meanwhile, HS-10296 significantly potentiated the effects of famitinib on inhibiting the proliferation and migration of HUVEC, which may be through synergistic inhibition of ERK phosphorylation in HUVEC, suggesting that HS-10296 may improve the inhibition of angiogenesis by famitinib. Moreover, combination of HS-10296 and famitinib exerted synergistic antitumor activity in NCI-H1975 and PC-9 xenograft models, and this effect may be accomplished by synergistic inhibition of phosphorylation of AKT and ERK and tumor angiogenesis in tumor tissues.

Conclusions: Collectively, our results indicate that HS-10296 and famitinib exhibit significant synergistic antitumor activity, suggesting that the third-generation EGFR inhibitor combined with VEGFR inhibitor provides a promising strategy in the treatment of EGFR-mutant NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13902DOI Listing
April 2021

Development and preliminary validation of a self-rating anxiety inventory for maintenance haemodialysis patients.

Psychol Health Med 2021 Feb 18:1-13. Epub 2021 Feb 18.

Department of Nephrology, Daping Hospital, Third Military Medical University , Chongqing, China.

This study aimed to develop a self-rating anxiety inventory for maintenance haemodialysis patients (AI-MHD) and perform preliminary validation to provide a simple, effective, and highly specific practical tool for effective anxiety disorder screening in haemodialysis patients. Based on existing general anxiety disorder screening scales and common symptoms of MHD patients as a reference and after expert discussions and preliminary validation at a single dialysis centre, a self-rating AI-MHD containing 12 items was developed. Subsequently, the AI-MHD was applied in 4 dialysis centres and compared with GAD-7 and HADS-A. Further multicentre validation showed that Cronbach's alpha for the scale was 0.918; the AI-MHD score not only significantly differed between the anxiety disorders group and the non-anxiety disorders group (p<0.001) but also correlated with GAD-7 and HADS-A scores (p<0.001). In addition, the Kaiser-Meyer-Olkin (KMO) score was 0.847, and Bartlett's test of sphericity was significant (x=849.45, p<0.001). The anxiety disorder detection rate was 93%, and the specificity was 90%, which were significantly better than the screening results using the GAD-7 and HADS-A scales in the same groups. Although there were limitations, such as the sample size and regionality, the AI-MHD showed good efficacy and reliability in rating anxiety in MHD patients.
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http://dx.doi.org/10.1080/13548506.2021.1890159DOI Listing
February 2021

Intertwined Carbon Nanotubes and Ag Nanowires Constructed by Simple Solution Blending as Sensitive and Stable Chloramphenicol Sensors.

Sensors (Basel) 2021 Feb 9;21(4). Epub 2021 Feb 9.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, China.

Chloramphenicol (CAP) is a harmful compound associated with human hematopathy and neuritis, which was widely used as a broad-spectrum antibacterial agent in agriculture and aquaculture. Therefore, it is significant to detect CAP in aquatic environments. In this work, carbon nanotubes/silver nanowires (CNTs/AgNWs) composite electrodes were fabricated as the CAP sensor. Distinguished from in situ growing or chemical bonding noble metal nanomaterials on carbon, this CNTs/AgNWs composite was formed by simple solution blending. It was demonstrated that CNTs and AgNWs both contributed to the redox reaction of CAP in dynamics, and AgNWs was beneficial in thermodynamics as well. The proposed electrochemical sensor displayed a low detection limit of up to 0.08 μM and broad linear range of 0.1-100 μM for CAP. In addition, the CNTs/AgNWs electrodes exhibited good performance characteristics of repeatability and reproducibility, and proved suitable for CAP analysis in real water samples.
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http://dx.doi.org/10.3390/s21041220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915990PMC
February 2021

Use of Triangular Silver Nanoplates as Low Potential Redox Mediators for Electrochemical Sensing.

Anal Chem 2021 02 2;93(6):3295-3300. Epub 2021 Feb 2.

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.

Redox mediators can facilitate the electrochemical communication between targets and electrodes for material characterization and investigation. To provide an alternative to the chemical-based redox mediators, herein, we present a nanoparticle-based redox mediator, i.e., the trisodium citrates (TSC)-capped triangular silver nanoplates (Tri-Ag-NP), which demonstrates an efficient oxidative process at around 0.13 V (vs Ag/AgCl) with acceptable redox reversibility by exploiting the interaction between the carbonyl group of TSC and the Ag element of Tri-Ag-NP. The TSC of Tri-Ag-NPs can be selectively replaced by thiols and enable the obtained Tri-Ag-NP with changed electrochemical redox response, which could be utilized to determine various thiols at 0.13 V, a much lowered oxidative potential than traditional redox mediators, with a similar linear response range, response slope, and limit of detection (LOD). This work proposes a surface-engineering approach to design and develop electrochemical redox probes using Ag nanoparticles with particular morphology, indicating that the interaction between the carbonyl group and Ag nanoparticles might be extended to sensing application beyond the surface-enhanced Raman scattering.
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http://dx.doi.org/10.1021/acs.analchem.0c05342DOI Listing
February 2021

Aerobic exercise improves mitochondrial function in sarcopenia mice through Sestrin2 in an AMPKα2-dependent manner.

J Gerontol A Biol Sci Med Sci 2021 Jan 29. Epub 2021 Jan 29.

Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.

Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the elderly population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that outcomes induced by sarcopenia including muscle mass and strength loss, the cross-sectional area of gastrocnemius fibre decrease, chronic inflammation and dysfunctional mitochondria increase were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signalling axis mediates the beneficial impact of exercise on sarcopenia.
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http://dx.doi.org/10.1093/gerona/glab029DOI Listing
January 2021

Acute Diallyl Disulfide Administration Prevents and Reveres Lipopolysaccharide-Induced Depression-Like Behaviors in Mice via Regulating Neuroinflammation and Oxido-Nitrosative Stress.

Inflammation 2021 Jan 29. Epub 2021 Jan 29.

Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, #32 Xi'er Duan, 1ST Ring Road, Chengdu, 610072, Sichuan, China.

Neuroinflammation and oxidative stress play critical roles in pathogenesis of depression. Diallyl disulfide (DADS), an active compound in garlic oil, has been shown to exhibit obvious anti-inflammatory and anti-oxidative activities. Preliminary evidence indicates that depression is associated with high levels of pro-inflammatory cytokines and oxidative markers, suggesting that inhibition of neuroinflammatory response and oxidative stress may be beneficial for depression interruption. Here, we investigated the antidepressant effect of DADS as well as it mechanisms in a depression-like model induced by lipopolysaccharide (LPS). Similarly to imipramine (10 mg/kg), a clinical antidepressant, DADS (40 or 80 mg/kg), which was administered 1 h before LPS treatment (pre-LPS) or 1.5 h and 23.5 h after LPS treatment (post-LPS), prevented and reversed LPS (100 μg/kg)-induced increase in immobility time in the tail suspension test (TST) and forced swim test (FST) in mice. Mechanistic studies revealed that DADS pre-treatment or post-treatment at the dose of 40 and 80 mg/kg prevented and reversed (i) LPS-induced increases in interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) levels in the hippocampus and prefrontal cortex, (ii) LPS-induced increases in contents of malondialdehyde (MDA), a parameter reflecting high levels of oxidative stress, and (iii) LPS-induced decreases in contents of GSH, a marker reflecting weakened anti-oxidative ability, in the hippocampus and prefrontal cortex in mice. These results indicate that DADS is comparable to imipramine in effectively ameliorating LPS-induced depression-like behaviors in mice, providing a potential value for DADS in prevention and/or therapy of depression.
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http://dx.doi.org/10.1007/s10753-021-01423-0DOI Listing
January 2021

Protein Hydrolysate of Silkworm Pupa Prevents Memory Impairment Induced by Oxidative Stress in Scopolamine-Induced Mice via Modulating the Cholinergic Nervous System and Antioxidant Defense System.

Prev Nutr Food Sci 2020 Dec;25(4):389-399

Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Korea.

Silkworm pupae () is an edible insect that has been reported to contain high-quality proteins, lipids, minerals, and vitamins, and to possess high antioxidant activity. However, there have been no studies on the neuroprotective effects of silkworm pupae. Therefore, we investigated a water extract of silkworm pupae with protease (WSP) as a functional and therapeutic candidate for neurodegenerative disorders. First, we evaluated the effect of WSP on oxidative stress-induced mouse hippocampal neuronal cells (HT-22 cells). Cell viability diminished by addition of glutamate but was significantly recovered by WSP treatment. Furthermore, WSP significantly decreased the release of lactate dehydrogenase and generation of intracellular reactive oxygen species in oxidative stress-induced cells. In addition, in scopolamine-treated mice, WSP attenuated memory impairment, as demonstrated in the Morris water maze and passive avoidance tests, indicating protection of neuronal cells against oxidative damage. Moreover, WSP prevented scopolamine-induced increases in acetylcholinesterase activity and decreases in choline-acetyltransferase activity. Finally, treatment with WSP enhanced the antioxidant defense system by regulating the activities of antioxidant enzymes. Overall, this study showed that WSP exerted antioxidant and memory enhancing action against oxidative stress.
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http://dx.doi.org/10.3746/pnf.2020.25.4.389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813599PMC
December 2020

High density fermentation of probiotic E. coli Nissle 1917 towards heparosan production, characterization, and modification.

Appl Microbiol Biotechnol 2021 Feb 22;105(3):1051-1062. Epub 2021 Jan 22.

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

Heparosan is a naturally occurring non-sulfated glycosaminoglycan. Heparosan serves as the substrate for chemoenzymatic synthesis of biopharmaceutically important heparan sulfate and heparin. Heparosan is biologically inert molecule, non-toxic, and non-immunogenic and these qualities of heparosan make it an ideal drug delivery vehicle. The critical-to-quality (CTQ) attributes for heparosan applications include composition of heparosan, absence of any unnatural moieties, and heparosan molecular weight size and unimodal distribution. Probiotic bacteria E. coli Nissle 1917 (EcN) is a natural producer of heparosan. The current work explores production of EcN heparosan and process parameters that may impact the heparosan CTQ attributes. Results show that EcN could be grown to high cell densities (OD 160-180) in a chemically defined media. The fermentation process is successfully scaled from 5-L to 100-L bioreactor. The chemical composition of heparosan from EcN was confirmed using nuclear magnetic resonance. Results demonstrate that heparosan molecular weight distribution may be influenced by fermentation and purification conditions. Size exclusion chromatography analysis shows that the heparosan purified from fermentation broth results in bimodal distribution, and cell-free supernatant results in unimodal distribution (average molecular weight 68,000 Da). The yield of EcN-derived heparosan was 3 g/L of cell free supernatant. We further evaluated the application of Nissle 1917 heparosan for chemical modification to prepare N-sulfo heparosan (NSH), the first intermediate precursor for heparin and heparan sulfate. KEY POINTS: • High cell density fermentation, using a chemically defined fermentation media for the growth of probiotic bacteria EcN (E. coli Nissle 1917, a natural producer of heparosan) is reported. • Process parameters towards the production of monodispersed heparosan using probiotic bacteria EcN (Nissle 1917) has been explored and discussed. • The media composition and the protocol (SOPs and batch records) have been successfully transferred to contract manufacturing facilities and industrial partners.
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http://dx.doi.org/10.1007/s00253-020-11079-9DOI Listing
February 2021

PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors.

Breast Cancer Res 2021 Jan 21;23(1):10. Epub 2021 Jan 21.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518060, China.

Background: Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed.

Methods: Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16, or separately p18, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers.

Results: Heterozygous germline or epithelium-specific deletion of Brca1 in p18- or p16-deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells.

Conclusions: Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.
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http://dx.doi.org/10.1186/s13058-021-01387-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819225PMC
January 2021

Electro-catalytic amplified sensor for determination of N-acetylcysteine in the presence of theophylline confirmed by experimental coupled theoretical investigation.

Sci Rep 2021 Jan 13;11(1):1006. Epub 2021 Jan 13.

Sen Research Group, Biochemistry Department, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus, 43100, Kütahya, Turkey.

The 1,l/-bis(2-phenylethan-1-ol)ferrocene, 1-butyl-3-methylimidazolium hexafluoro phosphate (BMPF6) and NiO-SWCNTs were used to modify carbon paste electrode (BPOFc/BMPF6/NiO-SWCNTs/CPE), which could act as an electro-catalytic tool for the analysis of N-acetylcysteine in this work. The BPOFc/BMPF6/NiO-SWCNTs/CPE with high electrical conductivity showed two completely separate signals with oxidation potentials of 432 and 970 mV for the first time that is sufficient for the determination of N-acetylcysteine in the presence of theophylline. The BPOFc/BMPF6/NiO-SWCNTs/CPE showed linear dynamic ranges of 0.02-300.0 μM and 1.0-350.0 μM with the detection limit of ~ 8.0 nM and 0.6 μM for the measurement of N-acetylcysteine and theophylline, respectively. In the second part, understanding the nature of interaction, quantum conductance modulation, electronic properties, charge density, and adsorption behavior of N-acetylcysteine on NiO-SWCNTs surface from first-principle studies through the use of theoretical investigation is vital for designing high-performance sensor materials. The N-acetylcysteine molecule was chemisorbed on the NiO-SWCNTs surface by suitable adsorption energies (- 1.102 to - 5.042 eV) and reasonable charge transfer between N-acetylcysteine and NiO-SWCNTs.
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http://dx.doi.org/10.1038/s41598-020-79872-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806823PMC
January 2021

QSAR-assisted-MMPA to expand chemical transformation space for lead optimization.

Brief Bioinform 2021 Jan 9. Epub 2021 Jan 9.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P. R. China.

Matched molecular pairs analysis (MMPA) has become a powerful tool for automatically and systematically identifying medicinal chemistry transformations from compound/property datasets. However, accurate determination of matched molecular pair (MMP) transformations largely depend on the size and quality of existing experimental data. Lack of high-quality experimental data heavily hampers the extraction of more effective medicinal chemistry knowledge. Here, we developed a new strategy called quantitative structure-activity relationship (QSAR)-assisted-MMPA to expand the number of chemical transformations and took the logD7.4 property endpoint as an example to demonstrate the reliability of the new method. A reliable logD7.4 consensus prediction model was firstly established, and its applicability domain was strictly assessed. By applying the reliable logD7.4 prediction model to screen two chemical databases, we obtained more high-quality logD7.4 data by defining a strict applicability domain threshold. Then, MMPA was performed on the predicted data and experimental data to derive more chemical rules. To validate the reliability of the chemical rules, we compared the magnitude and directionality of the property changes of the predicted rules with those of the measured rules. Then, we compared the novel chemical rules generated by our proposed approach with the published chemical rules, and found that the magnitude and directionality of the property changes were consistent, indicating that the proposed QSAR-assisted-MMPA approach has the potential to enrich the collection of rule types or even identify completely novel rules. Finally, we found that the number of the MMP rules derived from the experimental data could be amplified by the predicted data, which is helpful for us to analyze the medicinal chemical rules in local chemical environment. In summary, the proposed QSAR-assisted-MMPA approach could be regarded as a very promising strategy to expand the chemical transformation space for lead optimization, especially when no enough experimental data can support MMPA.
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http://dx.doi.org/10.1093/bib/bbaa374DOI Listing
January 2021

Bovine serum albumin-stabilized silver nanoclusters with anodic electrochemiluminescence peak at 904 nm in aqueous medium and applications in spectrum-resolved multiplexing immunoassay.

Biosens Bioelectron 2021 Mar 28;176:112934. Epub 2020 Dec 28.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan, 250014, PR China. Electronic address:

Near-infrared electrochemiluminescence (NIR ECL) luminophores are strongly anticipated in ECL bioimaging and spectrum-resolved multiplexing assays. Herein, bovine serum albumin-stabilized Ag nanoclusters (BSA-Ag NCs) are demonstrated promising NIR ECL performance, exhibiting strong anodic ECL spectrum peak at 904 nm in aqueous medium. The ECL intensity of BSA-Ag NCs-triethanolamine system was enhanced 3.2 times by adding TiO nanoparticles as co-reactant accelerator. In a spectrum-resolved triplex-color ECL multiplexing immunoassay, CdSe NCs, CdTe NCs and BSA-Ag NCs were used as the ECL tags, carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9) and cardiac troponin I (cTnI) were chosen as model analytes. The ECL peaks of three antigen-NCs pairs were simultaneously measured via one ECL potential scan. The composite of carbon nanotubes-TiO nanoparticles-chitosan was served as the conductivity and co-reactant accelerators, enhancing the ECL intensity by 16 folds. With the integral intensity over the ECL peaks as the analytical signal to improve further the signal-to-noise ratio, the limits of detection were 0.035 mU mL for CA125, 0.087 mU mL for CA19-9, and 0.016 pg mL for cTnI, respectively.
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http://dx.doi.org/10.1016/j.bios.2020.112934DOI Listing
March 2021

Identification of the antidepressive properties of C1, a specific inhibitor of Skp2, in mice.

Behav Pharmacol 2021 Jan 6;Publish Ahead of Print. Epub 2021 Jan 6.

Department of Pharmacy, The Seventh People's Hospital of Changzhou, Changzhou Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou Department of Pharmacology, School of Pharmacy, Nantong University Invasive Technology Department, Nantong First People's Hospital, the Second Affiliated Hospital of Nantong University Department of Respiratory Medicine, Nantong First People's Hospital, the Second Affiliated Hospital of Nantong University, Nantong Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

We have reported that SMIP004, an inhibitor of S-phase kinase-associated protein 2 (Skp2), displays antidepressant-like activities in stress-naïve and chronically stressed mice. Here, we investigated the antidepressant-like effect of C1, another inhibitor of Skp2, in mouse models following acute or chronic drug administration at different doses and treatment times by using the tail suspension test (TST), forced swimming test (FST), and social interaction test (SIT). The time- and dose-dependent results showed that the antidepressant-like effect of C1 occurred 8 days after the drug treatment, and C1 produced antidepressant-like activities at the dose of 5 and 10 but not 1 mg/kg in male or female mice. C1 administration (5 mg/kg) also induced antidepressant-like effects in stress-naïve mice in a three-times administration mode within 24 h (24, 5, and 1 h before the test) but not in an acute administration mode (1 h before the test). The C1 and fluoxetine co-administration produced additive effect on depression-like behaviors in stress-naïve mice. The antidepressant-like effect of C1 was not associated with the change in locomotor activity, as no increased locomotor activity was observed in different treatment modes. Furthermore, the long-term C1 treatment (5 mg/kg) was found to ameliorate the depression-like behaviors in chronic social defeat stress-exposed mice, suggesting that C1 can produce antidepressant-like actions in stress conditions. Since C1 is a specific inhibitor of Skp2, our results demonstrate that inhibition of Skp2 might be a potential strategy for the treatment of depression, and Skp2 may be potential target for the development of novel antidepressants.
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http://dx.doi.org/10.1097/FBP.0000000000000604DOI Listing
January 2021

Enhanced Near-Infrared Electrochemiluminescence from Trinary Ag-In-S to Multinary Ag-Ga-In-S Nanocrystals via Doping-in-Growth and Its Immunosensing Applications.

Anal Chem 2021 02 8;93(4):2160-2165. Epub 2021 Jan 8.

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.

Screening toxic-element-free and biocompatible electrochemiluminophores was crucial for electrochemiluminescence (ECL) evolution. Herein, l-glutathione (GSH)-capped Ag-Ga-In-S (AGIS) nanocrystals (NCs) were prepared by doping Ag-In-S (AIS) NCs in a doping-in-growth way and utilized as a model for both ECL modulating and developing multinary NC-based electrochemiluminophores with enhanced ECL performance than trinary NCs. AGIS NCs not only primarily preserved the morphology, size, phase structure, and water monodisperse characteristics of AIS NCs with broadened band gap but also demonstrated obviously enhanced oxidative-reduction ECL than AIS NCs. Importantly, ECL of AGIS NCs was located at the near-infrared region with a maximum emission wavelength of 744 nm and could be utilized for an ECL immunoassay with human prostate-specific antigen (PSA) as a model, which exhibited a linearity range from 0.05 pg/mL to 1.0 ng/mL and a low limit of detection of 0.01 pg/mL (S/N = 3). This work provided a promising alternative to the traditional binary NCs for developing toxic-element-free and biocompatible electrochemiluminophores with efficient near-infrared ECL.
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http://dx.doi.org/10.1021/acs.analchem.0c03975DOI Listing
February 2021

Identification of the antidepressive properties of C1, a specific inhibitor of Skp2, in mice.

Behav Pharmacol 2021 Feb;32(1):62-72

Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

We have reported that SMIP004, an inhibitor of S-phase kinase-associated protein 2 (Skp2), displays antidepressant-like activities in stress-naïve and chronically stressed mice. Here, we investigated the antidepressant-like effect of C1, another inhibitor of Skp2, in mouse models following acute or chronic drug administration at different doses and treatment times by using the tail suspension test (TST), forced swimming test (FST), and social interaction test (SIT). The time- and dose-dependent results showed that the antidepressant-like effect of C1 occurred 8 days after the drug treatment, and C1 produced antidepressant-like activities at the dose of 5 and 10 but not 1 mg/kg in male or female mice. C1 administration (5 mg/kg) also induced antidepressant-like effects in stress-naïve mice in a three-times administration mode within 24 h (24, 5, and 1 h before the test) but not in an acute administration mode (1 h before the test). The C1 and fluoxetine co-administration produced additive effect on depression-like behaviors in stress-naïve mice. The antidepressant-like effect of C1 was not associated with the change in locomotor activity, as no increased locomotor activity was observed in different treatment modes. Furthermore, the long-term C1 treatment (5 mg/kg) was found to ameliorate the depression-like behaviors in chronic social defeat stress-exposed mice, suggesting that C1 can produce antidepressant-like actions in stress conditions. Since C1 is a specific inhibitor of Skp2, our results demonstrate that inhibition of Skp2 might be a potential strategy for the treatment of depression, and Skp2 may be potential target for the development of novel antidepressants.
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http://dx.doi.org/10.1097/FBP.0000000000000604DOI Listing
February 2021

Primary malignant melanomas of the female lower genital tract: clinicopathological characteristics and management.

Am J Cancer Res 2020 1;10(12):4017-4037. Epub 2020 Dec 1.

Department of Obstetrics and Gynecology, Second Hospital of Jilin University Changchun, Jilin, P. R. China.

The female lower genital tract melanomas mainly include vulvar, vaginal and cervical melanoma. There is little clinical data on the melanomas thus making them highly lethal with their prognosis being worse than for cutaneous melanoma and other gynecological malignancies. Surgery is still the primary treatment for gynecological melanomas with wide local resection (WLE) of tumors with adequate margins being preferred for early-stage vulvar melanoma while complete resection of the primary tumor is the standard treatment for early-stage cervical and vaginal melanoma. Sentinel lymph node biopsy seems to avoid unnecessary complete regional lymphadenectomy. However, it should be chosen cautiously. Recently discovered molecular changes have provided new hopes for effective systemic treatment of female genital tract melanomas. In this review, we summarize the pathogenesis and clinicopathological characteristics of these rare melanomas with particular emphasis on new therapies and clinical management methods that may affect prognosis. The review aims to provide a viable direction for clinicians to diagnose and treat female lower genital tract melanomas.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783736PMC
December 2020

Temporal quantum noise reduction acquired by an electron-multiplying charge-coupled-device camera.

Opt Express 2020 Dec;28(25):37538-37545

Electron-multiplying charge-coupled-device cameras (EMCCDs) have been used to observe quantum noise reductions in beams of light in the transverse spatial degree of freedom. For the quantum noise reduction in the temporal domain, 'bucket detectors,' usually composed of photodiodes with operational amplifiers, are used to register the intensity fluctuations in beams of light within the detectors' bandwidth. Here, we report on measurements of the temporal quantum noise reduction in bright twin beams using an EMCCD camera. The four-wave mixing process in an atomic rubidium vapor cell is used to generate the bright twin beams of light. We observe ∼ 25% of temporal quantum noise reduction with respect to the shot-noise limit in images captured by the EMCCD camera. The temporal images captured by our technique are potentially important in obtaining dynamical information on evolving systems.
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http://dx.doi.org/10.1364/OE.408795DOI Listing
December 2020