Publications by authors named "Yingying Sun"

146 Publications

Scalable synthesis of NaMVF (M = Mn, Fe, and Co) as high-performance cathode materials for sodium-ion batteries.

Chem Commun (Camb) 2021 Oct 15. Epub 2021 Oct 15.

Jiangsu Key Laboratory of New Power Batteries, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.

We demonstrate an economical polytetrafluoroethylene-assisted fluorination method to synthesize three binary sodium-rich fluorides NaMVF (M = Mn, Fe, and Co). The optimal NaFeVF cathode delivers a high reversible capacity of 146.5 mA h g based on active Fe/Fe and V/V redox reactions in sodium-ion batteries. A steady cycling performance with a high capacity retention of 95% over 200 cycles is achieved owing to the negligible structural change during Na insertion/extraction.
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http://dx.doi.org/10.1039/d1cc04449dDOI Listing
October 2021

Lysyl hydroxylase 1 (LH1) deficiency promotes angiotensin II (Ang II)-induced dissecting abdominal aortic aneurysm.

Theranostics 2021 21;11(19):9587-9604. Epub 2021 Sep 21.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice. Furthermore, targeting thrombospondin-1 with TAX2 strongly inhibited the proinflammatory process, matrix metalloproteinase (MMP) activity and vascular smooth muscle cells (VSMCs) apoptosis, ultimately decreasing the incidence of dissecting AAA. Restoration of LH1 protein expression in LH1-deficient mice by intraperitoneal injection of an adeno-associated virus normalized thrombospondin-1 levels, subsequently alleviating dissecting AAA formation and preserving aortic structure and function. Consistently, in human AAA specimens, decreased LH1 expression was associated with increased thrombospondin-1 levels. LH1 deficiency contributes to dissecting AAA pathogenesis, at least in part, by upregulating thrombospondin-1 expression, which subsequently enables proinflammatory processes, MMP activation and VSMCs apoptosis. Our study provides evidence that LH1 is a potential critical therapeutic target for AAA.
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http://dx.doi.org/10.7150/thno.65277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490513PMC
September 2021

Expression and Clinical Significance of the NCAPH, AGGF1, and FOXC2 Proteins in Serous Ovarian Cancer.

Cancer Manag Res 2021 21;13:7253-7262. Epub 2021 Sep 21.

Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.

Purpose: Recurrence and metastasis are the most common causes of high mortality rates in patients with serous ovarian cancer (SOC). Non-structural maintenance of chromosomes (non-SMC) condensin I complex subunit H (NCAPH) is a newly identified essential oncoprotein whose function in SOC pathogenesis has not been reported yet. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an effective promoter of angiogenesis in humans, leading to cancer cell infiltration and progression. Forkhead box C2 (FOXC2) plays a pivotal role in epithelial-to-mesenchymal transition (EMT). The present study analyzed the correlations among the expressions of these three proteins and their relationships with the clinicopathological characteristics and survival of patients with SOC.

Patients And Methods: The expressions of NCAPH, AGGF1, and FOXC2 were detected by the immunohistochemical examination of 153 SOC tissue samples and 30 serous ovarian cystadenoma tissue samples. Clinicopathologic and follow-up data of the patients were collected.

Results: The expressions of NCAPH, AGGF1, and FOXC2 were remarkably higher in the SOC tissue samples than in the serous ovarian cystadenoma tissue samples. The protein expressions were positively correlated with the histological tumor grade, the International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and intraperitoneal implantation, but were negatively correlated with the overall survival (OS). Moreover, multivariate analysis showed that the NCAPH, AGGF1, and FOXC2 expressions, FIGO stage, and histological tumor grade were independent adverse prognostic factors for OS in patients with SOC.

Conclusion: The results of this study show that the expressions of NCAPH, AGGF1, and FOXC2 are promising biomarkers and possible therapeutic targets in patients with SOC.
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http://dx.doi.org/10.2147/CMAR.S329688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464304PMC
September 2021

Electrochemiluminescent determination of prostate-specific antigen using [email protected](MoS/GO/o-MWNTs) nanohybrids as co-reaction accelerator and hyperbranched hybridization chain reaction for signal amplification.

Mikrochim Acta 2021 08 18;188(9):300. Epub 2021 Aug 18.

Department of Chemistry, Shenyang Medical College, Shenyang, 110034, China.

Three-dimensional flowerlike [email protected](MoS/GO/o-MWNTs) nanohybrids (abbreviated as AMGMs) were synthesized and then introduced into an electrochemiluminescence (ECL) system as a new co-reaction accelerator for the ultrasensitive prostate-specific antigen (PSA). The AMGMs not only served as a substrate with good conductivity and a large specific surface area for loading abundant primary antibodies but also acted as an effective co-reaction accelerator; the co-reaction accelerator could interact with a co-reactant rather than the luminophore to boost the generation of free radical intermediates, thereby producing abundant excited states of luminophores to amplify the ECL signal response. Additionally, an anticipated signal amplification strategy based on the hybridization chain reaction (HCR) was developed by gathering a large amount of a DNA initiator on gold nanoparticles. These gathered DNA initiators could generate multiple DNA concatemers and attach more signal molecules, which resulted in outstanding exponential signal amplification. Consequently, the ECL immunosensor demonstrated high sensitivity, with a linear range from 0.1 pg mL to 50 ng mL and a detection limit of 0.028 pg mL. In addition, the immunosensor displayed excellent stability and selectivity. It was evaluated by analyzing human serum sample. The recovery obtained was 98.80-112.00% and the RSD was 1.73-3.12%, indicating the immunosensor could be applied to the simultaneous detection of PSA in human serum samples. Graphical abstract.
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http://dx.doi.org/10.1007/s00604-021-04957-0DOI Listing
August 2021

Determining Diagnostic Criteria of Unexplained Recurrent Implantation Failure: A Retrospective Study of Two Three or More Implantation Failure.

Front Endocrinol (Lausanne) 2021 22;12:619437. Epub 2021 Jul 22.

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The definition of recurrent implantation failure (RIF) differs clinically, one of the most controversial diagnostic criteria is the number of failed treatment cycles. We tried to investigate whether the two implantation failure could be included in the diagnostic criteria of RIF.

Methods: A retrospective analysis of the clinical data of patients (N=1518) aged under 40 years with two or more implantation failure, recruited from the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2019.

Results: After adjusting for confounding factors by using binary logistic regression, the results showed that partial general information and: distribution of associated factors were significant differences such as maternal age (=1.054, =0.001), type of cycle (=2.040, <0.001), stage of embryos development (=0.287, <0.001), number of embryos transferred (=0.184, <0.001), female factor (tubal pathology) (=0.432, =0.031) and male factor (=1.734, =0.002) between the groups with two and three or more unexplained implantation failure. And further explored whether these differential factors had a significant negative impact on pregnancy outcome, the results showed that: for patients who had three unexplained implantation failure, in the fourth cycle of ET, the live birth rate decreased significantly with age (=0.921, <0.001), and the live birth rate of blastocyst transfer was significantly higher than that of cleavage embryo transfer (=1.826, =0.007). At their first assisted pregnancy treatment after the diagnosis of RIF according to these two different definitions, there were no significant difference in the biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate and abortion rate (>0.05), but the live birth rate (35.64% 42.95%, =0.004) was significantly different. According to the definition of 'two or more failed treatment cycles', the live birth rate of the first ET treatment after RIF diagnosis was significantly lower than that of patients according to the definition of 'three or more failed treatment cycles'.

Conclusion: For patients with unexplained recurrent implantation failure, two implantation failure cannot be included in the diagnostic criteria of RIF. This study supports the generally accepted definition of three or more failed treatment cycles for RIF.
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http://dx.doi.org/10.3389/fendo.2021.619437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339466PMC
July 2021

Molecular Imaging, How Close to Clinical Precision Medicine in Lung, Brain, Prostate and Breast Cancers.

Mol Imaging Biol 2021 Jul 16. Epub 2021 Jul 16.

NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, 766 Xiangan N street, Harbin, 150028, Heilongjiang, China.

Precision medicine is playing a pivotal role in strategies of cancer therapy. Unlike conventional one-size-fits-all chemotherapy or radiotherapy modalities, precision medicine could customize an individual treatment plan for cancer patients to acquire superior efficacy, while minimizing side effects. Precision medicine in cancer therapy relies on precise and timely tumor biological information. Traditional tissue biopsies, however, are often inadequate in meeting this requirement due to cancer heterogeneity, poor tolerance, and invasiveness. Molecular imaging could detect tumor biology characterization in a noninvasive and visual manner, and provide information about therapeutic targets, treatment response, and pharmacodynamic evaluation. This summates to significant value in guiding cancer precision medicine in aspects of patient screening, treatment monitoring, and estimating prognoses. Although growing clinical evidences support the further application of molecular imaging in precision medicine of cancer, some challenges remain. In this review, we briefly summarize and discuss representative clinical trials of molecular imaging in improving precision medicine of cancer patients, aiming to provide useful references for facilitating further clinical translation of molecular imaging to precision medicine of cancers.
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http://dx.doi.org/10.1007/s11307-021-01631-yDOI Listing
July 2021

Organic Cation Transporters are Involved in Fluoxetine Transport Across the Blood-Brain Barrier in Vivo and in Vitro.

Curr Drug Deliv 2021 Jul 8. Epub 2021 Jul 8.

Zhejiang Key Laboratory of Neuropsychiatric Drug Research, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), No.182, Tianmu Shan Road, 310013 Hangzhou, China.

Background: The research and development of drugs for the treatment of central nervous system diseases faces many challenges at present. One of the most important questions to be answered is, how does the drug cross the blood-brain barrier to get to the target site for pharmacological action. Fluoxetine is widely used in clinical antidepressant therapy. However, the mechanism by which fluoxetine passes through the BBB also remains unclear. Under physiological pH conditions, fluoxetine is an organic cation with a relatively small molecular weight (<500), which is in line with the substrate characteristics of organic cation transporters (OCTs). Therefore, this study aimed to investigate the interaction of fluoxetine with OCTs at the BBB and BBB-associated efflux transporters. This is of great significance for fluoxetine to better treat depression. Moreover, it can provide a theoretical basis for clinical drug combinations.

Methods: In vitro BBB model was developed using human brain microvascular endothelial cells (hCMEC/D3), and the cellular accumulation was tested in the presence or absence of transporter inhibitors. In addition, an in vivo trial was performed in rats to investigate the effect of OCTs on the distribution of fluoxetine in the brain tissue. Fluoxetine concentration was determined by a validated UPLC-MS/MS method.

Results: The results showed that amantadine (an OCT1/2 inhibitor) and prazosin (an OCT1/3 inhibitor) significantly decreased the cellular accumulation of fluoxetine (P <.001). Moreover, we found that N-methylnicotinamide (an OCT2 inhibitor) significantly inhibited the cellular uptake of 100 and 500 ng/mL fluoxetine (P <.01 and P <.05 respectively). In contrast, corticosterone (an OCT3 inhibitor) only significantly inhibited the cellular uptake of 1000 ng/mL fluoxetine (P <.05). The P-glycoprotein (P-gp) inhibitor, verapamil, and the multidrug resistance resistance-associated proteins (MRPs) inhibitor, MK571, significantly decreased the cellular uptake of fluoxetine. However, intracellular accumulation of fluoxetine was not significantly changed when fluoxetine was incubated with the breast cancer resistance protein (BCRP) inhibitor Ko143. Furthermore, in vivo experiments proved that corticosterone and prazosin significantly inhibited the brain-plasma ratio of fluoxetine at 5.5 h and 12 h, respectively.

Conclusion: OCTs might play a significant role in the transport of fluoxetine across the BBB. In addition, P-gp, BCRP, and MRPs seemed not to mediate the efflux transport of fluoxetine.
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http://dx.doi.org/10.2174/1567201818666210708122326DOI Listing
July 2021

A Hyperthermophilic Argonaute From With Specificity on Guide Binding Pattern.

Front Microbiol 2021 9;12:654345. Epub 2021 Jun 9.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Argonaute proteins (Agos) from thermophilic archaea are involved in several important processes, such as host defense and DNA replication. The catalytic mechanism of Ago from different microbes with great diversity and genome editing potential is attracting increasing attention. Here, we describe an Argonaute from hyperthermophilic (Ago), with a typical DNA-guided DNA endonuclease activity but adopted with only a short guide 15-20 nt length rather than a broad guide selectivity for reported Agos. Ago performed the precise cleavage of phosphodiester bonds between 10 and 11 nt on the target strand (counting from the guide strand) guided strictly by 5'-phosphorylated DNA at temperatures ranging from 75 to 99°C. The cleavage activity was regulated by the divalent cations Mn, Mg, Co, and Ni. In addition, Ago possesses guide/target mismatch tolerance in the seed region but is sensitive to mismatches in the 3'-guide region. Notably, the EMSA assay revealed that the Ago-guide-target ternary complex exhibited a stronger binding affinity for short 15 and 16 nt guide DNAs than longer guides. Moreover, we performed structural modeling analyses that implied the unique PAZ domain of Ago for 3'-guide recognition and binding to affect guide length specificity. This study broadens our understanding of thermophilic Agos and paves the way for their use in DNA manipulation.
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http://dx.doi.org/10.3389/fmicb.2021.654345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248672PMC
June 2021

Parameter Design and Performance Evaluation of a Large-Swath and High-Resolution Space Camera.

Sensors (Basel) 2021 Jun 15;21(12). Epub 2021 Jun 15.

Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083, China.

A rotary-scan space camera with an area sensor can achieve large width and high-resolution imaging. Designing system parameters properly is important for the application of the rotary-scan space camera. We model the swath, resolution, and overlap rate between frames for such a camera. An optimum algorithm combining the linear weighting method and the Monte Carlo method for system parameter design is proposed based on the model. Then, the performance of the designed system is evaluated using the grid point method. The designed systems can achieve swaths of more than 1000 km and less than 1 m resolution without leakage during the imaging. In the evaluation, the designed system can cover 82.13% of the observation region at the height of 500 km in 6.5 min, and the average repeated observation frequency is 3.26 times per 118 s. The design method is simple and effective in the initial design of the rotary-scan space camera's system parameters. The system designed can provide "no-leakage and wide coverage by quick scan" and "high-frequency repeated observation over a long visibility period." This will greatly improve earth observation ability in wide-area search and rescue missions.
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http://dx.doi.org/10.3390/s21124106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232262PMC
June 2021

Effects of dezocine on PAED scale and Ramsay sedation scores in patients undergoing NUSS procedure.

Am J Transl Res 2021 15;13(5):5468-5475. Epub 2021 May 15.

Anhui Provincial Children's Hospital Hefei, Anhui Province, China.

Objective: To investigate the effects of dezocine on pediatric anesthesia emergence delirium (PAED) and Ramsay sedation scores in patients undergoing Nuss procedures (minimally invasive surgery for repairing pectus excavatum).

Methods: Altogether, 100 patients with pectus excavatum who underwent Nuss procedures in our hospital were selected and randomly divided into group A (n=50) and group B (n=50). General anesthesia was carried out for each patient, with an anaesthetic of sufentanil for group A, and dezocine plus sufentanil for group B. The visual analogue scale (VAS) score and Ramsay sedation score were recorded at extubation (T0), 10 min after extubation (T1), 20 min after extubation (T2), 30 min after extubation (T3) and 60 min after extubation (T4) for assessment of pain intensity and sedative effect; PAED scale score was applied to observe the emergence delirium at awakening, 15 min after awakening and 30 min after awakening. Quality of recovery-15 (QoR-15) scale score was used to evaluate the quality of early rehabilitation 1 d after operation and 2 d after operation. The occurrence of adverse reactions was recorded.

Results: The VAS scores at T0, T1, T2, T3 and T4 in group B were lower than those in group A, and there was statistical significance between group A and group B (P<0.001). VAS scores at T1, T2 and T3 were lower than those recorded at T0 in both groups (P<0.01), while no significant difference was noted at other time points (P>0.05). Ramsay sedation scores were increased at T0, T1, T2, T3 and T4 in group B in comparison to that in group A (all P<0.001), while the scores recorded at T4 in group A and T3 and T4 in group B were increased compared with those recorded at T0 (all P<0.01), and there was no significant difference at other time points (all P>0.05). Compared with group A, PAED scores in group B were downregulated at each time point after wakening up (all P<0.01), while QoR-15 scores in group B were increased at 1 d and 2 d after surgery (all P<0.05); there was no significant difference in adverse reactions between the two groups (all P>0.05).

Conclusion: Sufentanil combined with dezocine is efficacious in general analgesia and sedation, which can reduce emergence agitation, improves the quality of rehabilitation and is relatively safe for patients undergoing minimally invasive repairing of pectus excavatum.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205843PMC
May 2021

Biogeochemical Mobility of Contaminants from a Replica Radioactive Waste Trench in Response to Rainfall-Induced Redox Oscillations.

Environ Sci Technol 2021 07 10;55(13):8793-8805. Epub 2021 Jun 10.

UNSW Water Research Centre and School of Civil and Environmental Engineering, The University of New South Wales, Sydney 2052, Australia.

Results of investigations into factors influencing contaminant mobility in a replica trench located adjacent to a legacy radioactive waste site are presented in this study. The trench was filled with nonhazardous iron- and organic matter (OM)-rich components, as well as three contaminant analogues strontium, cesium, and neodymium to examine contaminant behavior. Imposed redox/water-level oscillations, where oxygen-laden rainwater was added to the anoxic trench, resulted in marked biogeochemical changes including the removal of aqueous Fe(II) and circulation of dissolved carbon, along with shifts to microbial communities involved in cycling iron (, ) and methane generation (, ). Contaminant mobility depended upon element speciation and rainfall event intensity. Strontium remained mobile, being readily translocated under hydrological perturbations. Strong ion-exchange reactions and structural incorporation into double-layer clay minerals were likely responsible for greater retention of Cs, which, along with Sr, was unaffected by redox oscillations. Neodymium was initially immobilized within the anoxic trenches, due to either secondary mineral (phosphate) precipitation or via the chemisorption of organic- and carbonate-Nd complexes onto variably charged solid phases. Oxic rainwater intrusions altered Nd mobility via competing effects. Oxidation of Fe(II) led to partial retention of Nd within highly sorbing Fe(III)/OM phases, whereas pH decreases associated with rainwater influxes resulted in a release of adsorbed Nd to solution with both pH and OM presumed to be the key factors controlling Nd attenuation. Collectively, the behavior of simulated contaminants within this replica trench provided unique insights into trench water biogeochemistry and contaminant cycling in a redox oscillatory environment.
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http://dx.doi.org/10.1021/acs.est.1c01604DOI Listing
July 2021

A functional variant of the long noncoding RNA AL110200 is associated with the risk of ischaemic stroke recurrence.

Eur J Neurol 2021 08 1;28(8):2708-2715. Epub 2021 Jun 1.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background And Purpose: This study aimed to test the hypothesis that long noncoding RNA (lncRNA) AL110200 exerts a proinflammatory effect on atherosclerosis and that the variant rs901681 contributes to ischaemic stroke incidence and recurrence.

Methods: The expression of AL110200 was analyzed in THP-1 cells treated with oxidized low-density lipoprotein and in human peripheral blood in a coronary heart disease and control population to determine the role of AL110200 in atherosclerosis. The effect of AL110200 on cell adhesion and invasion was tested. The plasma level of leukotriene B4 and rs901681 genotype distribution were assessed in 220 participants. In 1004 ischaemic stroke patients and 1434 controls, the association between rs901681 and stroke incidence was analyzed by logistic regression, and the association of rs901681 and stroke prognosis was analyzed using Kaplan-Meier analysis and the Cox proportional hazards model.

Results: Increased expression of AL110200 was observed in THP-1 cells under oxidized low-density lipoprotein treatment. Knockdown of AL110200 reduced the adhesive and invasive ability of THP-1 cells. AL110200 expression in peripheral blood was significantly higher in the coronary heart disease group than in the controls. The GG genotype of rs901681 is associated with reduced plasma leukotriene B4. In the ischaemic stroke population, rs901681 was not associated with ischaemic stroke incidence (p = 0.686). Patients carrying rs901681 GG had a lower risk for stroke recurrence at age ≥60 years (p = 0.001), cardiovascular stroke death (p = 0.022) and all-cause mortality (p = 0.034) in the all-age group.

Conclusions: AL110200 might exert a proinflammatory effect on atherosclerosis, and the variant rs901681 might be a strong predictor of stroke prognosis in ischaemic stroke patients.
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http://dx.doi.org/10.1111/ene.14895DOI Listing
August 2021

Synthesis and biological evaluation of 17-cyanopyridine derivatives of pregnenolone as potential anti-prostate cancer agents.

Steroids 2021 07 24;171:108841. Epub 2021 Apr 24.

Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China. Electronic address:

A series of new 17-cyanopyridine derivatives of pregnenolone have been synthesized, and their anti-proliferative activities against different human cancer cell lines were tested. The extensive structure-activity relationship (SAR) data suggested that the introduction of 2-amino-4-aryl-3-cyanopyridine to the D ring of pregnenolone may increase the anti-cancer activity. Among the products, the most potent compound 4j exhibited good growth inhibition against all the tested cells especially for PC- 3 cells with an IC value of 2.0 μM. Further mechanistic studies showed that 4j inhibited the formation of cell colonies and migration, increased the level of reactive oxygen species (ROS) in PC-3 cells in a concentration-dependent manner, and induced necroptosis through the phosphorylation of receptor interacting protein 1/3 (P-RIP1/3) and phosphorylation of mixed lineage kinase domain-like protein (P-MLKL) pathway. The 17-pregnenolone cyanopyridine derivatives hold promising potential as anti-proliferative agents, and the most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity.
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http://dx.doi.org/10.1016/j.steroids.2021.108841DOI Listing
July 2021

Simultaneous SERS detection of illegal food additives rhodamine B and basic orange II based on Au nanorod-incorporated melamine foam.

Food Chem 2021 Apr 3;357:129741. Epub 2021 Apr 3.

Testing Innovation Research Center, Centre Testing International Group Co Ltd, Shenzhen 518000, China.

In food safety assessment, surface-enhanced Raman spectroscopy (SERS) is a novel detection method with the advantages of being fast, easy, and of high sensitivity. However, many SERS substrate synthesis methods are complex, and there are only a few studies on the simultaneous detection of multiple substances. In this study, a new, simple, low-cost SERS substrate was synthesised for the first time to simultaneously detect illegal food additives rhodamine B and basic orange II in chilli products. A lightweight, porous, and low-cost material of melamine foam (MF) was employed as the SERS synthesis template. The substrate's SERS effect on, and sensitivity to, rhodamine B and basic orange II were demonstrated. The molecular vibration and SERS enhancement mechanisms of the two target molecules were analysed by density functional theory (DFT) calculations. The results reveal that this fabricated substrate has great application potential for the supervision and testing industry.
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http://dx.doi.org/10.1016/j.foodchem.2021.129741DOI Listing
April 2021

Protective effect of selenomethionine on T-2 toxin-induced liver injury in New Zealand rabbits.

BMC Vet Res 2021 Apr 9;17(1):153. Epub 2021 Apr 9.

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471000, Henan, China.

Background: T-2 toxin is a mycotoxin produced by Fusarium species that is highly toxic to animals. Recent studies have indicated that Selenomethionine (SeMet) have protective effect against mycotoxins-induced toxicity. The aim of the present study was to investigate the protective effect of SeMet on T-2-toxin-induced liver injury in rabbit and explore its molecular mechanism. Fifty rabbits (30 d, 0.5 ± 0.1 kg) were randomly divided into 5 groups: control group, T-2 toxin group, low, medium and high dose SeMet treatment group. The SeMet-treated group was orally pretreated with SeMet (containing selenium 0.2 mg/kg, 0.4 mg/kg and 0.6 mg/kg) for 21 days. On the 17th day, T-2 toxin group and SeMet-treated group were orally administered with T-2 toxin (0.4 mg/kg body weight) for 5 consecutive days.

Results: The results showed that low-dose SeMet significantly improved T-2 toxin-induced liver injury. We found that low-dose SeMet can reduce the level of oxidative stress and the number of hepatocyte apoptosis. Moreover, the levels of Bax, caspase-3 and caspase-9 were significantly reduced and the levels of Bcl-2 were increased.

Conclusions: Therefore, we confirmed that low-dose SeMet may protect rabbit hepatocytes from T-2 toxin by inhibiting the mitochondrial-caspase apoptosis pathway.
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http://dx.doi.org/10.1186/s12917-021-02866-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033731PMC
April 2021

Upregulated expression of leukocyte immunoglobulin-like receptor A3 in patients with severe aplastic anemia.

Exp Ther Med 2021 Apr 11;21(4):346. Epub 2021 Feb 11.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Severe aplastic anemia (SAA) is a rare and potentially life-threatening disease characterized by pancytopenia and bone marrow (BM) hypoplasia. In a previous study by our group, increased expression of leukocyte immunoglobulin-like receptors A (LILRA), LILRA3 in myeloid dendritic cells (mDCs) and LILRA5 in CD34 cells in SAA was detected using proteomics techniques, highlighting their potential role in disease pathogenesis. In the present study, the expression of LILRA1-6 mRNA was assessed in the BM mononuclear cells of patients with SAA using reverse transcription-quantitative (RT-q)PCR. The expression of homogenic LILRA3 and LILRA5 isoform on mDCs, as well as CD34, CD3CD8, CD19 and CD14 cells, was detected using flow cytometry. mDCs were then induced, cultured and sorted. The expression of LILRA3 was confirmed using RT-qPCR and western blot analyses. The serum levels of soluble LILRA3 were measured using ELISA. Furthermore, the relationship between LILRA3 expression and disease severity was assessed. The results indicated increased LILRA3 mRNA expression in patients with SAA. The percentage of LILRA3 in BM mDCs and CD34 cells was increased. Compared with controls, the relative LILRA3 mRNA expression and the relative protein intensity were highly increased in SAA mDCs. The serum LILRA3 levels in patients with SAA were also increased. The proportion of LILRA3CD11C human leukocyte antigen (HLA)-DR/CD11CHLA-DR cells was positively correlated with the ratio of LILRA3CD34/CD34 cells and the expression of LILRA3 mRNA. Taken together, the expression of LILRA3 on mDCs of patients with SAA was increased, which may affect the function of mDCs. LILRA3 may have a significant role in the immune pathogenesis of SAA.
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http://dx.doi.org/10.3892/etm.2021.9777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903422PMC
April 2021

Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity.

Vet Res 2021 Feb 22;52(1):30. Epub 2021 Feb 22.

Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China.

Host proteins interacting with pathogens are receiving more attention as potential therapeutic targets in molecular medicine. Streptococcus suis serotype 2 (SS2) is an important cause of meningitis in both humans and pigs worldwide. SS2 Enolase (Eno) has previously been identified as a virulence factor with a role in altering blood brain barrier (BBB) integrity, but the host cell membrane receptor of Eno and The mechanism(s) involved are unclear. This study identified that SS2 Eno binds to 40S ribosomal protein SA (RPSA) on the surface of porcine brain microvascular endothelial cells leading to activation of intracellular p38/ERK-eIF4E signalling, which promotes intracellular expression of HSPD1 (heat-shock protein family D member 1), and initiation of host-cell apoptosis, and increased BBB permeability facilitating bacterial invasion. This study reveals novel functions for the host-interactional molecules RPSA and HSPD1 in BBB integrity, and provides insight for new therapeutic strategies in meningitis.
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http://dx.doi.org/10.1186/s13567-020-00887-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898445PMC
February 2021

Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer.

Cell Death Dis 2021 02 19;12(2):202. Epub 2021 Feb 19.

The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin, China.

Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell-cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.
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http://dx.doi.org/10.1038/s41419-021-03491-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895950PMC
February 2021

Contribution of green organs to grain weight in dryland wheat from the 1940s to the 2010s in Shaanxi Province, China.

Sci Rep 2021 02 9;11(1):3377. Epub 2021 Feb 9.

College of Life Science, Yulin University, Yulin, 719000, China.

Eight dryland winter wheat cultivars (Triticum aestivum L.), which were widely cultivated from the 1940s to the 2010s in Shaanxi Province, China, were selected and grown in plots, and two water treatments (irrigation and drought) were used to identify the contribution of ears, leaves and stems to grain weight and grain number associated with cultivar replacement. The plant height and stem dry weight of the dryland wheat decreased significantly during the cultivar replacement process, but there was a remarkable increase in the dry matter translocation of stems under irrigation. Shaded-ear and defoliation treatment could decrease the grain number and grain weight, and the grain weight was more influenced. Both the leaf and ear are important photosynthetic sources for dryland wheat, and the contribution of ear assimilates showed a significant increase over time; however, the contribution of leaf assimilates showed a negative correlation with cultivation over time. The accumulation of stem assimilates and ear photosynthesis both increased the grain weight potential. In the future breeding process, cultivars with more assimilates stored in the stem and greater assimilative capacity of ears, especially a greater contribution of ear assimilates, are expected to increase the grain yield.
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http://dx.doi.org/10.1038/s41598-021-82718-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873244PMC
February 2021

Effects of film mulching on the distribution of phthalate esters in wheat grains from dryland.

Environ Sci Pollut Res Int 2021 Jun 30;28(22):27844-27851. Epub 2021 Jan 30.

College of Natural Resources and Environment, Northwest A&F University, No. 3 Taicheng Road, Yangling, 712100, Shaanxi, China.

The application of plastic film in field crop production elevated the phthalate esters (PAEs) accumulation in wheat grains, which poses potential risks to human health. However, the variation of grain PAEs contents in different dryland areas is not clear, and the distribution of PAEs in different tissues of grains has not been studied yet. In the present study, field experiments in five sites (three provinces) with two treatments (soil with and without film mulching) were carried out to study the concentration and distribution of PAEs in grains and the effects of environmental factors on them. Results showed that the total PAE concentration (∑PAEs) in wheat grains ranged from 445 to 764 μg/kg, mainly in the forms of di-(2-ethylhexyl)-phthalate (DEHP), dibutyl phthalate (DBP), and diisobutyl phthalate (DIBP). Compared with control, total PAE concentrations in soils and wheat grains were significantly higher in treatments with film mulching. The effects of film on the proportion of PAEs in the flour and bran varied with experiment sites. Grain PAEs in the control groups presented significantly negative correlation with annual temperature, while there was a positive correlation between soil PAEs and bran PAEs in the film treatment. Results in this study are of great significance to comprehensively evaluate the effect of film mulching on grain safety in dryland wheat production.
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http://dx.doi.org/10.1007/s11356-021-12406-xDOI Listing
June 2021

Identification of circular RNA expression profiles and potential biomarkers for intracerebral hemorrhage.

Epigenomics 2021 Mar 28;13(5):379-395. Epub 2021 Jan 28.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, PR China.

To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. The circRNAs were involved mainly in lysine degradation and the immune system. This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.
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http://dx.doi.org/10.2217/epi-2020-0432DOI Listing
March 2021

Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells.

Aging (Albany NY) 2020 12 9;13(2):2231-2250. Epub 2020 Dec 9.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.

Myocardial infarction is a cardiovascular disease with high mortality. Human umbilical cord mesenchymal stem cells (hUC-MSCs) with strong self-renewal capacity and multipotency, provide the possibility of replacing injured cardiomyocytes. hUC-MSCs were cultured on polyacrylamide hydrogels with stiffnesses corresponding to Young's modulus of 13-16kPa and 62-68kPa which mimic the stiffnesses of healthy heart tissue and fibrotic myocardium. The expression of early myocardial markers Nkx2.5, GATA4, Mesp1 and the mature myocardial markers cTnT, cTnI, α-actin were detected by RT-PCR and Western Blot, which showed that soft matrix (13-16 kPa) tended to induce the differentiation of hUC-MSCs into myocardium, compared with stiff matrix (62-68 kPa). Piezos are mechanically sensitive non-selective cation channels. The expression of Piezo1 increased with the stiffness gradient of 1-10kPa, 13-16kPa, 35-38kPa and 62-68kPa on the 1 day, but Piezo2 expression was irregular. The expression of integrin β1 and calcium ions were also higher on stiff substrate than on soft substrate. hUC-MSCs tend to differentiate into myocardium on the matrix stiffness of 13-16 kPa. The relationship among matrix stiffness, Piezo1 and myocardial differentiation needs further validation.
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http://dx.doi.org/10.18632/aging.202244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880396PMC
December 2020

MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway.

Int Immunopharmacol 2021 Jan 29;90:107142. Epub 2020 Nov 29.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Acute lung injury (ALI), a common respiratory distress syndrome in the intensive care unit (ICU), is mainly caused by severe infection and shock. Epithelial and capillary endothelial cell injury, interstitial edema and inflammatory cell infiltration are the main pathological changes observed in ALI animal models. Maresin conjugates in tissue regeneration (MCTR) are a new family of anti-inflammatory proteins. MCTR3 is a key enhancer of the host response, that promotes tissue regeneration and reduces infection; however, its role and mechanism in ALI are still unclear. The purpose of our research was to assess the protective effects of MCTR3 against ALI and its underlying mechanism. The work in this study was conducted in a murine model and the pulmonary epithelial cell line MLE-12. In vivo, MCTR3 (2 ng/g) was given 2 h after lipopolysaccharide (LPS) injection. We found that the treatment of mice with LPS-induced ALI with MCTR3 significantly reduced the cell number and protein levels in the bronchoalveolar lavage fluid (BALF); decreased the production of inflammatory cytokines; alleviated oxidative stress and cell apoptosis, consequently decreased lung injury; and restored pulmonary function. These protective effects of MCTR3 were dependent on down-regulation of the PTEN-induced putative kinase 1 (PINK1) pathway. Additionally, in MLE-12 cells stimulated with LPS, MCTR3 inhibited cell death, inflammatory cytokine levels and oxidative stress via the ALX/PINK1 signaling pathway. Thus, we conclude that MCTR3 protected against LPS-induced ALI partly through inactivation of the ALX/PINK1 mediated mitophagy pathway.
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http://dx.doi.org/10.1016/j.intimp.2020.107142DOI Listing
January 2021

Ratiometric fluorescent nanoprobe based on CdTe/SiO/folic acid/silver nanoparticles core-shell-satellite assembly for determination of 6-mercaptopurine.

Mikrochim Acta 2020 11 18;187(12):665. Epub 2020 Nov 18.

Pharmaceutical Analysis Division, School of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, People's Republic of China.

A sensitive and robust fluorescent assay of 6-MP is described which relies on the facile assembly of a fluorescence nanoprobe by design of silica nanosphere encapsulated CdTe quantum dots (CdTe QDs) as scaffold, coupling with chemically tethered folic acid (FA)-protected silver nanoparticles (AgNPs) that function as responsive element. In this way a stable ternary core-shell-satellite nanostructure with dual-emission signals can be established. On binding to the target molecules, 6-MP, FA molecules initially occupied by AgNPs are liberated to give dose-dependent fluorescence emission, which can further form a self-calibration ratiometric fluorescence assay using CdTe QDs as an internal reference. The nanoprobe color vividly changes from red to blue, enabling the direct visual detection. The linear concentration range is 0.15~50 μM with the detection limit of 67 nM. By virtue of the favorable selectivity and robust assays, the nanoprobe was applied to 6-MP detection in urine samples, with recoveries from 97.3 to 106% and relative standard deviations (RSD) less than 5%. Graphical abstract.
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http://dx.doi.org/10.1007/s00604-020-04628-6DOI Listing
November 2020

Efficacy and safety of Xiaochaihu decoction for subacute thyroiditis: A protocol of systematic review and meta-analysis.

Medicine (Baltimore) 2020 Nov;99(46):e23011

Hospital of Chengdu University of Traditional Chinese Medicine.

Background: Subacute thyroiditis (SAT) is a transient and self-limiting inflammatory thyroid disease. There is no clear evidence for specific etiology, but it is generally thought to occur after viral infection. Characteristics of SAT include severe pain of the anterior neck, enlarged firm thyroid, disordered thyroid function, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), typical ultrasound findings (hypoechoic areas) and low thyroid uptake of radioactive iodine or technetium-99 m because of the destructive etiology of the hyperthyroidism. Evidences showed Xiaochaihu decoction (XCHD) has a significant effect on improving the symptoms of SAT patients. The purpose of this study is to assess the safety and effectiveness of XCHD for patients with SAT.

Methods And Analysis: The literature that has been identified via searching 6 Chinese electronic databases and eight English electronic databases from inception to September 21, 2020 will be included in the study. Research selection, data extraction as well as research quality assessment will be completed by 2 experienced researchers independently. The primary outcome is remission rate. Data analysis will be conducted by the RevMan 5 software, and GRADE will help to assess the level of evidence. The heterogeneity of data will be investigated by a heterogeneity x test, as well as the Higgins I test. A subgroup analyses and sensitivity analysis will be conducted to explore the sources of heterogeneity.

Results: The results of this study will be published in a peer-reviewed journal.

Conclusion: This study will draw a conclusion about whether XCHD is safe and effective in treating SAT on the basis of evidence-based medicine. This conclusion will provide areliable scientific evidence for the alternative treatment for the management of SAT. OSF REGISTRATION NUMBER:: https://osf.io/8hbue.
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http://dx.doi.org/10.1097/MD.0000000000023011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668520PMC
November 2020

[Research progress on methylation of histones H3K9 and H3K27 in early-stage embryos].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Nov;37(11):1296-1300

Reproduction Center of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

With the in-depth exploration of all stages in early-stage embryos, in particular zygotic genome activation and first cell lineage differentiation, researchers have found that early embryonic epigenetics follows a strict pattern of temporal and spatial modification. Previous studies have determined the inhibitory effect of H3K9me3 and H3K27me3 on genomic expression, and found that they are involved in many core biological events in the genome such as chromatin reprogramming, genomic imprinting, maintenance of embryonic stem cell pluripotency and somatic cell nuclear transfer, though the detailed molecular mechanism has remained elusive. From the point of developmental biology and epigenetics, this article has expounded the research progress on the methylation of H3K9 and H3K27 histones in early-stage embryos, which may provide a clue for the complex mechanism of embryonic development and improvement of culture method for embryos in vitro.
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http://dx.doi.org/10.3760/cma.j.cn511374-20191227-00669DOI Listing
November 2020

Effectiveness of the Iron Chelator CN128 in Mitigating the Formation of Dopamine Oxidation Products Associated with the Progression of Parkinson's Disease.

ACS Chem Neurosci 2020 11 14;11(21):3646-3657. Epub 2020 Oct 14.

Water Research Centre and School of Civil and Environmental Engineering, The University of New South Wales, Sydney, New South Wales 2052, Australia.

The occurrence and progression of Parkinson's disease (PD) has been associated with the observation of elevated iron concentrations in the (SNpc). While the reasons for the impact of elevated iron concentrations remain unclear, one hypothesis is that the presence of labile iron induces the oxidation of dopamine (DA) to toxic quinones such as aminochrome (DAC) and reactive oxygen species (ROS). As such, one of the proposed therapeutic strategies has been the use of iron chelators such as deferiprone (DFP) (which is recognized to have limitations related to its rapid degradation in the liver) to reduce the concentration of labile iron. In this study, a detailed investigation regarding the novel iron chelator, CN128, was conducted and a kinetic model developed to elucidate the fundamental behavior of this chelator. The results in this work reveal that CN128 is effective in alleviating the toxicity induced by iron and DA to neurons when DA is present at moderate concentrations. When all the iron is chelated by CN128, the formation of DAC and the oxidation of DA can be reduced to levels identical to that in the absence of iron. The production of HO is lower than that generated via the autoxidation of the same amount of DA. However, when severe leakage of DA occurs, the application of CN128 is insufficient to alleviate the associated toxicity. This is attibuted to the less important role of iron in the production of toxic intermediates at high concentrations of DA. CN128 is superior to DFP with regard to the reduction in formation of DAC and elevation in DA concentration. In summary, the results of this study suggest that prodromal application of the chelator CN128 could be effective in preventing the onset and slowing the early stage development of PD symptoms associated with oxidants and toxic intermediates resulting from the iron-mediated oxidation of the neurotransmitter dopamine with CN128 likely to be superior to DFP in view of its greater availability and less problematic side effects.
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http://dx.doi.org/10.1021/acschemneuro.0c00557DOI Listing
November 2020

Non-invasive decision support for NSCLC treatment using PET/CT radiomics.

Nat Commun 2020 10 16;11(1):5228. Epub 2020 Oct 16.

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Two major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during therapy. Thus, there is a compelling need to identify comprehensive biomarkers that can be used longitudinally to help guide therapy choice. Herein, we report a F-FDG-PET/CT-based deep learning model, which demonstrates high accuracy in EGFR mutation status prediction across patient cohorts from different institutions. A deep learning score (EGFR-DLS) was significantly and positively associated with longer progression free survival (PFS) in patients treated with EGFR-TKIs, while EGFR-DLS is significantly and negatively associated with higher durable clinical benefit, reduced hyperprogression, and longer PFS among patients treated with ICIs. Thus, the EGFR-DLS provides a non-invasive method for precise quantification of EGFR mutation status in NSCLC patients, which is promising to identify NSCLC patients sensitive to EGFR-TKI or ICI-treatments.
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http://dx.doi.org/10.1038/s41467-020-19116-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567795PMC
October 2020

Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo.

J Med Virol 2021 06 1;93(6):3428-3438. Epub 2020 Nov 1.

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan, China.

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections and there are currently no safer or more effective drugs available. It is important to find novel medications for RSV infection. A series of steroidal pyridines were synthesized for screening and evaluation of their antiviral activity and investigation of their antiviral mechanism of action. Compound 3l had the highest antiviral activity, with a half-maximal effective concentration (EC ) of 3.13 μM. Compound 3l was explored for its effects in vitro on RSV 2 h before infection (pretreatment), at the time of infection (competition), and 2 h after infection (postinfection). Toll-like receptor (TLR)-3, retinoic acid-inducible gene (RIG)-I, interleukin (IL)-6, and interferon (IFN)-β were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by compound 3l. Decreased expression of TLR-3, RIG-I, IL-6, IFN-β, and IL-10 was also found in vivo. The results indicated that compound 3l exerted its antiviral effects mainly through inhibition of viral replication and downregulation of inflammatory factors.
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http://dx.doi.org/10.1002/jmv.26604DOI Listing
June 2021

How to reprogram human fibroblasts to neurons.

Cell Biosci 2020 12;10:116. Epub 2020 Oct 12.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021 People's Republic of China.

Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical factors in the process of reprogramming human fibroblasts into neurons, such as safe and minimally invasive, it has a more promising application prospect. Therefore, this paper also summarizes some successful physical mechanisms of utilizing fibroblasts to acquire neurons, which will provide new ideas for somatic cell reprogramming.
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http://dx.doi.org/10.1186/s13578-020-00476-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549215PMC
October 2020
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