Publications by authors named "Jun Xu"

2,794 Publications

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The role of exosomes in lung cancer metastasis and clinical applications: an updated review.

J Transl Med 2021 Jul 19;19(1):312. Epub 2021 Jul 19.

Clinical Laboratory, Children's Hospital of Soochow University, Suzhou, 215000, People's Republic of China.

Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell-cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.
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http://dx.doi.org/10.1186/s12967-021-02985-1DOI Listing
July 2021

[Corrigendum] Integrated transcriptomic and epigenetic data analysis identifies aberrant expression of genes in acute myeloid leukemia with MLL‑AF9 translocation.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.

Following the publication of this paper, the authors have realized that the final article did not indicate in the Authors' Contribution section that Fangce Wang and Zheng Li made equal contributions to this work (FW and ZL performed most of the statistical analyses and drafted the initial version of the manuscript). Therefore, the affiliations for this paper should have been written as follows (changes are highlighted in bold): FANGCE WANG, ZHENG LI, GUANGMING WANG, XIAOXUE TIAN, JIE ZHOU, WENLEI YU, ZHUOYI FAN, LIN DONG, JINYUAN LU, JUN XU, WENJUN ZHANG and AIBIN LIANG Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092; Medical Center for Stem Cell Engineering and Transformation, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China. Contributed equally. The authors confirm that there are no further errors in the paper, and all the authors agree to this correction. The authors and the Editor apologize for any inconvenience caused. [the original article was published in 21: 883‑893, 2020, DOI: 10.3892/mmr.2019.10849].
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http://dx.doi.org/10.3892/mmr.2021.12295DOI Listing
September 2021

New volumetric capnography-derived parameter: a potentially valuable tool for detecting hyperventilation during cardiopulmonary resuscitation in a porcine model.

J Thorac Dis 2021 Jun;13(6):3467-3477

Emergency Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: Volumetric capnography is increasingly being applied in cardiopulmonary resuscitation. However, during cardiopulmonary resuscitation, the abnormal ventilation state affects the monitoring effect of the most commonly used capnography-derived parameter, the partial carbon dioxide end-tidal pressure (PetCO). In this study, we evaluated the ability of a new volumetric capnography-derived parameter, the ratio between the PetCO and the volume of carbon dioxide (CO) eliminated per min and per kilogram of body weight, for detecting hyperventilation during cardiopulmonary resuscitation.

Methods: We used 12 porcine models of primary ventricular fibrillation-induced cardiac arrest. Ventricular fibrillation was induced and left untreated for 4 min. Standardized chest compressions were performed throughout the experiment using mechanical cardiopulmonary resuscitation. Following 5 min of normal ventilation as a washout period, each animal underwent 4 types of ventilation. The main outcome measures were the PetCO, the ratio between the PetCO and the volume of CO eliminated per min and per kilogram of body weight with each ventilation type.

Results: Different ventilation types had a significant effect on the volumetric capnography-derived parameters. The PetCO and ratio between the PetCO and the volume of CO eliminated per min and per kilogram of body weight values during cardiopulmonary resuscitation was significantly higher in non-hyperventilating than in hyperventilating animals. The ratio reflected hyperventilation accurately and immediately, with an area under the curve (AUC) of 0.98. The optimal cut-off point of the ratio for discriminating hyperventilation from non-hyperventilation was 6.36, with a sensitivity and specificity of 0.99 and 0.89, respectively.

Conclusions: The ratio between the PetCO and the volume of CO eliminated per min and per kilogram of body weight showed good performance in discriminating hyperventilation from non-hyperventilation and was sensitive to changes in ventilation status. This ratio may be a valuable clinical indicator for monitoring the ventilation status during cardiopulmonary resuscitation.
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http://dx.doi.org/10.21037/jtd-21-50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264707PMC
June 2021

Silver-Nanoparticle-Embedded Hybrid Nanopaper with Significant Thermal Conductivity Enhancement.

ACS Appl Mater Interfaces 2021 Jul 19. Epub 2021 Jul 19.

Plant Fiber Material Science Research Center, State Key Laboratory of Pulp and Paper Engineering, School of Light Industry and Engineering, South China University of Technology, No. 381 Wushan Road, Tianhe District, Guangzhou 510640, China.

Nanopapers derived from nanofibrillated cellulose (NFC) are urgently required as attractive substrates for thermal management applications of electronic devices because of their lightweight, easy cutting, cost efficiency, and sustainability. In this paper, we provided a facile fabrication strategy to construct hybrid nanopapers composed of dialdehyde nanofibrillated cellulose (DANFC) and silver nanoparticles (AgNPs), which exhibited a favorable thermal conductivity property. AgNPs were in situ proceeded on the surface of DANFC by the silver mirror reaction inspired by the aldehyde groups. Owing to the intermolecular hydrogen bonds inside the hybrid nanopapers, the DANFC enables the uniform dispersion of AgNPs as well as promotes the formation of the hierarchical structure. It was found that the AgNPs-coated DANFC (DANFC/Ag) hybrid nanopapers could easily form an effective thermally conductive pathway for phonon transfer. As a result, the thermal conductivity (TC) of the obtained DANFC/Ag hybrid nanopapers containing only 1.9 vol % of Ag was 5.35 times higher than that of the pure NFC nanopapers along with a significantly TC enhancement per vol % Ag of 230.0%, which was supposed to benefit from the continuous heat transfer pathway constructed by the connection of AgNPs decorated on the cellulose nanofibers. The DANFC/Ag hybrid nanopapers possess potential applications as thermal management materials in the next-generation portable electronic devices.
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http://dx.doi.org/10.1021/acsami.1c08894DOI Listing
July 2021

Can bag-valve mask ventilation with positive end-expiratory pressure reduce hypoxia during intubation? A prospective, randomized, double-blind trial.

Trials 2021 Jul 17;22(1):460. Epub 2021 Jul 17.

Emergency Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Hypoxia is one of the life-threatening complications of endotracheal intubation. Supplemental oxygen and ventilation play a vital role in preventing hypoxia. Bag-valve mask (BVM) ventilation is frequently used before intubation, and its ability to improve oxygenation was recently confirmed. It is still unclear if positive end-expiratory pressure (PEEP) added to BVM ventilation can further reduce hypoxia during intubation.

Methods: This will be a prospective, randomized, double-blind trial to determine if PEEP combined with BVM ventilation can reduce the incidence of hypoxia during intubation compared with conventional BVM ventilation. The lowest oxygen saturation and incidence of complications will be compiled to verify the comparative effectiveness and safety of the two groups.

Discussion: BMV ventilation with PEEP is hoped to further reduce the incidence of hypoxia during intubation.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000035156 . Registered on August 2, 2020. It had begun enrollment after passing ethical review but before registration.
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http://dx.doi.org/10.1186/s13063-021-05413-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285778PMC
July 2021

Dynamics in Bacterial Community Affected by Mesoscale Eddies in the Northern Slope of the South China Sea.

Microb Ecol 2021 Jul 17. Epub 2021 Jul 17.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Mesoscale eddies are common oceanographic processes that can enhance primary productivity by transporting nutrients to the euphotic zone. In the northern South China Sea (SCS), eddies were frequently found to promote the exchange between the nutrient-rich shelf water and the oligotrophic water at the slope area. However, the response of bacterial community to eddy perturbations remains unclear. In the present study, we examined the variation of bacterial community under the impact of eddies in early spring and summer. The results showed that both the summer cyclonic eddy and spring anticyclonic eddy enhanced the bacterial abundance in surface water. The bacterial community composition and their functional potentials of surface samples were also influenced by the summer cyclonic eddy, while no significant change was observed in the case of spring anticyclonic eddy. Salinity and nutrients, which varied between the inside and outside of the eddies, were the significant factors explaining the differentiation of the community composition and related functions. Taken together, the results of our present study reveal the effects of mesoscale eddies on the bacterial community and associated metagenomes, providing a better understanding of the dynamics of bacteria in the slope ecosystem of the SCS.
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http://dx.doi.org/10.1007/s00248-021-01816-6DOI Listing
July 2021

Determination and analysis of monosaccharides in Polygonatum cyrtonema Hua polysaccharides from different areas by ultra-high-performance liquid chromatography quadrupole trap tandem mass spectrometry.

J Sep Sci 2021 Jul 16. Epub 2021 Jul 16.

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.

We wanted to explore a new method for the determination of monosaccharides in Polygonatum cyrtonema Hua polysaccharide using the ultra-high-performance liquid chromatography quadrupole trap tandem mass spectrometry. In this study, hydrochloric acid was used instead of trifluoroacetic acid to hydrolyze polysaccharides and hydrolysis time was greatly reduced from 5-9 h to 1 h. The 1-phenyl-3-methyl-5-pyrazolone was used for pre-column derivatization of monosaccharides. The parameters of linearity (R >0.999), stability (1.63%-2.52%), intra-day and inter-day precision (0.69%-0.95%, 1.81%-2.77%), repeatability (1.89%-2.65%) and recovery (97.63%-102.24%) of the method were verified. Satisfactory validation results showed this method could be used to determine the target components. The results indicated the polysaccharide contained glucose, mannose, rhamnose, galactose, ribose and arabinose. Technique for order preference by similarity to an ideal solution and principal component analysis were used to build an evaluation model based on the monosaccharide composition. The evaluation results showed samples from the Qingyang County of Anhui Province were the best when the monosaccharides were used as the evaluation index. Therefore, a new method was established to detect the monosaccharide content of polysaccharides from Polygonatum cyrtonema Hua and comprehensively evaluate the quality of Chinese medicines with polysaccharides as the main active ingredient. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100263DOI Listing
July 2021

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2.

Bioengineered 2021 Dec;12(1):3824-3836

Department of Orthopedic, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin City, Jiangsu Province, China.

This study was designed to study functions of Circ_0000020 during osteogenic differentiation. First, we used RT-qPCR to detect the expression of Circ_0000020, miR-142-5p and osteogenesis-related genes, whereas western blot analysis detected the expression of osteogenesis markers after the osteogenic differentiation of primary BMSCs isolated from rats. Alkaline phosphatase (ALP) activity and alizarin red Sstaining validated osteoblast phenotypes. Flow cytometry was used to detect cell apoptosis. Sh-Circ_0000020 was used to study the function of Circ_0000020 in osteogenic differentiation of BMSCs. Luciferase assay and RNA immunoprecipitation were used to validate the interaction between Circ_0000020 and miR-142-5p, and BMP2 and miR-142-5p. Co-transfection of miR-142-5p and sh-Circ_0000020 was used to verify the downstream signaling pathway. Circ_0000020 expression was up-regulated during osteogenic differentiation, whereas miR-142-5p expression was significantly decreased. Silencing Circ_0000020 inhibited osteogenic differentiation and promoted apoptosis, and inhibited ALP activity and mineralization ability. Moreover, Circ_0000020 interacts directly with miR-142-5p which binds to the BMP2 3'UTR and inhibits its expression. Additionally, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 rescued down-regulated BMP2, increased the expression osteogenesis-related gene expressions, and thereby rescued the inhibition of osteogenic differentiation induced by Circ_0000020 silencing. Furthermore, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 reversed Circ_0000020 silencing-induced downregulation of p-Smad1/5/8, Runx2, and Osterix protein levels. Circ_0000020 regulates BMP2 expression through sponging miR-142-5p as ceRNA, thereby positively regulating BMSCs osteogenic differentiation through Circ_0000020/miR-142-5p/BMP2/SMAD-dependent signaling pathway.
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http://dx.doi.org/10.1080/21655979.2021.1949514DOI Listing
December 2021

Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction.

Cardiovasc Res 2021 Jul 14. Epub 2021 Jul 14.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No.167 Bei Li Shi Road, Xicheng District, Beijing, 100037, People's Republic of China.

Aims: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms.

Method And Results: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation.

Conclusion: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.

Translational Perspective: Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.
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http://dx.doi.org/10.1093/cvr/cvab237DOI Listing
July 2021

Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs.

Chem Sci 2021 Jul 17;12(25):8778-8783. Epub 2021 May 17.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University Huaxi District Guiyang 550025 China

4,5-Dihydropyridazinones bearing an aryl substituent at the C6-position are important motifs in drug molecules. Herein, we developed an efficient protocol to access aryl-dihydropyridazinone molecules carbene-catalyzed asymmetric annulation between dinucleophilic arylidene hydrazones and bromoenals. Key steps in this reaction include polarity-inversion of aryl aldehyde-derived hydrazones followed by chemo-selective reaction with enal-derived α,β-unsaturated acyl azolium intermediates. The aryl-dihydropyridazinone products accessed by our protocol can be readily transformed into drugs and bioactive molecules.
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http://dx.doi.org/10.1039/d1sc01891dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246082PMC
July 2021

Mechanistic insights into the inhibitory effect of theaflavins on virulence factors production in Streptococcus mutans.

AMB Express 2021 Jul 9;11(1):102. Epub 2021 Jul 9.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China.

Streptococcus mutans is the primary etiological agent associated with cariogenic process. The present study aimed to investigate the antibacterial and anti-virulence activities of theaflavins (TFs) to Streptococcus mutans UA159 as well as the underlying mechanisms. The results showed that TFs were capable of suppressing the acid production, cell adherence, water-insoluble exopolysaccharides production, and biofilm formation by S. mutans UA159 with a dosage-dependent manner while without influencing the cell growth. By a genome-wide transcriptome analysis (RNA-seq), we found that TFs attenuated the biofilm formation of S. mutans UA159 by inhibiting glucosyltransferases activity and the production of glucan-binding proteins (GbpB and GbpC) instead of directly blocking the expression of genes coding for glucosyltransferases. Further, TFs inhibited the expression of genes implicated in peptidoglycan synthesis, glycolysis, lipid synthesis, two-component system, signaling peptide transport (comA), oxidative stress response, and DNA replication and repair, suggesting that TFs suppressed the virulence factors of S. mutans UA159 by affecting the signal transduction and cell envelope stability, and weakening the ability of cells on oxidative stress resistance. In addition, an upregulated expression of the genes involved in protein biosynthesis, amino acid metabolism, and transport system upon TFs treatment indicated that cells increase the protein synthesis and nutrients uptake as one self-protective mechanism to cope with stress caused by TFs. The results of this study increase our current understanding of the anti-virulence activity of TFs on S. mutans and provide clues for the use of TFs in the prevention of dental caries.
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http://dx.doi.org/10.1186/s13568-021-01263-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271058PMC
July 2021

Impurities in Nanocrystal Thin-Film Transistors Fabricated by Cation Exchange.

J Phys Chem Lett 2021 Jul 9;12(28):6514-6518. Epub 2021 Jul 9.

Cation exchange is a versatile tool used to alter the composition of nanostructures and thus to design next-generation catalysts and photonic and electronic devices. However, chemical impurities inherited from the starting materials can degrade device performance. Here, we use a sequential cation-exchange process to convert PbSe into CdSe nanocrystal thin films and study their temperature-dependent electrical properties in the platform of the thin-film transistor. We show that residual Pb impurities have detrimental effects on the device turn-on, hysteresis, and electrical stability, and as the amount increases from 2% to 7%, the activation energy for carrier transport increases from 38(3) to 62(2) meV. Selection and surface functionalization of the transistor's gate oxide layer and low-temperature atomic-layer deposition encapsulation of the thin-film channel suppress these detrimental effects. By conversion of the nanocrystal thin films layer upon layer, impurities are driven away from the gate-oxide interface and mobilities improve from 3(1) to 32(3) cm V s.
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http://dx.doi.org/10.1021/acs.jpclett.1c01551DOI Listing
July 2021

Inhibiting Ferroptosis through Disrupting the NCOA4-FTH1 Interaction: A New Mechanism of Action.

ACS Cent Sci 2021 Jun 6;7(6):980-989. Epub 2021 May 6.

Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Ferroptosis is an iron-dependent form of oxidative cell death, and the inhibition of ferroptosis is a promising strategy with which to prevent and treat neurological diseases. Herein we report a new ferroptosis inhibitor with a novel mechanism of action. It is demonstrated that nuclear receptor coactivator 4 (NCOA4), a cargo receptor for ferritinophagy, is the target of . Compound blocks ferroptosis by reducing the amount of bioavailable intracellular ferrous iron through disrupting the NCOA4-FTH1 protein-protein interaction. Further studies indicate that directly binds to recombinant protein NCOA4 and effectively blocks the NCOA4-FTH1 interaction. In a rat model of ischemic stroke, significantly ameliorates the ischemic-refusion injury. With the first ligand , this work reveals that NCOA4 is a promising drug target. Additionally, is the first NCOA4-FTH1 interaction inhibitor. This work paves a new road to the development of ferroptosis inhibitors against neurological diseases.
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http://dx.doi.org/10.1021/acscentsci.0c01592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227600PMC
June 2021

Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes.

JAMA Netw Open 2021 Jul 1;4(7):e2115991. Epub 2021 Jul 1.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Importance: Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated.

Objective: To investigate PRT choices based on dynamic MRD in patients with IR-AML.

Design, Setting, And Participants: This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020.

Exposures: Receipt of chemotherapy, auto-SCT, or allo-SCT.

Main Outcomes And Measures: The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival.

Results: Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007).

Conclusions And Relevance: This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.15991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264648PMC
July 2021

Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors.

Fitoterapia 2021 Jun 30:104984. Epub 2021 Jun 30.

Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. Electronic address:

Ferroptosis is a new type of cell death, which involves central neuronal system. Inhibition of ferroptosis is a promising strategy to prevent and treat neurological diseases. Thirteen phloroglucinols (1-13) were obtained from the whole plants of Hypericum japonicum. Of them, compounds 1-3 are new ones. Their structures were elucidated by extensive analysis of spectroscopic data and X-ray diffraction. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis. Two new compounds 2-3 showed significant inhibitory effect with EC of 0.48 ± 0.14 μM and 0.94 ± 0.14 μM, respectively. DPPH free radical scavenging abilities of all compounds were assessed to evaluate their antioxidant effect. This work first reports the anti-ferroptosis activity of phloroglucinols.
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http://dx.doi.org/10.1016/j.fitote.2021.104984DOI Listing
June 2021

Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons.

Nat Commun 2021 07 1;12(1):4075. Epub 2021 Jul 1.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese academy of Science, Shanghai, 200032, China.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.
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http://dx.doi.org/10.1038/s41467-021-24236-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249382PMC
July 2021

Strand-specific effect of Rad26 and TFIIS in rescuing transcriptional arrest by CAG trinucleotide repeat slip-outs.

Nucleic Acids Res 2021 Jul;49(13):7618-7627

Division of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences; University of California, San Diego, La Jolla, CA 92093, USA.

Transcription induced CAG repeat instability is associated with fatal neurological disorders. Genetic approaches found transcription-coupled nucleotide excision repair (TC-NER) factor CSB protein and TFIIS play critical roles in modulating the repeat stability. Here, we took advantage of an in vitro reconstituted yeast transcription system to investigate the underlying mechanism of RNA polymerase II (Pol II) transcriptional pausing/stalling by CAG slip-out structures and the functions of TFIIS and Rad26, the yeast ortholog of CSB, in modulating transcriptional arrest. We identified length-dependent and strand-specific mechanisms that account for CAG slip-out induced transcriptional arrest. We found substantial R-loop formation for the distal transcriptional pausing induced by template strand (TS) slip-out, but not non-template strand (NTS) slip-out. In contrast, Pol II backtracking was observed at the proximal transcriptional pausing sites induced by both NTS and TS slip-out blockage. Strikingly, we revealed that Rad26 and TFIIS can stimulate bypass of NTS CAG slip-out, but not TS slip-out induced distal pausing. Our biochemical results provide new insights into understanding the mechanism of CAG slip-out induced transcriptional pausing and functions of transcription factors in modulating transcription-coupled CAG repeat instability, which may pave the way for developing potential strategies for the treatment of repeat sequence associated human diseases.
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http://dx.doi.org/10.1093/nar/gkab573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287942PMC
July 2021

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Front Psychiatry 2021 14;12:566990. Epub 2021 Jun 14.

Department of Emergency Medicine, The First Affiliate Hospital of Xinjiang Medical University, Wulumuqi, China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.
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http://dx.doi.org/10.3389/fpsyt.2021.566990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236535PMC
June 2021

Preoperative Prediction of G1 and G2/3 Grades in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors Using Multimodality Imaging.

Acad Radiol 2021 Jun 23. Epub 2021 Jun 23.

Department of Radiology, Changhai Hospital, Naval Medical University, Changhai road 168, Shanghai 200434, China. Electronic address:

Objectives: We aimed to develop and validate a multimodality radiomics model for the preoperative prediction of nonfunctional pancreatic neuroendocrine tumor (NF-pNET) grade (G).

Methods: This retrospective study assessed 123 patients with surgically resected, pathologically confirmed NF-pNETs who underwent multidetector computed tomography and MRI scans between December 2012 and May 2020. Radiomic features were extracted from multidetector computed tomography and MRI. Wilcoxon rank-sum test and Max-Relevance and Min-Redundancy tests were used to select the features. The linear discriminative analysis (LDA) was used to construct the four models including a clinical model, MRI radiomics model, computed tomography radiomics model, and mixed radiomics model. The performance of the models was assessed using a training cohort (82 patients) and a validation cohort (41 patients), and decision curve analysis was applied for clinical use.

Results: We successfully constructed 4 models to predict the tumor grade of NF- pNETs. Model 4 combined 6 features of T2-weighted imaging radiomics features and 1 arterial-phase computed tomography radiomics feature, and showed better discrimination in the training cohort (AUC = 0.92) and validation cohort (AUC = 0.85) relative to the other models. In the decision curves, if the threshold probability was 0.07-0.87, the use of the radiomics score to distinguish NF-pNET G1 and G2/3 offered more benefit than did the use of a "treat all patients" or a "treat none" scheme in the training cohort of the MRI radiomics model.

Conclusion: The LDA classifier combining multimodality images may be a valuable noninvasive tool for distinguishing NF-pNET grades and avoid unnecessary surgery.
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http://dx.doi.org/10.1016/j.acra.2021.05.017DOI Listing
June 2021

HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML.

J Exp Clin Cancer Res 2021 Jun 24;40(1):210. Epub 2021 Jun 24.

Department of Haematology, Tongji Hospital, Tongji University School of Medicine, 1239 Siping Road, 200092, Shanghai, P.R. China.

Background: Leukaemia stem cells (LSCs) are responsible for the initiation, maintenance, and recurrence of acute myeloid leukaemia (AML), an aggressive haematological malignancy associated with drug resistance and relapse. Identifying therapeutic LSC targets is critical to curing AML.

Methods: Bioinformatics databases were used to identify therapeutic LSC targets. The conditional knockout mice were used to analyse the role of HCK in leukaemogenesis or normal haematopoiesis. Colony-forming assays, cell counting, and flow cytometry were used to detect the viability and function of leukaemia cells. RT-PCR, western blotting, and RNA sequencing were used to detect mRNA and protein expression.

Result: HCK is expressed at higher levels in LSCs than in haematopoietic stem cells (HSCs), and high HCK levels are correlated with reduced survival time in AML patients. Knockdown of HCK leads to cell cycle arrest, which results in a dramatic decrease in the proliferation and colony formation in human AML cell lines. Moreover, HCK is required for leukemogenesis and leukaemia maintenance in vivo and in vitro. HCK is necessary for the self-renewal of LSCs during serial transplantation and limiting dilution assay. The phenotypes resulting from HCK deficiency can be rescued by CDK6 overexpression in the human cell line. RNA sequencing and gene expression have demonstrated that HCK may sustain cell cycle entry and maintain the self-renewal ability of LSCs through activating the ERK1/2-c-Myc-CDK6 signalling axis. In contrast, HCK deletion does not affect normal haematopoiesis or haematopoietic reconstruction in mice.

Conclusions: HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML and may be an ideal therapeutic target for eradicating LSCs without influencing normal haematopoiesis.
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http://dx.doi.org/10.1186/s13046-021-02007-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223385PMC
June 2021

Improved light output from thick β-GaO scintillation crystals via graded-refractive-index photonic crystals.

Opt Express 2021 Jun;29(12):18646-18653

β-GaO is a promising candidate as a fast scintillation crystal for radiation detection in fast X-ray imaging and high-energy physics experiments. However, total internal reflection severely limits its light output. Conventional photonic crystals can improve the light output, but such improvement decreases dramatically with increased scintillator thickness due to the strong backward reflection by the photonic crystals. Here, graded-refractive-index photonic crystals composed of nanocone arrays are designed and fabricated on the surfaces of β-GaO crystals with various thicknesses. Compared to the conventional photonic crystals, there is still an obvious light output improvement by using the graded-refractive-index photonic crystals when the thickness of the crystals is increased by three times. The effect of thickness on the improved light output is investigated with numerical simulations and experiments. Overall, the graded-refractive-index photonic crystals are beneficial to the improvement of light output from thick scintillators.
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http://dx.doi.org/10.1364/OE.428671DOI Listing
June 2021

Host-Guest Interaction-Based Dual response core/shell nanoparticles as efficient siRNA carrier for killing breast cancer cells.

Colloids Surf B Biointerfaces 2021 Sep 11;205:111918. Epub 2021 Jun 11.

Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China; MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, 510632, China. Electronic address:

How to overcome multiple obstacles to achieve the efficient and safe delivery of therapeutic genes is still the key to gene therapy. To address this issue, a cationic carrier consisting of polyamide-amine (HPAA-peptide-Fc) modified by an enzyme-responsive polypeptide as the core and hyperbranched polyglycerol derivative (CD-HPG) as the shell was synthesized by self-assembly. The obtained HPAA-peptide-HPG could form the compact nanocomplex with siPlk1, thus confirming the stable load of genes and subsequent targeted gene delivery. And the nanogenes could significantly induce apoptotic effect via the down-expression of Plk1 protein in breast cancer cells. Moreover, compared to polyethylenimine, HPAA-peptide-HPG exhibited superior biocompatibility through hemolysis and cell viability assays because of the shielding function of CD-HPG, thereby being beneficial to increasing the circulation time of the complex when administrated in vivo. Such an efficient and safe gene delivery complex (HPAA-peptide-HPG) presents a good example of rational design of cationic supramolecular vesicles for stimulus-responsive siRNA transport, which should be encouraged in cancer gene therapy.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111918DOI Listing
September 2021

An Integrated Strategy for Purification by Combining Solid-Phase Extraction with Dispersive-Solid-Phase Extraction for Detecting 22 Pesticides and Metabolite Residues in Fish.

J Agric Food Chem 2021 Jun 18;69(25):7199-7208. Epub 2021 Jun 18.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, People's Republic of China.

A robust isotope-labeled internal standard method was established for the detection of 22 pesticides and metabolite residues in four kinds of fish; two were from freshwater fish, and two were from marine fish. Pesticides with wide application possibilities in rice in China, strong leaching to water, or high bioconcentration factors (BCF) in fish were selected. The samples were extracted with 1% acetic acid-99% acetonitrile. The extracts were first purified by solid-phase extraction (PEP-plus), cleaned with dispersive-solid-phase extraction (PSA and C18), and finally analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that good linearities for the target compounds were observed in the range of 0.1-100 ng/mL, and the correlation coefficient () of each compound was greater than 0.99. The recoveries of the method were within 70-120% with RSDs <20% at three different spiked concentration levels (0.5, 5, and 100 ng/g). The quantitative limit of the method was 0.5-5 ng/g. The method is shown to be sensitive and accurate and can meet the demands for the quantitative analysis of pesticides in fish.
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http://dx.doi.org/10.1021/acs.jafc.0c08040DOI Listing
June 2021

Tension hydropneumothorax in a Boerhaave syndrome patient: A case report.

World J Emerg Med 2021 ;12(3):235-237

Emergency Department, Peking Union Medical College Hospital, Beijing 100730, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188275PMC
January 2021

Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II.

Nat Chem Biol 2021 Jun 17. Epub 2021 Jun 17.

Division of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.

The development of unnatural base pairs (UBPs) has greatly increased the information storage capacity of DNA, allowing for transcription of unnatural RNA by the heterologously expressed T7 RNA polymerase (RNAP) in Escherichia coli. However, little is known about how UBPs are transcribed by cellular RNA polymerases. Here, we investigated how synthetic unnatural nucleotides, NaM and TPT3, are recognized by eukaryotic RNA polymerase II (Pol II) and found that Pol II is able to selectively recognize UBPs with high fidelity when dTPT3 is in the template strand and rNaMTP acts as the nucleotide substrate. Our structural analysis and molecular dynamics simulation provide structural insights into transcriptional processing of UBPs in a stepwise manner. Intriguingly, we identified a novel 3'-RNA binding site after rNaM addition, termed the swing state. These results may pave the way for future studies in the design of transcription and translation strategies in higher organisms with expanded genetic codes.
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http://dx.doi.org/10.1038/s41589-021-00817-3DOI Listing
June 2021

Cumulative risk assessment of dietary exposure to triazole fungicides from 13 daily-consumed foods in China.

Environ Pollut 2021 Jun 9;286:117550. Epub 2021 Jun 9.

Institute of Plant Protection, Chinese Academy of Agricultural Sciences, State Key Laboratory for Biology of Plant Diseases and Insect Pests, Key Laboratory of Control of Biological Hazard Factors (Plant Origin) for Agricultural product Quality and Safety, Ministry of Agriculture, Beijing, 100193, People's Republic of China.

The agroeconomic benefits of the routine use of triazole fungicides on crops have been evident for more than 40 years. However, increasing evidence shows that residues of triazoles are ubiquitous in various foods and thus could pose a potential health risk to humans. We analyzed 3406 samples of 13 food commodities that were collected from markets in 9 regions across China, and assessed the health risk of both chronic and acute exposure to the triazoles for Chinese children (1-6 years old) and the general population. Among all samples, 55.52% had triazoles in concentrations of 0.10-803.30 μg/kg, and 29.77% of samples contained a combination of 2-7 triazoles. Tebuconazole and difenoconazole were the most commonly found triazoles in the foods, being detected in 33.44% and 30.45% of samples, respectively. Chronic and acute cumulative risk assessment for total triazoles based on a relative potency factor method revealed that exposure to triazoles from these particular commodities was below the levels that might pose a health risk (chronic hazard index range, 5.90×10 to 1.83×10; acute hazard index range, 7.77×10 to 0.39, below 1). Notably, dietary exposure risk for children was greater than that for the general population-particularly for the acute intake of mandarin, grape, and cucumber (acute hazard index values of 0.35-0.39). Despite the low health risk, the potential hazards of exposure to triazoles should raise public concern owing to their ubiquitous presence in common foods and potential cumulative effects.
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http://dx.doi.org/10.1016/j.envpol.2021.117550DOI Listing
June 2021

Score for Predicting Active Cancer in Patients with Ischemic Stroke: A Retrospective Study.

Biomed Res Int 2021 25;2021:5585206. Epub 2021 May 25.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke.

Methods: This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system.

Results: Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.06-0.48, < 0.01), elevated serum fibrinogen (OR = 1.72, 95% CI: 1.33-2.22, < 0.01) and D-dimer levels (OR = 1.43, 95% CI: 1.24-1.64,  <0.01), and stroke of undetermined etiology (OR = 22.87, 95% CI: 9.91-52.78, < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 g/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77-0.89, < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke.

Conclusions: We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.
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http://dx.doi.org/10.1155/2021/5585206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169246PMC
May 2021

Chemo-selective cross reaction of two enals carbene-catalyzed dual activation.

Chem Sci 2020 Sep 18;11(46):12533-12539. Epub 2020 Sep 18.

Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering Ministry of Education, Guizhou University Huaxi District Guiyang 550025 China.

A dual catalytic chemo-selective cross-coupling reaction of two enals is developed. One enal (without α-substitution) is activated by an NHC catalyst to form an acylazolium enolate intermediate that undergoes Michael-type addition to another enal molecule bearing an alkynyl substituent. Mechanistic studies indicate that non-covalent interactions between the alkynyl enal and the NHC·HX catalyst play important roles in substrate activation and enantioselectivity control. Many of the possible side reactions are not observed. Our reaction provides highly chemo- and diastereo-selective access to chiral lactones containing functionalizable 1,3-enyn units with excellent enantioselectivities (95 to >99% ee).
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http://dx.doi.org/10.1039/d0sc03297bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162827PMC
September 2020

SyntaLinker: automatic fragment linking with deep conditional transformer neural networks.

Chem Sci 2020 Jul 22;11(31):8312-8322. Epub 2020 Jul 22.

Center of Chemistry and Chemical Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou 510530 China

Linking fragments to generate a focused compound library for a specific drug target is one of the challenges in fragment-based drug design (FBDD). Hereby, we propose a new program named SyntaLinker, which is based on a syntactic pattern recognition approach using deep conditional transformer neural networks. This state-of-the-art transformer can link molecular fragments automatically by learning from the knowledge of structures in medicinal chemistry databases ( ChEMBL database). Conventionally, linking molecular fragments was viewed as connecting substructures that were predefined by empirical rules. In SyntaLinker, however, the rules of linking fragments can be learned implicitly from known chemical structures by recognizing syntactic patterns embedded in SMILES notations. With deep conditional transformer neural networks, SyntaLinker can generate molecular structures based on a given pair of fragments and additional restrictions. Case studies have demonstrated the advantages and usefulness of SyntaLinker in FBDD.
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http://dx.doi.org/10.1039/d0sc03126gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163338PMC
July 2020