Publications by authors named "Jing Sun"

3,283 Publications

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Molecular Engineered Crown-Ether-Protein with Strong Adhesion over a Wide Temperature Range from -196 to 200°C.

Angew Chem Int Ed Engl 2022 Jun 21. Epub 2022 Jun 21.

Tsinghua University, Department of Chemistry, qinghua yuan, 100084, Beijing, CHINA.

The inherently tenuous adhesion strength and limited environmental tolerance of supramolecular adhesives severely restrict their application scenarios. It is challenging for the development of robust adhesives with extreme temperature tolerance. Herein, we report a new type of temperature-resistant crown-ether-protein (CEP) adhesive by harnessing synergistic host-guest molecular interactions between engineered crown ether and protein building blocks. The outputs of CEP adhesive demonstrate ultrahigh shearing adhesion strength of ~22 MPa over a wide temperature range from -196 to 200°C, superior to other established supramolecular or polymeric adhesives. The temperature-induced phase transition and internal bound water stablized the system and led to superb adhesion under extreme conditions. Thus, this work pioneers a molecular engineering approach for the generation of adhesives with tailored applications in extreme settings.
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http://dx.doi.org/10.1002/anie.202207425DOI Listing
June 2022

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording.

Mater Horiz 2022 Jun 20. Epub 2022 Jun 20.

National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, Sichuan, China.

A flexible non-transient electrical platform that can realize bidirectional neural communication from living tissues is of great interest in neuroscience to better understand basic neuroscience and the nondrug therapy of diseases or disorders. The development of soft, biocompatible, and conductive neural interface with mechanical coupling and efficient electrical exchange is a new trend but remains a challenge. Herein, we designed a multifunctional neural electrical communication platform in the form of a mechanically compliant, electrically conductive, and biocompatible hydrogel electrode. Silk fibroin (SF) obtained from cocoons was compounded with aldehyde-hyaluronic acid (HA-CHO) with a dynamic network to delay or interrupt the β-sheet-induced hardening of SF chains, resulting in the fabrication of a hydrogel matrix that is mechanically matched to biological tissues. Moreover, the incorporation of functionalized carbon nanotubes (CNTs) facilitated interaction and dispersion and enabled the formation of a hydrogel electrode with a high-current percolation network, thus contributing toward improving the electrical properties in terms of conductivity, impedance, and charge storage capabilities. These advances allow high-efficiency stimulation and the recording of neural signals during implantation. Overall, a wide range of animal experiments demonstrate that the platform exhibits minimal foreign body responses, thus showing it to be a promising electrophysiology interface for potential applications in neuroscience.
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http://dx.doi.org/10.1039/d2mh00533fDOI Listing
June 2022

[Cost-benefit analysis of Ying Yang Bao (YYB) intervention in 6 to 23 months rural infants].

Wei Sheng Yan Jiu 2022 May;51(3):432-436

NHC Key Laboratory of Trace Element Nutrition, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To study on the cost-benefit from anemia and stunting reduction of Ying Yang Bao(YYB) intervention in 6 to 23 months rural infants in the six counties of Shanxi, Hubei and Yunnan provinces.

Methods: YYB was distributed to 6-23 months infants in 6 counties by YYB nutrition intervention project. The numbers of childhood recovered from stunting and anemia was collected by a designed project monitoring plan. The cost-benefit was analyzed with PROFILING model as a nutritional microeconomic tool.

Results: Total numbers of monitored infants was 10 672 while the total cost of YYB intervention was estimated 2.57 million RMB. From 2012 to 2020, the total benefit was 14.92 million RMB from recover of stunting and anemia by YYB project and the average cost-benefit ratio of 6 counties was 1∶5.8. Sensitivity analysis showed the result of this study was stable.

Conclusion: The YYB nutrition intervention for infants aged 6-23 months in the six counties of Shanxi, Hubei and Yunnan provinces showed a high cost-benefit ratio.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.015DOI Listing
May 2022

[Gut microbiota in Tibetan, Mongolian and Zhuang children aged 10-12 years old in 2016].

Wei Sheng Yan Jiu 2022 May;51(3):411-416

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To study the composition of gut microbiota of Tibetan, Mongolian and Zhuang children.

Methods: A total of 100 school-age children aged 10-12 were randomly selected from three ethnic groups in 2016, the Tibetan in Bayi County, Tibet, the Mongolian in Zha Qi, Inner Mongolia, and the Zhuang in Shanglin County, Nanning, Guangxi. Fecal samples were collected for high-throughput sequencing and bioinformatics analysis to compare the structural differences of gut microbiota of children from the three ethnic groups in the above areas.

Results: The result of α diversity analysis showed that the diversity and richness of gut microbiota of children from three ethnic groups in the surveyed area were different in pairwise comparison. The dominant phyla and genera of Tibetan children's gut bacteria are Firmicutes(54.01%), Bacteroidetes(31.13%), Prevotella(15.72%) and Faecalibacterium(15.46%). The dominant phyla and genera of Mongolian children's gut bacteria are Firmicutes(54.89%), Bacteroidetes(17.85%), Proteobacteria(15.99%), Faecalibacterium(20.84%) and Escherichia(17.52%). While in Zhuang children, the dominant phyla and genera are Firmicutes(50.86%), Bacteroidetes(34.74%), Prevotella(18.40%), Bacteroides(17.78%) and Faecalibacterium(14.68%).

Conclusion: The composition and structure of gut microbiota of Tibetan and Zhuang children in the three regions are similar, while the structure of gut microbiota of Mongolian children is obviously different from those of the first two regions.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.011DOI Listing
May 2022

Functional analysis of mutations endowing rAAV2-retro with retrograde tracing capacity.

Neurosci Lett 2022 Jun 16:136746. Epub 2022 Jun 16.

Shenzhen Key Laboratory for Molecular Biology of Neural Development, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, China. Electronic address:

Recombinant adeno-associated viruses (rAAVs) are widespread vectors in neuroscience research. However, the nearly absent retrograde access to projection neurons hampers their application in functional dissection of neural circuits and in therapeutic intervention. Recently, engineering of the AAV2 capsid has generated an AAV variant, called rAAV2-retro, with exceptional retrograde functionality. This variant comprises a 10-mer peptide insertion at residue 587 and two point mutations (LADQDYTKTA + V708I + N382D). Here, we evaluated the contribution of each mutation to retrograde transport in prefrontal cortex -striatum and amygdala-striatum pathways, respectively. Results showed that disruption of the inserted decapeptide almost completely abolishes the retrograde access to neurons projecting to striatum. Eliminating N382D has little effect on the retrograde functionality. Restoring another mutation V708I, however, even improves its performance in amygdala-striatum pathway. Parallel comparison within same animal further confirms this conflicting effect of V708I. These results demonstrate a pivotal role of decapeptide insertion in gaining the capacity of retrograde transport and highlight a neural circuit-dependent contribution of V708I. It suggests constant and custom engineering of rAAV2-retro might be required to tackle the challenge of tremendous neuronal heterogeneity.
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http://dx.doi.org/10.1016/j.neulet.2022.136746DOI Listing
June 2022

The efficacy of cognitive behavioral therapy-based intervention on patients with diabetes: A meta-analysis.

Diabetes Res Clin Pract 2022 Jun 16;189:109965. Epub 2022 Jun 16.

School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland Q422, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland Q422, Australia. Electronic address:

Aims: This meta-analysis aims to update former meta-analyses from randomized controlled trials (RCT) focused on the efficacy of CBT for diabetes.

Methods: Five databases were searched for RCTs. Primary outcomes were glycated hemoglobin (HbA), fasting blood glucose (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). Secondary outcomes were depression, anxiety and distress symptoms, quality of life, sleep quality.

Results: 32 RCTs were included. Results revealed that CBT could reduce HbA: -0.14% (95% CI: -0.25 to -0.02%, P = 0.020); FBS: -15.48 mg/dl (95% CI: -30.16 to -0.81 mg/dl, P = 0.040); DBP: -2.88 mmHg (95% CI: -4.08 to -1.69 mmHg, P < 0.001); depression symptoms: -0.90 (95% CI: -1.22 to -0.57, P < 0.001); anxiety symptoms: -0.28 (95% CI: -0.50 to -0.07, P = 0.009); improve sleep quality: -0.92 (95% CI: -1.77 to -0.07, P = 0.030). Subgroup analysis indicated that CBT has siginificantly reduced HbA when delivered as a group-based and face-to-face method, and psycho-education, behavioral, cognitive, goal-setting, homework assignment strategies were applied as central strategies.

Conclusion: CBT was an effective treatment for diabetes patients, significantly reduced their HbA, FBS, DBP, depression and anxiety symptoms, and improved sleep quality.
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http://dx.doi.org/10.1016/j.diabres.2022.109965DOI Listing
June 2022

Shared genetics between autism spectrum disorder and attention-deficit/hyperactivity disorder and their association with extraversion.

Psychiatry Res 2022 Jun 13;314:114679. Epub 2022 Jun 13.

Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China; Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

Background: Deciphering the genetic relationships between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) may uncover underlining shared pathophysiology as well as inform treatment.

Methods: The summary results of genome-wide association studies on ADHD, ASD, and extraversion were utilized for the analyzes. Genetic correlations between ADHD, ASD, and extraversion were tested using linkage disequilibrium score regression. Causal relationships between ADHD, ASD, and extraversion were investigated using Mendelian randomization (MR) analysis. Novel pleiotropic genomic loci shared by ADHD and ASD were identified using a cross-trait meta-analysis.

Results: Extraversion was positively correlated with ADHD (r = 0.205) and negatively correlated with ASD (r = -0.193). The MR analysis showed that ADHD confers a causal effect on ASD (OR: 1.35, 95% confidence interval (CI):1.20-1.52) and vice versa (1.46, 1.38-1.55). Extraversion exerts a causal effect on ADHD only (1.19, 1.05-1.33). The cross-trait meta-analysis identified three novel pleiotropic genomic loci for ADHD and ASD, involving two pleiotropic genes, LINC00461 and KIZ.

Conclusions: Our study provides new insights into the shared genetics of ADHD and ASD and their connections with extraversion.
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http://dx.doi.org/10.1016/j.psychres.2022.114679DOI Listing
June 2022

research of combination therapy for multidrug-resistant Klebsiella pneumoniae bloodstream infections.

J Int Med Res 2022 Jun;50(6):3000605221106705

Clinical Medical Laboratory Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, PR China.

Objective: Multidrug-resistant (MDR KP) bloodstream infections are a serious problem. The objective of this study was to investigate the effects of appropriate combination therapies on MDR KP bloodstream infections.

Methods: MDR KP strains isolated from clinical samples were assessed for antibiotic susceptibility using the broth microdilution method. Twenty consecutive MDR KP clinical isolates from patients with bloodstream infections were examined in this study. The experiments were conducted at the Bacterial Laboratory of Tongde Hospital from March to August 2021. Antibiotic combination tests were performed using the minimum inhibitory concentration (MIC) test, and the sum of the fractional inhibitory concentration was used to assess synergy.

Results: Following treatment with a combination of two antibiotic agents, the MIC50 and MIC90 values decreased compared with that before treatment. MIC50 decreased by at least 50%, with one value reduced to 6.25% of the pretreatment value. None of the antibiotic combinations were antagonistic. Combination of polymyxin B with rifampicin or tigecycline had a synergistic effect on 70% and 65% of the strains, respectively.

Conclusions: combination therapies with two active drug agents (polymyxin B plus rifampicin or tigecycline) had a better effect on MDR KP infections compared with that in other regimens.
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http://dx.doi.org/10.1177/03000605221106705DOI Listing
June 2022

Retraction notice to "Iron chelator-induced up-regulation of Ndrg1 inhibits proliferation and EMT process by targeting Wnt/β-catenin pathway in colon cancer cells" [Biochem. Biophys. Res. Commun. 506/1 (2018) 114-121].

Biochem Biophys Res Commun 2022 Jul;615:172

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China. Electronic address:

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The Editor-in-Chief has decided to retract this paper as the results cannot be relied upon. The authors contacted the editorial office admitting to outsourcing some of the experiments, specifically identifying that the Western Blot images were generated by a third-party laboratory. The authors tried to validate the results of the paper and obtain the raw data but were unable to do so, and offered to run additional experiments to correct the paper. The authors claim that the results and conclusions are still valid. The authors utilised potentially fraudulent data to generate their conclusions in this paper, which is in significant violation of journal policies and scientific best practice. The paper is therefore retracted.
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http://dx.doi.org/10.1016/j.bbrc.2022.05.097DOI Listing
July 2022

Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.

Eur J Epidemiol 2022 Jun 16. Epub 2022 Jun 16.

Department of Big Data in Health Science School of Public Health, and Centre of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption ("drinks per week") and pathological drinking behaviours ("alcohol use disorder" and "problematic alcohol use"), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose-response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption ("drinks per week") was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.
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http://dx.doi.org/10.1007/s10654-022-00886-1DOI Listing
June 2022

Androgen receptor-mediated CD8 T cell stemness programs drive sex differences in antitumor immunity.

Immunity 2022 Jun 10. Epub 2022 Jun 10.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

The incidence and mortality rates of many non-reproductive human cancers are generally higher in males than in females. However, the immunological mechanism underlying sexual differences in cancers remains elusive. Here, we demonstrated that sex-related differences in tumor burden depended on adaptive immunity. Male CD8 T cells exhibited impaired effector and stem cell-like properties compared with female CD8 T cells. Mechanistically, androgen receptor inhibited the activity and stemness of male tumor-infiltrating CD8 T cells by regulating epigenetic and transcriptional differentiation programs. Castration combined with anti-PD-L1 treatment synergistically restricted tumor growth in male mice. In humans, fewer male CD8 T cells maintained a stem cell-like memory state compared with female counterparts. Moreover, AR expression correlated with tumor-infiltrating CD8 T cell exhaustion in cancer patients. Our findings reveal sex-biased CD8 T cell stemness programs in cancer progression and in the responses to cancer immunotherapy, providing insights into the development of sex-based immunotherapeutic strategies for cancer treatment.
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http://dx.doi.org/10.1016/j.immuni.2022.05.012DOI Listing
June 2022

Multiplex immunochromatographic platform based on crystal violet tag for simultaneous detection of streptomycin and chloramphenicol.

Food Chem 2022 Nov 3;393:133351. Epub 2022 Jun 3.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Antibiotic abuse has caused serious health risks for human beings for long. To address the problem, novel and facile detection techniques are highly desired. Here, an effective multiplex immunochromatographic platform (MICP) with synthesis-free and cost-effective merits is established for simultaneous detection of antibiotics on a single immunochromatographic assay (ICA) strip. Adopting crystal violet (CV) as a signal tag for multiplex ICA allows for direct coupling with multiple antibodies in several minutes. By combining CV and ICA perfectly, this convenient strategy offers improvements in convenience, speed, flexibility, and portability, eventually ensuring the optimized effectiveness of this approach. As a result, the established platform is successfully used to detect streptomycin (STR) and chloramphenicol (CAP) with visual detection mode, and the obtained total recoveries of milk and honey real samples changed from 83.82 to 113.38% with total RSD values of 0.48 to 4.15%.
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http://dx.doi.org/10.1016/j.foodchem.2022.133351DOI Listing
November 2022

An endolysin Salmcide-p1 from bacteriophage fmb-p1 against gram-negative bacteria.

J Appl Microbiol 2022 Jun 11. Epub 2022 Jun 11.

College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, Jiangsu Province, China.

Aims: A novel endolysin Salmcide-p1 was developed as a promising candidate of new preservative and a supplement to effective enzyme preparations against gram-negative bacterial contaminations.

Methods And Results: Salmcide-p1 was identified by complementing the genomic sequence of a virulent Salmonella phage fmb-p1. Salmcide-p1 of 112 μg ml could quickly kill Salmonella incubated with 100 mmol l EDTA, with no haemolytic activity. Meanwhile, Salmcide-p1 had a high activity of lysing Salmonella cell wall peptidoglycan. At different temperatures (4-75°C), pH (4-11) and NaCl concentration (10-200 mmol l ), the relative activity of Salmcide-p1 was above 60%. At 4°C, the combination of Salmcide-p1 and EDTA-2Na could inhibit the number of Salmonella Typhimurium CMCC 50115 in skim milk to less than 4 log CFU ml by 3 days, and the number of Shigella flexneri CMCC 51571 was lower than 4 log CFU ml by 9 days.

Conclusions: Salmcide-p1 had a wide bactericidal activity against gram-negative bacteria and showed a broader anti-Salmonella spectrum than the phage fmb-p1. The combination strategy of Salmcide-p1 and EDTA-2Na could significantly inhibit the growth of gram-negative bacteria inoculated in skim milk.

Significance And Impact Of The Study: Bacteriophage endolysin as an antibacterial agent is considered to be a new strategy against bacterial contamination.
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http://dx.doi.org/10.1111/jam.15661DOI Listing
June 2022

Effects of Peroxyl Radicals on the Structural Characteristics and Fatty Acid Composition of High-Density Lipoprotein from Duck Egg Yolk.

Foods 2022 Jun 1;11(11). Epub 2022 Jun 1.

Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Science, Wuhan 430072, China.

In this study, high-density lipoprotein (HDL) from duck egg yolk was subjected to oxidation with a system based on 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-derived peroxyl radicals. The effects of peroxyl radicals on the protein carbonyl, free sulfhydryl, secondary/tertiary structure, surface hydrophobicity, solubility, particle size distribution, zeta potential and fatty acid composition of HDL were investigated by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier-transform infrared spectroscopy (FTIR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The results indicated that the content of protein carbonyl was significantly increased, that of free sulfhydryl was obviously reduced, and the ordered secondary structure was also decreased with increasing AAPH concentration. In addition, the surface hydrophobicity and solubility of HDL showed apparent increases due to the exposure of hydrophobic groups and aggregation of protein caused by oxidation. The fatty acid composition of HDL exhibited pronounced changes due to the disrupted protein-lipid interaction and lipid oxidation by AAPH-derived peroxyl radicals. These results may help to elucidate the molecular mechanism for the effect of lipid oxidation products on the oxidation of duck yolk proteins.
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http://dx.doi.org/10.3390/foods11111634DOI Listing
June 2022

Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study.

Blood Adv 2022 Jun 9. Epub 2022 Jun 9.

Department of Hematology, Hebei Institute of Hematology, The Second Hospital of Hebei Medical University, Hebei, China.

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nation-wide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China during 2005-2020, the mortality rate from ICH was 33.80% in ITP adults (48/142). We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10×109/L at ICH, a combination of serious infections, grade of preceding bleeding events and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic curves for the internal and external validation were 0.954 (95% CI: 0.910~0.998) and 0.942 (95% CI: 0.871~1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.
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http://dx.doi.org/10.1182/bloodadvances.2022007226DOI Listing
June 2022

An Integrated Strategy to Identify and Quantify the Quality Markers of Xinkeshu Tablets Based on Spectrum-Effect Relationship, Network Pharmacology, Plasma Pharmacochemistry, and Pharmacodynamics of Zebrafish.

Front Pharmacol 2022 23;13:899038. Epub 2022 May 23.

NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Xinkeshu tablets (XKST), a traditional Chinese patent medicine (CPM), have served in the clinical treatment of cardiovascular diseases (CVDs) for decades. However, its pharmacodyamic material basis was still unclear, and the holistic quality control has not been well established due to the lack of systematic research on the quality markers. In this experiment, the heart rate recovery rate of a zebrafish larva was used to evaluate the traditional pharmacological effect of XKST i.e., antiarrhythmic effect. The HPLC fingerprints of 16 batches of XKST samples were obtained, and antiarrhythmic components of XKST were identified by establishing the spectrum-effect relationship between HPLC fingerprints and heart rate recovery rate of zebrafish larva with orthogonal signal correction and partial least squares regression (OSC-PLSR) analysis. The anticardiovascular disease components of XKST were identified by mapping the targets related to CVDs in network pharmacology. The compounds of XKST absorbed and exposed were identified by ultra-high performance liquid chromatography Q-Exactive high-resolution mass spectrometry (UHPLC-Q-Exactive HRMS). Based on the earlier studies, combined with five principles for identifying quality markers and verified by a zebrafish arrhythmia model, danshensu, salvianolic acid A, salvianolic acid B, daidzein, and puerarin were identified as quality markers of XKST. In total, 16 batches of XKST samples were further quantified with the method established in this study. Our study laid the foundation for the quality control of XKST. The integrated strategy used in the study of XKST could be applied for the identification and quantification of quality markers of other CPMs as well.
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http://dx.doi.org/10.3389/fphar.2022.899038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170229PMC
May 2022

The risk and consequences of breakthrough SARS-CoV-2 infection in solid organ transplant recipients relative to non-immunosuppressed controls.

Am J Transplant 2022 Jun 8. Epub 2022 Jun 8.

Division of Nephology, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Clinical outcomes in solid organ transplant (SOT) recipients with breakthrough COVID (BTCo) after two doses of mRNA vaccination compared to the non-immunocompromised/immunosuppressed (ISC) general population, are not well described. In a cohort of adult patients testing positive for COVID-19 between December 10, 2020 and April 4, 2022, we compared the cumulative incidence of BTCo in a non-ISC population to SOT recipients (overall and by organ type) using the National COVID Cohort Collaborative (N3C) including data from 36 sites across the United States. We assessed the risk of complications post-BTCo in vaccinated SOT recipients versus SOT with unconfirmed vaccination status (UVS) using multivariable Cox proportional hazards and logistic regression. BTCo occurred in 4776 vaccinated SOT recipients over a median of 149 days (IQR 99-233), with the highest cumulative incidence in heart recipients. The relative risk of BTCo was greatest in SOT recipients (relative to non-ISC) during the pre-Delta period (HR 2.35, 95% CI 1.80-3.08). The greatest relative benefit with vaccination for both non-ISC and SOT cohorts was in BTCo mortality (HR 0.37, 95% CI 0.36-0.39 for non-ISC; HR 0.67, 95% 0.57-0.78 for SOT relative to UVS). While the relative benefit of vaccine was less in SOT than non-ISC, SOT patients still exhibited significant benefit with vaccination.
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http://dx.doi.org/10.1111/ajt.17117DOI Listing
June 2022

Exploring the comorbidity mechanisms between asthma and idiopathic pulmonary fibrosis and the pharmacological mechanisms of Bu-Shen-Yi-Qi decoction therapy via network pharmacology.

BMC Complement Med Ther 2022 Jun 7;22(1):151. Epub 2022 Jun 7.

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Backgrounds: Asthma and idiopathic pulmonary fibrosis (IPF) are common chronic diseases of the respiratory system in clinical practice. However, the relationship and molecular links remain unclear, and the current treatment's efficacy is disappointing. Bu-Shen-Yi-Qi (BSYQ) decoction has proven effective in treating various chronic airway inflammatory diseases, including asthma and IPF. But the underlying pharmacological mechanisms are still to be elucidated.

Methods: This study searched the proteins related to asthma and IPF via TTD, CTD, and DisGeNET databases and then submitted to the STRING to establish the protein-protein interaction (PPI) network. The co-bioinformatics analysis was conducted by Metascape. The active ingredients of BSYQ decoction were screened from TCMSP, ETCM, BATMAN-TCM databases, and HPLC/MS experiment. The corresponding targets were predicted based on TCMSP, ETCM, and BATMAN-TCM databases. The shared targets for asthma and IPF treatment were recognized, and further GO and KEGG analyses were conducted with the DAVID platform. Finally, molecule docking via Autodock Vina was employed to predict the potential binding mode between core potential compounds and targets.

Results: Finally, 1333 asthma-related targets and 404 IPF-related proteins were retrieved, 120 were overlapped between them, and many of the asthma-related proteins fall into the same statistically significant GO terms with IPF. Moreover, 116 active ingredients of BSYQ decoction were acquired, and 1535 corresponding targets were retrieved. Eighty-three potential compounds and 56 potential targets were recognized for both asthma and IPF treatment. GO and KEGG analysis indicated that the inflammation response, cytokine production, leukocyte differentiation, oxygen level response, etc., were the common pathological processes in asthma and IPF, which were regulated by BSYQ decoction. Molecule docking further predicted the potential binding modes between the core potential compounds and targets.

Conclusion: The current study successfully clarified the complex molecule links between asthma and IPF and found the potential common targets. Then we demonstrated the efficacy of BSYQ decoction for asthma and IPF treatment from the angle of network pharmacology, which may provide valuable references for further studies and clinical use.
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http://dx.doi.org/10.1186/s12906-022-03637-7DOI Listing
June 2022

In vitro degradation and erosion behavior of commercial PLGAs used for controlled drug delivery.

Drug Deliv Transl Res 2022 Jun 7. Epub 2022 Jun 7.

Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.

Copolymers of lactic (or lactide) and glycolic (or glycolide) acids (PLGAs) are among the most commonly used materials in biomedical applications, such as parenteral controlled drug delivery, due to their biocompatibility, predictable degradation rate, and ease of processing. Besides manufacturing variables of drug delivery vehicles, changes in PLGA raw material properties can affect product behavior. Accordingly, an in-depth understanding of polymer-related "critical quality attributes" can improve selection and predictability of PLGA performance. Here, we selected 19 different PLGAs from five manufacturers to form drug-free films, submillimeter implants, and microspheres and evaluated differences in their water uptake, degradation, and erosion during in vitro incubation as a function of L/G ratio, polymerization method, molecular weight, end-capping, and geometry. Uncapped PLGA 50/50 films from different manufacturers with similar molecular weights and higher glycolic unit blockiness and/or block length values showed faster initial degradation rates. Geometrically, larger implants of 75/25, uncapped PLGA showed higher water uptake and faster degradation rates in the first week compared to microspheres of the same polymers, likely due to enhanced effects of acid-catalyzed degradation from PLGA acidic byproducts unable to escape as efficiently from larger geometries. Manufacturer differences such as increased residual monomer appeared to increase water uptake and degradation in uncapped 50/50 PLGA films and poly(lactide) implants. This dataset of different polymer manufacturers could be useful in selecting desired PLGAs for controlled release applications or comparing differences in behavior during product development, and these techniques to further compare differences in less reported properties such as sequence distribution may be useful for future analyses of PLGA performance in drug delivery.
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http://dx.doi.org/10.1007/s13346-022-01177-8DOI Listing
June 2022

Association Between Sleep Duration and Albuminuria in Patients with Type 2 Diabetes: A Cross-Sectional Study in Ningbo, China.

Diabetes Metab Syndr Obes 2022 30;15:1667-1675. Epub 2022 May 30.

Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, People's Republic of China.

Purpose: Type 2 diabetes mellitus (T2DM) can lead to microvascular complications including diabetic kidney disease. Albuminuria is an important marker to diagnose kidney injury in T2DM patients and healthy sleep duration is important for maintaining good health in patients with T2DM. However, the association between sleep duration and albuminuria in T2DM patients is unclear. Thus, this study aimed to investigate the association between sleep duration and albuminuria in patients with T2DM in Ningbo, China.

Methods: A cross-sectional study was conducted at National Metabolic Management Centre (MMC) - Ningbo First Hospital from March 2018 to February 2021. Adult patients with T2DM were included in the study. The sleep duration (daytime and nocturnal) was self-reported. Albuminuria was defined as the presence of urinary albumin-creatinine ratio ≥30 mg/g. Logistic regression analyses were performed to identify the association.

Results: There were 2688 T2DM patients in the study. In the unadjusted model (1), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: OR 1.36, 95% CI 1.09-1.71; ≥61 minutes: 1.73, 1.33-2.24). Similarly, after adjusting for age and sex (model 2), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: 1.34, 1.07-1.68; ≥61 minutes: 1.69, 1.30-2.20). After adjusting for age, sex, physical activity, smoking, alcohol drinking, overweight/obesity, hypertension, hyperuricaemia, duration of T2DM, glycated haemoglobin, angiotensin-converting enzyme inhibitors/angiotensin receptor blocker usage and nocturnal sleep duration (model 3), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: 1.33, 1.04-1.71; ≥61 minutes: 1.71, 1.29-2.26). However, no relationship was found between nocturnal sleep duration and albuminuria.

Conclusion: Longer daytime sleep is found to be associated with albuminuria in patients with T2DM in Ningbo, China but no association is found between nocturnal sleep duration and albuminuria. The findings are exploratory, and there is a need for longitudinal studies on this topic.
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http://dx.doi.org/10.2147/DMSO.S366064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166454PMC
May 2022

Functional analysis and expression profile of human platelets infected by EBV in vitro.

Infect Genet Evol 2022 Aug 3;102:105312. Epub 2022 Jun 3.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China. Electronic address:

Platelet activation is commonly detected after infection by multiple viruses such as human immunodeficiency virus (HIV), H1N1 influenza, Hepatitis C virus (HCV), Ebola virus (EBV), and Dengue virus (DENV). Non-coding RNAs (ncRNAs) constitute the majority of the human transcribed genome, but the biology of platelet ncRNAs is largely unexplored. In this study, we performed microarray profiling to characterize the expression profile of human platelets infected with EBV in vitro after 2 h. A total of 187 long non-coding RNAs (lncRNAs) displayed differences, of which 114 were upregulated and 73 were downregulated; 78 microRNAs (miRNAs) showed differences, including 73 upregulated and 5 downregulated; 808 mRNAs displayed differences, among which 367 were upregulated and 441 were downregulated. Gene ontology (GO) analysis mostly related to G protein-coupled receptor signaling pathway, detection of chemical stimulus involved in sensory perception of smell and regulation of transcription by RNA polymerase II. Pathway analysis showed that the differentially expressed genes were mainly enriched in cell metabolism and immune-related response. A ceRNA network was established based on predicting regulatory pairs in differentially expressed genes, in which hsa-miR-6877-3p had the highest regulatory capability (degree = 31), FAM230A was the lncRNA with the highest regulatory capability (degree = 28). According to the EBV related miRNA regulation network, it revealed that ebv-miR-BART19-3p had the most target genes and BRWD1, FAM126B, TFRC and JMY were the genes most regulated by EBV-related miRNAs. After overlapping the three networks, we found that the EIFAK2 gene was strongly correlated with autologous ncRNAs, including hsa-miR-1972, hsa-miR-504-3p and hsa-miR-6825-5p, as well as with EBV ncRNAs, including EBER1, EBER2, miR-BART7-3p and miR-BART16. The present study contributes to a better understanding of the expression profiling of ncRNAs and their functions in platelets activated by EBV in vitro, and paves the way to further study on platelet function.
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http://dx.doi.org/10.1016/j.meegid.2022.105312DOI Listing
August 2022

Expression of tumour transcription factor GLI1 in canine mammary tumours tissue.

Vet Med Sci 2022 Jun 6. Epub 2022 Jun 6.

College of Veterinary Medicine, YangZhou University, YangZhou, China.

Background: Mammary tumor is one of the most common diseases of canine in pet clinics.

Objectives: This study investigates the distribution and expression of the tumor transcription factor GLI1 and the downstream proteins, Bmi1 and Sox2, in canine mammary tumors and paracancerous tissues.

Methods: Cancerous and paracancerous normal mammary tissues were detected using western blotting (WB), and immunohistochemistry.

Results: The results showed that the histopathology of different types in mammary tumors by microscopic observation. GLI1/Bmi1/Sox2 expression was significantly higher in canine mammary invasive carcinoma than in ductal carcinoma and adjacent normal mammary tissues (p < 0.01). The expression of GLI1 in invasive carcinoma tissues was significantly higher than Bmi1 and Sox2, while Sox2 expression in ductal carcinoma tissues was significantly higher than GLI1 and Bmi1 (p < 0.01). GLI1/Bmi1/Sox2 all showed positive reactions in both mammary tumor and adjacent normal mammary tissues with immunohistochemistry. GLI1 and Sox2 showed strong positive staining in the cytoplasm of invasive mammary carcinoma and ductal carcinoma cells, and weak positive staining in the nuclei. The positive Bmi1 reaction was mainly concentrated in the cytoplasm of invasive carcinoma and ductal carcinoma cells, while the positive reaction on the cell membrane was weak.

Conclusions: We speculate that GLI1 and related proteins play an important role in regulating the proliferation and differentiation of tumors. Therefore, it provides important reference for the pathogenesis and pathogenicity of canine mammary tumor.
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http://dx.doi.org/10.1002/vms3.830DOI Listing
June 2022

COVID-19-inspired "artificial virus" to combat drug-resistant bacteria by membrane-intercalation- photothermal-photodynamic multistage effects.

Chem Eng J 2022 Oct 31;446:137322. Epub 2022 May 31.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China.

COVID-19 threatens human life because of the super destructiveness produced from its coronal morphology and strong transmembrane infection based on spike glycoprotein. Inspired by the coronal morphology of COVID-19 and its means of infecting, we designed an "artificial virus" with coronal morphology based on the concept of "defeating superbacteria with superviruses" by self-assembling a transacting activator of transduction peptide with triple-shell porous graphitic carbon nitride (g-CN) embedded with cobalt nanoparticles to forcefully infect methicillin-resistant (MRSA). The results confirmed that this "artificial virus" had unique properties of crossing the bacterial cell membrane barrier, heating the internal bacterial microenvironment and triggering ROS outbreak, based on its coronal morphology, membrane penetration, temperature-rising and heat insulation, oxidase-like activity and excellent visible-light harvesting properties. It had a high sterilization efficiency of 99.99% at 20 min, which was 18.6 times that of g-CN, and the efficiency remained at 99.99% after 3 rounds of recycling and reuse. Additionally, it can rapidly inactivate bacteria in river water and accelerate wound healing.
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http://dx.doi.org/10.1016/j.cej.2022.137322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153178PMC
October 2022

miR143-3p-Mediated NRG-1-Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia.

Biol Psychiatry 2022 Mar 26. Epub 2022 Mar 26.

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: Olanzapine is an effective antipsychotic medication for treatment-resistant schizophrenia (TRS); however, the therapeutic effectiveness of olanzapine has been found to vary in individual patients. It is imperative to unravel its resistance mechanisms and find reliable targets to develop novel precise therapeutic strategies.

Methods: Unbiased RNA sequencing analysis was performed using homogeneous populations of neural stem cells derived from induced pluripotent stem cells in 3 olanzapine responder (reduction of Positive and Negative Syndrome Scale score ≥25%) and 4 nonresponder (reduction of Positive and Negative Syndrome Scale score <25%) inpatients with TRS. We also used a genotyping study from patients with TRS to assess the candidate genes associated with the olanzapine response. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9-mediated genome editing, neurologic behavioral tests, RNA silencing, and microRNA sequencing were used to investigate the phenotypic mechanisms of an olanzapine resistance gene in patients with TRS.

Results: Neuregulin-1 (NRG-1) deficiency-induced mitochondrial dysfunction is associated with olanzapine treatment outcomes in TRS. NRG-1 knockout mice showed schizophrenia-relevant behavioral deficits and yielded olanzapine resistance. Notably, miR143-3p is a critical NRG-1 target related to mitochondrial dysfunction, and miR143-3p levels in neural stem cells associate with severity to olanzapine resistance in TRS. Meanwhile, olanzapine resistance in NRG-1 knockout mice could be rescued by treatment with miR143-3p agomir via intracerebral injection.

Conclusions: Our findings provide direct evidence of olanzapine resistance resulting from NRG-1 deficiency-induced mitochondrial dysfunction, and they link olanzapine resistance and NRG-1 deficiency-induced mitochondrial dysfunction to an NRG-1/miR143-3p axis, which constitutes a novel biomarker and target for TRS.
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http://dx.doi.org/10.1016/j.biopsych.2022.03.012DOI Listing
March 2022

Association between polymorphisms of ABCB1 and prognosis in esophageal squamous cell carcinoma patients treated with taxane.

J Gene Med 2022 Jun 4:e3434. Epub 2022 Jun 4.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), The VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, Beijing, China.

Background: In China, most esophageal cancer patients are squamous cell carcinomas and are treated with taxane-containing regimens; however, few studies have examined taxane pharmacokinetics genes and esophageal squamous cell carcinoma (ESCC) prognosis.

Methods: In total, 227 pathologically confirmed ESCC patients receiving chemotherapy with taxane were included in the analysis. We genotyped seven SNPs (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; and ABCC1 rs246221 and ABCC2 rs3740066) and analyzed their relationship with overall survival.

Results: With a retrospective cohort study design, by Cox regression and semi-Bayesian shrinkage, in the genetic recessive model, the variant homozygote of ABCB1 rs1045642 was inversely associated with survival (semi-Bayesian shrinkage crude hazard ratio = 1.82, 95% confidence interval = 1.00, 3.31; p = 0.0482).

Conclusions: Because of inherent defects of the research itself, the finding that the ABCB1 rs1045642 variant was related to poor prognosis in ESCC patients treated with taxane-containing regimens needs to be tested in a larger population and by using more genetic and molecular mechanism experiments.
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http://dx.doi.org/10.1002/jgm.3434DOI Listing
June 2022

Mucus-permeable polymyxin B-hyaluronic acid/ poly (lactic-co-glycolic acid) nanoparticle platform for the nebulized treatment of lung infections.

J Colloid Interface Sci 2022 Oct 21;624:307-319. Epub 2022 May 21.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.

The aim of this study was to improve the bioavailability of polymyxin B (PMB) in pulmonary nebulized drug delivery. To this end, we developed a nano-delivery system that penetrates the mucus barrier of the lung. Hydrophilic hyaluronic acid (HA) was combined with a water-in-oil system containing a poly (lactic acid)-glycolic acid copolymer of PMB to prepare [email protected] nanoparticles (NPs) with good surface properties. [email protected] NPs with suitable electrical properties, particle size, and good hydrophilicity prevented strong interactions between the NPs and mucus, thereby allowing more drugs to enter deeper into the lung. Compared to the free drug PMB, NPs had more than 2-fold higher mucus penetration efficiency in vitro and better delivery to infected alveolar cells during in vivo nebulization. NPs had better biocompatibility, which further reduced the drug toxicity. More importantly, NPs showed better antimicrobial therapeutic efficacy in the treatment of lung infections in mice. These findings may provide support for the clinical application of nebulized pulmonary antibiotics.
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http://dx.doi.org/10.1016/j.jcis.2022.05.121DOI Listing
October 2022

Domino reaction of bindone and 1,3-dipolarophiles for the synthesis of diverse spiro and fused indeno[1,2-]fluorene-7,12-diones.

Org Biomol Chem 2022 Jun 22;20(24):4964-4969. Epub 2022 Jun 22.

College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China.

The base promoted domino reaction of bindone ([1,2'-biindenylidene]-1',3,3'-trione) with common 1,3-dipolarophiles showed interesting molecular diversities, from which the unique spiro and fused indeno[1,2-]fluorine derivatives were conveniently synthesized in satisfactory yields. In the presence of a base, bindone underwent formal [3 + 3] cycloaddition with satylidene malononitriles to give dispiro[indene-2,4'-fluorene-1',3''-indoline]. It also underwent formal [4 + 2] cycloaddition with 4-arylidene-pyrazol-3-ones to give diastereoisomeric spiro[indeno[1,2-]fluorene-5,4'-pyrazole]. On the other hand, a triethylamine promoted reaction of three molecules of 1,3-indanediones and isatins in toluene afforded spiro[diindeno[2,1-:2',1'-]anthracene-11,3'-indoline] derivatives through the domino [4 + 2] cycloaddition and ring-expansion process.
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http://dx.doi.org/10.1039/d2ob00815gDOI Listing
June 2022

Preoperative c-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

J Surg Oncol 2022 Jun 2. Epub 2022 Jun 2.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

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http://dx.doi.org/10.1002/jso.26927DOI Listing
June 2022

Preparation of a Novel Type of Zwitterionic Polymer and the Antifouling PDMS Coating.

Biomimetics (Basel) 2022 Apr 21;7(2). Epub 2022 Apr 21.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.

As awareness of environmental protection increases, environmentally friendly coatings have been receiving great interest. Zwitterionic polymers are considered promising candidates due to their biocompatibility and excellent antifouling properties. In this paper, a type of polypeptoid containing zwitterions on the side chain was synthesized via ring-opening polymerization (ROP) and post-modification. This obtained polypeptoid was subsequently grafted onto the surface of polydimethylsiloxane (PDMS) via plasma and UV-induced surface polymerization. Surface morphology and protein adsorption tests of the resulting coating were systematically carried out. The results show that the modified coating has excellent antifouling properties and thus has great potential for environmentally friendly coating applications.
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http://dx.doi.org/10.3390/biomimetics7020050DOI Listing
April 2022

Verification of genetic differences and immune cell infiltration subtypes in the neuroblastoma tumour microenvironment during immunotherapy.

World J Surg Oncol 2022 May 28;20(1):169. Epub 2022 May 28.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Background: Improved understanding of the tumour microenvironment (TME) has enabled remarkable advancements in research on cancer progression in the past few years. It is crucial to understand the nature and function of the TME because precise treatment strategies, including immunotherapy, for managing specific cancers have received widespread attention. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research was to analyse tumour immune cell infiltration (ICI) in the microenvironment of NB.

Methods: We applied the CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected, and ICI scores were acquired. Subgroups with high ICI scores determined based on the presence of immune activation signalling pathways had better overall survival.

Results: Genes involved in the immunosuppressive heparan sulphate glycosaminoglycan biosynthesis signalling pathway were markedly enriched in the low ICI score subgroup. It was inferred that patients with high ICI NB subtypes were more likely to respond to immunotherapy and have a better prognosis than those of patients with low ICI NB subtypes.

Conclusion: Notably, our ICI data not only provide a new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment but also offer new ideas for the development of NB precision immunotherapy methods.
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http://dx.doi.org/10.1186/s12957-022-02641-yDOI Listing
May 2022
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