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Bacterial microcompartment-mimicking Pickering emulsion droplets for detoxification of chemical threats under sweet conditions

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Science China Chemistry 2024年

作者： Xiao Xu Wenqi Xie Ting Wu Chen Chen Xiaoning Chen Yuheng Yang Hao Lian Hao Chen Xiaofeng Cheng Zhitong Chen Guojun Chen Chaoqun Liu Lanlan Chen Yu He Zhaowei Chen Bernard P.Binks Huanghao Yang New Cornerstone Science Laboratory MOE Key Laboratory for Analytical Science of Food Safety and Biology College of ChemistryFuzhou University Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Department of Biomedical Engineering and the rosalind & morris goodman cancer research Institute McGill University School of Pharmacy Henan University Department of Chemistry University of Hull

Chemical warfare agents represent a severe threat to mankind and their efficient decontamination is a global necessity. However,traditional disposal strategies have limitations, including high energy consumption, use of aggressive reagents and generation of toxic byproducts. Here, inspired by the compartmentalized architecture and detoxification mechanism of bacterial microcompartments, we constructed oil-in-water Pickering emulsion droplets stabilized by hydrogen-bonded organic framework immobilized cascade enzymes for decontaminating mustard gas simulant(2-chloroethyl ethyl sulfide, CEES) under sweet conditions. Two exemplified droplet systems were developed with two-enzyme(glucose oxidase/chloroperoxidase) and threeenzyme(invertase/glucose oxidase/chloroperoxidase) cascades, both achieving over 6-fold enhancement in decontamination efficiency compared with free enzymes and >99% selectivity towards non-toxic sulfoxide. We found that the favored mass transfer of sugars and CEES from their respective phases to approach the cascade enzymes located at the droplet surface and the facilitated substrate channeling between proximally immobilized enzymes were key factors in augmenting the decontamination efficacy. More importantly, the robustness of immobilized enzymes enabled easy reproduction of both the droplet formation and detoxification performance over 10 cycles, following long-term storage and in far-field locations.

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Loss of T-cell protein tyrosine phosphatase in the intestinal epithelium promotes local inflammation by increasing colonic stem cell proliferation

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Cellular & Molecular Immunology 2018年第4期15卷 367-376页

作者： Stéphanie Bussières-Marmen Valérie Vinette Jeremy Gungabeesoon Isabelle Aubry Luis Alberto Pérez-Quintero Michel L Tremblay Department of Biochemistry McGill UniversityMontréalQuébecCanada rosalind and morris goodman cancer research centre MontréalQuébecCanada Department of Microbiology and Immunology McGill UniversityMontréalQuébecCanada

T-cell protein tyrosine phosphatase(TC-PTP)has a critical role in the development of the immune system and has been identified as a negative regulator of ***-nucleotide polymorphisms in the TC-PTP locus have been associated with increased susceptibility to inflammatory bowel diseases(IBDs)in *** further understand how TC-PTP is related to IBDs,we investigated the role of TC-PTP in maintaining the intestinal epithelial barrier using an in vivo genetic *** epithelial cell(IEC)-specific deletion of TC-PTP was achieved in a mouse model at steady state and in the context of dextran sulphate sodium(DSS)-induced ***(KO)of TC-PTP in IECs did not result in an altered intestinal ***,upon DSS treatment,IECspecific TC-PTP KO mice displayed a more severe colitis phenotype with a corresponding increase in the immune response and inflammatory cytokine *** absence of TC-PTP caused an altered turnover of IECs,which is further explained by the role of the tyrosine phosphatase in colonic stem cell(CoSC)*** results suggest a novel role for TC-PTP in regulating the homeostasis of CoSC *** supports the protective function of TC-PTP against IBDs,independently of its previously demonstrated role in intestinal immunity.

关键词： Colonic stem cells DSS-induced colitis intestinal epithelial barrier TC-PTP

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Preclinical-to-clinical Anti-cancer Drug Response Prediction and Biomarker Identification Using TINDL

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 535-550页

作者： David Earl Hostallero Lixuan Wei Liewei Wang Junmei Cairns Amin Emad Department of Electrical and Computer Engineering McGill UniversityMontrealQC H3A 0E9Canada Mila–Quebec Artificial Intelligence Institute MontrealQC H2S 3H1Canada Department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN 55905USA The rosalind and morris goodman cancer Institute McGill UniversityMontrealQC H3A 1A3Canada

Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized ***,we developed a deep learning framework called TINDL,completely trained on preclinical cancer cell lines(CCLs),to predict the response of cancer patients to different *** utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient ***,by making the deep learning black box interpretable,this model identifies a small set of genes whose expression levels are predictive of drug response in the trained model,enabling identification of biomarkers of drug *** data from two large databases of CCLs and cancer tumors,we showed that this model can distinguish between sensitive and resistant tumors for 10(out of 14)drugs,outperforming various other machine learning *** addition,our small interfering RNA(siRNA)knockdown experiments on 10 genes identified by this model for one of the drugs(tamoxifen)confirmed that tamoxifen sensitivity is substantially influenced by all of these genes in MCF7 cells,and seven of these genes in T47D ***,genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling *** summary,this study provides a powerful deep learning framework for prediction of drug response and identification of biomarkers of drug response in *** code can be accessed at https://***/ddhostallero/tindl.

关键词： Drug response Deep learning Explainable AI cancer Gene knockdown experiment

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The Transmission,Establishment and Cross-cultural Integration of Chinese Medicine in the Mainstream Healthcare,through the Eyes of a Generation of Visionaries and Pioneers

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Chinese Medicine and Culture 2024年第1期7卷 1-4页

作者： Ioannis Solos Charles Buck Saint George Clinic and research Institute Scottsdale 85251the United States of America Northern College of Acupuncture Micklegate YO16LJthe United Kingdom

It has historically been very difficult to trace the history of the westward transmission of Chinese medicine through the accounts of its protagonists. Many of the early scholars such as Jack Worsley, Dick Van Buren, and Joe goodman were reluctant to divulge information about the source of their knowledge, or their professional qualifications. Others, such as John Shen and Hong Yuan-bain were early 20th century immigrants who transmitted highly personalized versions of acupuncture and Chinese medicine to select disciples. Eventually, a new class of scholars appeared, including names such as Ted Kaptchuk, Peter Deadman, Nigel Wiseman, William morris, Peter Eckman, John Mc Donald, Charles Buck, and the late Giovanni Maciocia who looked for answers back in China, developed translation methodologies and terminology, compiled the main textbooks currently in use at TCM colleges, overcame enormous scholastic adversity, developed courses and pursued the regulation and accreditation of TCM in various countries. This special issue synopsizes the path towards the global acculturation of TCM over the last 50 years, the main protagonists, the enormous accomplishments they have achieved for the profession, their philosophy, their clinical perspectives and visions for the future.

关键词： Chinese medicine Cross-cultural integration Westward transmission James Reston Acupuncture History

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Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis

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Protein & Cell 2020年第3期11卷 187-201页

作者： Henry Y.Jiang Sara Najmeh Guy Martel Elyse MacFadden-Murphy Raquel Farias Paul Savage Arielle Leone Lucie Roussel Jonathan Cools-Lartigue Stephen Gowing Julie Berube Betty Giannias France Bourdeau Carlos HFChan Jonathan D.Spicer Rebecca McClure Morag Park Simon Rousseau Lorenzo E.Ferri Thoracic and Upper GI cancer research Laboratories Research Institute of McGill University Health Centre1001 Decarie BoulevardBlock ELab#E02-4134MontrealQC H4A 3J1Canada Department of Experimental Surgery and Department of Surgery McGill University1650 Cedar AvenueMontrealQC H3G 1A4Canada Meakins-Christie Laboratories Research Institute of McGill University Health Centre1001 Decarie BoulevardMontrealQC H4A 3J1Canada the rosalind and morris goodman cancer research centre McGill University1160 Pine AvenueMontrealQC H3A 1A3Canada Department of Surgery Roy J.and Lucille A.Carver College of MedicineUniversity of IowaUniversity of Iowa Hospitals and Clinics200 Hawkins DriveIowa CityIA 52242USA Department of Pathology Health Sciences North41 Ramsey Lake RoadSudburyONCanada

While emerging data suggest nucleotide oligomerization domain receptor 1(NOD1),a cytoplasmic pattern recognition receptor,may play an important and complementary role in the immune response to bacterial infection,its role in cancer metastasis is entirely ***,we sought to determine the effects of NOD1 on ***1 expression in paired human primary colon cancer,human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting(WB).Clinical significance of NOD1 was assessed using TCGA survival data.A series of in vitro and in vivo functional assays,including adhesion,migration,and metastasis,was conducted to assess the effect of NOD1.C12-iE-DAP,a highly selective NOD1 ligand derived from gram-negative bacteria,was used to activate ***130,a specific NOD1 inhibitor,was used to block C12-iE-DAP *** knockdown(KD)of NOD1 in human colon cancer cells(HT29)was constructed with shRNA lentiviral transduction and the functional assays were thus ***,the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase *** data demonstrate that NOD1 is highly expressed in human colorectal cancer(CRC)and human and murine CRC cell ***,we demonstrate that this increased NOD1 expression negatively impacts survival in patients with ***,we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion,migration and *** effects are predominantly mediated via the p38 mitogen activated protein kinase(MAPK)*** is the first study implicating NOD1 in cancer metastasis,and thus identifying this receptor as a putative therapeutic target.

关键词： NOD1 iE-DAP ML130 colon cancer metastasis cancer-extracellular matrix adhesion cancer migration p38 MAPK activation intravital microscopy survival analysis

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