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Recent advances using cyclopropanols and cyclobutanols in ring-openingasymmetric synthesis

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Green Synthesis and Catalysis 2022年第3期3卷 219-226页

作者： Hong Yan gregory S.Smith Fen-Er Chen Institute of Pharmaceutical Science and Technology College of ChemistryFuzhou UniversityFuzhou 350108China Engineering Center of Catalysis and Synthesis for Chiral Molecules Department of ChemistryFudan UniversityShanghai 200433China Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs Fudan UniversityShanghai 200433China Department of Chemistry University of Cape TownRondeboschCape Town 7700South Africa

Due to high ring strain energies,cyclopropanols and cyclobutanols have a strong tendency of breaking theendocyclic C–C bonds to participate in versatile organic *** an inherent three-dimensionalstructure,cyclopropanols and cyclobutanols have the advantage of synthesizing linear or cyclic molecules withstereogenic centers via ring-opening asymmetric *** are three strategies for the ring-opening ofcyclopropanols and cyclobutanols usually involved in asymmetric synthesis:1)β-carbon elimination of metalalkoxide;2)radical ring-opening;3)ring-opening via semipinacol *** present review has high-lighted the progress developed in the last five years.

关键词： Cyclopropanol Cyclobutanol Ring-opening C–C bond cleavage Asymmetric synthesis

Regression of recurrent granulosa cell tumor liver metastases following selective internal radiation therapy

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Hepatobiliary & Pancreatic Diseases International 2023年第4期22卷 406-408页

作者： Omar A Mownah John D Leahy Jeffrey Summers Stephen M gregory Nigel D Heaton Institute of Liver Studies King’s Healthcare PartnersKing’s College Hospital NHS Foundation TrustDenmark HillLondon SE59RSUK Department of Oncology Maidstone and Tunbridge Wells NHS TrustMaidstone ME169QQUK

Granulosa cell tumor(GCT)is the most common sex cordstromal tumor,comprising 5%of all ovarian malignancies[1].The disease course is indolent,and the majority of cases present at stage ***,metastases may develop with potential sites being peritoneum,lung,brain,liver and bone[2].Due to the rarity of the disease,published evidence for management of granulosa cell tumor liver metastases(GCTLM)is *** resection is the optimal treatment in instances where there is a high chance of achieving complete resection[3].With regards to unresectable GCTLM there is a paucity of evidence to guide treatment strategy.

关键词： metastases liver lung

RP215 and GHR106 Monoclonal Antibodies and Potential Therapeutic Applications

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Open Journal of Immunology 2023年第3期13卷 61-85页

作者： gregory Lee Center for Reproductive Health University of British Columbia Vancouver Canada

During the last two decades, two distinct monoclonal antibodies, RP215 and GHR106 were generated, respectively and extensively characterized, biologically and immunologically. Both antibodies target separately specific pan cancer markers and are being evaluated preclinically for potential therapeutic applications in cancer immunotherapy and/or fertility regulations. RP215 was shown to react specifically with carbohydrate-associated epitope located in the heavy chain variable regions of cancer cell expressed specific immunoglobulins, designated as CA215 which are distinct from those of normal B cell origins. The cancerous immunoglobulins may function to react with specific human serum proteins to facilitate growth/proliferation as well as protection of cancer cells in circulations. RP215-based enzyme immunoassays were designed to monitor serum CA215 levels among cancer patients. On the other hand, GHR106 was generated against N1-29 oligopeptide located in the extracellular domains of human GnRH receptor found either in the anterior pituitary or in most of the cancer cells. In vitro culture of cancer cells revealed that either of these two antibodies can induce apoptosis of cancer cells following 24 - 48 hours incubations. Anti-tumor activities of both antibodies were evaluated by typical nude mouse experiments. Either one was shown to effectively reduce the volumes of implanted tumors, dose-dependently. Humanized forms of either antibody were made available in CAR (chimeric antigen receptor)-T cell constructs. They were shown separately to induce cytotoxic killings of cancer cells in vitro by releasing cytokines upon incubations of tumor cells with either of CAR-T cell constructs. In addition, GHR106 also acts as GnRH antagonist by a specific targeting to pituitary GnRH receptor for reversible suppressions of reproductive hormones such as LH, testosterone or estradiol. Based on the above preclinical assessments, it can be generally concluded that both RP215 and GHR10

关键词： RP215 GHR106 Cancer Immunotherapy Fertility Regulation CAR-T Cell Constructs CA215

Think global,cube local:an Earth Observation Data Cube’s contribution to the Digital Earth vision

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Big Earth Data 2023年第3期7卷 831-859页

作者： Martin Sudmanns Hannah Augustin Brian Killough gregory Giuliani Dirk Tiede Alex Leith Fang Yuan Adam Lewis Department of Geoinformatics Paris Lodron University SalzburgSalzburgAustria NASA Langley ResearchCenter HamptonVAUSA Institute for Environmental Sciences University of GenevaenviroSPACEGenevaSwitzerland Institute for Environmental Sciences University of GenevaGRID-GenevaGenevaSwitzerland Geoscience Australia CanberraACTAustralia Group on Earth Observations(GEO)DigitalEarth Africa GenevaSwitzerland

The technological landscape for managing big Earth observation(EO)data ranges from global solutions on large cloud infrastructures with web-based access to self-hosted *** data cubes are a leading technology for facilitating big EO data analysis and can be deployed on different spatial scales:local,national,regional,or *** EO data cubes with a geographic focus(“local EO data cubes”)have been ***,their alignment with the Digital Earth(DE)vision and the benefits and trade-offs in creating and maintaining them ought to be further *** investigate local EO data cubes from five perspectives(science,business and industry,government and policy,education,communities and citizens)and illustrate four examples covering three continents at different geographic scales(Swiss Data Cube,semantic EO data cube for Austria,DE Africa,Virginia Data Cube).A local EO data cube can benefit many stakeholders and players but requires several technical *** developments include enabling local EO data cubes based on public,global,and cloud-native EO data streaming and interoperability between local EO data *** argue that blurring the dichotomy between global and local aligns with the DE vision to access the world’s knowledge and explore information about the planet.

关键词： Earth Observation data cube Digital Earth interoperability workflows open data cube

New Insights into Intravascular Imaging of Coronary Bifurcation Lesions and Left Main Stenosis:What Have We Accomplished?

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Cardiology Discovery 2022年第3期2卷 182-190页

作者： Massoud A.Leesar gregory O.Von Mering Hani Jneid Division of Cardiology University of AlabamaBirminghamAlabama 35294USA Division of Cardiology University of Texas Medical BranchTaxas 77555USA

Coronary bifurcation lesions(CBL)are one of the most challenging lesions to treat in interventional *** imaging including intravascular ultrasound(IVUS)and optical coherence tomography(OCT)is paramount for the assessment of lesion characteristics and suboptimal stent results and to improve the outcome of percutaneous coronary intervention(PCI).After upgrading the use of IVUS and OCT by the American College of Cardiology/American Heart Association guidelines,their use has ***,there has been significant improvement in image quality and the profile of system(ie,IVUS catheter size).The main indication for the use of IVUS includes:assessment of lesion characteristics,optimization of stent deployment,optimal stent expansion,exclusion of plaque burden>50%,and edge *** imaging plays a significant role in the assessment and treatment of left main(LM)coronary artery stenosis and *** particular,the use of intravascular imaging for alleviating mechanical issues during stenting and managing stent thrombosis has significantly ***,a compelling body of evidence has shown that the use of IVUS or OCT during PCI leads to optimal stenting results and mitigates the risk of adverse cardiac ***,to date,the American College of Cardiology/American Heart Association Guidelines have assigned a Class IIb recommendation for IVUS or OCT,while the European Society of Cardiology Guidelines upgraded it to the Class IIa *** review summarized the role of IVUS and OCT for the assessment of stenosis and stent optimization in patients with CBL and LM *** addition,we discuss new insights into the role of IVUS-and OCT-guided stenting in patients with CBL and LM stenosis provided by the ongoing randomized trials.

关键词： Tomography,optical coherence Intravascular ultrasound Coronary interventions

A pilot prospective prevalence study of chronic rhinosinusitis associated with inflammatory bowel disease

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第4期8卷 339-344页

作者： India Dhillon Jennifer Ham Ximena Maul gregory Rosenfeld Andrew Thamboo Division of Otolaryngology St.Paul's Sinus CentreUniversity of British ColumbiaVancouverBritish ColumbiaCanada Division of Gastroenterology University of British ColumbiaVancouverBritish ColumbiaCanada

Background:Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the gastrointestinal ***-intestinal manifestations such as pulmonary diseases have been *** rhinosinusitis(CRS),an inflammatory condition of the sinonasal mucosa,has been associated with several lung *** the relationship between lung and intestinal pathologies,and lung and sinus pathologies,we aimed to determine the prevalence of IBD among CRS ***:Pilot prevalence ***-two CRS patients were screened for IBD symptoms from October 2018 to January ***-reported disease symptoms and overall quality of life were evaluated using the Sino-Nasal Outcome Test 22(SNOT-22),Short Inflammatory Bowel Disease Questionnaire(SIBDQ),and EuroQol 5 Dimension 5 Level(EQ-5D-5L)*** Modified Lund-Kennedy(MLK)endoscopic and Lund-Mackay(LM)grading systems were used to confirm CRS *** who reported subjective symptoms of IBD were referred to a gastroenterologist clinic for further ***:Twenty of the 92(20.2%,95%CI:12.6%-29.8%)CRS patients reported symptoms of IBD and four individuals(4.26%,95%CI:1.17%-10.50%)were sub-sequently diagnosed with *** to patients without IBD symptoms(n=72),those with symptoms(n=20)reported significantly worse SNOT-22(P=0.002),SIBDQ(P<0.05),and EQ-5D-3L(P=0.0063)***,these patients did not exhibit significantly different MLK(P=0.81)or LM(P=0.04)***:The prevalence of IBD may be elevated among individuals with CRS relative to the general Canadian *** pilot study suggests that CRS with IBD is associated with lower quality of *** cross-sectional studies with larger sample sizes are required.

关键词： chronic rhinosinusitis microbiome Modified Lund–Kennedy quality of life Sino-Nasal Outcome Test 22(SNOT-22)

Synthesis of the C50 diastereomers of the C33–C51 fragment of stambomycin D

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Organic Chemistry Frontiers 2022年第2期9卷 445-449页

作者： Yongchen Wang Venkaiah Chintalapudi Haraldur G.Gudmundsson gregory L.Challis Edward A.Anderson Chemistry Research Laboratory University of Oxford12 Mansfield RoadOxfordOX13TAUK Department of Chemistry and Warwick Integrative Synthetic Biology Centre University of WarwickCoventryCV47ALUK Department of Biochemistry and Molecular Biology and ARC Centre of Excellence for Innovations in Peptide and Protein Science Biomedicine Discovery InstituteMonash UniversityClaytonVictoria 3800Australia

As products of genome mining,the stereochemical assignment of the macrolide antibiotics stambomycins A-D has been made on the basis of sequence analysis of the associated polyketide synthase,aside from two stereocentres at C28 and *** we describe syntheses of the two C50 diastereomers of the C33-C51 region of the stambomycins,which support the PKS-based configurational assignment,and establish a strategy suitable for access to the extended stambomycin framework.

关键词： stereo assignment centre

Transcriptional coactivator MED1 in the interface of anti-estrogen and anti-HER2 therapeutic resistance

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Cancer Drug Resistance 2022年第2期5卷 498-510页

作者： gregory Bick Jasmine Zhang Elyse E.Lower Xiaoting Zhang Department of Cancer Biology Vontz Center for Molecular StudiesUniversity of Cincinnati College of MedicineCincinnatiOH 45267USA Department of Internal Medicine University of Cincinnati College of MedicineCincinnatiOH 45267USA. University of Cincinnati Cancer Center University of Cincinnati College of MedicineCincinnatiOH 45267USA.

Breast cancer is one of the most common cancer and leading causes of death in women in the United States and *** 90%of breast cancers belong to ER+or HER2+subtypes and are driven by key breast cancer genes Estrogen Receptor and HER2,*** the advances in anti-estrogen(endocrine)and anti-HER2 therapies for the treatment of these breast cancer subtypes,unwanted side effects,frequent recurrence and resistance to these treatments remain major clinical *** studies have identified ER coactivator MED1 as a key mediator of ER functions and anti-estrogen treatment ***,MED1 is also coamplified with HER2 and activated by the HER2 signaling cascade,and plays critical roles in HER2-mediated tumorigenesis and response to anti-HER2 treatment as ***,MED1 represents a novel crosstalk point of the HER2 and ER pathways and a highly promising new therapeutic target for ER+and HER2+breast cancer *** this review,we will discuss the recent progress on the role of this key ER/HER2 downstream effector MED1 in breast cancer therapy resistance and our development of an innovative RNA nanotechnology-based approach to target MED1 for potential future breast cancer therapy to overcome treatment resistance.

关键词： MED1 transcription cofactor estrogen receptor HER2 therapy resistance RNA nanotechnology

Quantifying relations between altered hydrology and fish community responses for streams in Minnesota

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Ecological Processes 2022年第1期11卷 536-560页

作者： Jeffrey R.Ziegeweid gregory D.Johnson Aliesha L.Krall Kara Fitzpatrick Sara B.Levin U.S.Geological Survey California Water Science Center6000 J StPlacer HallSacramentoCA 85819USA U.S.Geological Survey Upper Midwest Water Science Center2280 Woodale DrMounds ViewMN 55112USA Minnesota Pollution Control Agency 520 Lafayette RdSt.PaulMN 55155USA Minnesota Pollution Control Agency 7678 College RoadSuite 105BaxterMN 56425USA

Background:Altered hydrology is a stressor on aquatic life,but quantitative relations between specific aspects of streamflow alteration and biological responses have not been developed on a statewide scale in *** sub-sets regression analysis was used to develop linear regression models that quantify relations among five categories of hydrologic metrics(i.e.,duration,frequency,magnitude,rate-of-change,and timing)computed from streamgage records and six categories of biological metrics(i.e.,composition,habitat,life history,reproductive,tolerance,trophic)computed from fish-community samples,as well as fish-based indices of biotic integrity(FIBI)scores and FIBI scores normalized to an impairment threshold of the corresponding stream class(FIBI_BCG4).Relations between hydrology and fish community responses were examined using three hydrologic datasets that represented periods of record,long-term changes,and short-term changes to flow regimes in streams of ***:Regression models demonstrated significant relations between hydrologic explanatory metrics and fish-based biological response metrics,and the five regression models with the strongest linear relations explained over 70%of the variability in the biological metric using three hydrologic metrics as explanatory ***-based biological metrics demonstrated the strongest linear relations to hydrologic *** most commonly used hydrologic metrics were related to bankfull flows and aspects of flow ***:Final regression models represent paired streamgage records and biological samples throughout the State of Minnesota and encompass differences in stream orders,hydrologic landscape units,and watershed *** methods can support evaluations of stream fish communities and facilitate targeted efforts to improve the health of fish *** also can be applied to locations outside of Minnesota with continuous streamgage data and fish-community sampl

关键词： EflowStats Best subset regression Altered hydrology Fish community Indices of biotic integrity Ecological flows