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Deformable microlaser force sensing

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光：科学与应用（英文版） 2024年第6期13卷 1196-1209页

作者： Eleni Dalaka Joseph S.Hill jonathan H.H.Booth Anna Popczyk Stefan R.Pulver Malte c.Gather Marcel Schubert centre of Biophotonics SUPASchool of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsUK Institute for Bioengineering of catalonia BarcelonaSpain centre of Biophotonics SUPASchool of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsUK Humboldt centre for Nano-and Biophotonics Department of ChemistryUniversity of CologneKölnGermany Humboldt centre for Nano-and Biophotonics Department of ChemistryUniversity of CologneKölnGermany School of Psychology and Neuroscience University of St AndrewsSt Mary's QuadSouth StreetSt AndrewsUK Humboldt centre for Nano-and Biophotonics Department of ChemistryUniversity of CologneKölnGermany School of Psychology and Neuroscience University of St AndrewsSt Mary's QuadSouth StreetSt AndrewsUK

Mechanical forces are key regulators of cellular behavior and function,affecting many fundamental biological processes such as cell migration,embryogenesis,immunological responses,and pathological *** force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in ***,current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue,reducing their application to 2D cell cultures and highly transparent biological ***,we introduce DEFORM,deformable microlaser force sensing,a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal *** is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer *** validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force,DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila *** furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution,thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis,tissue remodeling,and tumor invasion.

关键词： Spectrum analysis

Gouty destruction of a patellar tendon reconstruction and novel revision reconstruction technique: A case report

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World Journal of Orthopedics 2024年第7期15卷 675-682页

作者： carl c Edge jonathan Widmeyer Omar Protzuk Maya Johnson Robert O’connell Department of Orthopaedic Surgery Division of Sports MedicineVirginia Commonwealth University Health SystemRichmondVA 23298-0153United States Division of Sports Medicine OrthowestCarroltonGA 30117United States

BAcKGROUND Gout is a disease characterized by hyperuricemia,and resultant deposition of uric acid crystals in *** typically manifested as intraarticular crystals or tophi,gout can also cause pathology at *** deposition within tendinous structures put them at risk for traumatic and degenerative ***,allografts can also be at risk of rupture in the setting of severe *** present the case of a 56-year-old female with severe gouty disease who sustained a re-rupture of a patellar tendon allograft *** SUMMARY A 56-year-old female presented to clinic after feeling her left knee pop and collapse beneath her while descending *** had a history of tophaceous gout and left patellar tendon rupture with reconstruction and multiple revisions over the course of 19 *** patient presented with pain and extensor lag.A magnetic resonance image demonstrated a ruptured patellar tendon allograft reconstruction and avulsion fracture at the tibial *** patient was treated with a novel intervention of Achilles allograft with bone block in a unique configuration with a dermal allograft incorporated into the *** was made non-weight bearing in the operative extremity in extension for the first four weeks postoperatively and was then progressed to active flexion over the course of eight *** twelve weeks,she was able to fully extend her operative knee and at five months she was resuming her normal activities and *** Failed patellar tendon reconstruction due to gouty infiltration is treated with dermal allograft augmented Achilles tendon reconstruction with bone block.

关键词： Gout Patella Reconstruction Dermal allograft Revision case report

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal cOVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward jonathan A Fallowfield Peter c Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BAcKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(cOVID-19),while preexisting MASLD increases the risk of LI and the development of cOVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-coV-2)which causes cOVID-19,uses angiotensin-converting expression enzyme 2(AcE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic AcE2 levels are altered during progression of MASLD and in patients who died with severe *** AcE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe cOVID-19,using AcE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** AcE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,AcE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but AcE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry cOVID-19 cOVID-19-associated cholangiopathy

Identity and Identification: William Langland Wrote The Romance of William of Palerne

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Journal of Literature and Art Studies 2024年第7期14卷 553-566页

作者： jonathan Packer(Kountouris) Athens Greece

This essay shows that William Langland/Longe Wille wrote The Romance of William of *** brings forward evidence from its text in two main ways:(1).synchronically,*** the text;and(2).diachronically,‘across time’.There is a comparison between this c.1360-61 work and the previous 1191-4 NE Old French/Picard poem Le Roman de Guillaume de Palerne specifically of three passages from each.

关键词： Langland William of Palerne Guillaume de Palerne Piers Plowman medieval studies attribution

PXR variants:the impact on drug metabolism and therapeutic responses

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Acta Pharmaceutica Sinica B 2016年第5期6卷 441-449页

作者： c.trent Brewer Taosheng chen Department of chemical Biology and Therapeutics St.Jude Children's Research Hospital Integrated Biomedical Sciences Program University of Tennessee Health Science Center

The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and *** protein isoforms of PXR exist,and they have differential transcriptional activity upon target genes; transcript variants 3(PXR3) and 4(PXR4) do not induce target gene expression,whereas transcript variants 1(PXR1) and 2(PXR2) respond to agonist by activating target gene *** protein variants also display differences in protein–protein interactions; PXR1 interacts with p53,whereas PXR3 does ***,the transcript variants of PXR that encode these protein isoforms are differentially regulated by methylation and deletions in the respective promoters of the variants,and their expression differs in various human cancers and also in cancerous tissue compared to adjacent normal ***1 and PXR4 m RNA are downregulated by methylation in cancerous tissue and have divergent effects on cellular proliferation when ectopically *** detailed and comparative mechanistic studies are required to predict the effect of PXR transcript variant expression on carcinogenesis,therapeutic response,and the development of toxicity.

关键词： Pregnane X receptor Transcript variants Drug metabolism Therapeutic responses Toxicity

Electrocatalytic cO_(2) reduction to c_(2)H_(4): From lab to fab

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Journal of Energy chemistry 2024年第3期90卷 540-564,I0012页

作者： Zeyu Guo Fabao Yang Xiaotong Li Huiwen Zhu Hainam Do Kam Loon Fow jonathan D.Hirst Tao Wu Qiulin Ye Yaqi Peng Hao Bin Wu Angjian Wu Mengxia Xu Department of chemical and Environmental Engineering and New Materials InstituteUniversity of Nottingham Ningbo ChinaNingbo 315100ZhejiangChina Key Laboratory of carbonaceous Waste Processing and Process Intensification of Zhejiang Province University of Nottingham Ningbo ChinaNingbo 315100ZhejiangChina Nottingham Ningbo china Beacons of Excellence Research and Innovation Institute University of Nottingham Ningbo ChinaNingbo 315100ZhejiangChina State Key Laboratory of clean Energy Utilization Department of Energy EngineeringZhejiang UniversityHangzhou 310027ZhejiangChina Institute for composites Science Innovation(IncSI)and State Key Laboratory of Silicon and Advanced Semiconductor Materials School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027ZhejiangChina School of chemistry University of NottinghamUniversity ParkNottingham NG72RDUK Baima Lake Laboratory Hangzhou 310053ZhejiangChina

The global concerns of energy crisis and climate change,primarily caused by carbon dioxide(cO_(2)),are of utmost ***,the electrocatalytic cO_(2) reduction reaction(cO_(2)RR) to high value-added multi-carbon(c_(2+)) products driven by renewable electricity has emerged as a highly promising solution to alleviate energy shortages and achieve carbon *** these c_(2+) products,ethylene(c_(2)H_(4))holds particular importance in the petrochemical ***,this review aims to establish a connection between the fundamentals of electrocatalytic cO_(2) reduction reaction to ethylene(cO_(2)RRto-c_(2)H_(4)) in laboratory-scale research(lab) and its potential applications in industrial-level fabrication(fab).The review begins by summarizing the fundamental aspects,including the design strategies of high-performance cu-based electrocatalysts and advanced electrolyzer ***,innovative and value-added techniques are presented to address the inherent challenges encountered during the implementations of cO_(2)RR-to-c_(2)H_(4) in industrial ***,case studies of the technoeconomic analysis of the cO_(2)RR-to-c_(2)H_(4) process are discussed,taking into factors such as costeffectiveness,scalability,and market *** review concludes by outlining the perspectives and challenges associated with scaling up the cO_(2)RR-to-c_(2)H_(4) *** insights presented in this review are expected to make a valuable contribution in advancing the cO_(2)RR-to-c_(2)H_(4) process from lab to fab.

关键词： cO_(2) electroreduction reaction Ethylene Gas diffusion electrode Machine learning Density functional theory Techno-economic analysis

chemosensitizing Effect of Monk Fruit Extract on Human Bladder cancer cells

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Journal of cancer Therapy 2024年第6期15卷 250-264页

作者： Sensuke Konno jonathan Wong Andrew Penunuri Kelvin Zheng Muhammad choudhury Department of Urology New York Medical College Valhalla New York USA

The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (cPL), carboplatin (cBL), mitomycin c (MMc), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only cPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The cPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of cPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.

关键词： Monk Fruit Anticancer Bladder cancer chemosensitization Lakanto

The favorable impact of PIK3cA mutations on survival: an analysis of 2587 patients with breast cancer

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chinese Journal of cancer 2012年第7期31卷 327-334页

作者： Amaury G. Dumont Sarah N.Dumont jonathan c. trent Department of Experimental Pediatrics University of Texas-MD Anderson Cancer CenterHouston Texas United States Division of Hematology and Oncology University of Miami-Sylvester Comprehensive Cancer CenterMiami Florida United States

The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3cA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3cA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3cA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3cA mutation have a better clinical outcome than those with a wild-type PIK3cA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3cA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3cA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3cA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3cA mutations is critical for the development of optimally personalized therapeutics against breast can

关键词：肿瘤患者乳腺癌突变转基因小鼠肌动蛋白细胞骨架磷脂酰肌醇-3 信号通路乳腺肿瘤

Nearly invariant subspaces for shift semigroups

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Science china Mathematics 2022年第9期65卷 1895-1908页

作者： Yuxia Liang jonathan R.Partington School of Mathematical Sciences Tianjin Normal UniversityTianjin 300387China School of Mathematics University of LeedsLeeds LS 29JTUK

Let{T(t)}_(t≥0) be a c_(0)-semigroupon an infinite-dimensional separable Hilbert space;a suitable definition of near{T(t)^(*)}_(t≥0) invariance of a subspace is presented in this paper.A series of prototypical examples for minimal nearly{S(t)^(*)}_(t≥0) invariant subspaces for the shift semigroup{S(t)}_(t≥0) on L^(2)(0,∞)are demonstrated,which have close links with near T_(θ)^(*)invariance on Hardy spaces of the unit disk for an inner functionθ.Especially,the corresponding subspaces on Hardy spaces of the right half-plane and the unit disk are related to model *** work further includes a discussion on the structure of the closure of certain subspaces related to model spaces in Hardy spaces.

关键词： nearly invariant subspace c_(0)-semigroup shift semigroup model space