162 research outputs found
Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
No full textYanjun Lu,1,* Zhiyan Li,2,* Xudong Zhu,1 Qingwei Zeng,1 Song Liu,1 Wenxian Guan1 1Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Division of Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Liu; Wenxian Guan, Email [email protected]; [email protected]: The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability to activate tumor-specific immune responses for tumor killing. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune pathway that activates antitumor immunity by producing type I interferons. Cyclic dinucleotides (CDNs), produced by cGAS sensing cytoplasmic abnormal DNA, are major intermediate activating molecules in the STING pathway. Nowadays, CDNs and their derivatives have widely worked as powerful STING agonists in tumor immunotherapy. However, their clinical translation is hindered by the negative electrical properties, sensitivity to hydrolytic enzymes, and systemic toxicity. Recently, various CDN delivery systems have made significant progress in addressing these issues, either through monotherapy or in combination with other treatment modalities. This review details recent advances in CDNs-based pharmaceutical development or delivery strategies for enriching CDNs at tumor sites and activating the STING pathway.Keywords: cyclic dinucleotides, stimulator of interferon genes pathway, immunotherap
Graphene size-dependent modulation of graphene frameworks contributing to the superior thermal conductivity of epoxy composites
No full textVacuum filtration is a highly effective and easy scale-up approach and has been widely used to fabricate graphene monoliths, such as graphene paper and graphene frameworks for various applications. In general, the microstructure of filtrated monoliths exhibits layer-by-layer stacking of graphene sheets due to the directional flow-induced assembly process. In this work, we found that the horizontally oriented structure of filtrated graphene frameworks can be modulated to an approximately isotropic arrangement by lowering the lateral size of graphene sheets. This size-dependent microstructure transition from anisotropic to isotropic was further confirmed by measuring the in- and through-plane thermal conductivity of the graphene/epoxy composites with different arrangements of graphene frameworks as a filler. Optimally, we obtained an epoxy composite embedded with a quasi-isotropic graphene framework (QIGF) by a simple two-step process: vacuum filtration of small graphene sheets to obtain the framework followed by the infiltration of epoxy resin. Based on the interconnected graphene sheets with an approximately isotropic arrangement, QIGF provides heat channels of graphene-graphene along both the in- and through-plane directions within epoxy. With a low graphene loading of 5.5 wt%, QIGF/epoxy (QIGF/EP) presents in- and through-plane thermal conductivities of 10.0 and 5.4 W mK(-1), respectively, which are equivalent to approximate to 55 and 29 times higher than those of neat epoxy. As compared to the current graphene/epoxy composites prepared by various methods, our QIGF/EP has the highest thermal conductivity value with this level of filler loading. Our findings provide an insight for the development of polymer composites for thermal management applications in industry
Hemocoagulase might not control but worsen gastrointestinal bleeding in an elderly patient with type II respiratory failure
No full textHemocoagulase has been successfully used for the management of bleeding in patients undergoing surgery. Local spray of hemocoagulase during endoscopic therapy may be effective for the management of gastrointestinal bleeding. In China, intravenous infusion of hemocoagulase is given by some physicians for the treatment of gastrointestinal bleeding. However, the potential adverse events secondary to hemocoagulase, such as hypofibrinogenemia, are poorly recognized. In this paper, we reported an elderly patient with type II respiratory failure in whom hemocoagulase might induce hypofibrinogenemia and further worsen gastrointestinal bleeding. We highlighted that fibrinogen levels should be cautiously monitored in patients receiving hemocoagulase
Circulating lncRNA ITSN1‐2 is upregulated, and its high expression correlates with increased disease severity, elevated inflammation, and poor survival in sepsis patients
No full textThe influencing factors and generation path of digital health literacy among adolescents: evidence from 18 provinces in China
No full textIntroductionThis study explores the generation path and influencing factors of digital health literacy (DHL) among adolescents (aged 12–22), addressing gaps in the research by giving insufficient attention to underage youth and the lack of qualitative exploration.MethodsAdopting grounded theory, 74 semistructured online interviews were conducted with adolescents across 18 Chinese provinces, generating 190 thousand words of anonymized text. Through open, axial, and selective coding, 33 initial concepts, 14 core categories, and 6 main categories (literacy foundation, active exploration, passive arousal, positive effects, negative impact, and practical problems) were identified.ResultsThe results show that a literacy foundation (digital equipment/channels), active exploration (self-improvement/disease management), and passive arousal (media influence/environmental immersion) promote adolescent DHL, whereas negative impacts (health anxiety/information security) and practical problems (misinformation/supply shortages) hinder it. DHL benefits adolescents individually (fostering health actions, conceptual reconstruction, and habit formation) and socially (enabling digital feedback for health knowledge dissemination). This study also constructed an adolescent DHL generation path model and identified three paths, including the cognitive-environmental synergy path, action-technology driven path, and anxiety-action transformation path, collectively revealing the diverse formation mechanisms of adolescents’ DHL.DiscussionPractical suggestions for improving adolescents’ DHL were proposed. The results provided insights into enhancing adolescent DHL and support the optimization of adolescents’ health trajectory via digital tools
Erratum to: Identification and characterization of the rhizosphere phosphate-solubilizing bacterium Pseudomonas frederiksbergensis JW-SD2, and its plant growth-promoting effects on poplar seedlings
No full text
Influence of ultra-low interfacial tension system on nonlinear seepage law of low permeability core
No full textThe starting pressure gradient in low permeability reservoir leads to the nonlinear characteristics of fluid flow, which makes the development mode of low permeability reservoir different from that of medium and high permeability reservoir.In order to study the nonlinear seepage phenomenon in the low permeability reservoir of Xinli Oilfield, taking the natural low permeability core of Xinli Oilfield as the research object, the influence of ultra-low interfacial tension system on the start-up pressure gradient of single-phase and two-phase fluid in Xinli low permeability cores was analyzed through the porous media seepage experiment of precision pressure tests.The results show that for any fluid, the low permeability core of Xinli Oilfield shows nonlinear seepage characteristics, and there is a certain threshold pressure gradient.The value of pseudo starting pressure gradient of low permeability cores is higher than that of starting pressure gradient, and both of them decrease with the increase of permeability, and the relationship between them is power.The ultra-low interfacial tension system can obviously reduce the minimum starting pressure gradient and quasi starting pressure gradient of low permeability cores.For cores with different permeability, the relationship between the two-phase critical starting pressure gradient and water saturation shows a similar change law, that is, the two-phase critical starting pressure gradient firstly increases and then decreases with the increase of average water saturation.Under different permeability, the highest critical pressure gradient of water flooding and ultra-low interfacial tension system flooding is compared.The highest point of critical pressure gradient in ultra-low interfacial tension system is obviously smaller than that in water flooding.This shows that the decrease of interfacial tension can significantly reduce the two-phase critical pressure gradient during oil displacement, and the ultra-low interfacial tension system improves the injectivity of the reservoir.This study provides a reference for the selection of development mode after water flooding in Xinli low permeability reservoir
The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model
No full textabstract: Background
The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.
Methods
To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.
Results
Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.
Conclusions
The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.013035
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