Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout evolution.The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction.Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types.Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and metastasis.Furthermore,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer invasiveness.The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects.Moreover,the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells.Therefore,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling.This review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer.Additionally,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

Biomimetic hybrid hydrogel for hemostasis,adhesion prevention and promoting regeneration after partial liver resection

Partial liver resection is an established treatment for hepatic disorders.However,surgical bleeding,intra-abdominal adhesion and rapid liver regeneration are still major challenges after partial liver resection,associated with morbidity and mortality.Herein,a biomimetic hybrid hydrogel,composed of oxidized hyaluronic acid,glycol chitosan and MenSCs-derived conditioned medium(CM),is presented to address these issues.The hybrid hydrogel is formed through reversible Schiff base,and possesses injectability and self-healing capability.Moreover,hybrid hydrogel exhibits the capabilities of hemostasis,anti-infection,tissue adhesion and controllable release of cargoes.Based on in vivo studies of the multifunctional hybrid hydrogel,it is demonstrated that acute bleeding in partial liver resection can be ceased immediately by virtue of the hemostasis features of hybrid hydrogel.Also,a significant reduction of intra-abdominal adhesion is confirmed in hybrid hydrogel-treated resection surface.Furthermore,upon the treatment of hybrid hydrogel,hepatic cell proliferation and tissue regeneration can be significantly improved due to the controllably released cytokines from MenSCs-derived CM,exerting the effects of mitogenesis and anti-inflammation in vivo.Thus,the biomimetic hybrid hydrogel can be a promising candidate with great potential for application in partial liver resection.

Two-step preparation of carbon nanotubes/Ru02/polyindole ternary nanocomposites and their application as high-performance supercapacitors

A ternary single-walled carbon nanotubes/RuO2/polyindole(SWCNT/RuO2/PIn)nanocomposite was fabricated by the oxidation polymerization of indole on the prefabricated SWCNT/RuO2 binary nanocomposites.The nanocomposite was measured by FTIR,XRD,SEM,TEM,EDS and XPS,together with the electrochemical technique.The electrochemical results demonstrated that the symmetric supercapacitor used SWCNT/RuO2/PIn as electrodes presented 95%retention rate after 10000 cycles,superior capacitive performance of1203 F·g^-1 at1 A·g^-1,and high energy density of 33 w h·kg^-1 at 5000 W·kg^-1.The high capacitance performance of SWCNT/RuO2/PIn nanocomposite was mainly ascribed to the beneficial cooperation effect among components.This indicated that the SWCNT/RuO2/PIn nanocomposite would be a good candidate for high-performance supercapacitors.

Transcriptomics Curation of SARS-CoV-2 Related Host Genes in Mice With COVID-19 Comorbidity:A Pilot Study

The pandemic of coronavirus disease 2019(COVID-19),a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2,is causing substantial morbidity and mortality.Along with the respiratory symptoms,underlying diseases in senior patients,such as diabetes,hypertension,and coronary heart disease,are the most common comorbidities,which cause more severe outcomes and even death.During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2,the key protein involved is the angiotensin I converting enzyme 2(ACE2),which is located on the membrane of host cells.Here,we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains.Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets,Ace2 and other potentially involved genes such as Furin,Tmprss2,Ang,and Ang2 were examined.We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains(db/db,ob/ob and diet-induced obese).With the most abundant datasets present,the liver shows a medium Ace2 expression level compared with the lungs,pancreatic islets,brain and even T cells.Age is a more critical factor for Ace2 expression in db/db compared with the other two strains.Besides Ace2,the other four host genes showed varied levels of correlation to each other.To accelerate research on the interaction between COVID-19 and underlying diseases,the Murine4Covid transcriptomics database(www.geneureka.org/Murine4Covid)will facilitate the design of research on COVID-19 and comorbidities.