Dynamical behavior of memristor-coupled heterogeneous discrete neural networks with synaptic crosstalk

Synaptic crosstalk is a prevalent phenomenon among neuronal synapses,playing a crucial role in the transmission of neural signals.Therefore,considering synaptic crosstalk behavior and investigating the dynamical behavior of discrete neural networks are highly necessary.In this paper,we propose a heterogeneous discrete neural network(HDNN)consisting of a three-dimensional KTz discrete neuron and a Chialvo discrete neuron.These two neurons are coupled mutually by two discrete memristors and the synaptic crosstalk is considered.The impact of crosstalk strength on the firing behavior of the HDNN is explored through bifurcation diagrams and Lyapunov exponents.It is observed that the HDNN exhibits different coexisting attractors under varying crosstalk strengths.Furthermore,the influence of different crosstalk strengths on the synchronized firing of the HDNN is investigated,revealing a gradual attainment of phase synchronization between the two discrete neurons as the crosstalk strength decreases.

Nanoparticle enhanced combination therapy for stem-like progenitors defined by single-cell transcriptomics in chemotherapy-resistant osteosarcoma

The adaptation of osteosarcoma cells to therapeutic pressure impedes the efficacy of chemotherapy for osteosarcoma.However,the characteristics and cellular organization of therapy-resistant cells in osteosarcoma tumors remain elusive.Here,we utilized single-cell transcriptomics to systematically map the cell-type-specific gene expression in a chemotherapy-resistant osteosarcoma tumor.Our data demonstrated the VEGFR2-JMJD3-abundant subsets as quiescent stem-like cells,thereby establishing the hierarchy of therapy-resistant actively cycling progenitor pools(JMJD3-abundant)in osteosarcoma.VEGFR2 inhibitor and JMJD3 inhibitor synergistically impeded osteosarcoma cell propagation and tumor growth.Although osteosarcoma cells are predisposed to apoptosis induced by the synergistic therapy through activation of the CHOP pro-apoptotic factor via the endoplasmic reticulum(ER)stress,the stem-like/progenitor cells exhibit an adaptive response,leading to their survival.Reduction in cellular glutathione levels in stem-like/progenitor cells caused by the treatment with a glutathione synthesis inhibitor increases ER stress-induced apoptosis.Importantly,the marked therapeutic improvement of synergistic therapy against stem-like/progenitor cells was achieved by using glutathione-scavenging nanoparticles,which can load and release the drug pair effectively.Overall,our study provides a framework for understanding glutathione signaling as one of the therapeutic vulnerabilities of stem-like/progenitor cells.Broadly,these findings revealed a promising arsenal by encapsulating glutathione-scavenging nanoparticles with co-targeting VEGFR2 and JMJD3 to eradicate chemotherapy-resistant osteosarcoma.

An adhesive and resilient hydrogel for the sealing and treatment of gastric perforation

Adhesive hydrogels have been recently proposed as a potential option to seal and treat gastric perforation(GP)which causes high mortality despite advancements in surgical treatments.However,to be effective,the hydrogels must have sufficient tissue adhesiveness,tough mechanical property,tunable biodegradability and ideally are easy to apply and form.Herein,we report an adhesive and resilient hydrogel for the sealing and treatment of gastric perforation.The hydrogel consists of a bioactive,transglutaminase(TG)-crosslinked gelatin network and a dynamic,borate-crosslinked poly-N-[Tris(hydroxymethyl)methyl]acrylamide(PTH)network.The hydrogel can be formed in situ,facilitating easy delivery to the GP and allowing for precise sealing of the defects.In vivo experiments,using a perforated stomach mouse model,shows that the adhesive hydrogel plug effectively seals GP defects and promotes gastric mucosa regeneration.Overall,this hydrogel represents a promising biomaterial for GP treatment.