Time scales of epidemic spread and risk perception on adaptive networks

Incorporating dynamic contact networks and delayed awareness into a contagion model with memory, we study the spreading patterns of infectious diseases in connected populations. It is found that the spread of an infectious disease is not only related to the past exposures of an individual to the infected but also to the time scales of risk perception reflected in the social network adaptation. The epidemic threshold $p_{c}$ is found to decrease with the rise of the time scale parameter s and the memory length T, they satisfy the equation $p_{c} =\frac{1}{T}+ \frac{\omega T}{a^s(1-e^{-\omega T^2/a^s})}$. Both the lifetime of the epidemic and the topological property of the evolved network are considered. The standard deviation $\sigma_{d}$ of the degree distribution increases with the rise of the absorbing time $t_{c}$, a power-law relation $\sigma_{d}=mt_{c}^\gamma$ is found

Precision gas therapy by ultrasound‐triggered for anticancer therapeutics

Abstract In recent years, ultrasound, as an external stimuli that can activate different types of naonocatalysts for therapy, has attracted extensive attention. One characteristic that makes ultrasound a particularly attractive trigger stimulus for nanomedicine is that it can be applied to the deep regions of the body noninvasively in a focused way. Different biological effects can be achieved by integrating ultrasound with nanocatalysts, and nanodroplets. Gas therapy, as a green antitumor treatment, has attracted substantial attention. The development of nanotechnology and nanomedicine has made gas therapy more precious by controlled release under internal, and outside factors and targeted delivery. In this article, an overview of ultrasound‐based gas therapy on antitumor therapy has been provided. First, we explored the mechanism of ultrasound‐triggered gas release. Second, we list the common gas release pathways and their mechanism in response to ultrasound activity. Third, exemplary instances of gas‐generating facilities under ultrasound controllable are explored, with an emphasis on their originality and guiding principles. The impact of the gas‐generating platform as a tumor therapy has also been considered. Finally, the difficulties and future prospects for this effective therapeutic approach are examined

Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways

Stromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely noncoding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent antiviral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine antiviral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy-resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of antiviral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate crosstalk with BrCa cells by utilizing exosomes to instigate antiviral signaling. This expands BrCa subpopulations adept at resisting therapy and reinitiating tumor growth

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

Therapeutic blocking of the PD1 pathway results in significant tumor responses but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB), and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors. Both type I and II interferons maintain this resistance program. Crippling the program genetically or pharmacologically interferes with multiple inhibitory pathways, and expands distinct T cell populations with improved function despite expressing markers of severe exhaustion. Consequently, tumors resistant to multi-agent ICB are rendered responsive to ICB monotherapy. Finally, we observe that biomarkers for interferon-driven resistance associate with clinical progression after anti-PD1 therapy. Thus, the duration of tumor interferon signaling augments adaptive resistance and inhibition of the interferon response bypasses requirements for combinatorial ICB therapies