RESUMEN
The massive infiltration of suppressor immune cells within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is a major cause of treatment resistance. Reducing this infiltration may represent a potentially effective therapeutic strategy. Sphingomyelin synthase 2 (SMS2) is a crucial enzyme for sphingomyelin synthesis, contributing significantly to the integrity and function of the plasma membrane. In this study, we developed a self-assembling SMS2 siRNA gene expression plasmid for in vivo delivery. The SMS2 siRNA specifically inhibits SMS2 expression while preserving the expression and activity of SMS1. Administration of the self-assembling SMS2 siRNA suppresses tumor growth in a murine model of Panc02 pancreatic carcinoma, modulates the polarization of tumor-associated macrophages (TAMs), and reduces the infiltration of tumor-associated neutrophils (TANs) by regulating the NF-κB/CXCL5 pathway. Consequently, utilizing SMS2 siRNA to improve the local immunosuppressive microenvironment holds promise for pancreatic cancer therapy.
RESUMEN
We present an encoding scheme of a single logical qubit with single-sided quantum dot (QD)-cavity systems, which is immune to the collective decoherence. By adjusting the Purcell factor to satisfy the balanced reflection condition, the detrimental effects of unbalanced reflection between the coupled and uncoupled QD-cavity systems can be effectively suppressed. Furthermore, the fidelity of each step can be increased to unity regardless of the strong coupling regime and the weak coupling regime of cavity quantum electrodynamics (QED) with the assistance of waveform correctors. The scheme requires QD-cavity systems and simple linear optical elements, which can be implemented with the currently experimental techniques.
RESUMEN
With the aging and older adults' mental health problems in China, more attention has been paid to the restorative environment. As an important restorative environment in the city, the mental health restorative effect of park environment has been confirmed. However, further exploration is needed to determine whether winter parks have positive effects, their differences from non-winter parks, and the specific pathways of these effects. Therefore, this study constructed a "full path" for the restorative effects of older adults' mental health in parks under seasonal differences, including four components: perceived environment, affective feedback, behavioral feedback, and restorative effect, forming four pathways. Based on this, this study obtained 211 and 240 sample data in winter and non-winter parks, and verified the validity of various hypotheses and mediation paths using structural equation models. It found that: (1) overall restorative effects existed in different seasons; (2) in winter, perceived environmental assessment was not a direct antecedent of restorative effects, and affective feedback and Moderate and Vigorous Physical Activity (MVPA) feedback were important mediating factors, and the chain mediated pathway existed; (3) in non-winter, both direct, indirect and chain mediated effects existed, and affective feedback and Low Physical Activity (LPA) feedback were important mediating factors. Based on this, this study divided parks into "affective inducing" and "behavioral promoting" types, and proposed corresponding planning priorities to positively intervene in planning and design practices.