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Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth
Crossing the blood–brain barrier (BBB) and reaching intracranial tumours is a clinical challenge for current targeted interventions including antibody-based therapies, contributing to poor patient outcomes. Increased cell surface density of human epidermal growth factor receptor 3 (HER3) is associated with a growing number of metastatic tumour types and is observed on tumour cells that acquire resistance to a growing number of clinical targeted therapies. Here we describe the evaluation of HER3-homing nanobiological particles (nanobioparticles (NBPs)) on such tumours in preclinical models and our discovery that systemic NBPs could be found in the brain even in the absence of such tumours. Our subsequent studies described here show that HER3 is prominently associated with both mouse and human brain endothelium and with extravasation of systemic NBPs in mice and in human-derived BBB chips in contrast to non-targeted agents. In mice, systemically delivered NBPs carrying tumoricidal agents reduced the growth of intracranial triple-negative breast cancer cells, which also express HER3, with improved therapeutic profile compared to current therapies and compared to agents using traditional BBB transport routes. As HER3 associates with a growing number of metastatic tumours, the NBPs described here may offer targeted efficacy especially when such tumours localize to the brain.
Associations of mucinous differentiation and mucin expression with immune cell infiltration and prognosis in colorectal adenocarcinoma
The production of extracellular mucus and expression of mucins are commonly aberrant in colorectal cancer, yet their roles in tumour progression remain unclear.
Host factor PLAC8 is required for pancreas infection by SARS-CoV-2
Although COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology is still under debate. Here, we investigate the consequences of SARS-CoV-2 pancreatic infection and the role of the host factor Placenta-associated protein (PLAC8).
Pancreatic organogenesis mapped through space and time
The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization. Signals from the mesenchyme, neurons, and endothelial cells instruct epithelial cell differentiation during pancreatic development. To understand the cellular diversity and spatial organization of the developing pancreatic niche, we mapped the spatial relationships between single cells over time. We found that four transcriptionally unique subtypes of mesenchyme in the developing pancreas spatially coordinate throughout development, with each subtype at fixed locations in space and time in relation to other cells, including beta cells, vasculature, and epithelial cells. Our work provides insight into the mechanisms of pancreatic development by showing that cells are organized in a space and time manner.
Determinants of consumer intention to use autonomous delivery vehicles: based on the planned behavior theory and normative activation model
Autonomous delivery vehicles (ADVs) that provide contactless services have attracted much academic and practical attention in China in recent years. Despite this, there is a lack of in-depth research on what motivates customers to embrace ADVs. The study integrates the theory of planned behavior (TPB) and normative activation model (NAM) and explores how environmental factors, situational factors, and individual factors affect original TPB constructs and ultimately consumers’ intention to use ADVs. Structural equation modeling was performed on survey data of 561 Chinese consumers through an online sampling platform. The results show that among the factors affecting consumer intention, word-of-mouth recommendations have the greatest impact, followed by perceived enjoyment, COVID-19 risk, ascription of responsibility, subjective norm, attitude, and perceived behavioral control. The results not only make important theoretical contributions to the technology acceptance fields but also provide helpful references to logistics enterprises, ADVs technology providers, and policymakers.
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