Neurons sometimes completely fill available space in their receptive fields with evenly spaced dendrites to uniformly sample sensory or synaptic information. The mechanisms that enable neurons to sense and innervate all space in their target tissues are poorly understood. Using somatosensory neurons as a model, we show that heparan sulfate proteoglycans (HSPGs) Dally and Syndecan on the surface of epidermal cells act as local permissive signals for the dendritic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the entire skin. Using long-term time-lapse imaging with intact larvae, we found that dendrites grow into HSPG-deficient areas but fail to stay there. HSPGs are necessary to stabilize microtubules in newly formed high-order dendrites. In contrast to C4da neurons, non-space-filling sensory neurons that develop in the same microenvironment do not rely on HSPGs for their dendritic growth. Furthermore, HSPGs do not act by transporting extracellular diffusible ligands or require leukocyte antigen-related (Lar), a receptor protein tyrosine phosphatase (RPTP) and the only known HSPG receptor, for promoting dendritic growth of space-filling neurons. Interestingly, another RPTP, Ptp69D, promotes dendritic growth of C4da neurons in parallel to HSPGs. Together, our data reveal an HSPG-dependent pathway that specifically allows dendrites of space-filling neurons to innervate all target tissues in.

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The development of liposome-based drugs was severely limited due to inefficient loading strategies. Herein, we developed a click reaction-mediated loading procedure by designing an enzyme-sensitive maleimide (MAL) tag for ferrying...

Background Pathological complete response (pCR) is the goal of neoadjuvant chemotherapy (NACT). We aimed to develop a nomogram to predict the probability of achieving pCR in estrogen receptor-positive (ER+), HER2-negative (HER2−) breast cancer patients. Methods A total of 273 ER+, HER2− breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to screen the predictive factors to develop the nomograms. The discrimination and calibration abilities were assessed by the C-index, receiver operating characteristic curve (AUC), and calibration plot. Results There were 28 patients (10.3%) with overall pCR, 38 patients (13.9%) with breast pCR after NACT. ER expression, PgR expression, the neutrophil-to-lymphocyte ratio (NLR) and the Ki-67 index were independent predictive factors for achieving overall pCR. These indicators had good discrimination and calibration ability (AUC 0.843). The nomogram for breast pCR was established based on ER expression, PgR expression, the NLR, and the Ki-67 index and showed great discriminatory ability, with an AUC of 0.810. The calibration curve showed that the predictive ability of the nomogram was a good fit to actual observations. Conclusion The nomograms exhibited a sufficient discriminatory ability for predicting pCR after NACT in ER+, HER2− breast cancer patients. Utilizing these nomograms will enable us to identify patients at high probability for pCR after NACT and provide a reference for preoperative adjuvant therapy.