A patent mining approach to accurately identifying Innovative Industrial Clusters based on the multivariate DBSCAN algorithm

Innovative Industrial Clusters (IIC), characterized by geographical aggregation and technological collaboration among technology enterprises and institutions, serve as pivotal drivers of regional economic competitiveness and technological advancements. Prior research on cluster identification, crucial for IIC analysis, has predominantly emphasized geographical dimensions while overlooking technological proximity. Addressing these limitations, this study introduces a comprehensive framework incorporating multiple indices and methods for accurately identifying IIC using patent data. To unearth latent technological insights within patent documents, Latent Dirichlet Allocation (LDA) is employed to generate topics from a collection of terms. Utilizing the applicants’ names and addresses recorded in patents, an Application Programming Interface (API) map systems facilitates the extraction of geographic locations. Subsequently, a Multivariate Density‑Based Spatial Clustering of Applications with Noise (MDBSCAN) algorithm, which accounts for both technological and spatial distances, is deployed to delineate IIC. Moreover, a bipartite network model based on patent geographic information collected from the patent is constructed to analyze the technological distribution on the geography and development mode of IIC. The utilization of the model and methodologies is demonstrated through a case study on the China flexible electronics industry (FEI). The findings reveal that the clusters identified via this novel approach are significantly correlated with both technological innovation and geographical factors. Moreover, the MDBSCAN algorithm demonstrates notable superiority over other algorithms in terms of computational precision and efficiency, as evidenced by the case analysis

Discovery of [11C]MK-6884: a positron emission tomography (PET) imaging agent for the study of M4 muscarinic receptor positive allosteric modulators (PAMs) in neurodegenerative diseases

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [11C]MK-6884

A Tubular Flexible Triboelectric Nanogenerator with a Superhydrophobic Surface for Human Motion Detecting

The triboelectric nanogenerator (TENG) is a newly arisen technology for mechanical energy harvesting from the environment, such as raindrops, wind, tides, and so on. It has attracted widespread attention in flexible electronics to serve as self-powered sensors and energy-harvesting devices because of its flexibility, durability, adaptability, and multi-functionalities. In this work, we fabricated a tubular flexible triboelectric nanogenerator (TF-TENG) with energy harvesting and human motion monitoring capabilities by employing polydimethylsiloxane (PDMS) as construction material, and fluorinated ethylene propylene (FEP) films coated with Cu as the triboelectric layer and electrode, serving in a free-standing mode. The tube structure has excellent stretchability that can be stretched up to 400%. Modifying the FEP films to obtain a superhydrophobic surface, the output performance of TF-TENG was increased by at least 100% compared to an untreated one. Finally, as the output of TF-TENG is sensitive to swing angle and frequency, demonstration of real-time monitoring of human motion state was realized when a TF-TENG was worn on the wrist

Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier

Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated anti-migraine efficacy. One remaining question is where do these blockers act? We hypothesized that the trigeminal ganglion could be one possible site. We examined the binding sites of a CGRP receptor antagonist (MK-3207) and related this to the expression of CGRP and its receptor in rhesus trigeminal ganglion. Pituitary adenylate cyclase-activating polypeptide (PACAP) and glutamate were examined and related to the CGRP system. Furthermore, we examined if the trigeminal ganglion is protected by the blood-brain barrier (BBB). Autoradiography was performed with [(3)H]MK-3207 to demonstrate receptor binding sites in rhesus trigeminal ganglion (TG). Immunofluorescence was used to correlate binding and the presence of CGRP and its receptor components, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), and the distribution of PACAP and glutamate in rhesus and rat TG. Evans blue was used to examine large molecule penetration into the rat TG. High receptor binding densities were found in rhesus TG. Immunofluorescence revealed expression of CGRP, CLR and RAMP1 in trigeminal cells. CGRP positive neurons expressed PACAP but not glutamate. Some neurons expressing CLR and RAMP1 co-localized with glutamate. Evans blue revealed that the TG is not protected by BBB. This study demonstrates CGRP receptor binding sites and expression of the CGRP receptor in rhesus and rat TG. The expression pattern of PACAP and glutamate suggests a possible interaction between the glutamatergic and CGRP system. In rat the TG is outside the BBB, suggesting that molecules do not need to be CNS-penetrant to block these receptors

Localization of CGRP Receptor Components, CGRP, and Receptor Binding Sites in Human and Rhesus Cerebellar Cortex.

The cerebellum is classically considered to be mainly involved in motor processing, but studies have suggested several other functions, including pain processing. Calcitonin-gene-related peptide (CGRP) is a neuropeptide involved in migraine pathology, where there is elevated release of CGRP during migraine attacks and CGRP receptor antagonists have antimigraine efficacy. In the present study, we examined CGRP and CGRP receptor binding sites and protein expression in primate cerebellar cortex. Additionally, mRNA expression of the CGRP receptor components, calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1), was examined. In addition, expression of procalcitonin was studied. We observed high [(3)H]MK-3207 (CGRP receptor antagonist) binding densities in the molecular layer of rhesus cerebellar cortex; however, due to the limit of resolution of the autoradiographic image the exact cellular localization could not be determined. Similarly, [(125)I]CGRP binding was observed in the molecular layer and Purkinje cell layer of human cerebellum. CLR and RAMP1 mRNA was expressed within the Purkinje cell layer and some expression was found in the molecular layer. Immunofluorescence revealed expression of CGRP, CLR, and RAMP1 in the Purkinje cells and in cells in the molecular layer. Procalcitonin was found in the same localization. Recent research in the biology of cerebellum indicates that it may have a role in nociception. For the first time we have identified CGRP and CGRP receptor binding sites together with CGRP receptor expression through protein and mRNA localization in primate cerebellar cortex. These results point toward a functional role of CGRP in cerebellum. Further efforts are needed to evaluate this

Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence and autoradiography.

Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved

2D Behaviors of Excitons in Cesium Lead Halide Perovskite Nanoplatelets

Fundamental to understanding and predicting the optoelectronic properties of semiconductors is the basic parameters of excitons such as oscillator strength and exciton binding energy. However, such knowledge of CsPbBr₃ perovskite, a promising optoelectronic material, is still unexplored. Here we demonstrate that quasi-two-dimensional (quasi-2D) CsPbBr₃ nanoplatelets (NPLs) with 2D exciton behaviors serve as an ideal system for the determination of these parameters. It is found that the oscillator strength of CsPbBr₃ NPLs is up to 1.18 × 10⁴, higher than that of colloidal II–VI NPLs and epitaxial quantum wells. Furthermore, the exciton binding energy is determined to be of ∼120 meV from either the optical absorption or the photoluminescence analysis, comparable to that reported in colloidal II–VI quantum wells. Our work provides physical understanding of the observed excellent optical properties of CsPbBr₃ nanocrystals and would benefit the prediction of high-performance excitonic devices based on such materials

Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation

Introduction Herein, we developed an engineered extracellular vehicle (EV)-based method for ameliorating inflammatory responses in psoriasis. Methods EVs, derived from annexin A1 (ANXA1) overexpressing T cells, were co-extruded with M2 macrophage membrane to obtain engineered EVs. In vitro, the effect of engineered EVs on macrophage polarization was evaluated by real-time PCR. In imiquimod (IMQ)-induced psoriasis-like mouse model, the efficacy of engineered EVs in ameliorating psoriatic inflammation was evaluated by Psoriasis Area and Severity Index (PASI) score and immunohistochemistry staining after subcutaneous injection of EVs. Results The engineered EVs not only preserved the high stability of M2 macrophage membrane but also retained the macrophage reprogramming potential of ANXA1 overexpressed in T cells. In the psoriasis-like mouse model, subcutaneous injection of engineered EVs successfully reduced the PASI score and the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Along with high biosafety, the administration of EVs also rescued the histomorphological changes of spleen, liver, and kidney. Conclusions The engineered EVs exhibited the potential to alleviate inflammation of psoriasis, providing new insights and potential strategies for the immunotherapies of psoriasis