A Two-Step Approach for Narrowband Source Localization in Reverberant Rooms

This paper presents a two-step approach for narrowband source localization within reverberant rooms. The first step involves dereverberation by modeling the homogeneous component of the sound field by an equivalent decomposition of planewaves using Iteratively Reweighted Least Squares (IRLS), while the second step focuses on source localization by modeling the dereverberated component as a sparse representation of point-source distribution using Orthogonal Matching Pursuit (OMP). The proposed method enhances localization accuracy with fewer measurements, particularly in environments with strong reverberation. A numerical simulation in a conference room scenario, using a uniform microphone array affixed to the wall, demonstrates real-world feasibility. Notably, the proposed method and microphone placement effectively localize sound sources within the 2D-horizontal plane without requiring prior knowledge of boundary conditions and room geometry, making it versatile for application in different room types

In vivo real-time imaging of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness with visible spatially modulated light

We present the real-time single snapshot multiple frequency demodulation - spatial frequency domain imaging (SSMD-SFDI) platform implemented with a visible digital mirror device that is capable of imaging and monitoring dynamic turbid medium and processes over a large field of view. One challenge in quantitative imaging of biological tissue such as the skin is the complex structure rendering techniques based on homogeneous medium models to fail. To address this difficulty we have also developed a novel method that maps the layered structure to a homogeneous medium for spatial frequency domain imaging. The varying penetration depth of spatially modulated light on its wavelength and modulation frequency is used to resolve the layered structure. The efficacy of the real-time SSMD-SFDI platform and this two-layer model is demonstrated by imaging forearms of 6 healthy subjects under the reactive hyperemia protocol. The results show that our approach not only successfully decouples light absorption by melanin from that by hemoglobin and yields accurate determination of cutaneous hemoglobin concentration and oxygen saturation, but also provides reliable estimation of the scattering properties, the melanin content and the epidermal thickness in real time. Potential applications of our system in imaging skin physiological and functional states, cancer screening, and microcirculation monitoring are discussed at the end. © 2017 Optical Society of Americ

Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes

Protease-activated receptor 2 (PAR-2), which is abundantly expressed in astrocytes, is known to play major roles in brain inflammation. However, the influence of the natural agonist of PAR-2, tryptase, on proinflammatory mediator releasedfrom astrocytes remains uninvestigated. In the present study, we found that tryptase at lower concentrations modestly reduced intracellular ROS production but significantly increased IL-6 and TNF-α secretion at higher concentrations without affecting astrocytic viability and proliferation. The actions of tryptase were alleviated by specific PAR-2 antagonist FSLLRY-NH2 (FS), indicating that the actions of tryptase were via PAR-2. PI3K/AKT inhibitor LY294002 reversed the effect of tryptase on IL-6 production, whereas inhibitors specific for p38, JNK, and ERK1/2 abolished the effect of tryptase on TNF-α production, suggesting that different signaling pathways are involved. Moreover, tryptase-induced activation of MAPKs and AKT was eliminated by FS, implicating that PAR-2 is responsible for transmitting tryptase biosignals to MAPKs and AKT. Tryptase provoked also expression of TGF-β and CNTF in astrocytes. The present findings suggest for the first time that tryptase can regulate the release of cytokines from astrocytes via PAR-2-MAPKs or PAR-2-PI3K/AKT signaling pathways, which reveals PAR-2 as a new target actively participating in the regulation of astrocytic functions

Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism

Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions

Stromal-Derived NRG1 Enables Oncogenic KRAS Bypass in Pancreas Cancer

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a survival factor. Genetic depletion or pharmacological inhibition of ERBB2/3 or NRG1 abolished KRAS* bypass and synergized with KRA

Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery

Purpose: The goal of the present study was to synthesize mucoadhesive polymer -thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular drug delivery. Methods: A new method for preparing TCS was developed, and the characteristics were determined using Fourier transform infrared spectroscopy and the degree of thiol immobilized was measured by Ellman's reagent. Human corneal epithelium (HCE) cells were incubated with different concentrations of TCS for 48 h to determine the cell viabilities. CS/ TCS-SA NPs were prepared and optimized by a modified ionic gelation method. The particle sizes, zeta potentials, Scanning electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo studies of the two types of NP were compared. Results: The new method enabled a high degree of thiol substitution of TCS, up to 1,411.01±4.02 μmol/g. In vitro cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs, TCS-SA NPs were more stable, with higher mucoadhesive properties and could deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo. Conclusions: TCS-SA NPs have better delivery capability, suggesting they have good potential for ocular drug delivery applications

Preparation and In Vitro

For preventing premature drug release in neutral environment and avoiding them being trapped into the endosomal/lysosomal system, we developed a novel iron silicate@liposome hybrid (ILH) formulation, which can be used as a carrier to transport doxorubicin (DOX) in a pH-sensitive manner and to escape from endosomal/lysosomal trapping through “proton-sponge” effect. The high intensity of photoacoustic signal from in vitro photoacoustic imaging (PAI) experiments suggests that it is a promising candidate for PAI agent, providing the potential for simultaneously bioimaging and cancer-targeting drug delivery. Cytotoxicity of our formulation toward tumor cells was remarkably higher than free DOX (48.4±7.7% and 26.2±8.4%, P<0.001). Confocal laser scanning microscopy experiments showed the enhanced transportation and enrichment process of DOX in QSG-7703 cells. Taking together, we developed an easy approach to construct a multifunctional anticancer drug delivery/imaging system with a potency as a PAI agent. The strategy of combining drug carrier and imaging agent is an emerging platform for further construction of nanoparticle and may play a significant role in cancer therapy and diagnosis

Systematic analysis of the role and significance of target genes of active ingredients of traditional Chinese medicine injections in the progression and immune microenvironment of hepatocellular carcinoma

Background: Traditional Chinese medicine in China is an important adjuvant therapy for the treatment of hepatocellular carcinoma (HCC) and traditional Chinese medicines injections have a wide range of clinical applications. The purpose of this study was to identify the active ingredients and related genes of traditional Chinese medicine injections that can treat hepatocellular carcinoma.Methods: Effective small molecule components were extracted from 14 types of traditional Chinese medicines from 8 injections and the main gene targets were identified. The 968 patients with HCC were classified based on the target gene set, and the characteristics of patients with different subtypes were analyzed. Patients with two subtypes of HCC were compared with normal tissues and cirrhosis to identify important gene targets related to traditional Chinese medicines in HCC progression.Results: In this study, 138 important genes associated with traditional Chinese medicines were identified and two HCC subtypes were identified. By analyzing the differences between the two subtypes, 25 related genes were associated with HCC subtypes. Through clinical and pharmacological analysis, this study identified quercetin as an important traditional Chinese medicines small molecule and secreted phosphoprotein 1 (SPP1) as an important oncogene in HCC.Conclusion: Traditional Chinese medicines injection is an important adjuvant treatment modality for HCC. SPP1 is an important oncogene in HCC

Single-Cell CRISPR Immune Screens Reveal Immunological Roles of Tumor Intrinsic Factors

Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance