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The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cell activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could affect nidogen-1 accessibility. Phosphoproteomics revealed that the 'AKI protector' Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin [beta]1 to induce Wnt in tubules to mitigate AKI. Altogether, our results support that fibroblastselective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis., Introduction Acute kidney injury (AKI) is a clinical syndrome characterized by an abrupt decline in renal function within a few hours or days, which is associated with high morbidity and [...]

Background Osteoarthritis has a high rate of disability and deformity, and can be combined with several physical and mental diseases. However, the early symptoms of the disease are not obvious. At present, there are problems in the management of osteoarthritis in the community such as uncoordinated management, inadequate methods and imperfect systems. Objective To construct and evaluate an informatics-based multidisciplinary management model for osteoarthritis patients in community, to promote the management of community osteoarthritis patients and improve the prognosis of the patients. Methods First a multidisciplinary management model of osteoarthritis patients in the community was constructed, including hierarchical management process of patients based on risk factor stratification, the multidisciplinary management team and its division of diagnosis and treatment, then an informatics based multidisciplinary management process was constructed, and information software development was completed. From July 2019 to July 2020, 80 patients with knee osteoarthritis who attended the general outpatient clinics of Dinghai and Daqiao Community Health Service Centers in Shanghai, and the orthopedics outpatient clinics of Yangpu District Central Hospital were randomly assigned into multidisciplinary management groups and general management group, with 40 patients in each group. The patients in general group were given conventional treatment, while the patients in multidisciplinary group were adopted information-based multidisciplinary management. Visual analogue scale (VAS) scores, Western Ontario McMaster University (WOMAC) osteoarthritis index score, the simplified scale of Arthritis Quality Of Life Measurement Scale (AIMS2) scores, Health Literacy Management Scale (HeLMS) scores, and body mass index (BMI) were assessed before and after 12 weeks of management, respectively. Results Before treatment, there were no significant differences in VAS score, WOMAC osteoarthritis index score, AIMS2 score, Helms score, and BMI between patients with knee osteoarthritis in the multidisciplinary and general groups (P>0.05) . After 12 weeks of treatment, the VAS and WOMAC score of both the multidisciplinary and general groups went down, and the health literacy AIMS2 scores and Helms total score were higher after treatment than those before. The difference was statistically significant (P

Due to the explosive rise of multimodal content in online social communities, cross-modal learning is crucial for accurate fake news detection. However, current multimodal fake news detection techniques face challenges in extracting features from multiple modalities and fusing cross-modal information, failing to fully exploit the correlations and complementarities between different modalities. To address these issues, this paper proposes a fake news detection model based on a one-dimensional CCNet (1D-CCNet) attention mechanism, named BTCM. This method first utilizes BERT and BLIP-2 encoders to extract text and image features. Then, it employs the proposed 1D-CCNet attention mechanism module to process the input text and image sequences, enhancing the important aspects of the bimodal features. Meanwhile, this paper uses the pre-trained BLIP-2 model for object detection in images, generating image descriptions and augmenting text data to enhance the dataset. This operation aims to further strengthen the correlations between different modalities. Finally, this paper proposes a heterogeneous cross-feature fusion method (HCFFM) to integrate image and text features. Comparative experiments were conducted on three public datasets: Twitter, Weibo, and Gossipcop. The results show that the proposed model achieved excellent performance. [ABSTRACT FROM AUTHOR]

A random copolymer (PTBM), utilized as deep ultra-violet (DUV) photoresist, was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization with tert-butyl methacrylate (tBMA), methyl methacrylate (MMA), triphenylsulfonium p-styrenesulfonate (TPS-SS), and functional poly (sesquicarbonylsiloxanes) (POSS-MA) as the monomer components, and 4-cyano-4-[(dodecylsulfanylthiocarbonyl) sulfanyl]pentanoic acid (CDSPA) as the RAFT reagent. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR) proved successful synthesis. Ultraviolet absorption spectroscopy (UV) analysis verified the transparency of the polymer in the DUV band. RAFT polymerization kinetics showed that the polymerization rate conformed to the first-order kinetic relationship, and the polymerization process exhibited a typical controlled free radical polymerization behavior. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and static thermo-mechanical analysis (TMA) showed that the incorporation of POSS groups improved the thermal properties of the copolymer. According to scanning electron microscopy (SEM) images, the copolymerization of photoacid monomers (TPS-SS) resulted in photoresist copolymers exhibiting good resistance to acid diffusion and low roughness. [ABSTRACT FROM AUTHOR]

MPS IIIC is a lysosomal storage disease caused by mutations in heparan‐α‐glucosaminide N‐acetyltransferase (HGSNAT), for which no treatment is available. Because HGSNAT is a trans‐lysosomal‐membrane protein, gene therapy for MPS IIIC needs to transduce as many cells as possible for maximal benefits. All cells continuously release extracellular vesicles (EVs) and communicate by exchanging biomolecules via EV trafficking. To address the unmet need, we developed a rAAV‐hHGSNATEV vector with an EV‐mRNA‐packaging signal in the 3′UTR to facilitate bystander effects, and tested it in an in vitro MPS IIIC model. In human MPS IIIC cells, rAAV‐hHGSNATEV enhanced HGSNAT mRNA and protein expression, EV‐hHGSNAT‐mRNA packaging, and cleared GAG storage. Importantly, incubation with EVs led to hHGSNAT protein expression and GAG contents clearance in recipient MPS IIIC cells. Further, rAAV‐hHGSNATEV transduction led to the reduction of pathological EVs in MPS IIIC cells to normal levels, suggesting broader therapeutic benefits. These data demonstrate that incorporating the EV‐mRNA‐packaging signal into a rAAV‐hHGSNAT vector enhances EV packaging of hHGSNAT‐mRNA, which can be transported to non‐transduced cells and translated into functional rHGSNAT protein, facilitating cross‐correction of disease pathology. This study supports the therapeutic potential of rAAVEV for MPS IIIC, and broad diseases, without having to transduce every cell. [ABSTRACT FROM AUTHOR]

The symmetry of neuron discharging has some relationship with the electrophysiological characteristics and dynamic behavior of a neuron, and has a close relation with the symmetry of ion channels, current balance, neuron type, synaptic transmission, and network effects. Among them, the feedback and interactions in the network have a particularly direct impact on the symmetrical discharge of a neuron element. This work introduces a memristor as a synapse into a neuron cell, taking the membrane potential back to ion channels, and therefore various symmetric firing behaviors of Hindmarsh–Rose (HR) neurons are observed, including chaos and various periodic firings. By further adjusting the feedback, coexisting symmetrical discharge of the neuron is achieved. Furthermore, the impact of frequency variations on the memristor synapse is analyzed, and thus the operating regimes of memristor and resistor are classified and discussed. Circuit simulations prove the neural chaotic firings along with their symmetrized discharging processes, demonstrating the effectiveness of symmetrical control of chaotic discharge. Finally, applying the symmetrical system to DNA image encryption can effectively protect the security of images. [ABSTRACT FROM AUTHOR]