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Objective: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). Methods: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. Results: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74–27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27–18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. Conclusion: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists. [ABSTRACT FROM AUTHOR]

Epigenetic inactivation of GADD45A is a common occurrence in different types of cancer. However, little is known regarding its association with radiosensitivity in cervical cancer (CC). Thus, the present study aimed to investigate the association between aberrant GADD45A methylation and radiosensitivity in CC. SiHa, HeLa and CaSki CC cells were treated with 5-azacytidine (5-azaC), with or without irradiation. The expression levels of GADD45A and AKT related molecules were detected via reverse transcription-quantitative PCR and western blot analyses. The methylation status of GADD45A was assessed via methylation-specific PCR and cell proliferation assays, while clonogenic assays and flow cytometric analysis were performed to assess the function of the genes (GADD45A and AKT) in the CC cell lines. The results demonstrated that methylation of GADD45A was significantly higher in the radioresistant tissues (63.16%) compared with the radiosensitive samples (33.33%). In addition, the surviving fraction of SiHa cells following irradiation with 2 Gy was demonstrated to be highest amongst the three CC cells (CaSki, 57±9.5%; HeLa, 70±4% and SiHa, 75±10%). The survival rate of SiHa cells following treatment with 5-azaC and ionizing radiation (IR) significantly decreased as the radiation dose increased, compared with treatment with IR alone. Following overexpression of GADD45A or treatment with 5-azaC, the radiosensitivity of SiHa cells significantly increased compared with both the control vector and PBS treated groups. In addition, the AKT inhibitor, MK-2206, increased the radiosensitivity of SiHa cells. Notably, aberrant methylation of GADD45A was associated with decreased radiosensitivity in CC, and the PI3K/AKT signaling pathway was essential for radioresistance, which was mediated through downregulation of GADD45A. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia., Methods: Astrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT‒PCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis protein expression., Results: Our findings demonstrated that astrocyte-derived exosomes were internalized by neurons both in vitro and in vivo . Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect., Conclusion: Astrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Liao, Lang, Qin, Jiao, Shao, Deng and She.)

In the surface ehanced Raman scattering (SERS) technology, not only to improve the making process of SERS substrates, to be fast and easily, but also to enhance the SERS enhance factor, an easy replacement reaction between zinc and silver nitrate solution has been adopted to prepare silver micro-structures SERS-active substrate. The silver micro-substrates have many advantages. These substrates have good stability, well preservation, an easy making method and a fast making process. The surface profile of the silver microparticles is investigated by scanning electron microscope (SEM). The silver microstructures are dendritic shape in a symmetrical fashion with symmetrical distribution. When the time of the replace reaction is 40, 50 and 60 s, respectively, the average lengths of "trunks" in the silver dendritic microsubstractes are about 3, 5 and 10 μm, and the lengths of the "branches" are about 700 nm, 2 μm and 3 μm, respectively. The result shows that the longer time the replacement reaction takes, the longer lengths of the "trunks" and "branches" in the silver dendritic microsubstractes become. With the time of replace reaction increasing, the "trunk" and "branch" in the silver dendritic microsubstractes grow longer and a large amount of nano-level "leaves" grow out from the "branches" of the silver dendritic microsubstractes, so the silver micro size dendrates have nano level structure on surface. In order to investigate the SERS-active substrates application in SERS, a Fourier transform Raman spectrograph with a 1 064 nm laser wavelength is used to measure the SERS spectra. And good SERS spectra have been obtained by using dendritic silver microsubstrates on the silicon chip as a SERS substract, and Rhodamine 6G (R6G) as a molecule probe. It is found that the silver micro-substrates have good Raman characteristics. And comparing these SERS spectra, it gets the conclution that the spectra with best SERS enhance effect are obtained when R6G is obsorbed on the silver dendritic micro-substractes whose preparing time is 40s, and at that time, the analytical enhancement factor for SERS signals is approximately 10(3). And when the silicon ships are dealed with surfactants Polyvinylpyrrolidone (PVP) and keeping the other conditions the same as before, the SERS enhance effect of the spectra becomes better, and the enhancement factor turn to be approximately 10(4). What's more, the silver microstructures can be preserved several monthes under deionized water and the repeatment of the expriment result is well in general.