Uterine cancer (also known as endometrial cancer) can seriously affect the female reproductive system, and histopathological image analysis is the gold standard for diagnosing endometrial cancer. Due to the limited ability to model the complicated relationships between histopathological images and their interpretations, existing computer-aided diagnosis (CADx) approaches using traditional machine learning algorithms often failed to achieve satisfying results. In this study, we develop a CADx approach based on a convolutional neural network (CNN) and attention mechanisms, called HIENet. In the ten-fold cross-validation on ~3,300 hematoxylin and eosin (H&E) image patches from ~500 endometrial specimens, HIENet achieved a 76.91 ± 1.17% (mean ± s. d.) accuracy for four classes of endometrial tissue, i.e., normal endometrium, endometrial polyp, endometrial hyperplasia, and endometrial adenocarcinoma. Also, HIENet obtained an area-under-the-curve (AUC) of 0.9579 ± 0.0103 with an 81.04 ± 3.87% sensitivity and 94.78 ± 0.87% specificity in a binary classification task that detected endometrioid adenocarcinoma. Besides, in the external validation on 200 H&E image patches from 50 randomly-selected female patients, HIENet achieved an 84.50% accuracy in the four-class classification task, as well as an AUC of 0.9829 with a 77.97% (95% confidence interval, CI, 65.27%~87.71%) sensitivity and 100% (95% CI, 97.42%~100.00%) specificity. The proposed CADx method outperformed three human experts and five CNN-based classifiers regarding overall classification performance. It was also able to provide pathologists better interpretability of diagnoses by highlighting the histopathological correlations of local pixel-level image features to morphological characteristics of endometrial tissue.

The tumor immune microenvironment (TIME) is one of the significant hallmarks of cancer and has the important role of largely determining the malignancy level of tumors. As an approach to break through this bottleneck of tumor treatment methods, the TIME can be reprogrammed by certain nanomaterials. Here, we coated C-novyi-spores with melittin-RADA₃₂ nanofiber hybrid peptide and loaded the immunomodulator metformin to obtain MRM-coated spores as a powerful antitumor nanodrug against glioblastoma (GBM), which is based on the activation of the TIME. MRM-coated spores exhibit extended-release profiles and an enhanced killing effect on GBM both in vitro and in vivo. Furthermore, MRM-coated spores can educate the innate and adaptive immune system by inducing sustainable CD8⁺ T cell responses, promoting M1 macrophage polarization, and regulating the expression of HIF1-α, PDL1, and CXCL9 in TIME. In intracranial applications, MRM-coated spores showed excellent biosafety and a strong therapeutic effect. In summary, peptide hydrogels provide a promising strategy in which advantages of different treatment methods can be incorporated to synthesize potent antitumor drugs with mild side effects from bacteria-mediated nanomaterials.

Radiation-induced ototoxicity is associated with inflammation response and excessive reactive oxygen species in the cochlea. However, the effectiveness of many drugs in clinical settings is limited due to anatomical barriers in the inner ear and pharmacokinetic instability. To address this issue, we developed an injectable hydrogel called RADA₃₂-HRN-dexamethasone (RHD). The RHD hydrogel possesses self-anti-inflammatory properties and can self-assemble into nanofibrous structures, ensuring controlled and sustained release of dexamethasone in the local region. Flow cytometry analysis revealed that the uptake of FITC-conjugated RHD gel by hair cells increased in a time-dependent manner. Compared to free dexamethasone solutions, dexamethasone-loaded RHD gel achieved a longer and more controlled release profile of dexamethasone. Additionally, RHD gel effectively protected against the inflammatory response, reduced excessive reactive oxygen species production, and reversed the decline in mitochondrial membrane potentials induced by ionizing radiation, leading to attenuation of apoptosis and DNA damage. Moreover, RHD gel promoted the recovery of outer hair cells and partially restored auditory function in mice exposed to ionizing radiation. These findings validated the protective effects of RHD gel against radiation-induced ototoxicity in both cell cultures and animal models. Furthermore, RHD gel enhanced the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which was inhibited by ionizing radiation, thereby promoting the survival of hair cells. Importantly, intratympanic injections of RHD gel exhibited excellent biosafety and do not interfere with the anti-tumor effects of radiotherapy. In summary, our study demonstrates the therapeutic potential of injectable dexamethasone-loaded RHD hydrogel for the treatment of radiation-induced hearing loss by regulating the mTOR signaling pathway.

Purpose: To investigate the influence of microRNA-378g (miR-378g) on radiosensitivity and metastasis of nasopharyngeal carcinoma cells and study how miR-378g regulated Src homology region 2 domain-containing phosphatase-1 (SHP-1) expression. Materials and methods: Polymerase chain reaction (PCR) was used to detect the expression level of miR-378g and SHP-1 mRNA in different nasopharyngeal carcinoma (NPC) cell lines. MiR-378g mimics were transfected into NPC cells and radiosensitivity was determined by colony formation assay. Cell apoptotic rate was determined by flow cytometry analysis. Cell invasion was examined by transwell assay. SHP-1 transcriptional activity was examined by luciferase assay. SHP-1 expression level was determined by Western blot. Lentivirus containing SHP-1 gene and miR-378g mimics were co-transfected into NPC cells and radiosensitivity and metastasis were detected by colony formation assay and transwell assay again. Results: Expression of miR-378g and SHP-1 mRNA was negatively correlated in NPC cell lines. MiR-378g mimics enhanced radiosensitivity, promoted apoptosis and decreased invasion in NPC cells. SHP-1 expression was inhibited by miR-378g mimics. Luciferase reporter assay showed that miR-378g directly targeted SHP-1 by binding to 3′ untranslated region (3′UTR) of SHP-1 mRNA. Overexpression of SHP-1 partially inversed the effect of miR-378g mimics on radiosensitivity, but had no effect on cell invasion. Conclusion: MiR-378g enhanced radiosensitivity partially by targeting SHP-1 in NPC cells. Cell invasion was also partially inhibited by miR-378g, but the effect was not mediated by SHP-1.