Exosomes Mediate the Production of Oxaliplatin Resistance and Affect Biological Behaviors of Colon Cancer Cell Lines.

BACKGROUND: Colon cancer has high mortality rate which making it one of the leading causes of cancer deaths. Oxaliplatin is a common chemotherapeutic drug, but it has disadvantages such as drug resistance. OBJECTIVE: The purpose of this study is to explore the mechanism of exosomes in the resistance of oxaliplatin and verify whether elemene and STAT3 inhibitors reverse the resistance to oxaliplatin. METHODS: Related cell line models were constructed and the proliferation, migration, invasion, apoptosis and resistance to oxaliplatin were evaluated for all three cells of HCT116/L, sensitive cell HCT116 and HCT116+HCT116/L-exosomes (HCT116-exo). It was to explore probable signaling pathways and mechanisms by Western blotting. RESULTS: HCT116-exo drug-resistant chimeric cells showed greater capacity for proliferation, migration and invasion than HCT116 sensitive cells. After the above cells were treated with oxaliplatin, the apoptosis rate of chimeric drug-resistant cells HCT116-exo and its IC50 increased compared with the sensitive cells HCT116. The proliferation, invasion and migration of cells treated with STAT3 inhibitor or ß-elemene combined with oxaliplatin reduced compared with those treated with oxaliplatin or ß-elemene alone. The STAT3 inhibitor or ß-elemene in combination with oxaliplatin increased the rate of apoptosis relative to oxaliplatin or ß-elemene alone. Drug-resistant cell exosomes could promote the EMT process, related to the participation of FGFR4, SHMT2 and STAT3 inhibitors. CONCLUSION: Drug-resistant cell exosomes could induce resistance, and improve the capacity of colon cancer towards proliferate, invade, migrate and promote the EMT process. The ß-elemene combined with oxaliplatin could reverse the above results which might be related to the STAT3 pathway and EMT pathway in colon cancer.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

3D printing of multi-unit gastro-retentive tablets for the pulsatile release of artesunate.

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates.

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

microRNA-486-5p Regulates DNA Damage Inhibition and Cisplatin Resistance in Lung Adenocarcinoma by Targeting AURKB.

Lung adenocarcinoma (LUAD) severely affects human health, and cisplatin (DDP) resistance is the main obstacle in LUAD treatment, the mechanism of which is unknown. Bioinformatics methods were utilized to predict expression and related pathways of AURKB in LUAD tissues, as well as the upstream regulated microRNAs. qRT-PCR assayed expression of AURKB and microRNA-486-5p. RIP and dual-luciferase experiments verified the binding and interaction between the two genes. CCK-8 was used to detect cell proliferation ability and IC50 values. Flow cytometry was utilized to assess the cell cycle. Comet assay and western blot tested DNA damage and γ-H2AX protein expression, respectively. In LUAD, AURKB was upregulated, but microRNA-486-5p was downregulated. The targeted relationship between the two was confirmed by RIP and dual-luciferase experiments. Cell experiments showed that AURKB knock-down inhibited cell proliferation, reduced IC50 values, induced cell cycle arrest, and caused DNA damage. The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.

Multifunctional Two-Dimensional Bi2Se3 nanodisks as a Non-Inflammatory photothermal agent for glioma treatment.

Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi2Se3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi2Se3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi2Se3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi2Se3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi2Se3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi2Se3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.

Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway.

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.

The expression and clinical significance of serine hydroxymethyltransferase2 in gastric cancer.

Background: Gastric cancer (GC) is one of the most common malignant tumours in the digestive system. Serine hydroxymethyltransferase 2 (SHMT2) is one of the key enzymes associated with serine metabolism. However, the prognostic role of SHMT2 in GC carcinogenesis has yet to be studied. Methods: The expression of SHMT2 in human tumors and normal tissues was detected by the Assistant for Clinical Bioinformatics and Immunohistochemistry (IHC). The relationship of the expression of SHMT2 with clinical characteristics and survival data was analysed by the chi-square test, survival analysis and online databases. Finally, the correlation between SHMT2 expression and associated signalling channels, and molecules was analysed by online databases. Results: SHMT2 was strongly expressed in numerous human cancers. The expression rate of SHMT2 was 56.44% in GC (P = 0.018). The survival analysis indicated that patients with high expression of SHMT2 had the worse overall survival (OS; log-rank P = 0.007). The expression of SHMT2 was correlated with tumour size (P = 0.034) and, TNM stage (P = 0.042). In particular, SHMT2, vessel invasion and M stage were independent factors for OS in GC (P = 0.044, P < 0.001, P < 0.001). The SHMT2 gene was substantially correlated with cell signalling pathways. Conclusions: SHMT2 is highly expressed in GC and is associated with a poor prognosis. The exploration of its mechanism may be related to tumour proliferation, DNA repair and replication. SHMT2 is an independent prognostic risk factor and a potential biomarker for the diagnosis and treatment of GC.

BMP-ACVR1 Axis is Critical for Efficacy of PRC2 Inhibitors in B-Cell Lymphoma.

EZH2 is the catalytic subunit of the histone methyltransferase Polycomb Repressive Complex 2 (PRC2), and its somatic activating mutations drive lymphoma, particularly the germinal center B-cell type. Although PRC2 inhibitors, such as tazemetostat, have demonstrated anti-lymphoma activity in patients, the clinical efficacy is not limited to EZH2-mutant lymphoma. In this study, Activin A Receptor Type 1 (ACVR1), a type I Bone Morphogenetic Protein (BMP) receptor, is identified as critical for the anti-lymphoma efficacy of PRC2 inhibitors through a whole-genome CRISPR screen. BMP6, BMP7, and ACVR1 are repressed by PRC2-mediated H3K27me3, and PRC2 inhibition upregulates their expression and signaling in cell and patient-derived xenograft models. Through BMP-ACVR1 signaling, PRC2 inhibitors robustly induced cell cycle arrest and B cell lineage differentiation in vivo. Remarkably, blocking ACVR1 signaling using an inhibitor or genetic depletion significantly compromised the in vitro and in vivo efficacy of PRC2 inhibitors. Furthermore, high levels of BMP6 and BMP7, along with ACVR1, are associated with longer survival in lymphoma patients, underscoring the clinical relevance of this study. Altogether, BMP-ACVR1 exhibits anti-lymphoma function and represents a critical PRC2-repressed pathway contributing to the efficacy of PRC2 inhibitors.

Superhydrophobic Antifrosting 7075 Aluminum Alloy Surface with Stable Cassie-Baxter State Fabricated through Direct Laser Interference Lithography and Hydrothermal Treatment.

Frost formation and accumulation can have catastrophic effects on a wide range of industrial activities. Hence, a dual-scale surface with a stable Cassie-Baxter state is developed to mitigate the frosting problem by utilizing direct laser interference lithography assisted with hydrothermal treatment. The high Laplace pressure tolerance under the evaporation stimulus and prolonged Cassie-Baxter state maintenance under the condensation stimulus demonstrate the stable Cassie-Baxter state. The dual-scale surface exhibits a lengthy frost-delaying time of up to 5277 s at -7 °C due to the stable Cassie-Baxter state. The self-removal of frost is achieved by promoting the mobility of frost melts driven by the released interfacial energy. In addition, the dense flocculent frost layer is observed on the single-scale micro surface, whereas the sparse pearl-shaped frost layer with many voids is obtained on the dual-scale surface. This work will aid in understanding the frosting process on various-scale superhydrophobic surfaces and in the design of antifrosting surfaces.

Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma.

Background: Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC). Methods: Based on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments. Results: This study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration. Conclusion: PANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.

Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy.

Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity. Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer. HfC NPs possessed satisfactory near-infrared (NIR) absorption, good photothermal conversion efficiency (PTCE, 36.8 %) and photothermal stability. Furthermore, holding large surface areas and intrinsic redox-active sites, HfC NPs exhibited excellent anti-inflammatory properties due to their antioxidant and superoxide dismutase (SOD) enzymatic activities. In vitro and in vivo experiments confirmed that HfC NPs converted light energy into heat energy upon NIR laser irradiation to kill cancer cells through PTT and achieved a better therapeutic effect by anti-inflammatory effects after PTT. This work highlights that multifunctional HfC NPs can be applied in noninflammatory PTT with outstanding safety and efficacy.

Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells in vitro via mediating macrophages M2 polarization.

Lung cancer originating from the bronchial epithelium is the most common lung malignancy. It has been reported that programmed cell death 1 ligand 1 (PD-L1) and tumor-associated macrophages are closely related to the development of lung cancer. However, whether tumor-derived exosomal PD-L1 could mediate the regulation of macrophage polarization in lung cancer remains unclear. For this research, the level of PD-L1 in normal tissues and lung cancer tissues was evaluated using RT-qPCR. Next, the apoptosis of lung cancer cells was evaluated using flow cytometry assay. Then, the structure and morphology of vesicles were observed using transmission electron microscopy and nanoparticle tracking analysis. Later on, the internalization of exosomes by macrophage was observed using fluorescence microscopy. Our results showed that the level of PD-L1 was upregulated in tumor tissues and lung cancer cells. Knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. In addition, lung cancer cells-derived exosomal PD-L1 could be absorbed by macrophages. Meanwhile, exosomal PD-L1 was able to promote macrophages M2 polarization. Moreover, macrophages M2 polarization induced by exosomal PD-L1 further remarkably promoted the viability, migration, invasion, and epithelial-mesenchymal transition process of lung cancer cells. Collectively, knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. Tumor cell-derived exosomal PD-L1 could promote the growth of lung cancer cells by mediating macrophages M2 polarization. Thus, inhibiting macrophages M2 polarization might be a promoting therapy for the treatment of lung cancer.

Primary pulmonary meningioma: A case report.

Meningioma is a common benign tumor originating in the brain, but primary pulmonary meningioma is very rare. It is usually benign, slow-growing, and responds well to treatment. The most common manifestation is an isolated pulmonary nodule that radiologically resembles a benign primary lung tumor. Herein, we report a case of a complete thoracoscopic resection of a primary pulmonary meningioma.

c-JUN-induced upregulation of LINC00174 contributes to colorectal cancer proliferation and invasion through accelerating USP21 expression.

Colorectal cancer (CRC) is one of the most common human malignancies due to its invasiveness and metastasis. Recent studies revealed the pivotal roles of long noncoding RNAs (lncRNAs) in tumorigenesis and progressions of various tumors. However, the biological roles and molecular mechanisms of long intergenic noncoding RNA 00174 (LINC00174) in human CRC remain unclear. Here, we report that LINC00174 expression was higher in human CRC tissues and cell lines than in adjacent normal tissues and a colon epithelial cell line (FHC). High expression of LINC00174 was positively correlated with poor overall and disease-free survival in patients with CRC. Loss- and gain-of-function of LINC00174 demonstrated its critical roles in promoting cell proliferation, apoptosis resistance, migration, and invasion of CRC cells in vitro. Moreover, overexpression of LINC00174 enhanced tumor growth in vivo. Mechanistic experiments revealed that LINC00174 could bind to microRNA (miR)-2467-3p and augment the expression and function of ubiquitin-specific peptidase 21 (USP21). Rescue assays found that miR-2467-3p inhibition can offset the actions of LINC00174 or USP21 knockdown in CRC cells. Additionally, transcriptional factor c-JUN transcriptionally activated LINC00174 expression and mediated LINC00174-induced malignant phenotypes of CRC cell lines. Totally, our findings shed light on a new therapeutic strategy in modulating LINC00174/miR-2467-3p, which may interfere with the expression of USP21, and revealed that LINC00174 could be a new therapeutic target or prognostic marker in CRC.

In Silico Selection and Validation of High-Affinity ssDNA Aptamers Targeting Paromomycin.

Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan-specific aptamers can be developed for challenging applications such as cancer targeting; however, the high flexibility of glycosidic bonds and scarcity of studies on glycan-aptamer binding mechanisms increased the difficulty of screening. In this work, the model of interactions between glycans and ssDNA aptamers synthesized based on the sequence of rRNA genes was developed. Our simulation-based approach revealed that paromomycin as a representative example of glycans is preferred to bind base-restricted stem structures of aptamers because they are more critical in stabilizing the flexible structures of glycans. Combined experiments and simulations have identified two optimal mutant aptamers. Our work would provide a potential strategy that the glycan-binding rRNA genes could act as the initial aptamer pools to accelerate aptamer screening. In addition, this in silico workflow would be potentially applied in the more extensive in vitro development and application of RNA-templated ssDNA aptamers targeting glycans.

Oral konjac glucomannan for prevention of ionizing radiation-induced injury by regulating gut microbiota and increasing short chain fatty acids.

Ionizing radiation-induced injury commonly happens in radiotherapy, leading to damages of the hematopoietic and gastrointestinal systems. Radioprotective medications are mainly applied in hospitals, although only injections are available and their gut protection is limited. Here, oral konjac glucomannan (KGM), a natural macromolecule and soluble dietary fiber, was used against ionizing radiation-induced injury. The mice were fed with KGM (0.4 g/kg) for 3 days or injected with a clinical medication amifostine before 6.5 Gy γ-ray whole body irradiation (WBI) or 13 Gy whole abdominal irradiation (WAI). In the WBI experiments, KGM improved blood cell recovery and bone marrow cell proliferation in the femur and spleen, though its effect was weaker than or similar to that of amifostine. In the WBI experiments, the gut protection of KGM was similar to or a little better than that of amifostine, involving regenerated crypts numbers, villus length, and gut permeability. Moreover, KGM remarkably enhanced the survival rates of WBI and WAI mice, consistent with amifostine. KGM, as a prebiotic, enhanced gut microbiota abundance, probiotic numbers, and short chain fatty acid production, maintaining gut homeostasis. Moreover, KGM inhibited the apoptosis of irradiated human intestinal epithelial cells. KGM is a promising natural macromolecule against ionizing radiation-induced injury.

The biomarkers related to immune infiltration to predict distant metastasis in breast cancer patients.

Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis. Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism. Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful. Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.

Potential applications of drug delivery technologies against radiation enteritis.

INTRODUCTION: The incidence of abdominal tumors, such as colorectal and prostate cancers, continually increases. Radiation therapy is widely applied in the clinical treatment of patients with abdominal/pelvic cancers, but it often unfortunately causes radiation enteritis (RE) involving the intestine, colon, and rectum. However, there is a lack of suitable treatment options for effective prevention and treatment of RE. AREAS COVERED: Conventional clinical drugs for preventing and treating RE are usually applied by enemas and oral administration. Innovative gut-targeted drug delivery systems including hydrogels, microspheres, and nanoparticles are proposed to improve the prevention and curation of RE. EXPERT OPINION: The prevention and treatment of RE have not attracted sufficient attention in the clinical practice, especially compared to the treatment of tumors, although RE takes patients great pains. Drug delivery to the pathological sites of RE is a huge challenge. The short retention and weak targeting of conventional drug delivery systems affect the therapeutic efficiency of anti-RE drugs. Novel drug delivery systems including hydrogels, microspheres, and nanoparticles can allow drugs long-term retention in the gut and targeting the inflammation sites to alleviate radiation-induced injury.

TrEnD: A transformer-based encoder-decoder model with adaptive patch embedding for mass segmentation in mammograms.

BACKGROUND: Breast cancer is one of the most prevalent malignancies diagnosed in women. Mammogram inspection in the search and delineation of breast tumors is an essential prerequisite for a reliable diagnosis. However, analyzing mammograms by radiologists is time-consuming and prone to errors. Therefore, the development of computer-aided diagnostic (CAD) systems to automate the mass segmentation procedure is greatly expected. PURPOSE: Accurate breast mass segmentation in mammograms remains challenging in CAD systems due to the low contrast, various shapes, and fuzzy boundaries of masses. In this paper, we propose a fully automatic and effective mass segmentation model based on deep learning for improving segmentation performance. METHODS: We propose an effective transformer-based encoder-decoder model (TrEnD). Firstly, we introduce a lightweight method for adaptive patch embedding (APE) of the transformer, which utilizes superpixels to adaptively adjust the size and position of each patch. Secondly, we introduce a hierarchical transformer-encoder and attention-gated-decoder structure, which is beneficial for progressively suppressing interference feature activations in irrelevant background areas. Thirdly, a dual-branch design is employed to extract and fuse globally coarse and locally fine features in parallel, which could capture the global contextual information and ensure the relevance and integrity of local information. The model is evaluated on two public datasets CBIS-DDSM and INbreast. To further demonstrate the robustness of TrEnD, different cropping strategies are applied to these datasets, termed tight, loose, maximal, and mix-frame. Finally, ablation analysis is performed to assess the individual contribution of each module to the model performance. RESULTS: The proposed segmentation model provides a high Dice coefficient and Intersection over Union (IoU) of 92.20% and 85.81% on the mix-frame CBIS-DDSM, while 91.83% and 85.29% for the mix-frame INbreast, respectively. The segmentation performance outperforms the current state-of-the-art approaches. By adding the APE and attention-gated module, the Dice and IoU have improved by 6.54% and 10.07%. CONCLUSION: According to extensive qualitative and quantitative assessments, the proposed network is effective for automatic breast mass segmentation, and has adequate potential to offer technical assistance for subsequent clinical diagnoses.