Thermal Conductivity and Sintering Mechanism of Aluminum/Diamond Composites Prepared by DC-Assisted Fast Hot-Pressing Sintering.

A novel DC-assisted fast hot-pressing (FHP) powder sintering technique was utilized to prepare Al/Diamond composites. Three series of orthogonal experiments were designed and conducted to explore the effects of sintering temperature, sintering pressure, and holding time on the thermal conductivity (TC) and sintering mechanism of an Al-50Diamond composite. Improper sintering temperatures dramatically degraded the TC, as relatively low temperatures (≤520 °C) led to the retention of a large number of pores, while higher temperatures (≥600 °C) caused unavoidable debonding cracks. Excessive pressure (≥100 MPa) induced lattice distortion and the accumulation of dislocations, whereas a prolonged holding time (≥20 min) would most likely cause the Al phase to aggregate into clusters due to surface tension. The optimal process parameters for the preparation of Al-50diamond composites by the FHP method were 560 °C-80 MPa-10 min, corresponding to a density and TC of 3.09 g cm-3 and 527.8 W m-1 K-1, respectively. Structural defects such as pores, dislocations, debonding cracks, and agglomerations within the composite strongly enhance the interfacial thermal resistance (ITR), thereby deteriorating TC performance. Considering the ITR of the binary solid-phase composite, the Hasselman-Johnson model can more accurately predict the TC of Al-50diamond composites for FHP technology under an optimal process with a 3.4% error rate (509.6 W m-1 K-1 to 527.8 W m-1 K-1). The theoretical thermal conductivity of the binary composites estimated by data modeling (Hasselman-Johnson Model, etc.) matches well with the actual thermal conductivity of the sintered samples using the FHP method.

Analysis for Causes of Corneal Melt After the Boston Keratoprosthesis Type I: The Chinese People's Liberation Army General Hospital Experience.

PURPOSE: The purpose of this study was to evaluate the long-term incidence, risk factors, and the management of corneal melt following Boston type I keratoprosthesis (B-KPro I) implantation. METHODS: This is a retrospective observational case series. Data were collected regarding demographics, preoperative characteristics, incidence, and outcomes of corneal melt in 102 patients who underwent B-KPro I in the Chinese PLA General Hospital between 2011 and 2018, with a follow-up period ranging from 4 to 11 years. RESULTS: Chemical burn was the most common indication for B-KPro I (n = 56; 53.8%), followed by ocular trauma (n = 26; 25.0%). During the follow-up period (107 ± 25.7 months), corneal melt occurred in 60 cases among 37 eyes (35.6%), with an incidence of 20.2% at 1 year after surgery. Fourteen cases presented with recurrent corneal melt. Patients with multiple corneal allograft failures had a higher risk of corneal melt. Thermal burns, compared with alkali burns, significantly elevated the odds ratio (OR) of corneal melt (OR, 5.11; 95% confidence interval, 1.05-24.86; P = 0.043). CONCLUSIONS: Corneal melt significantly reduced the retention time of KPro (P < 0.01), and its coexistence with other complications further shortened the retention time. A specific pattern of corneal melt occurrence was identified, with a peak incidence at 1 year postoperatively. Our findings suggest variations in the risk of corneal melt among different indications, with thermal burns carrying the highest OR. Moreover, each previous failed keratoplasty doubled the risk of corneal melt after B-KPro I.

Construction and validation of nomogram model for predicting the risk of ventricular arrhythmia after emergency PCI in patients with acute myocardial infarction.

OBJECTIVE: To make predictions about the risk of MVA (Malignant Ventricular Arrhythmia) after primary PCI (Percutaneous Coronary Intervention) in patients with AMI (Acute Myocardial Infarction) through constructing and validating the Nomogram model. METHODS: 311 AMI patients who suffered from emergency PCI in Hefei Second People's Hospital from January 2020 to May 2023 were selected as the training set; 253 patients suffering from the same symptom in Hefei First People's Hospital during the same period were selected as the validation set. Risk factors were further screened by means of multivariate logistic and stepwise regression. The nomogram model was constructed, and then validated by using C-index, ROC curve, decision curve and calibration curve. RESULTS: Multivariate logistic analysis revealed that urea, systolic pressure, hypertension, Killip class II-IV, as well as LVEF (Left Ventricular Ejection Fraction) were all unrelated hazards for MVA after emergency PCI for AMI (P<0.05); a risk prediction nomogram model was constructed. The C-index was calculated to evaluate the predictive ability of the model. Result showed that the index of the training and the validation set was 0.783 (95% CI: 0.726-0.84) and 0.717 (95% CI: 0.65-0.784) respectively, which suggested that the model discriminated well. Meanwhile, other tools including ROC curve, calibration curve and decision curve also proved that this nomogram plays an effective role in forecasting the risk for MVA after PCI in AMI patients. CONCLUSIONS: The study successfully built the nomogram model and made predictions for the development of MVA after PCI in AMI patients.

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis Stereotactic Radiosurgery Outcome Prediction.

PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evaluated, including 26 BMs that developed biopsy-confirmed local failure post-SRS. The SRS spatial dose distribution (Dmap) of each BM was registered to the planning contrast-enhanced T1 (T1-CE) magnetic resonance imaging (MRI). Axial slices of the Dmap, T1-CE, and planning target volume (PTV) segmentation (PTVseg) intersecting the BM center were extracted within a fixed field of view determined by the 60% isodose volume in Dmap. A spherical projection was implemented to transform planar image content onto a spherical surface using multiple projection centers, and the resultant T1-CE/Dmap/PTVseg projections were stacked as a 3-channel variable. Four Visual Geometry Group (VGG-19) deep encoders were used in an ensemble design, with each submodel using a different spherical projection formula as input for BM outcome prediction. In each submodel, clinical features after positional encoding were fused with VGG-19 deep features to generate logit results. The ensemble's outcome was synthesized from the 4 submodel results via logistic regression. In total, 10 model versions with random validation sample assignments were trained to study model robustness. Performance was compared with (1) a single VGG-19 encoder, (2) an ensemble with a T1-CE MRI as the sole image input after projections, and (3) an ensemble with the same image input design without clinical feature inclusion. RESULTS: The ensemble model achieved an excellent area under the receiver operating characteristic curve (AUCROC: 0.89 ± 0.02) with high sensitivity (0.82 ± 0.05), specificity (0.84 ± 0.11), and accuracy (0.84 ± 0.08) results. This outperformed the MRI-only VGG-19 encoder (sensitivity: 0.35 ± 0.01, AUCROC: 0.64 ± 0.08), the MRI-only deep ensemble (sensitivity: 0.60 ± 0.09, AUCROC: 0.68 ± 0.06), and the 3-channel ensemble without clinical feature fusion (sensitivity: 0.78 ± 0.08, AUCROC: 0.84 ± 0.03). CONCLUSIONS: Facilitated by the spherical image projection method, a deep ensemble model incorporating Dmap and clinical variables demonstrated excellent performance in predicting BM post-SRS local failure. Our novel approach could improve other radiation therapy outcome models and warrants further evaluation.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

Effects of Viable and Heat-Inactivated Bifidobacterium longum D42 on Proliferation and Apoptosis of HT-29 Human Colon Cancer Cells.

Bifidobacterium longum is a common probiotic; both viable and heat-inactivated Bifidobacterium longum have many probiotic effects, such as anticancer effects. But some mechanisms of anticancer effects are still unclear, especially for heat-inactivated probiotics. In this study, we analyzed the effects of viable and heat-inactivated Bifidobacterium longum D42 on human colon cancer cells (HT-29). Cell proliferation, membrane permeability and apoptosis were detected by using the CCK-8 method, LDH method and Annexin V-FITC/PI kits. The ROS level and mitochondrial membrane potential were examined using the fluorescent probes DCFH-DA and JC-1. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot were used to detect the expression of mitochondrial apoptosis pathway genes and proteins. The results showed that viable and heat-inactivated Bifidobacterium longum D42 at concentrations of 1 × 106 CFU/mL significantly inhibited the proliferation of and increased the level of LDH release of HT-29 colon cancer cells. We found that they could increase the apoptosis rate of HT-29 cells. Moreover, they could also induce apoptosis by inducing cells to produce ROS and destroying the mitochondrial membrane potential of cells. Further studies found that they could increase the mRNA transcription and protein expression levels of the Caspase-3, Caspase-9 and Bax genes in cells, and reduce the mRNA transcription and protein expression levels of the Bcl-2 gene. In summary, our findings revealed that viable and heat-inactivated Bifidobacterium longum D42 have inhibitory effects on proliferation and promote the apoptosis of human colon cancer cells, and also have certain adjuvant drug therapeutic effects and have potential application value in the adjuvant treatment of colon cancer.

Correlations of SDF-1ɑ and XRCC1 gene polymorphisms with the risk of renal cancer development and bioinformatics studies of SDF-1α and XRCC1 and the prognosis of renal cancer.

To study the relationships between stromal cell-derived factor-1 (SDF-1ɑ) and renal cell carcinoma (RCC) susceptibility and the presence of single nucleotide polymorphisms in the human X-ray cross-complementary repair gene (XRCC1). Compare SDF-1 based on RCC related data in the TCGA database α, The expression difference of XRCC1 between RCC tissue and normal tissue; Collect 166 newly diagnosed RCC cases and 166 healthy individuals who underwent physical examinations during the same period, and detect genotype using iMLDR method. The results The rs1801157 locus (C:T) of the SDF-1α gene was not significantly associated with the pathohistological type, the rs1799782 locus (G:A) of the XRCC1 gene was associated with the pathohistological type of RCC, and there were interactions between rs1799782 and smoking, alcohol consumption, pesticide exposure, hair dye, and urine holding. The rs1799782 locus of the XRCC1 gene may be a key factor in the pathogenesis and pathological development of RCC. High SDF-1ɑ expression is a protective factor for the overall survival of patients with RCC, and SDF-1ɑ and XRCC1 may be important for the treatment of RCC.

Artesunate inhibits macrophage-like phenotype switching of vascular smooth muscle cells and attenuates vascular inflammatory injury in atherosclerosis via NLRP3.

Inflammation is one of the main pathogenic factors of atherosclerosis (AS), and the phenotypic transformation of macrophages in human vascular smooth muscle cells (HVSMCs) contributes to the inflammatory injury of blood vessels and the formation of atherosclerotic plaques. Artesunate reportedly exerts anti-inflammatory activity against AS. Herein, we aimed to explore the artesunate-mediated anti-inflammatory and HVSMC phenotypic switch effects against AS and elucidate potential underlying mechanisms. In vitro, artesunate decreased expression of NLRP3, caspase-1, and interleukin (IL)- 1ß. Artesunate significantly inhibited low-density lipoprotein (LDL) expression in HVSMCs and macrophages. In vivo, artesunate reduced atherosclerotic plaque formation in high-fat diet (HFD)-fed ApoE-/- mice, as well as decreased NLRP3 and CD68 expression in atherosclerotic plaques. Artesunate decreased serum levels of triglycerides and increased high-density lipoprotein levels in HFD-med mice; however, serum levels of total cholesterol and LDL were unaltered. Treatment with artesunate substantially increased α-smooth muscle actin expression in aortic tissues while inhibiting expression levels of NLRP3, IL-1ß, heparinase, matrix metalloproteinase 9, and Krüppel-like factor 4 (KLF4). Collectively, our findings suggest that artesunate-mediated effects may involve inhibition of the ERK1/2/NF-κB/IL-1ß pathway in HVSMCs via the downregulation of NLRP3 expression. Thus, artesunate could serve as a novel strategy to treat AS by inhibiting AS plaque formation and suppressing macrophage-like phenotype switching of HVSMCs.

Induction of lung progenitor cell-like organoids by porcine pluripotent stem cells.

Organoids are in vitro 3D models that are generated using stem cells to study organ development and regeneration. Despite the extensive research on lung organoids, there is limited information on pig lung cell generation or development. Here, we identified five epithelial cell types along with their characteristic markers using scRNA-seq. Additionally, we found that NKX2.1 and FOXA2 acted as the crucial core transcription factors in porcine lung development. The presence of SOX9/SOX2 double-positive cells was identified as a key marker for lung progenitor cells. The Monocle algorithm was used to create a pseudo-temporal differentiation trajectory of epithelial cells, leading to the identification of signaling pathways related to porcine lung development. Moreover, we established the differentiation method from porcine pluripotent stem cells (pPSCs) to SOX17+ FOXA2+ definitive endoderm (DE) and NKX2.1+ FOXA2+ CDX2- anterior foregut endoderm (AFE). The AFE is further differentiated into lung organoids while closely monitoring the differentiation process. We showed that NKX2.1 overexpression facilitated the induction of lung organoids and supported subsequent lung differentiation and maturation. This model offers valuable insights into studying the interaction patterns between cells and the signaling pathways during the development of the porcine lung.

Integrative analysis of LAG3 immune signature and identification of a LAG3-related genes prognostic signature in kidney renal clear cell carcinoma.

Immune checkpoint blockade (ICB) therapy has resulted in improved overall survival in kidney renal clear cell carcinoma (KIRC), but most treated patients fail to show durable clinical responses. Lymphocyte activation gene-3 (LAG3) is a novel inhibitory immune checkpoint, but its expression pattern, prognostic value, and immunological role in KIRC remain unknown. In this study, we utilized TCGA_KIRC RNA-sequencing data to analyze the relationship between LAG3 expression and clinical features. The single-cell sequencing data and tissue immunofluorescence are employed to investigate the subcellular localization of LAG3 in KIRC. Kaplan-Meier plotter, TIMER, and TISIDB were used to assess the association between LAG3 expression and prognosis, as well as its correlation with immune-related components. We constructed the LAG3 interaction network by using STRING, GeneMANIA, BioGRID, and HitPredict databases. We found that LAG3 is upregulated and correlates with poor prognostic phenotype in KIRC. LAG3 is predominantly expressed on exhausted CD8+ T cells and shows strong co-expression with PDCD1 in KIRC. Moreover, our findings indicated that LAG3 not only inhibits T cell activation but also potentially regulates cell adhesion in KIRC. In conclusion, our study implies that LAG3 can serve as a potential prognostic biomarker for KIRC. Furthermore, blocking both LAG3 and PDCD1 may alleviate resistance to anti-PDCD1 therapy, providing novel insights for immunotherapy decision-making in KIRC patients.

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.

A Force-Matched Approach to Large-Strain Nonlinearity in Elasticity Imaging for Breast Lesion Characterization.

OBJECTIVE: Ultrasound elasticity imaging is a class of ultrasound techniques with applications that include the detection of malignancy in breast lesions. Although elasticity imaging traditionally assumes linear elasticity, the large strain elastic response of soft tissue is known to be nonlinear. This study evaluates the nonlinear response of breast lesions for the characterization of malignancy using force measurement and force-controlled compression during ultrasound imaging. METHODS: 54 patients were recruited for this study. A custom force-instrumented compression device was used to apply a controlled force during ultrasound imaging. Motion tracking derived strain was averaged over lesion or background ROIs and matched with compression force. The resulting force-matched strain was used for subsequent analysis and curve fitting. RESULTS: Greater median differences between malignant and benign lesions were observed at higher compressional forces (p-value < 0.05 for compressional forces of 2-6N). Of three candidate functions, a power law function produced the best fit to the force-matched strain. A statistically significant difference in the scaling parameter of the power function between malignant and benign lesions was observed (p-value = 0.025). CONCLUSIONS: We observed a greater separation in average lesion strain between malignant and benign lesions at large compression forces and demonstrated the characterization of this nonlinear effect using a power law model. Using this model, we were able to differentiate between malignant and benign breast lesions. SIGNIFICANCE: With further development, the proposed method to utilize the nonlinear elastic response of breast tissue has the potential for improving non-invasive lesion characterization for potential malignancy.

Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies.

Pharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4-5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of "fast-to-FIH" approaches in combination with BeiGene's de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.

Age- and sex-stratified detection rates and associated factors of colorectal neoplasia in the Tianjin colorectal cancer screening program from 2012 to 2020.

PURPOSE: Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia. PATIENTS AND METHODS: This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy. RESULTS: A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years. CONCLUSIONS: These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.

The antipsychotic drug penfluridol inhibits N-linked glycoprotein processing and enhances T-cell-mediated tumor immunity.

Aberrant N-linked glycosylation is a prominent feature of cancers. Perturbance of oligosaccharide structure on cell surfaces directly affects key processes in tumor development and progression. In spite of the critical role played by N-linked glycans in tumor biology, the discovery of small molecules that specifically disturbs the N-linked glycans is still under investigation. To identify more saccharide-structure-perturbing compounds, a repurposed drug screen by using a library consisting of 1530 FDA-approved drugs was performed. Interestingly, an antipsychotic drug, penfluridol, was identified as being able to decrease cell surface Wheat germ agglutinin (WGA) staining. In the presence of penfluridol, cell membrane glycoproteins PD-L1 shifted to a lower molecular weight. Further studies demonstrated that penfluridol treatment caused an accumulation of high-mannose oligosaccharides, especially Man5-7GlcNAc2 glycan structures. Mechanistically, this effect is due to direct targeting of MAN1A1 mannosidase, a Golgi enzyme involved in N-glycan maturation. Moreover, we found that altered glycosylation of PD-L1 caused by penfluridol disrupted interactions between PD-1 and PD-L1, resulting in activation of T-cell tumor immunity. In a mouse xenograft and glioma model, penfluridol enhanced the anti-tumor effect of the anti-PD-L1 antibody in vivo. Overall, these findings revealed an important biological activity of the antipsychotic drug penfluridol as an inhibitor of glycan processing and proposed a repurposed use of penfluridol in anti-tumor therapy through activation of T-cell immunity.

Single-Atom Nanoenzyme-Based Autoluminescence System for Cancer Cell Imaging and Mitochondrial-Targeted Therapy.

The autoluminescence nanoplatform based on a single-atom catalyst has the potential to achieve accurate tumor diagnosis and treatment. Taking advantage of this, glycyrrhetinic acid (GA) and chitosan-modified single Fe-N-C atom catalysts (SAF NPs) loaded with luminol-curcumin (Cur) were fabricated (SAF-LCCG). Once delivered to the tumor, this autoluminescence SAF-LCCG could target the mitochondria to restrain tumor metastasis and promote the production of hydrogen peroxide (H2O2). Then, SAF NPs with Fenton-like properties could actively utilize intracellular H2O2 to produce ·OH for chemodynamic therapy. After that, excess ·OH and H2O2 were transmitted to luminol to emit blue-violet chemiluminescence (CL) for cancer cell imaging. Synchronously, light was transferred to Cur to produce reactive oxygen species (ROS) which realized photodynamic therapy. Besides, Cur could be served as a chemotherapeutic drug to enhance intracellular ROS for penetrating therapy. More importantly, the massive accumulation of ROS in cancer cells can promote the CL intensity of luminol, which realized the cyclic ROS amplification. This autoluminescence nanoplatform was developed for accurate cancer cell imaging, effective inhibition of tumor metastasis, and synergistic and penetrated treatment of tumors.

Development of a multi-feature-combined model: proof-of-concept with application to local failure prediction of post-SBRT or surgery early-stage NSCLC patients.

Objective: To develop a Multi-Feature-Combined (MFC) model for proof-of-concept in predicting local failure (LR) in NSCLC patients after surgery or SBRT using pre-treatment CT images. This MFC model combines handcrafted radiomic features, deep radiomic features, and patient demographic information in an integrated machine learning workflow. Methods: The MFC model comprised three key steps. (1) Extraction of 92 handcrafted radiomic features from the GTV segmented on pre-treatment CT images. (2) Extraction of 512 deep radiomic features from pre-trained U-Net encoder. (3) The extracted handcrafted radiomic features, deep radiomic features, along with 4 patient demographic information (i.e., gender, age, tumor volume, and Charlson comorbidity index), were concatenated as a multi-dimensional input to the classifiers for LR prediction. Two NSCLC patient cohorts from our institution were investigated: (1) the surgery cohort includes 83 patients with segmentectomy or wedge resection (7 LR), and (2) the SBRT cohort includes 84 patients with lung SBRT (9 LR). The MFC model was developed and evaluated independently for both cohorts, and was subsequently compared against the prediction models based on only handcrafted radiomic features (R models), patient demographic information (PI models), and deep learning modeling (DL models). ROC with AUC was adopted to evaluate model performance with leave-one-out cross-validation (LOOCV) and 100-fold Monte Carlo random validation (MCRV). The t-test was performed to identify the statistically significant differences. Results: In LOOCV, the AUC range (surgery/SBRT) of the MFC model was 0.858-0.895/0.868-0.913, which was higher than the three other models: 0.356-0.480/0.322-0.650 for PI models, 0.559-0.618/0.639-0.682 for R models, and 0.809/0.843 for DL models. In 100-fold MCRV, the MFC model again showed the highest AUC results (surgery/SBRT): 0.742-0.825/0.888-0.920, which were significantly higher than PI models: 0.464-0.564/0.538-0.628, R models: 0.557-0.652/0.551-0.732, and DL models: 0.702/0.791. Conclusion: We successfully developed an MFC model that combines feature information from multiple sources for proof-of-concept prediction of LR in patients with surgical and SBRT early-stage NSCLC. Initial results suggested that incorporating pre-treatment patient information from multiple sources improves the ability to predict the risk of local failure.

Roles of IL-33 in the Pathogenesis of Cardiac Disorders.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is believed to play important roles in different diseases by binding to its specific receptor suppression of tumorigenicity 2 (ST2). In the heart, IL-33 is expressed in different cells including cardiomyocytes, fibroblasts, endothelium, and epithelium. Although many studies have been devoted to investigating the effects of IL-33 on heart diseases, its roles in myocardial injuries remain obscure, and thus further studies are mandatory to unravel the underlying molecular mechanisms. We highlighted the current knowledge of the molecular and cellular characteristics of IL-33 and then summarized its major roles in different myocardial injuries, mainly focusing on infection, heart transplantation, coronary atherosclerosis, myocardial infarction, and diabetic cardiomyopathy. This narrative review will summarize current understanding and insights regarding the implications of IL-33 in cardiac diseases and its diagnostic and therapeutic potential for cardiac disease management.