Analysis of risk characteristics for early progression and late progression in locally advanced rectal cancer patients: a large population-based and validated study.

BACKGROUND AND OBJECTIVE: The current study aimed to explore the factors influencing early progression (EP) and late progression (LP) in locally advanced rectal cancer (LARC) patients. METHODS: The patients were classified into EP and LP groups using one year as a cutoff. The random survival forest model was utilized to calculate the probability of time-to-progression. Besides, inverse probability of treatment weighting (IPTW) analysis and the Surveillance, Epidemiology, and End Results (SEER) were conducted to validate our results. RESULTS: Our study revealed that PNI, CEA level, and pathological stage were independent prognostic factors for PFS both in EP group and LP group. For EP group patients, Group 1 had the highest probability of progression at the 9th month of follow-up, while Group 2 exhibited the highest probability at the 6th month. Group 3, on the other hand, showed two peaks of progression at the 4th and 8th months of follow-up. As for LP group patients, Groups 4, 5, and 6 all exhibited peaks of progression between the 18th and 24th months of follow-up. Furthermore, our results suggested that PNI was also an independent prognostic factor affecting OS in both EP group and LP group. Finally, the analysis of IPTW and SEER database further confirmed our findings. CONCLUSIONS: Our results indicated a significant correlation between immune and nutritional status with PFS and OS in both EP and LP groups. These insights can aid healthcare professionals in effectively identifying and evaluating patients' nutritional status, enabling them to develop tailored nutrition plans and interventions.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Mitochondrial ribosomal protein S24 is associated with immunosuppressive microenvironment and cold tumor in lung adenocarcinoma.

Objective: MRPS24 (Mitochondrial Ribosomal Protein S24) belongs to the mitochondrial ribosomal protein family, which participates in the protein synthesis of the mitochondrion. However, the relationship of MRPS24 with lung adenocarcinoma (LUAD) remained unknown. We aimed to identify its immunological and functional mechanisms in LUAD. Methods: The analysis of MRPS24 expression, clinical features, diagnosis, prognosis, function analysis, genetic alteration, copy number variations, methylation, and tumor microenvironment was investigated by the TCGA, UCSC Xena, GEO, HPA, GEPIA, cBioPortal, MethSurv, TIMER, TIMER2.0, and TISIDB databases. Results: MRPS24 was found to be more abundant in LUAD tumor tissue than in normal tissue. High levels of MRPS24 expression were found to be an independent prognostic factor by multivariate analysis. Functional analysis revealed that MRPS24 expression was associated with the immune, cell cycle and methylation. MRPS24 methylation level was inversely linked with its expression (p < 0.001). Patients with low MRPS24 methylation had a worse prognosis than those with high methylation (p < 0.05). In addition, the result revealed that the MRPS24 expression was inversely linked to the immune cell infiltration in LUAD. Finally, the validations of the expression level, prognosis, and immune cell infiltration of MRPS24 were in accordance with our previous results. Conclusions: This study systematically explored that MRPS24 expression was significantly correlated with prognosis, tumorigenesis, genetic alteration, copy number variations, methylation, and immune cell infiltration in LUAD. MRPS24 might be a potential immune-related biomarker in the development and treatment of LUAD, thereby acting as a promising predictor of immunotherapy response in LUAD.

Calculation of additional load and deformation of the receiving well enclosure structure caused by shield tunneling.

The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

Prognostic and immunological implications of glutathione metabolism genes in lung adenocarcinoma: A focus on the core gene SMS and its impact on M2 macrophage polarization.

Glutathione metabolism (GM) is a crucial part of various metabolic and pathophysiological processes. However, its role in lung adenocarcinoma (LUAD) has not been comprehensively studied. This study aimed to explore the potential relationship between GM genes, the prognosis, and the immune microenvironment of patients with LUAD. We constructed a risk signature model containing seven GM genes using Lasso combined Cox regression and validated it using six GEO datasets. Our analysis showed that it is an independent prognostic factor. Functional enrichment analysis revealed that the GM genes were significantly enriched in cell proliferation, cell cycle regulation, and metabolic pathways. Clinical and gene expression data of patients with LUAD were obtained from the TCGA database and patients were divided into high- and low-risk groups. The high-risk patient group had a poor prognosis, reduced immune cell infiltration, poor response to immunotherapy, high sensitivity to chemotherapy, and low sensitivity to targeted therapy. Subsequently, single-cell transcriptome analysis using the GSE143423 and GSE127465 datasets revealed that the core SMS gene was highly enriched in M2 Macrophages. Finally, nine GEO datasets and multiple fluorescence staining revealed a correlation between the SMS expression and M2 macrophage polarization. Our prognostic model in which the core SMS gene is closely related to M2 macrophage polarization is expected to become a novel target and strategy for tumor therapy.

Prediction of liver metastasis and recommended optimal follow-up nursing in rectal cancer.

We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.

Sensitive, Robust, Wide-Range, and High-Consistency Capacitive Tactile Sensors with Ordered Porous Dielectric Microstructures.

Flexible capacitive tactile sensors show great promise in personalized healthcare monitoring and human-machine interfaces, but their practical application is normally hindered because they rarely possess the required comprehensive performance, that is, high pressure sensitivity and fast response within a broad pressure range, high structure robustness, performance consistency, etc. This paper aims to engineer flexible capacitive pressure sensors with highly ordered porous dielectric microstructures and a 3D-printing-based fully solution-processable fabrication process. The proposed dielectric layer with uniformly distributed interior microporous can not only increase its compressibility and dynamic response within an extended pressure range but also enlarge its contact area with electrodes, contributing to a simultaneous improvement in the sensitivity, response speed, detection range, and structure robustness. Meanwhile, owing to its superior abilities in complex structure manufacturing and dimension controlling, the proposed 3D-printing-based fabrication process enables the consistent fabrication of the porous microstructure and thus guarantees device consistency. As a result, the prepared pressure sensors exhibit a high sensitivity of 0.21 kPa-1, fast response and relaxation times of 112 and 152 ms, an interface bonding strength of more than 455.2 kPa, and excellent performance consistency (≤5.47% deviation among different batches of sensors) and tunability. Encouraged by this, the pressure sensor is further integrated with a wireless readout circuit and realizes wireless wearable monitoring of various biosignals (pulse waves and heart rate) and body movements (from slight finger touch to large knee bending). Finally, the influence law of the feature parameters of the porous microstructure on device performance is established by the finite element method, paving the way for sensor optimization. This study motivates the development of flexible capacitive pressure sensors toward practical application.

In Situ Rapid-Formation Sprayable Hydrogels for Challenging Tissue Injury Management.

Rapid-acting, convenient, and broadly applicable medical materials are in high demand for the treatment of extensive and intricate tissue injuries in extremely medical scarcity environment, such as battlefields, wilderness, and traffic accidents. Conventional biomaterials fail to meet all the high criteria simultaneously for emergency management. Here, a multifunctional hydrogel system capable of rapid gelation and in situ spraying, addressing clinical challenges related to hemostasis, barrier establishment, support, and subsequent therapeutic treatment of irregular, complex, and urgent injured tissues, is designed. This hydrogel can be fast formed in less than 0.5 s under ultraviolet initiation. The precursor maintains an impressively low viscosity of 0.018 Pa s, while the hydrogel demonstrates a storage modulus of 0.65 MPa, achieving the delicate balance between sprayable fluidity and the mechanical strength requirements in practice, allowing flexible customization of the hydrogel system for differentiated handling and treatment of various tissues. Notably, the interactions between the component of this hydrogel and the cell surface protein confer upon its inherently bioactive functionalities such as osteogenesis, anti-inflammation, and angiogenesis. This research endeavors to provide new insights and designs into emergency management and complex tissue injuries treatment.

The comparison and analysis of nutritional qualities of Chinese mitten crabs (Eriocheir sinensis) in rice field and pond culture modes.

The nutritional quality of three edible parts (gonads, hepatopancreas and muscles) of Chinese mitten crabs (CMCs) from rice field culture and pond culture was firstly compared in our current study. It was found that the contents of mineral elements and volatile compounds in rice CMCs were superior to those in pond CMCs, and the antioxidant enzyme activities of rice CMCs were markedly higher than those of pond CMCs. Besides, the total free amino acid levels in the edible parts of pond CMCs were higher than those of rice CMCs. Compared with other tissues, the nucleotide and equivalent umami concentrations of the gonads in female rice CMCs were the maximum. Overall, both types of crabs demonstrated good nutritional quality, which met human nutrition and dietary needs. In comparison, the quality of rice CMCs was better than that of pond CMCs.

A large-scale study integrating nutritional indicators and clinicopathological parameters to evaluate prognosis, follow-up, and postoperative chemotherapy decisions in rectal cancer patients.

OBJECTIVE: The aim of this study was to evaluate the role of nutritional indicators and clinicopathological parameters in predicting the progression and prognosis for pathological stage II-III rectal cancer (RC) patients without neoadjuvant radiotherapy. In addition, we sought to explore the high-risk population who may require postoperative chemotherapy. METHODS: A total of 894 consecutive RC patients were enrolled in this study. Univariate and multivariate Cox analysis were performed to identify the independent risk factors for PFS and OS. The nomogram and calibration curves were conducted according to multivariable analysis result. Kaplan-Meier survival curves and log-rank tests were performed for different groups. Finally, random survival forest (RSF) model was developed to predict the probability of progression. RESULTS: Our results revealed that CEA level, pathological stage, tumor deposit, and PNI were independently associated with PFS in RC patients. Similarly, the results indicated that CEA level, pathological stage, tumor deposit, PNI, and NRI were independently associated with OS. RSF model revealed that group 1 had the highest risk of progression at the 12th month of follow-up, group 2 had the highest risk of progression at the 15th month of follow-up, while group 3 had the highest risk of progression at the 9th month of follow-up. Besides, subgroup analysis suggested that the high-risk group needs postoperative adjuvant chemotherapy, while patients in the low- and moderate-risk groups may not need postoperative adjuvant chemotherapy. Finally, we validated our results with the SEER database. CONCLUSIONS: In conclusion, we demonstrated that preoperative nutritional indicator and clinicopathological parameters could act as auxiliary prognostication tools for RC patients without neoadjuvant radiotherapy. We also established follow-up strategies for different groups of patients. Collectively, incorporating nutritional assessment into risk stratification for RC resection is crucial and should be an integral part of preoperative planning.

Prognostic and immunological role of cancer-associated fibroblasts-derived exosomal protein in esophageal squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor microenvironment (TME) and play significant roles in tumor initiation, progression, and immune evasion. Despite this, the specific exosomal proteins derived from CAFs and their functions in esophageal squamous cell carcinoma (ESCC) remain unknown. Therefore, this study aims to investigate the impact and prognostic significance of CAFs-derived exosomal proteins in ESCC. MATERIALS AND METHODS: Exosomes obtained from CAFs and normal fibroblasts (NFs) were isolated using ultracentrifugation, and the protein expression profiles of the exosomes were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor proliferation was assessed using CCK-8 and colony formation assays, while cell invasion and migration were evaluated using transwell assays. Lasso regression analysis was employed to establish a signature based on CAFs-derived exosomal proteins using the TCGA database. The immunological and prognostic roles of this signature were comprehensively investigated through survival analysis, gene set enrichment analysis (GSEA), immune analysis, immunotherapy response analysis, and drug sensitivity analysis. The GSE160269 dataset was utilized for single-cell transcriptome analysis to further elucidate the role of the signature in the TME. Additionally, cDNA microarray analysis was utilized to validate the prognostic value of the signature. RESULTS: Our findings demonstrate that exosomes derived from CAFs significantly enhance the proliferation, invasion, and migration of esophageal cancer cells. We identified 842 differentially expressed exosomal proteins through LC-MS/MS analysis, and two key proteins were utilized to establish a risk signature. Survival analysis revealed a significantly worse prognosis in the high-risk group, with multivariate analysis indicating that the risk score serves as an independent prognostic factor. Moreover, we observed a significant correlation between the risk score and immune cell infiltration, immunotherapy response, and sensitivity to chemotherapeutic treatments in the study population. Lastly, single-cell transcriptome analysis further revealed the expression patterns of TNFRSF10B and ILF3 in different cell subpopulations. CONCLUSION: In conclusion, our study has successfully established a robust prognostic signature based on CAFs-derived exosomal proteins, which can serve as a reliable biomarker for predicting prognosis and evaluating the immune microenvironment in ESCC.

Electrophysiological In Vitro Study of Long-Range Signal Transmission by Astrocytic Networks.

Astrocytes are diverse brain cells that form large networks communicating via gap junctions and chemical transmitters. Despite recent advances, the functions of astrocytic networks in information processing in the brain are not fully understood. In culture, brain slices, and in vivo, astrocytes, and neurons grow in tight association, making it challenging to establish whether signals that spread within astrocytic networks communicate with neuronal groups at distant sites, or whether astrocytes solely respond to their local environments. A multi-electrode array (MEA)-based device called AstroMEA is designed to separate neuronal and astrocytic networks, thus allowing to study the transfer of chemical and/or electrical signals transmitted via astrocytic networks capable of changing neuronal electrical behavior. AstroMEA demonstrates that cortical astrocytic networks can induce a significant upregulation in the firing frequency of neurons in response to a theta-burst charge-balanced biphasic current stimulation (5 pulses of 100 Hz × 10 with 200 ms intervals, 2 s total duration) of a separate neuronal-astrocytic group in the absence of direct neuronal contact. This result corroborates the view of astrocytic networks as a parallel mechanism of signal transmission in the brain that is separate from the neuronal connectome. Translationally, it highlights the importance of astrocytic network protection as a treatment target.

Advanced Glycation End Products' Receptor DNA Methylation Associated with Immune Infiltration and Prognosis of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

Background: Advanced glycation end products' receptor (AGER) is a multiligand receptor that interacts with a wide range of ligands. Previous studies have shown that abnormal AGER expression is closely related to immune infiltration and tumorigenesis. However, the AGER DNA methylation relationship between prognosis and infiltrating immune cells in LUAD and LUSC is still unclear. Methods: AGER expression in pan-cancer was obtained by using the UALCAN databases. Kaplan-Meier plotter showed the correlation of AGER mRNA expression levels and clinicopathological parameters. The protein expression levels for AGER were derived from Human Protein Atlas Database Analysis. The copy number, somatic mutation, and DNA methylation of AGER were presented with UCSC Xena database. TIMER platform and TISIDB website were used to show the correlation between AGER expression and tumor immune cell infiltration level. Results: The expression level of AGER was significantly reduced in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Low expression of AGER was significantly correlated with histology, stage, lymph node metastasis, and tumor protein 53 (TP53) mutation and could be used as a potential indicator of poor prognosis of LUAD and LUSC. Moreover, AGER expression was positively correlated with the infiltrating immune cells. Further analysis showed that copy number variation (CNV), mutation, and DNA methylation were involved in AGER downregulation. In addition, we also found that hypermethylated AGER was significantly correlated with tumor-infiltrating lymphocytes. Conclusion: AGER may be a candidate for the prognostic biomarker of LUAD and LUSC related to tumor immune microenvironment.

Glutathione limits RUNX2 oxidation and degradation to regulate bone formation.

Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since elevated ROS has been shown to have deleterious effects on osteoblasts. Moreover, excessive ROS is thought to underlie many of the skeletal phenotypes associated with aging and sex steroid deficiency in mice and humans. The mechanisms by which osteoblasts regulate ROS and how ROS inhibits osteoblasts are not well understood. Here, we demonstrate that de novo glutathione (GSH) biosynthesis is essential in neutralizing ROS and establish a proosteogenic reduction and oxidation reaction (REDOX) environment. Using a multifaceted approach, we demonstrate that reducing GSH biosynthesis led to acute degradation of RUNX2, impaired osteoblast differentiation, and reduced bone formation. Conversely, reducing ROS using catalase enhanced RUNX2 stability and promoted osteoblast differentiation and bone formation when GSH biosynthesis was limited. Highlighting the therapeutic implications of these findings, in utero antioxidant therapy stabilized RUNX2 and improved bone development in the Runx2+/- haplo-insufficient mouse model of human cleidocranial dysplasia. Thus, our data establish RUNX2 as a molecular sensor of the osteoblast REDOX environment and mechanistically clarify how ROS negatively impacts osteoblast differentiation and bone formation.

The development and validation of a nomogram for predicting brain metastases after chemotherapy and radiotherapy in male small cell lung cancer patients with stage III.

OBJECTIVE: The purpose of this research was to develop a model for brain metastasis (BM) in limited-stage small cell lung cancer (LS-SCLC) patients and to help in the early identification of high-risk patients and the selection of individualized therapies. METHODS: Univariate and multivariate logic regression was applied to identify the independent risk factors of BM. A receiver operating curve (ROC) and nomogram for predicting the incidence of BM were then conducted based on the independent risk factors. The decision curve analysis (DCA) was performed to assess the clinical benefit of prediction model. RESULTS: Univariate regression analysis showed that the CCRT, RT dose, PNI, LLR, and dNLR were the significant factors for the incidence of BM. Multivariate analysis showed that CCRT, RT dose, and PNI were independent risk factors of BM and were included in the nomogram model. The ROC curves revealed the area under the ROC (AUC) of the model was 0.764 (95% CI, 0.658-0.869), which was much higher than individual variable alone. The calibration curve revealed favorable consistency between the observed probability and predicted probability for BM in LS-SCLC patients. Finally, the DCA demonstrated that the nomogram provides a satisfactory positive net benefit across the majority of threshold probabilities. CONCLUSIONS: In general, we established and verified a nomogram model that combines clinical variables and nutritional index characteristics to predict the incidence of BM in male SCLC patients with stage III. Since the model has high reliability and clinical applicability, it can provide clinicians with theoretical guidance and treatment strategy making.

Prognostic value of pre-therapeutic nutritional risk factors in elderly patients with locally advanced esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or radiotherapy.

BACKGROUND: The nutritional status of cancer patients is a crucial factor in determining their prognosis. The objective of this study was to investigate and compare the prognostic value of pretreatment nutrition-related indicators in elderly esophageal squamous cell carcinoma (ESCC). Risk stratification was performed according to independent risk factors and a new nutritional prognostic index was constructed. METHODS: We retrospectively reviewed 460 older locally advanced ESCC patients receiving definitive chemoradiotherapy (dCRT) or radiotherapy (dRT). This study included five pre- therapeutic nutrition-related indicators. The optimal cut-off values for these indices were calculated from the Receiver Operating Curve (ROC). Univariate and multivariate COX analyses were employed to determine the association between each indicator and clinical outcomes. The predictive ability of each independently nutrition-related prognostic indicator was assessed using the time-dependent ROC (time-ROC) and C-index. RESULTS: Multivariate analyses indicated that the geriatric nutrition risk index (GNRI), body mass index (BMI), the controlling nutritional status (CONUT) score, and platelet-albumin ratio (PAR) could independently predict overall survival (OS) and progression-free survival (PFS) in elderly patients with ESCC (all p < 0.05), except for prognostic nutritional index (PNI). Based on four independently nutrition-related prognostic indicators, we developed pre-therapeutic nutritional prognostic score (PTNPS) and new nutritional prognostic index (NNPI). No-risk (PTNPS = 0-1 point), moderate-risk (PTNPS = 2 points), and high-risk (PTNPS = 3-4 points) groups had 5-year OS rates of 42.3%, 22.9%, and 8.8%, respectively (p < 0.001), and 5-year PFS rates of 44.4%, 26.5%, and 11.3%, respectively (p < 0.001). The Kaplan-Meier curves showed that the mortality of elderly ESCC patients in the high-risk group was higher than that in the low-risk group according to the NNPI. Analysis of time-AUC and C-index revealed that the NNPI (C-index: 0.663) had the greatest predictive power on the prognosis in older ESCC patients. CONCLUSIONS: In elderly ESCC patients, the GNRI, BMI, CONUT score, and PAR can be used as objective assessment measures for the risk of nutrition-related death. Compared to the other four indexes, the NNPI has the greatest prognostic value for prognosis, and elderly patients with a higher nutritional risk have a poor prognosis, which is helpful in guiding early clinical nutrition intervention.

Higher radiation dose on immune cells is associated with radiation-induced lymphopenia and worse prognosis in patients with locally advanced esophageal squamous cell carcinoma.

Background: To explore the effective dose to immune cells (EDIC) for better prognosis while avoiding radiation-induced lymphopenia (RIL) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Materials and methods: Overall, 381 patients with locally advanced ESCC receiving definitive radiotherapy with or without chemotherapy (dRT ± CT) between 2014 and 2020 were included in this study. The EDIC model was calculated by radiation fraction number and mean doses to the heart, lung, and integral body. The correlation between EDIC and clinical outcomes was analyzed using Cox proportional hazards regression, and risk factors for RIL were determined by logistic regression analysis. Results: The median EDIC was 4.38 Gy. Multivariate analysis revealed that low-EDIC significantly improved the OS of patients when compared with high-EDIC (HR = 1.614, P = 0.003) and PFS (HR = 1.401, P = 0.022). Moreover, high-EDIC was associated with a higher incidence of grade 4 RIL (OR = 2.053, P = 0.007) than low-EDIC. In addition, we identified body mass index (BMI), tumor thickness, and nodal stage as independent prognostic factors of OS and PFS, while BMI (OR = 0.576, P = 0.046) and weight loss (OR = 2.214, P = 0.005) as independent risk factors of grade 4 RIL. In subgroup analyses, the good group had better clinical outcomes than the remaining two groups (P< 0.001). Conclusion: This study demonstrated that EDIC significantly correlates with poor clinical outcomes and severe RIL. Optimizing treatment plans to decrease the radiation doses to immune cells is critical for improving the outcomes.

Anchoring Filament Protein Ladinin-1 is an Immunosuppressive Microenvironment and Cold Tumor Correlated Prognosticator in Lung Adenocarcinoma.

Anchoring filament protein ladinin-1 (LAD1) codes for an anchor filament protein in the basement membrane. Here, we have aimed to determine its potential role in LUAD. According to the comprehensive analyses conducted in this study, we studied the expression, prognostic significance, function, methylation, copy number variations, and the immune cell infiltration of LAD1 in LUAD. A higher level of LAD1 gene expression was observed in the LUAD tumor tissues compared to the normal lung tissues (p < 0.001). Furthermore, the multivariate analysis indicated that a higher LAD1 gene expression level was the independent prognostic factor. Additionally, the DNA methylation level of the LAD1 was inversely linked to its expression (p < 0.001). We noted that the patients affected due to LAD1 hypomethylation showed a very low overall survival rate compared to the patients with a higher LAD1 methylation score (p < 0.05). Moreover, the results of the immunity analysis indicated that the LAD1 expression might be inversely linked to the immune cell infiltration degree, expression of the infiltrated immune cells, and the PD-L1 levels. Lastly, we supplemented some verification to increase the rigor of the study. The results suggested that high expression of LAD1 may be related to cold tumors. Hence, this indirectly reflects that the immunotherapy effect of LUAD patients with high LAD1 expression might be worse. Based on the role played by the LAD1 in the tumor immune microenvironment, it can be considered a potential biomarker for predicting the immunotherapy response to LUAD.

Investigation of Silicon Core-Based Fiber Bragg Grating for Simultaneous Detection of Temperature and Refractive Index.

In this article, we theoretically designed and simulated a silicon core fiber for the simultaneous detection of temperature and refractive index. We first discussed the parameters of the silicon core fiber for near single-mode operation. Second, we designed and simulated a silicon core-based fiber Bragg grating and applied it for simultaneous sensing of temperature and environmental refractive index. The sensitivities for the temperature and refractive index were 80.5 pm/°C and 208.76 dB/RIU, respectively, within a temperature range of 0 to 50 °C and a refractive index range of 1.0 to 1.4. The proposed fiber sensor head can provide a method with simple structure and high sensitivity for various sensing targets.

Isorhamnetin induces cell cycle arrest and apoptosis by triggering DNA damage and regulating the AMPK/mTOR/p70S6K signaling pathway in doxorubicin-resistant breast cancer.

BACKGROUND: Acquired resistance to doxorubicin (DOX) inevitably limits its clinical use against breast cancer (BC). Isorhamnetin (IS), a native flavonoid which extensively available in vegetables, fruits, and phytomedicine, has been deemed to the probable cancer chemopreventive agent in preceding explorations since it exhibits satisfied antitumor activity. So far, the strategy for alleviating DOX resistance by using IS as a sensitizer against resistant BC has not yet been covered. PURPOSE: To investigate the effect of IS on potentiating the chemoreceptivity of drug-resistant BC cells to DOX in vitro and in vivo and elucidate the possible molecular mechanisms. METHODS: MTS assays, colony formation assays, three-dimensional (3D) tumor spheroid model, and migration assay were deployed to verify the inhibiting action of IS in the presence or absence of DOX on resistant BC cells in vitro. Apoptosis, cell cycle regulation, and endocellular reactive oxygen species (ROS) were determined by flow cytometry. Protein levels were monitored by western blotting. Nuclear staining and EdU proliferation were photographed with a confocal laser scanning microscope. The effects of the IS and DOX combination on the tumorigenesis in the xenograft experiments were evaluated for further confirming the in vitro cytotoxicity. RESULTS: IS significantly inhibited cell proliferation and migration and enhanced the antitumor competence of DOX against resistant BC cells both in vitro and in vivo. Adjuvant IS (50 µM) effectively enhanced the proapoptotic impacts of DOX in resistant BC cells (35.38 ± 3.18%, vs. 5.83 ± 0.68% in the DOX group) by suppressing the expression of bcl 2 in addition to enhancing cleaved caspase 3, ultimately leading to DNA condensation and fragmentation. IS (20, 30, and 50 µM) treatments induced significant increases in the G2/M populations (41.60 ± 1.28%, 44.60 ± 1.14%, and 50.64 ± 0.67%, vs. 35.84 ± 1.56% in the untreated control in MCF7/ADR cells, p < 0.01) via regulating CDK1/Cyclin B1 complex expression, subsequently triggering the inhibition of BC proliferation. In addition, IS (10, 20, 30, and 50 µM) stimulated the production of interstitial ROS in MCF7/ADR cells, by 3.99-, 4.20-, 6.29-, and 6.78-fold, respectively, versus the untreated group (p < 0.001), which were involved in DNA damage and AMPK-caused intercept of the mTOR/p70S6K signaling. CONCLUSION: Our study suggested the anti-breast cancer actions of IS as a DOX sensitizer and expounded the underlying molecular mechanisms, showing that IS could be deemed to a capable alternative for resistant BC cure.