The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC). METHODS: The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed. RNA-seq, ATAC-seq, and ChIP-seq analyses were then conducted to investigate the genes and downstream signaling pathways regulated by JMJD2A, and functional validation experiments were performed to analyze the role of downstream regulated genes and pathways in ESCC malignant behavior and immune evasion. RESULTS: JMJD2A was significantly overexpressed in ESCC and anti-PD-1 therapy non-responders. Knockdown or deletion of JMJD2A significantly promoted the malignant behavior and immune evasion of ESCC. JMJD2A facilitated the structural changes in chromatin and promoted the binding of SMARCA4 to super-enhancers, thereby inducing the expression of GPX4. This resulted in the inhibition of radiation-induced DNA damage and cell ferroptosis, ultimately promoting the malignant behavior and immune evasion of ESCC cells. CONCLUSION: JMJD2A plays an indispensable role in the malignant behavior and immune evasion of ESCC. It regulates the binding of SMARCA4 to super-enhancers and affects the chromatin's epigenetic landscape, thereby promoting the expression of GPX4 and attenuating iron-mediated cell death caused by radiotherapy. Consequently, it triggers the malignant behavior and immune evasion of ESCC cells.

Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression.

Alterations in the tumor microenvironment are closely associated with the metabolic phenotype of tumor cells. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth and metastasis. Existing studies have suggested that lactate produced by tumor cells can activate CAFs, yet the precise underlying mechanisms remain largely unexplored. In this study, we initially identified that lactate derived from lung cancer cells can promote nuclear translocation of NUSAP1, subsequently leading to the recruitment of the transcriptional complex JUNB-FRA1-FRA2 near the DESMIN promoter and facilitating DESMIN transcriptional activation, thereby promoting CAFs' activation. Moreover, DESMIN-positive CAFs, in turn, secrete IL-8, which recruits TAMs or promotes M2 polarization of macrophages, further contributing to the alterations in the tumor microenvironment and facilitating lung cancer progression. Furthermore, we observed that the use of IL-8 receptor antagonists, SB225002, or Navarixin, significantly reduced TAM infiltration and enhanced the therapeutic efficacy of anti-PD-1 or anti-PD-L1 treatment. This finding indicates that inhibiting IL-8R activity can attenuate the impact of CAFs on the tumor microenvironment, thus restraining the progression of lung cancer.

Different lactate metabolism subtypes reveal heterogeneity in clinical outcomes and immunotherapy in lung adenocarcinoma patients.

Background: The excessive accumulation of lactate within the tumor microenvironment (TME) has been demonstrated to facilitate tumor advancement and evade the immune system. Nonetheless, the metabolic status of lactate in lung adenocarcinoma (LUAD) remains uncertain. Method: By analyzing the transcriptome profile of patients with LUAD, we created a lactate metabolism score (LMS) to predict survival. We then conducted a comprehensive examination of the biological functions and immune infiltration among different LMS patient groups. Moreover, we assessed the LMS predictive efficacy in chemotherapy and immunotherapy. Finally, we validated the detrimental phenotypic effects of SLC16A3 on LUAD cell lines (PC9 and A549) through in vitro experiments. We collected clinical samples to assess the prognostic impact of SLC16A3. Results: We constructed an LMS model with 6 lactate metabolism regulatory factors using LASSO regression. The high LMS model indicates worse clinical outcomes for LUAD patients. High LMS patients are associated with metabolic dysregulation and increased infiltration of M0 and M1 macrophages. Low LMS patients are related to upregulated citric acid metabolism pathways and memory immune cells. High LMS patients are suitable for traditional chemotherapy, while patients with low LMS are more likely to benefit from immunotherapy. Lastly, downregulating SLC16A3 significantly reduces the proliferative and invasive capabilities of LUAD cell lines. Clinical cohort shows that patients with high expression of SLC16A3 have a worse prognosis. Conclusions: The LMS model constructed based on the lactate metabolism pathway displays high effectiveness in predicting the outcome of patients with LUAD. LMS can offer direction regarding chemotherapy as well as immunotherapy in LUAD.

First report of large-berry coffee (Coffea liberica) anthracnose caused by Colletotrichum kahawae in China.

Large-berry coffee (Coffea liberica) is one of the three cultivated coffee species and a precious breeding germplasm in China (Yan et al, 2019). Anthracnose is a damaging epidemic disease on coffee worldwide (Mohammed et al. 2015). Between June and September 2022, anthracnose was observed on coffee plants in Puer area, Yunnan, China and disease incidence (% plants diseased) of 8.5%-28.2% was recorded in the field. The disease symptoms were observed at all growth stages. Lesions on leaves were circular or oval, with a white to gray central zone outlined by a brown margin and surrounded by a chlorotic halo, Φ5.1-18.5 mm; some lesions extended and coalesced later to form large, blighted areas, leading to complete leaf senescence, defoliation and bare blighted branches on heavily infected trees. The spots on coffee berries were oval or fusiform, sunken and brown-black; diseased berries became gray-black and dried-out but remained on the tree. Leaves with typical anthracnose lesions were collected from fields in Simao ( 22.07°E,100.98°N) to isolate the pathogen. Leaf pieces (5×5mm) from the lesion margin were cut, surface-sterilized with 75% ethanol and 2% NaClO, and cultured on PDA at 25°C. Three isolates with the same colony morphology were obtained by hyphal tip purification. Detached and intact leaves of 6-month coffee seedlings were inoculated with Φ5mm mycelial discs of the isolates. Anthracnose lesions developed on the inoculated leaves, with all 3 isolates, 7d after incubation in a growth chamber (25°C, > 90% RH and lighting 8 h/d at 11000 lux). Pathogens with the same colony morphology as those of the original isolates were re-isolated from the infected tissues of inoculated leaves, thus fulfilling Koch's Postulates. The ITS sequence (PP550861) for the isolate was PCR-amplified and Blast-n analyses showed 100 % (554/554bp) identity to Colletotrichum kahawae LWTJ01; so they were the same population and coded as KFTJ02. The actin (ACT), calmodulin(CAL), glyceraldehydes-3-phosphate dehydrogenase (GAPHD) and histone 3 (HIS3) genes (Qiu et al. 2020) were amplified from one of KFTJ02 isolates, sequenced and deposited in NCBI GenBank (OR842543, OR842544, OR842545 & OR842546). A phylogenetic tree was generated based on the concatenated sequences of the four genes and those of related Colletotrichum spp. using MEGA 6.0 and KFTJ02 clustered in the same clade with C. kahawae IMI319418 on the tree (Bootstrap sup.=88%). When cultured at 25°C on PDA for 7 days, its colonies were near round or ovoid, gray-white, contoured, Φ73.2-80.1 (76.2±2.3)mm or growth rate 10.2-11.1(8.1) mm/d (n=10). The hyphae were hyaline, septated, branching at near right angles. Conidial masses formed 14 days after incubation. The conidia were elliptical, hyaline, monocellular, 10.2-15.5 (12.7±1.06)×3.8-5.2 (4.3±0.52) µm (n=50). The appressoria were black-brown, oval or irregular, 7.8-9.3 (8.5±0.81)µm (n= 50). These morphological characteristics were consistent with those of C. kahawae (Bridge et al, 2008). Therefore, KFTJ02 was identified as C. kahawae, which has been found to infect Camellia oleifera, Areca catechu and Ficus microcarpa (Wei et al, 2023; Zhang et al, 2020; Lin 2023). The coffee berry disease pathogen (C. kahawae) is a quarantine species which has not been recorded and so it is first reported on coffee crops in China. Results of the present study provide important references for further studies on this disease.

Integrated analysis of purine metabolism assists in predicting prognosis and treatment decisions for patients with lung adenocarcinoma.

The incidence of lung cancer, especially lung adenocarcinoma (LUAD), has recently increased. Targeted therapy and immunotherapy combined with conventional treatment have shown surprising benefits in enhancing the LUAD patient's prognosis. For the purpose of guiding treatment planning and the prognosis of LUAD, more research is required. The particular aim of this work was to establish a purine metabolism scoring (PMS) model for the purpose of individually forecasting treatment outcomes and overall survival for patients who have LUAD. Clinical and whole genome data were obtained from the TCGA-LUAD cohort via "UCSC". The 25 driver purine metabolism-related prognostic genes were determined founded on univariate Cox regression. Then PMS was developed through stepwise LASSO Cox regression. Survival analysis indicated that patients who have PMS experienced worse outcomes. We validated the PGM2 effect on lung adenocarcinoma malignancy in in vitro experiments. Univariate as well as multivariate Cox regression suggested that PMS was an independent prognostic indicator for LUAD patients, which was confirmed in subgroup analysis. Functional assay demonstrated that immune response as well as cytotoxicity pathways have a connection with lower PMS, and patients who have low PMS possess an active immune microenvironment. Moreover, the LUAD patients who have low PMS showed greater sensitivity to immunotherapy, targeted therapy, as well as chemotherapy. Knockdown of PGM2 was discovered to decrease the proliferation, invasion, as well as migration of lung adenocarcinoma cells in an in vitro assay. Pertaining to this particular research, we created a PMS model and conducted a thorough analysis of purine metabolism in LUAD in order to determine prognosis and offer recommendations for treatment. This finding offered a fresh concept for the clinical management of LUAD and novel therapy protocols.

Is coffee, tea, and red wine consumption beneficial for individuals with hypertension?

OBJECTIVE: To investigate the associations of tea, coffee, and red wine intakes with health risks among individuals with hypertension. METHODS: This prospective cohort study included participants with hypertension from the UK Biobank cohort. Study exposures included self-reported intakes of coffee, tea, and red wine. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular mortality and cardiovascular disease. The associations of beverage intake with outcomes were analyzed using Cox regression models. The hazard ratios and 95% confidence intervals were estimated. RESULTS: A total of 187 708 participants with hypertension were included. The median follow-up period was 13.8 years. In individuals with hypertension, drinking one to two cups/day of coffee or three to four cups/day of tea was significantly associated with the lowest risk of all-cause mortality compared with less than one cup/day [hazard ratio for coffee, 0.943 (95% confidence interval, 0.908-0.979); hazard ratio for tea, 0.882 (95% confidence interval, 0.841-0.924)]. Red wine intake was inversely associated with all-cause mortality risk. Dose-response analysis revealed that high coffee intake (approximately greater than or equal to six cups/day) was significantly associated with increased risks of cardiovascular mortality and cardiovascular disease, but high tea and red wine intakes were not. Furthermore, replacing plain water with tea, but not coffee, significantly reduced the risks of all-cause mortality and cardiovascular disease. Replacing other alcoholic beverages with red wine also significantly reduced the risks of all three outcomes. CONCLUSIONS: These findings suggest that tea and red wine, but not coffee, can be part of a healthy diet for the hypertensive population.

T-cell exhaustion prediction algorithm in tumor microenvironment for evaluating prognostic stratification and immunotherapy effect of esophageal cancer.

Esophageal cancer (EC) is a common digestive malignancy that ranks sixth in cancer deaths, with a 5-year survival rate of 15%-25%. As a result, reliable prognostic biomarkers are required to accurately predict the prognosis of EC. T-cell exhaustion (TEX) is associated with poorer prognosis and immune infiltration in EC. In this study, nine risk genes were finally screened to constitute the prognostic model using least absolute shrinkage and selection operator analysis. Patients were divided into two groups based on the expression of the TEX-related genes: high-risk group and low-risk group. The expression of TEX-related genes differed significantly between the two groups. The findings revealed that the risk model developed was highly related to the clinical prognosis and amount of immune cell infiltration in EC patients. It was also significantly correlated with the therapeutic sensitivity of multiple chemotherapeutic agents in EC patients. Subsequently, we successfully constructed drug-resistant cell lines KYSE480/CDDP-R and KYSE180/CDDP-R to verify the correlation between PD-1 and drug resistance in EC. Then, we examined the mRNA and protein expression levels of PD-1 in parental and drug-resistant cells using qPCR and WB. It was found that the expression level of PD-1 was significantly increased in the plasma red of drug-resistant cells. Next, we knocked down PD-1 in drug-resistant cells and found that the resistance of EC cells to CDDP was significantly reduced. And the proportion of apoptotic cells in cells treated with 6 µM CDDP for 24 h was significantly in increase. The TEX-based risk model achieved good prediction results for prognosis prediction in EC patients. And it was also significantly associated with the level of immune cell infiltration and drug therapy sensitivity of EC patients. Additionally, the downregulation of PD-1 may be associated with increased drug sensitivity in EC and enhanced T-cell infiltration. The high-risk group had lower TIDE scores, indicating that the high-risk group benefits more after receiving immunotherapy. Thus, the TEX-based risk model can be used as a novel tumor prognostic biomarker.

[Retracted] miR­613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD.

[This retracts the article DOI: 10.3892/etm.2020.8540.].

Durable Multiblock Poly(biphenyl alkylene) Anion Exchange Membranes with Microphase Separation for Hydrogen Energy Conversion.

Anion exchange membrane fuel cells (AEMFCs) and water electrolysis (AEMWE) show great application potential in the field of hydrogen energy conversion technology. However, scalable anion exchange membranes (AEMs) with desirable properties are still lacking, which greatly hampers the commercialization of this technology. Herein, we propose a series of novel multiblock AEMs based on ether-free poly(biphenyl ammonium-b-biphenyl phenyl)s (PBPA-b-BPPs) that are suitable for use in high performance AEMFC and AEMWE systems because of their well-formed microphase separation structures. The developed AEMs achieved outstanding OH- conductivity (162.2 mS cm-1 at 80 °C) with a low swelling ratio, good alkaline stability, and excellent mechanical durability (tensile strength >31 MPa and elongation at break >147 % after treatment in 2 M NaOH at 80 °C for 3750 h). A PBPA-b-BPP-based AEMFC demonstrated a remarkable peak power density of 2.41 W cm-2 and in situ durability for 330 h under 0.6 A cm-2 at 70 °C. An AEMWE device showed a promising performance (6.25 A cm-2 at 2 V, 80 °C) and outstanding in situ durability for 3250 h with a low voltage decay rate (<28 µV h-1 ). The newly developed PBPA-b-BPP AEMs thus show great application prospects for energy conversion devices.

Polyporus umbellatus polysaccharide iron-based nanocomposite for synergistic M1 polarization of TAMs and combinational anti-breast cancer therapy.

M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.

Effects of Antibiotic Resistance Genes and Antibiotics on the Transport and Deposition Behaviors of Bacteria in Porous Media.

Antibiotics present in the natural environment would induce the generation of antibiotic-resistant bacteria (ARB), causing great environmental risks. The effects of antibiotic resistance genes (ARGs) and antibiotics on bacterial transport/deposition in porous media yet are unclear. By using E. coli without ARGs as antibiotic-susceptible bacteria (ASB) and their corresponding isogenic mutants with ARGs in plasmids as ARB, the effects of ARGs and antibiotics on bacterial transport in porous media were examined under different conditions (1-4 m/d flow rates and 5-100 mM NaCl solutions). The transport behaviors of ARB were comparable with those of ASB under antibiotic-free conditions, indicating that ARGs present within cells had negligible influence on bacterial transport in antibiotic-free solutions. Interestingly, antibiotics (5-1000 µg/L gentamicin) present in solutions increased the transport of both ARB and ASB with more significant enhancement for ASB. This changed bacterial transport induced by antibiotics held true in solution with humic acid, in river water and groundwater samples. Antibiotics enhanced the transport of ARB and ASB in porous media via different mechanisms (ARB: competition of deposition sites; ASB: enhanced motility and chemotaxis effects). Clearly, since ASB are likely to escape sites containing antibiotics, these locations are more likely to accumulate ARB and their environmental risks would increase.

Comprehensive Explorations of CCL28 in Lung Adenocarcinoma Immunotherapy and Experimental Validation.

Background: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy. Methods: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system. Results: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration. Conclusion: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.

A Novel Prognostic Biomarker CCR8 for Gastric Cancer and Anti-CCR8 Blockade Attenuate the Immunosuppressive Capacity of Tregs In Vitro.

Objective: To investigate the immunotherapeutic roles and functions of C-C Motif Chemokine Receptor 8 (CCR8) molecule in gastric cancer (GC). Materials and Methods: Clinicopathological features of 95 GC cases were collected by a follow-up survey. The expression level of CCR8 was measured by immunohistochemistry (IHC) staining and analyzed with the cancer genome atlas database. The relationship between CCR8 expression and Clinicopathological features of GC cases was evaluated by univariate and multivariate analysis. Flow cytometry was used to determine the expression of cytokines and the proliferation of CD4+ regulator T cells (Tregs) and CD8+ T cells. Results: An upregulated expression of CCR8 in GC tissues was associated with tumor grade, nodal metastasis, and overall survival (OS). Tumor-infiltrated Tregs with higher expression of CCR8 produced more IL10 molecules in vitro. In addition, anti-CCR8 blocking downregulated IL10 expression produced by CD4+ Tregs, and reversed the suppression by Tregs on the secretion and proliferation of CD8+ T cells. Conclusion: CCR8 molecule could be a prognostic biomarker for GC cases and a therapeutic target for immune treatments.

Prognostic Impact of Aberrantly Expressed Protein-coding Gene Associated With Gastric Cancer's Regulatory T Cells, Based on Online Databases.

Context: Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, and no effective cure exists for advanced GC. Clinicians believe that molecularly targeted therapy through PCGs may replace surgery, radiotherapy, and other treatments as a breakthrough in curing malignancies. Objective: The study intended to examine the impact of aberrant expression of the protein-coding genes (PCGs) associated with regulatory T cells on the prognosis of patients with gastric cancer (GC). Design: The research team performed a genetic study through research of genetic data in online databases. Setting: The study took place at Zhongda Hospital. Outcome Measures: The research team selected a publicly available dataset, genetic suppressor element 109476 (GSE109476), from the Gene Expression Omnibus (GEO) database for differential gene analysis, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for PCGs associated with regulatory T cells as well as the Gene Expression Profiling Interactive Analysis (GEPIA) database with the Kaplan-Meier Plotter database to analyze the expression of the above PCGs in GC and the prognostic impact on GC. Results: The GEO2R analysis found 315 differentially expressed PCGs in GSE109476, among which nine PCGs were associated with regulatory T cells: (1) chemokine (C-C motif) ligand 19 (CCL19), (2) CCL21, (3) C-C chemokine receptor type 7 (CCR7), (4) cluster of differentiation 70 (CD70), (5) ephrin B3 (EFNB3), (6) early growth response 3 (EGR3), (7) interleukin-7 receptor (IL7R), (8) galectin-1 (LGALS1), and (9) tumor necrosis factor (TNF) receptor superfamily member 13C (TNFRSF13C). The GEPIA database indicated that no significant differences existed between the expression of CCL19, CCL21, CD70, EFNB3, EGR3, IL7R, and TNFRSF13C in stomach adenocarcinoma (STAD) tissues and that in normal tissues (P > .05), while expressions of CCR7 and LGALS1 were significantly elevated in STAD tissues compared to the normal tissues (P < .05). The Kaplan-Meier Plotter database analysis, on the other hand, showed a significant relationship between all of the above-mentioned PCGs, except CCL19, and the prognosis of GC. Conclusions: CCL19, CCL21, CCR7, CD70, EFNB3, EGR3, IL7R, LGALS1, and TNFRSF13C are PCGs are differentially expressed in GC and closely associated with regulatory T cells. They may affect the occurrence and development of GC through a variety of pathways, including regulation of immune infiltration and inflammation, and are of great potential research value.

Development and validation of a prognostic model for esophageal carcinoma based on immune microenvironment using system bioinformatics.

Esophageal cancer (EC) is an aggressive malignancy that accounts for numerous cancer-related deaths worldwide. The multimodal combination therapy approach can be potentially used to treat EC effectively. However, distinct biomarker of significant specificity are still needed to develop individualized treatment strategies and provide accurate prognostic predictions. Therefore, we aimed to investigate the associated genes subtypes identified were, IFN-γDominant, Inflammatory, Lymphocyte Depleted, etc. and construct a risk model based on these genes to predict the overall survival (OS) of patients suffering from EC. Three immune subtypes were defined in the Cancer Genome Atlas (TCGA) cohort with different tumor microenvironment (TME) and clinical outcomes based on radio-differentiated immune genes. Subsequently, a risk model of immune characteristics included the immune cell infiltration levels and pathway activity was developed based on the genomic changes between the subtypes. In the TCGA dataset, as well as in subgroup analysis with different stages, gender, age, and pathological type, a high-risk score was identified as an adverse factor for OS using the method of the univariate Cox regression analysis and tROC analysis. Furthermore, it was observed that the high-risk group was characterized by depleted immunophenotype, active cell metabolism, and a high tumor mutation burden (TMB). The low-risk group was characterized by high TME abundance and active immune function. Differences in the biological genotypes may account for the differences in the prognosis and treatment response. Extensive research was carried out, and the results revealed that the low-risk group exhibited a significant level of therapeutic advantage in the field of immunotherapy. A risk model was developed based on the immune characteristics. It can be used to optimize risk stratification for patients suffering from EC. The results can potentially help provide new perspectives on treatment methods.

Extrachromosomal circular DNA: Current status and future prospects.

Extrachromosomal circular DNA (eccDNA) is a double-stranded DNA molecule found in various organisms, including humans. In the past few decades, the research on eccDNA has mainly focused on cancers and their associated diseases. Advancements in modern omics technologies have reinvigorated research on eccDNA and shed light on the role of these molecules in a range of diseases and normal cell phenotypes. In this review, we first summarize the formation of eccDNA and its modes of action in eukaryotic cells. We then outline eccDNA as a disease biomarker and reveal its regulatory mechanism. We finally discuss the future prospects of eccDNA, including basic research and clinical application. Thus, with the deepening of understanding and exploration of eccDNAs, they hold great promise in future biomedical research and clinical translational application.

Ultrasound-stimulated microbubbles contributes to radiotherapy in esophageal carcinoma.

This study aimed to explore the effect of ultrasound-stimulated microbubbles (USMBs) on tumor radiosensitivity in esophageal carcinoma (EC). The human EC cell line KYSE-510 and human umbilical vein endothelial cells (HUVECs) were exposed to radiation alone or in combination with USMBs. CCK-8, colony formation, and EdU assays were used to determine cell viability and proliferation. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. Western blotting showed that the protein levels were associated with apoptosis, epithelial-mesenchymal transition (EMT), and angiogenesis. An endothelial tube-forming assay was used to detect the angiogenic activity of HUVECs. Xenograft experiments were used to examine the effect of USMBs on EC radiosensitivity in vivo. The expression of Ki-67 in tumors was detected using immunohistochemistry. USMBs enhanced the suppressive effect of radiation on proliferation, migration, invasion, and EMT, and promoted radiation-induced apoptosis in EC cells in vitro. Angiogenesis in EC was suppressed by radiation and further inhibited by the combination of radiation and USMBs. In vivo experiments revealed that USMBs increased the radiosensitivity of ECs to tumor growth. Collectively, USMBs enhanced the effects of radiotherapy in esophageal carcinoma.

Ultrasound-Stimulated Microbubbles Inhibit Aggressive Phenotypes and Promotes Radiosensitivity of esophageal squamous cell carcinoma.

Ultrasound (US) is reported to improve the delivery efficiency of drugs loading onto large nanoparticles due to the sonoporation effect. Microbubbles (MBs) can be used as contrast agents of US expanding and contracting under low-amplitude US pressure waves. Ultrasound-stimulated microbubbles (USMBs) therapy is a promising option for the treatment of various cancers as a radiosensitizer. However, its role in esophageal squamous cell carcinoma (ESCC) remains unknown. In our study, human ESCC cell lines (KYSE-410, KYSE-1140) were treated with radiation solely, US alone, or radiation in combination with US or USMBs. The migration and invasion abilities of ESCC cells were examined by wound healing and Transwell assays. ESCC cell apoptosis was assessed using flow cytometry analysis and TUNEL assays. The levels of proteins associated with cell apoptosis and angiogenesis were measured by western blot analysis. A tube formation assay was performed to detect the ESCC cell angiogenesis. We found that USMBs at high levels most effectively most efficiently enhanced the effect of radiation, and significant changes in the viability (48%-51%), proliferation (1%), migration (63%-71%), invasion (52%) and cell apoptosis (31%-50%) of ESCC cells were observed compared with the control group in vitro. The ESCC angiogenesis was inhibited by US or radiation treatment and further inhibited by a combination of radiation and US or USMBs. USMBs at high levels most effectively enhanced the inhibitory effect of radiotherapy on ESCC cell apoptosis. Overall, USMBs enhanced the radiosensitivity of esophageal squamous cell carcinoma cells.Graphical abstractUSMBs treatment enhanced the anti-tumor effect of radiation on ESCC cell proliferation, migration, invasion, angiogenesis and apoptosis in vitro.1USMBs enhance the radiation-induced inhibition on ESCC cell growth2USMBs promote the radiation effect on ESCC cell apoptosis3USMBs enhance radiation-caused suppression on ESCC cell migration and invasion4USMBs enhance the suppression of radiation on ESCC angiogenesis[Figure: see text].