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BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.
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Rising ocean temperatures, a consequence of anthropogenic climate change, are increasing the frequency, intensity, and magnitude of extreme marine heatwaves (MHWs). These persistent anomalous warming events can have severe ecological and socioeconomic impacts, threatening ecologically and economically vital organisms such as bivalves and the ecosystems they support. Developing robust environmental and social frameworks to enhance the resilience and adaptability of bivalve aquaculture is critical to ensuring the sustainability of this crucial food source. This review synthesizes the current understanding of the physiological and ecological impacts of MHWs on commercially important bivalve species farmed globally. We propose an integrated risk assessment framework that encompasses environmental monitoring, farm-level preparedness planning, and community-level social support systems to safeguard bivalve aquaculture. Specifically, we examine heatwave prediction models, local mitigation strategies, and social programs that could mitigate the impacts on bivalve farms and vulnerable coastal communities economically dependent on this fishery. At the farm level, adaptation strategies such as selective breeding for heat-tolerant strains, optimized site selection, and adjustments to culture practices can improve survival outcomes during MHWs. Robust disease surveillance and management programs are essential for early detection and rapid response. Furthermore, we highlight the importance of stakeholder engagement, knowledge exchange, and collaborative governance in developing context-specific, inclusive, and equitable safeguard systems. Proactive measures, such as advanced forecasting tools like the California Current Marine Heat Wave Tracker developed by NOAA's Southwest Fisheries Science Center, enable preemptive action before losses occur. Coordinated preparation and response, underpinned by continuous monitoring and adaptive management, promise to protect these climate-vulnerable food systems and coastal communities. However, sustained research, innovation, and cross-sector collaboration are imperative to navigate the challenges posed by our rapidly changing oceans.
Subject(s)
Aquaculture , Bivalvia , Climate Change , Animals , Bivalvia/physiology , Extreme Weather , Environmental Monitoring , Ecosystem , Conservation of Natural Resources/methodsABSTRACT
Myocardial infarction (MI) is a common type of cardiovascular disease. The incidence of ventricular remodeling dysplasia and heart failure increases significantly after MI. The objective of this study is to investigate whether erythropoietin hepatocellular receptor B2 (EPHB2) can regulate myocardial injury after MI and explore its regulatory pathways. EPHB2 is significantly overexpressed in the heart tissues of MI mice. The downregulation of EPHB2 alleviates the cardiac function damage after MI. Knockdown EPHB2 alleviates MI-induced myocardial tissue inflammation and apoptosis, and myocardial fibrosis in mice. EPHB2 knockdown significantly inhibits the activation of mitogen activated kinase-like protein (MAPK) pathway in MI mice. Moreover, EPHB2 overexpression significantly promotes the phosphorylation of MAPK pathway-related protein, which can be reversed by MAPK-IN-1 (an MAPK inhibitor) treatment. In conclusion, silencing EPHB2 can mitigate MI-induced myocardial injury by inhibiting MAPK signaling in mice, suggesting that targeting EPHB2 can be a promising therapeutic target for MI-induced myocardial injury.
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In this work, incorporating nitropyraozles into tetranitroacetimidic acid (TNAA) resulted in two analogues of isomeric TNAA-like compounds (3 and 5). These compounds exhibit excellent densities, detonation performance, and high specific impulse, which are promising high-energy oxidizers that are comparable to AP and ADN. This structural modification strategy may have the potential to contribute significantly to the development of versatile, high-performance energetic oxidizers.
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Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well-known low penetration depth of external light. Here, ultrasound-mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound-induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof-of-concept sonosynthesis (sonoafterglow-induced photosynthesis) in cancer therapy. Chlorin e6, a typical small-molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue-penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia-inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.
Subject(s)
Cyanobacteria , Cyanobacteria/metabolism , Cyanobacteria/genetics , Mice , Animals , Humans , Photosynthesis , Nanoparticles , Neoplasms/therapy , Neoplasms/metabolism , Porphyrins/metabolism , Disease Models, Animal , Cell Line, Tumor , Chlorophyllides , Ferroptosis/genetics , Ultrasonic Therapy/methodsABSTRACT
A novel high-precision aptasensor of microcystin-RR (MC-RR) is developed based on a ratiometric self-powered photoelectrochemical platform. In detail, the defective MoS2/Ti3C2 nanocomposite with good photoelectric activity was designed to serve as the photoanode of the sensor for enhancing the signal and improving the detection sensitivity. In order to effectively eliminate external interferences, the key point of this ratiometric device is the introduction of the spatial-resolved technique, which includes the detection section and the reference section, generating reference signals and response signals, respectively. Moreover, output power was used as the detection signal, instead of the traditional photocurrent or photovoltage. Further, potassium persulfate was introduced as electron acceptor, which was beneficial for improving the electron transport efficiency, hindering electron-hole recombination, and significantly promoting the performance of the sensor. Finally, aptamer was adopted as recognition element to capture MC-RR molecules. The prepared sensor had a linear range from 10-12 to 10-6 M, and the detection limit was 5.6 × 10-13 M (S/N = 3). It has good precision, selectivity, and sensitivity, which shows great prospects in the on-site accurate analysis of samples with high energy output in the self-powered sensing field.
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Platinum-based chemotherapy is the standard postoperative adjuvant treatment for ovarian cancer (OC). Despite the initial response to chemotherapy, 85% of advanced OC patients will have recurrent disease. Relapsed disease and platinum resistance are the major causes of death in OC patients. In this study, we compared the global regulation of alternative polyadenylation (APA) in platinum-resistant and platinum-sensitive tissues of OC patients by analyzing a set of single-cell RNA sequencing (scRNA-seq) data from public databases and found that platinum-resistant patients exhibited global 3' untranslated region (UTR) shortening due to the different usage of polyadenylation sites (PASs). The APA regulator CSTF3 was the most significantly upregulated gene in epithelial cells of platinum-resistant OC. CSTF3 knockdown increased the sensitivity of OC cells to platinum. The lncRNA NEAT1 has two isoforms, short (NEAT1_1) and long (NEAT1_2) transcript, because of the APA processing in 3'UTR. We found that CSTF3 knockdown reduced the usage of NEAT1 proximal PAS to lengthen the transcript and facilitate the expression of NEAT1_2. Downregulation of the expression of NEAT1 (NEAT1_1/_2), but not only NEAT1_2, also increased the sensitivity of OC cells to platinum. Overexpressed NEAT1_1 reversed the platinum resistance of OC cells after knocking down CSTF3 expression. Furthermore, downregulated expression of CSTF3 and NEAT1_1, rather than NEAT1_2, was positively correlated with inactivation of the PI3K/AKT/mTOR pathway in OC cells. Together, our findings revealed a novel mechanism of APA regulation in platinum-resistant OC. CSTF3 directly bound downstream of the NEAT1 proximal PAS to generate the short isoform NEAT1_1 and was conducive to platinum resistance, which provides a potential biomarker and therapeutic strategy for platinum-resistant OC patients.
Subject(s)
Drug Resistance, Neoplasm , Ovarian Neoplasms , Polyadenylation , RNA, Long Noncoding , Animals , Female , Humans , Mice , Cell Line, Tumor , Cleavage And Polyadenylation Specificity Factor/metabolism , Cleavage And Polyadenylation Specificity Factor/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Platinum/pharmacology , Platinum/therapeutic use , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal TransductionABSTRACT
Ocean acidification and heatwaves caused by rising CO2 affect bivalves and other coastal organisms. Intertidal bivalves are vital to benthic ecosystems, but their physiological and metabolic responses to compound catastrophic climate events are unknown. Here, we examined Manila clam (Ruditapes philippinarum) responses to low pH and heatwaves. Biochemical and gene expression demonstrated that pH and heatwaves greatly affect physiological energy enzymes and genes expression. In the presence of heatwaves, Manila clams expressed more enzymes and genes involved in physiological energetics regardless of acidity, even more so than in the presence of both. In this study, calcifying organisms' biochemical and molecular reactions are more susceptible to temperature rises than acidity. Acclimation under harsh weather conditions was consistent with thermal stress increase at lower biological organization levels. These substantial temporal biochemical and molecular patterns illuminate clam tipping points. This study helps us understand how compound extreme weather and climate events affect coastal bivalves for future conservation efforts.
Subject(s)
Bivalvia , Seawater , Animals , Bivalvia/physiology , Seawater/chemistry , Hydrogen-Ion Concentration , Climate Change , Oceans and Seas , Ecosystem , Extreme WeatherABSTRACT
INTRODUCTION: Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. PATIENT CONCERNS: In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. DIAGNOSIS: Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. INTERVENTIONS: In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. OUTCOMES: Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. LESSONS: We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.
Subject(s)
Gout , Limb Salvage , Humans , Anti-Bacterial Agents/therapeutic use , Debridement/methods , Diabetic Foot/therapy , Diabetic Foot/surgery , Gout/complications , Limb Salvage/methods , Metatarsophalangeal Joint/surgery , Vancomycin/therapeutic use , Vancomycin/administration & dosageABSTRACT
Background: In China, traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese herb formulas with the effect of "yiqi jianpi jiedu huayu" (replenishing qi, strengthening spleen, and removing toxicity and blood stasis) are the common and efficient treatments for HCC. However, the mechanism of these formulas in treating HCC remain unclear. Objective: In this paper, our goal is to explore the potential mechanism of Phyllanthus urinaria L anti-neoplastic decoction (PAD), the representative formula of "yiqi jianpi jiedu huayu", in treating HCC. Design: The research team performed the network pharmacology and in vitro experiment (preparation of PAD aqueous extract, cell cultures and MTT assay, cell apoptosis assay, wound healing assay, transwell assays, western blot). Setting: The study took place in the Department of Hepatology, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), China. Outcome Measures: The active components and targets of PAD and HCC targets were screened by five Chinese herbs and two disease databases respectively. The network pharmacology was utilized to construct the relationship network between PAD and HCC, and the mechanism was predicted by pathway enrichment analysis. The experiment was performed to verify the intervention effect of PAD on HCC and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. Results: The relationship network between PAD and HCC suggested that PAD mainly regulated the potential therapeutic targets of HCC by key active components such as quercetin, luteolin, calycosin, wogonin, and pinocembrin. Pathway analysis demonstrated PAD could play an anti-HCC effect via multiple pathways (e.g., PI3K/Akt). Results of the experiment showed that PAD could effectively inhibit the proliferation and migration of HCC cells, and promote HCC cells apoptosis in a concentration-dependent behavior. Additionally, PAD could decrease the protein expression of phosphorylated PI3K/Akt. Conclusion: PAD mainly exerts an anti-HCC effect through multiple active components represented by quercetin and multiple pathways represented by the PI3K/Akt pathway. This study provided an experimental basis for the clinical application of PAD.
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Due to the coastal wetland degradation caused by human activities and environmental changes, many coastal wetland restoration studies have been carried out in China to restore the degraded ecosystems, but it still lacks a comprehensive assessment of restoration effectiveness at national scale. In this study, a meta-analysis of 78 field studies was conducted to quantitatively assess the restoration effectiveness of biodiversity and ecosystem services in China's coastal wetlands. At the same time, we evaluated the impact factors such as ecosystem types, restoration methods and measures, and restoration time on restoration effectiveness. The results show that coastal wetland ecological restoration has improved the biodiversity and ecosystem services by 36.8 % and 38.2 % respectively within the time range reported in the research literature, but neither has returned to the level of natural ecosystems. Biodiversity recovery is significantly positively correlated with the recovery of ecosystem services, indicating the simultaneous recovery outcome. Compared with degraded wetlands, the effectiveness of passive restoration is better than that of active restoration. In the mangrove ecosystem, invasive species removal is the most effective among the restoration measures, and the restoration effectiveness of polyculture plantations is better than that of monoculture plantations. When time ranges from 0 to 20 years, the recovery level of coastal wetlands tends to increase with the extension of restoration time. However, when the restoration time is >20 years, the recovery level decreases, which may be related to the lack of maintenance and management measures in the later stage. Our study showcases the scientific evidence for future coastal wetland ecological restoration in China.
Subject(s)
Biodiversity , Conservation of Natural Resources , Environmental Restoration and Remediation , Wetlands , China , Environmental Restoration and Remediation/methods , Conservation of Natural Resources/methods , EcosystemABSTRACT
BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.
Subject(s)
Cognition Disorders , Cognitive Dysfunction , East Asian People , Humans , Aged , Cognition Disorders/diagnosis , Cross-Sectional Studies , 8-Hydroxy-2'-Deoxyguanosine , Longevity , Aging/psychology , Risk Factors , Cognition , Cognitive Dysfunction/epidemiologyABSTRACT
BACKGROUND: The systemic treatment of advanced hepatocellular carcinoma is currently facing a bottleneck. EGCG, the primary active compound in green tea, exhibits anti-tumor effects through various pathways. However, there is a lack of study on EGCG-induced immunogenic cell death (ICD) in hepatocellular carcinoma. METHODS: In a previous study, we successfully synthesized folate-modified thermosensitive nano-materials, encapsulated EGCG within nanoparticles using a hydration method, and established the EGCG nano-drug delivery system. The viability of HepG2 cells post-EGCG treatment was assessed via the MTT and EdU assays. Cell migration and invasion were evaluated through wound healing experiments, Transwell assays, and Annexin V-FITC/PI assay for apoptosis detection. Additionally, the expression levels of damage-associated molecular patterns (DAMPs) were determined using immunofluorescence, ATP measurement, RT-qPCR, and Western Blot. RESULTS: The drug sensitivity test revealed an IC50 value of 96.94 µg/mL for EGCG in HepG2 cells after 48 h. EGCG at a low concentration (50 µg/mL) significantly impeded the migration and invasion of HepG2 cells, showing a clear dose-dependent response. Moreover, medium to high EGCG concentrations induced cell apoptosis in a dose-dependent manner and upregulated DAMPs expression. Immunofluorescence analysis demonstrated a notable increase in CRT expression following low-concentration EGCG treatment. As EGCG concentration increased, cell viability decreased, leading to CRT exposure on the cell membrane. EGCG also notably elevated ATP levels. RT-qPCR and Western Blot analyses indicated elevated expression levels of HGMB1, HSP70, and HSP90 following EGCG intervention. CONCLUSION: EGCG not only hinders the proliferation, migration, and invasion of hepatocellular carcinoma cells and induces apoptosis, but also holds significant clinical promise in the treatment of malignant tumors by promoting ICD and DAMPs secretion.
Subject(s)
Carcinoma, Hepatocellular , Catechin , Catechin/analogs & derivatives , Folic Acid , Liver Neoplasms , Humans , Catechin/pharmacology , Catechin/chemistry , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Hep G2 Cells , Folic Acid/chemistry , Folic Acid/pharmacology , Cell Movement/drug effects , Immunogenic Cell Death/drug effects , Nanospheres/chemistry , Apoptosis/drug effects , Cell Survival/drug effects , Temperature , Calreticulin/metabolismABSTRACT
The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.
Subject(s)
Blood-Brain Barrier , Ischemic Stroke , Animals , Humans , Mice , Atrophy , Endothelial Cells , Endothelium , PeroxiredoxinsABSTRACT
Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.
Subject(s)
Fusion Proteins, bcr-abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Drug Resistance, Neoplasm/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Signal TransductionABSTRACT
BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.
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Cancer-associated fibroblasts (CAFs) are an important component of the stroma. Studies showed that CAFs were pivotally in glioma progression which have long been considered a promising therapeutic target. Therefore, the identification of prognostic CAF markers might facilitate the development of novel diagnostic and therapeutic approaches. A total of 1333 glioma samples were obtained from the TCGA and CGGA datasets. The EPIC, MCP-counter, and xCell algorithms were used to evaluate the relative proportion of CAFs in glioma. CAF markers were identified by the single-cell RNA-seq datasets (GSE141383) from the Tumor Immune Single-Cell Hub database. Unsupervised consensus clustering was used to divide the glioma patients into different distinct subgroups. The least absolute shrinkage and selection operator regression model was utilized to establish a CAF-related signature (CRS). Finally, the prognostic CAF markers were further validated in clinical specimens by RTâqPCR. Combined single-cell RNA-seq analysis and differential expression analysis of samples with high and low proportions of CAFs revealed 23 prognostic CAF markers. By using unsupervised consensus clustering, glioma patients were divided into two distinct subtypes. Subsequently, based on 18 differentially expressed prognostic CAF markers between the two CAF subtypes, we developed and validated a new CRS model (including PCOLCE, TIMP1, and CLIC1). The nomogram and calibration curves indicated that the CRS was an accurate prognostic marker for glioma. In addition, patients in the high-CRS score group had higher immune infiltration and tumor mutation burden levels. Moreover, the CRS score had the potential to predict the response to immune checkpoint blockade (ICB) therapy and chemotherapy. Finally, the expression profiles of three CAF markers were verified by RTâqPCR. In general, our study classified glioma patients into distinct subgroups based on CAF markers, which will facilitate the development of individualized therapy. We also provided insights into the role of the CRS in predicting the response to ICB and chemotherapy in glioma patients.
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The intrinsically low electronic conductivity and slow ion diffusion kinetics limit further development of olivine LiFexMn1-xPO4 cathode materials. In this paper, with the aim of improving the performance of such materials and alleviating the Jahn-Taller effect of Mn3+ ion, a bimetallic oxalate precursor with gradient distribution of elemental concentration followed with an efficient process is applied to synthesize LiFe0.5Mn0.5PO4 nanocomposite. The results shown that with certain structural modulation of the precursor, the discharge capacity of synthesized LiFe0.5Mn0.5PO4 increased from 149â mAh g-1 to 156â mAh g-1 at 0.1â C, the cycling capacity was also remarkably improved. the Fe0.5Mn0.5C2O4 â 2H2O-1 precursor with gradient distribution of elemental concentration effectively restricts the reaction between electrode material and electrolyte, thereby alleviates the dissolution of Mn3+ ion, reduces the decay of capacity and improves the stability of the material.
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OBJECTIVE: To estimate the prevalence of depressive symptoms and to evaluate the associations of mild and significant depressive symptoms with cardiovascular events and plasma BNP levels (which are surrogate endpoints for cardiovascular events) among older adults in a population-based study. METHODS: A population-based prospective study of 1,432 elderly people (aged 70-84 years and without cardiovascular disease) was conducted, and the median duration of follow-up for participants with outcomes was 18 weeks. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15). The hazard ratios (HRs) for the time to events and time to death were calculated using the Cox regression analysis. Multiple linear regression models and Spearman rank correlations were used to examine the association of depressive symptoms with Log BNP values. RESULTS: The prevalence of mild (GDS-15 scores ≥ 6) and significant (GDS-15 scores ≥ 10) depressive symptoms were 7.3% and 2.0% at baseline, respectively. Older adults with significant depressive symptoms exhibited increased risks of time to death (HR: 12.56; 95% CI: 3.58-43.99) and composite cardiovascular endpoints (HR: 3.46; 95% CI: 1.19-3.75). Significant depressive symptoms were associated with Log BNP levels (ß=0.56, P = 0.02). Depressive symptom scores were also associated with Log BNP levels (rs=0.21, P = 0.04) in the older adults with depressive symptoms. CONCLUSIONS: Significant depressive symptoms were associated with a higher risk of cardiovascular events and higher BNP levels in the elderly.