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Search Results (487)

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29 pages, 30467 KiB  
Article
Clay-Hosted Lithium Exploration in the Wenshan Region of Southeastern Yunnan Province, China, Using Multi-Source Remote Sensing and Structural Interpretation
by Lunxin Feng, Zhifang Zhao, Haiying Yang, Qi Chen, Changbi Yang, Xiao Zhao, Geng Zhang, Xinle Zhang and Xin Dong
Minerals 2025, 15(8), 826; https://doi.org/10.3390/min15080826 (registering DOI) - 2 Aug 2025
Abstract
With the rapid increase in global lithium demand, the exploration of newly discovered lithium in the bauxite of the Wenshan area in southeastern Yunnan has become increasingly important. However, the current research on clay-type lithium in the Wenshan area has primarily focused on [...] Read more.
With the rapid increase in global lithium demand, the exploration of newly discovered lithium in the bauxite of the Wenshan area in southeastern Yunnan has become increasingly important. However, the current research on clay-type lithium in the Wenshan area has primarily focused on local exploration, and large-scale predictive metallogenic studies remain limited. To address this, this study utilized multi-source remote sensing data from ZY1-02D and ASTER, combined with ALOS 12.5 m DEM and Sentinel-2 imagery, to carry out remote sensing mineral identification, structural interpretation, and prospectivity mapping for clay-type lithium in the Wenshan area. This study indicates that clay-type lithium in the Wenshan area is controlled by NW, EW, and NE linear structures and are mainly distributed in the region from north of the Wenshan–Malipo fault to south of the Guangnan–Funing fault. High-value areas of iron-rich silicates and iron–magnesium minerals revealed by ASTER data indicate lithium enrichment, while montmorillonite and cookeite identification by ZY1-02D have strong indicative significance for lithium. Field verification samples show the highest Li2O content reaching 11,150 μg/g, with six samples meeting the comprehensive utilization criteria for lithium in bauxite (Li2O ≥ 500 μg/g) and also showing an enrichment of rare earth elements (REEs) and gallium (Ga). By integrating stratigraphic, structural, mineral identification, geochemical characteristics, and field verification data, ten mineral exploration target areas were delineated. This study validates the effectiveness of remote sensing technology in the exploration of clay-type lithium and provides an applicable workflow for similar environments worldwide. Full article
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23 pages, 4589 KiB  
Review
The Novel Achievements in Oncological Metabolic Radio-Therapy: Isotope Technologies, Targeted Theranostics, Translational Oncology Research
by Elena V. Uspenskaya, Ainaz Safdari, Denis V. Antonov, Iuliia A. Valko, Ilaha V. Kazimova, Aleksey A. Timofeev and Roman A. Zubarev
Med. Sci. 2025, 13(3), 107; https://doi.org/10.3390/medsci13030107 (registering DOI) - 1 Aug 2025
Viewed by 38
Abstract
Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the [...] Read more.
Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article
(This article belongs to the Special Issue Feature Papers in Section Cancer and Cancer-Related Diseases)
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24 pages, 5906 KiB  
Article
In Silico Mining of the Streptome Database for Hunting Putative Candidates to Allosterically Inhibit the Dengue Virus (Serotype 2) RdRp
by Alaa H. M. Abdelrahman, Gamal A. H. Mekhemer, Peter A. Sidhom, Tarad Abalkhail, Shahzeb Khan and Mahmoud A. A. Ibrahim
Pharmaceuticals 2025, 18(8), 1135; https://doi.org/10.3390/ph18081135 - 30 Jul 2025
Viewed by 285
Abstract
Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is [...] Read more.
Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol−1) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔGbinding values of −246.4, −242.3, and −150.6 kJ.mol−1, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article
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12 pages, 537 KiB  
Article
Surgical Versus Conservative Management of Supratentorial ICH: A Single-Center Retrospective Analysis (2017–2023)
by Cosmin Cindea, Samuel Bogdan Todor, Vicentiu Saceleanu, Tamas Kerekes, Victor Tudor, Corina Roman-Filip and Romeo Gabriel Mihaila
J. Clin. Med. 2025, 14(15), 5372; https://doi.org/10.3390/jcm14155372 - 30 Jul 2025
Viewed by 257
Abstract
Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative [...] Read more.
Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative management in patients with lobar, capsulo-lenticular, and thalamic ICH and to identify factors influencing mortality and the surgical decision. Methods: This single-center, retrospective cohort study included adult patients admitted to the County Clinical Emergency Hospital of Sibiu (2017–2023) with spontaneous supratentorial ICH confirmed via CT (deepest affected structure determining lobar, capsulo-lenticular, or thalamic location). We collected data on demographics, clinical presentation (Glasgow Coma Scale [GCS], anticoagulant use), hematoma characteristics (volume, extension), treatment modality (surgical vs. conservative), and in-hospital outcomes (mortality, length of stay). Statistical analyses included t-tests, χ2, correlation tests, and logistic regression to identify independent predictors of mortality and surgery. Results: A total of 445 patients were analyzed: 144 lobar, 150 capsulo-lenticular, and 151 thalamic. Surgical intervention was more common in patients with larger volumes and lower GCS. Overall, in-hospital mortality varied by location, reaching 13% in the lobar group, 20.7% in the capsulo-lenticular group, and 35.1% in the thalamic group. Within each location, surgical intervention did not significantly reduce overall in-hospital mortality despite the more severe baseline presentation in surgical patients. In lobar ICH specifically, no clear survival advantage emerged, although surgery may still benefit those most severely compromised. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower mortality (39.4% vs. 61.5%). In patients with large lobar ICH, surgical intervention was associated with mortality rates similar to those seen in less severe, conservatively managed cohorts. Multivariable adjustment confirmed GCS and hematoma volume as independent mortality predictors; age and volume predicted the likelihood of surgical intervention. Conclusions: Despite targeting more severe cases, neurosurgical evacuation did not uniformly lower in-hospital mortality. In lobar ICH, surgical patients with larger hematomas (~48 mL) and lower GCS (~11.6) had mortality rates (~13%) comparable to less severe, conservative cohorts, indicating that surgical intervention was associated with similar mortality rates despite higher baseline risk. However, these findings do not establish a causal survival benefit and should be interpreted in the context of non-randomized patient selection. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower observed mortality (39.4% vs. 61.5%). Thalamic ICH remained most lethal, highlighting the difficulty of deep-brain bleeds and frequent ventricular extension. Across locations, hematoma volume and GCS were the primary outcome predictors, indicating the need for timely intervention, better patient selection, and possibly minimally invasive approaches. Future prospective multicenter research is necessary to refine surgical indications and validate these findings. To our knowledge, this investigation represents the largest and most contemporary single-center cohort study of supratentorial intracerebral hemorrhage conducted in Romania. Full article
(This article belongs to the Section Brain Injury)
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27 pages, 5245 KiB  
Article
The Good, the Bad, or Both? Unveiling the Molecular Functions of LINC01133 in Tumors
by Leandro Teodoro Júnior and Mari Cleide Sogayar
Non-Coding RNA 2025, 11(4), 58; https://doi.org/10.3390/ncrna11040058 (registering DOI) - 30 Jul 2025
Viewed by 236
Abstract
Background/Objectives: Increasing evidence suggests that lncRNAs are core regulators in the field of tumor progression, with context-specific functions in oncogenic tumorigenesis. LINC01133, a lncRNA that has been identified as both an oncogene and a tumor suppressor, remains largely unexplored in terms of its [...] Read more.
Background/Objectives: Increasing evidence suggests that lncRNAs are core regulators in the field of tumor progression, with context-specific functions in oncogenic tumorigenesis. LINC01133, a lncRNA that has been identified as both an oncogene and a tumor suppressor, remains largely unexplored in terms of its molecular mechanisms. The purpose of this study was to conduct an in silico analysis, incorporating literature research on various cancer types, to investigate the structural and functional duality of LINC01133. This analysis aimed to identify pathways influenced by LINC01133 and evaluate its mechanism of action as a potential therapeutic target and diagnostic biomarker. Methods: In silico analyses and a narrative review of the literature were performed to predict conserved structural elements, functional internal loops, and overall conservation of the LINC01133 sequence among different vertebrate organisms, summarizing the empirical evidence regarding its roles as a tumor suppressor and tumor-promoting roles in various types of tumors. Results: LINC01133 harbors the evolutionarily conserved structural regions that might allow for binding to relevant driver signaling pathways, substantiating its specific functionality. Its action extends beyond classical tumor mechanisms, affecting proliferation, migration, invasion, and epigenetic pathways in various types of tumors, as indicated by the in silico results and narrative review of the literature we present here. Clinical outcome associations pointed to its potential as a biomarker. Conclusions: The dual character of LINC01133 in tumor biology further demonstrates its prospective therapeutic value, but complete elucidation of its mechanisms of action requires further investigation. This study establishes LINC01133 as a multifaceted lncRNA, supporting context-specific strategies in targeting its pathways, and calls for expanded research to harness its full potential in oncology. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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14 pages, 12586 KiB  
Article
Three-Dimensional Mineralization Prediction Using the Information Value Method: A Case Study of the Bainiuchang Ag Polymetallic Deposit, Southwest China
by Fuju Jia, Guolong Zheng, Guangzhi Meng, Long Jian, He Chang, Ping Pan, Jianguo Gao, Zhixiao Wu and Ceting Yang
Minerals 2025, 15(8), 783; https://doi.org/10.3390/min15080783 - 25 Jul 2025
Viewed by 228
Abstract
Three-dimensional geological modeling combined with the information value method offers a powerful approach for predicting mineralization in complex geological settings. This study applies these techniques to the Bainiuchang Ag polymetallic deposit in Southwest China. We constructed a detailed 3D geological model to identify [...] Read more.
Three-dimensional geological modeling combined with the information value method offers a powerful approach for predicting mineralization in complex geological settings. This study applies these techniques to the Bainiuchang Ag polymetallic deposit in Southwest China. We constructed a detailed 3D geological model to identify key geological factors influencing mineralization, such as the F3 fault, secondary faults, and the middle Cambrian Tianpeng Formation. Using the information value method, we evaluated the mineralization potential of each unit in the study area. Receiver operating characteristic (ROC) curves and fractal analysis were employed to determine an optimal threshold (information value > 2.6) for delineating high-potential exploration targets. Our results identified three priority targets (A1, A2, and A3), demonstrating the effectiveness of integrating 3D modeling with probabilistic mineral prospectivity mapping. This approach provides a robust framework for deep and peripheral exploration in structurally complex deposits, offering valuable insights for future mineral exploration efforts. Full article
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19 pages, 3009 KiB  
Article
PD-1-Positive CD8+ T Cells and PD-1-Positive FoxP3+ Cells in Tumor Microenvironment Predict Response to Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients
by Liubov A. Tashireva, Anna Yu. Kalinchuk, Elena O. Shmakova, Elisaveta A. Tsarenkova, Dmitriy M. Loos, Pavel Iamschikov, Ivan A. Patskan, Alexandra V. Avgustinovich, Sergey V. Vtorushin, Irina V. Larionova and Evgeniya S. Grigorieva
Cancers 2025, 17(14), 2407; https://doi.org/10.3390/cancers17142407 - 21 Jul 2025
Viewed by 324
Abstract
Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive [...] Read more.
Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive markers associated with therapeutic efficacy. Methods: We prospectively enrolled 16 patients with histologically confirmed, PD-L1–positive (CPS ≥ 1) gastric adenocarcinoma (T2–4N0–1M0). All patients received eight cycles of FLOT chemotherapy combined with pembrolizumab. Treatment response was assessed by Mandard tumor regression grading. Spatial transcriptomic profiling (10x Genomics Visium) and multiplex immunofluorescence were used to evaluate tumor-infiltrating immune cell subsets and PD-1 expression at baseline and after treatment. Results: Transcriptomic analysis differentiated the immune landscapes of responders from non-responders. Responders exhibited elevated expression of IL1B, CXCL5, HMGB1, and IFNGR2, indicative of an inflamed tumor microenvironment and type I/II interferon signaling. In contrast, non-responders demonstrated upregulation of immunosuppressive genes such as LGALS3, IDO1, and CD55, along with enrichment in oxidative phosphorylation and antigen presentation pathways. Multiplex immunofluorescence confirmed a higher density of FoxP3+ regulatory T cells in non-responders (median 5.36% vs. 2.41%; p = 0.0032). Notably, PD-1+ CD8+ T cell and PD-1+ FoxP3+ Treg frequencies were significantly elevated in non-responders, suggesting that PD-1 expression within cytotoxic and regulatory compartments may contribute to immune evasion. No substantial differences were observed in PD-L1 CPS or PD-1+ B cells and PD-1+ macrophages. Conclusions: Our findings identify PD-1+ CD8+ T cells and PD-1+ FoxP3+ Tregs as potential biomarkers of resistance to neoadjuvant chemoimmunotherapy in gastric cancer. Transcriptional programs centered on IL1B/CXCL5 and LGALS3/IDO1 define distinct immune phenotypes that may guide future combination strategies targeting both effector and suppressive arms of the tumor immune response. Full article
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18 pages, 2502 KiB  
Article
Epitope Variation in Hemagglutinin and Antibody Responses to Successive A/Victoria A(H1N1) Strains in Young and Older Adults Following Seasonal Influenza Vaccination: A Pilot Study
by Mónica Espinar-García, Isabel María Vallejo-Bermúdez, María Ángeles Onieva-García, Irene Reina-Alfonso, Luis Llapa-Chino, Pablo Álvarez-Heredia, Inmaculada Salcedo, Rafael Solana, Alejandra Pera and Alexander Batista-Duharte
Vaccines 2025, 13(7), 774; https://doi.org/10.3390/vaccines13070774 - 21 Jul 2025
Viewed by 350
Abstract
Background: Annual influenza vaccine updates target viral drift, but immune responses may be biased by original antigenic sin (OAS). Few studies have explored this across closely related strains. This study examines how OAS shapes responses to sequential influenza variants in the context of [...] Read more.
Background: Annual influenza vaccine updates target viral drift, but immune responses may be biased by original antigenic sin (OAS). Few studies have explored this across closely related strains. This study examines how OAS shapes responses to sequential influenza variants in the context of seasonal vaccination. Methods: We conducted a prospective, longitudinal study to assess the humoral immune response to the 2023–2024 seasonal influenza vaccine containing the A/Victoria/4897/2022 (H1N1) strain. Bioinformatic analyses compared the hemagglutinin (HA) sequences of A/Victoria/4897/2022 and the antigenically related A/Victoria/2570/2019 strain. B-cell epitopes were mapped with BepiPred-3.0 and BepiBlast, and their physicochemical properties analyzed via accessibility, β-turns, flexibility, and hydrophilicity. Antibody responses were measured pre- and 28 days post-Vaxigrip Tetra vaccination in young (18–35) and older (>65) adults, stratified by cytomegalovirus (CMV) serostatus. HA sequences showed >97% identity, with variations mainly in the globular head. Predicted B-cell epitopes overlapped variable sites, suggesting possible immune escape. Despite having been vaccinated against the 2022 strain, serology showed higher antibody titers against the 2019 HA strain in all participants. This pattern suggests a potential antigen imprinting effect, though confirmation awaits further analysis. Age groups differed: older adults showed greater variability, while younger CMV+ individuals tended toward stronger 2019 HA responses. Conclusions: These findings suggest a complex interplay of factors shaping immune responses, though the imprinting effect and the potential role of CMV warrant further exploration in larger, more focused studies. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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13 pages, 1056 KiB  
Article
Diagnostic Accuracy and Interrater Agreement of FDG-PET/CT Lymph Node Staging in High-Risk Endometrial Cancer: The SENTIREC-Endo Study
by Jorun Holm, André Henrique Dias, Oke Gerke, Annika Loft, Kirsten Bouchelouche, Mie Holm Vilstrup, Sarah Marie Bjørnholt, Sara Elisabeth Sponholtz, Kirsten Marie Jochumsen, Malene Grubbe Hildebrandt and Pernille Tine Jensen
Cancers 2025, 17(14), 2396; https://doi.org/10.3390/cancers17142396 - 19 Jul 2025
Viewed by 357
Abstract
Background/Objectives: The SENTIREC-endo study identified a safe sentinel lymph node mapping algorithm combined with PET-positive node dissection, matching radical pelvic and paraaortic lymphadenectomy in high-risk endometrial cancer. The present study evaluated the diagnostic accuracy of FDG-PET/CT for lymph node metastases in the same [...] Read more.
Background/Objectives: The SENTIREC-endo study identified a safe sentinel lymph node mapping algorithm combined with PET-positive node dissection, matching radical pelvic and paraaortic lymphadenectomy in high-risk endometrial cancer. The present study evaluated the diagnostic accuracy of FDG-PET/CT for lymph node metastases in the same population based on location, size, and Standardised Uptake Value (SUV), in addition to assessing interrater agreement across three Danish centres. Methods: This prospective multicentre study included women with high-risk endometrial cancer from the Danish SENTIREC study database (2017–2023). All patients underwent preoperative FDG-PET/CT. Diagnostic accuracy was evaluated against a pathology-confirmed reference standard. Interrater agreement was evaluated between trained specialists in Nuclear Medicine. Results: Among 227 patients, 52 patients (23%) had lymph node metastases. FDG-PET/CT identified lymph node metastases with 56% sensitivity (95% CI: 42–68) and 91% specificity (95% CI: 86–94). Positive and negative predictive values were 64% and 87%, respectively. Specificity for paraaortic nodes was high (97%), though sensitivity remained limited (56%). Lymph node size and SUVmax had moderate diagnostic value (AUC-ROC ~0.7). Interrater proportion of agreement was 95% and Cohen’s Kappa κ = 0.84 (95% CI: 0.73–0.94), the latter of which was ‘almost perfect’. Conclusions: FDG-PET/CT had limited sensitivity in lymph node staging in high-risk EC, and the diagnostic accuracy of FDG-PET/CT remains complementary to the sentinel node procedure. Due to its high specificity and strong interrater reliability, FDG-PET/CT is recommended for clinical implementation in combination with the sensitive sentinel node biopsy for the targeted dissection of PET-positive lymph nodes, particularly in paraaortic regions. Full article
(This article belongs to the Special Issue Lymph Node Dissection for Gynecologic Cancers)
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17 pages, 919 KiB  
Article
Necroptotic and Apoptotic Pathways in Sepsis: A Comparative Analysis of Pediatric and Adult ICU Patients
by George Briassoulis, Konstantina Tzermia, Kalliopi Bastaki, Marianna Miliaraki, Panagiotis Briassoulis, Athina Damianaki, Eumorfia Kondili and Stavroula Ilia
Biomedicines 2025, 13(7), 1747; https://doi.org/10.3390/biomedicines13071747 - 17 Jul 2025
Viewed by 339
Abstract
Background: Necroptosis, a regulated form of inflammatory cell death, is increasingly recognized as a key driver of sepsis and critical illness. The balance between necroptosis and apoptosis may influence immune responses and outcomes in ICU patients. Objective: To evaluate necroptosis- and apoptosis-related protein [...] Read more.
Background: Necroptosis, a regulated form of inflammatory cell death, is increasingly recognized as a key driver of sepsis and critical illness. The balance between necroptosis and apoptosis may influence immune responses and outcomes in ICU patients. Objective: To evaluate necroptosis- and apoptosis-related protein expression in critically ill pediatric and adult patients with sepsis/septic shock, trauma/SIRS, or cardiac conditions, and assess their association with clinical outcomes. Methods: In this prospective, observational study, 88 patients admitted to a tertiary ICU were categorized into four groups: sepsis/septic shock, trauma/SIRS, cardiac disease, and healthy controls. Serum levels of RIPK1, RIPK3, MLKL, A20, caspase-8, IL-1β, and IL-18 were measured within 24 h of admission using ELISA. Biomarkers were analyzed by disease group, age, and severity indices. Results: Patients with sepsis—both adults and children—exhibited significantly elevated levels of RIPK1, IL-1β, and IL-18 (p < 0.001) and reduced levels of caspase-8 (p = 0.015), indicating activation of the necroptosis pathway. A20 was significantly upregulated (p < 0.001) and independently associated with lactate levels. RIPK1, IL-1β, and IL-18 were positively correlated with ICU length of stay and illness severity, whereas caspase-8 showed an inverse correlation. ROC analysis demonstrated strong predictive performance for sepsis/septic shock using RIPK1 (AUC = 0.81), IL-18 (AUC = 0.71), and A20 (AUC = 0.71); conversely, caspase-8 was inversely associated with sepsis (AUC = 0.32). Conclusions: Necroptosis appears to play a central role in the pathophysiology of sepsis across age groups. Elevated levels of RIPK1, IL-1β, IL-18, and A20 may serve as biomarkers of disease severity, while reduced caspase-8 supports a shift away from apoptosis toward necroptotic cell death. These findings highlight the potential of necroptosis-related pathways as targets for risk stratification and therapeutic intervention in critically ill patients of all ages. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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27 pages, 22085 KiB  
Article
Sedimentary Characteristics and Petroleum Geological Significance of the Middle–Upper Triassic Successions in the Wushi Area, Western Kuqa Depression, Tarim Basin
by Yahui Fan, Mingyi Hu, Qingjie Deng and Quansheng Cai
Appl. Sci. 2025, 15(14), 7895; https://doi.org/10.3390/app15147895 - 15 Jul 2025
Viewed by 224
Abstract
As a strategic replacement area for hydrocarbon exploration in the Tarim Basin, the Kuqa Depression has been the subject of relatively limited research on the sedimentary characteristics of the Triassic strata within its western Wushi Sag, which constrains exploration deployment in this region. [...] Read more.
As a strategic replacement area for hydrocarbon exploration in the Tarim Basin, the Kuqa Depression has been the subject of relatively limited research on the sedimentary characteristics of the Triassic strata within its western Wushi Sag, which constrains exploration deployment in this region. This study focuses on the Wushi Sag, systematically analyzing the sedimentary facies types, the evolution of sedimentary systems, and the distribution patterns of the Triassic Kelamayi and Huangshanjie formations. This analysis integrates field outcrops, drilling cores, wireline logs, and 2D seismic data, employing methodologies grounded in foreland basin theory and clastic sedimentary petrology. The paleo-geomorphology preceding sedimentation was reconstructed through balanced section restoration to investigate the controlling influence of foreland tectonic movements on the distribution of sedimentary systems. By interpreting key seismic profiles and analyzing vertical facies successions, the study classifies and evaluates the petroleum accumulation elements and favorable source–reservoir-seal assemblages, culminating in the prediction of prospective exploration areas. The research shows that: (1) The Triassic in the Wushi Sag mainly develops fan-delta, braided-river-delta, and lacustrine–shallow lacustrine sedimentary systems, with strong planar distribution regularity. The exposed strata in the northern part are predominantly fan-delta and lacustrine systems, while the southern part is dominated by braided-river-delta and lacustrine systems. (2) The spatial distribution of sedimentary systems was demonstrably influenced by tectonic activity. Paleogeomorphological reconstructions indicate that fan-delta and braided-river-delta sedimentary bodies preferentially developed within zones encompassing fault-superposition belts, fault-transfer zones, and paleovalleys. Furthermore, Triassic foreland tectonic movements during its deposition significantly altered basin configuration, thereby driving lacustrine expansion. (3) The Wushi Sag exhibits favorable hydrocarbon accumulation configurations, featuring two principal source–reservoir assemblages: self-sourced structural-lithologic gas reservoirs with vertical migration pathways, and lower-source-upper-reservoir structural-lithologic gas reservoirs with lateral migration. This demonstrates substantial petroleum exploration potential. The results provide insights for identifying favorable exploration targets within the Triassic sequences of the Wushi Sag and western Kuqa Depression. Full article
(This article belongs to the Section Earth Sciences)
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13 pages, 1099 KiB  
Article
NF-κB as an Inflammatory Biomarker in Thin Endometrium: Predictive Value for Live Birth in Recurrent Implantation Failure
by Zercan Kalı, Pervin Karlı, Fatma Tanılır, Pınar Kırıcı and Serhat Ege
Diagnostics 2025, 15(14), 1762; https://doi.org/10.3390/diagnostics15141762 - 12 Jul 2025
Viewed by 430
Abstract
Background: Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (≤7 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-κB), a key transcription factor in inflammatory signaling, in impaired endometrial [...] Read more.
Background: Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (≤7 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-κB), a key transcription factor in inflammatory signaling, in impaired endometrial receptivity. However, its clinical relevance and prognostic value for live birth outcomes still need to be fully elucidated. Objective: We aim to evaluate the expression levels of endometrial NF-κB in patients with RIF and thin endometrium and to determine its potential as a predictive biomarker for live birth outcomes following IVF treatment. Methods: In this prospective case–control study, 158 women were categorized into three groups: Group 1 (RIF with thin endometrium, ≤7 mm, n = 52), Group 2 (RIF with normal endometrium, >7 mm, n = 38), and fertile controls (n = 68). NF-κB levels were assessed using ELISA and immunohistochemical histoscore. Pregnancy outcomes were compared across groups. ROC analysis and multivariable logistic regression were performed to assess the predictive value of NF-κB. Results: NF-κB expression was significantly elevated in Group 1 compared to Group 2 and controls (p = 0.0017). ROC analysis identified a cut-off value of 7.8 ng/mg for live birth prediction (AUC = 0.72, sensitivity 74%, specificity 75%). Multivariable analysis confirmed NF-κB is an independent predictor of live birth (p = 0.045). Histological findings revealed increased NF-κB staining in luminal and glandular epithelial cells in the thin endometrium group. Conclusions: Increased endometrial NF-κB expression is associated with thin endometrium and reduced live birth rates in RIF patients. NF-κB may serve not only as a biomarker of pathological inflammation but also as a prognostic tool for treatment stratification in IVF. Based on findings in the literature, the therapeutic targeting of NF-κB may represent a promising strategy to improve implantation outcomes. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Gynecological and Obstetric Diseases)
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16 pages, 857 KiB  
Review
The Role of Tissue Factor-Positive Microparticles in Gynecological Cancer-Associated Disseminated Intravascular Coagulation: Molecular Mechanisms and Clinical Implications
by Muqaddas Qureshi, Muhammad Tanveer Alam and Ahsanullah Unar
Onco 2025, 5(3), 33; https://doi.org/10.3390/onco5030033 - 10 Jul 2025
Viewed by 283
Abstract
Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF+ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles [...] Read more.
Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF+ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF+ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF+ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF+ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF+ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF+ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF+ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article
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19 pages, 3069 KiB  
Article
Identification of Common Hub Genes in COVID-19 and Comorbidities: Insights into Shared Molecular Pathways and Disease Severity
by Suresh Kumar, Jia-Jin Wee and K. J. Senthil Kumar
COVID 2025, 5(7), 105; https://doi.org/10.3390/covid5070105 - 8 Jul 2025
Viewed by 332
Abstract
Severe COVID-19 disproportionately impacts patients with comorbidities such as type 1 diabetes (T1D), type 2 diabetes (T2D), obesity (OBCD), cardiovascular disease (CVD), hypertension (HTN), and cerebrovascular disease (CeVD), affecting 10–30% of cases. This study elucidates shared molecular mechanisms by identifying common hub genes [...] Read more.
Severe COVID-19 disproportionately impacts patients with comorbidities such as type 1 diabetes (T1D), type 2 diabetes (T2D), obesity (OBCD), cardiovascular disease (CVD), hypertension (HTN), and cerebrovascular disease (CeVD), affecting 10–30% of cases. This study elucidates shared molecular mechanisms by identifying common hub genes and genetic variants across these conditions using an integrative bioinformatics approach. We curated 5463 COVID-19-related genes from DisGeNET, GeneCards, T-HOD, and other databases, comparing them with gene sets for T1D (324 genes), T2D (497), OBCD (835), CVD (1756), HTN (837), and CeVD (1421). Functional similarity analysis via ToppGene, hub gene prediction with cytoHubba, and Cytoscape-based protein–protein interaction networks identified four hub genes—CCL2, IL6, IL10, and TLR4—consistently shared across all conditions (p < 1.0 × 10−5). Enrichr-based gene ontology and KEGG analyses revealed cytokine signaling and inflammation as key drivers of COVID-19 cytokine storms. Polymorphisms like IL6 rs1800795 and TLR4 rs4986790 contribute to immune dysregulation, consistent with previous genomic studies. These genes suggest therapeutic targets, such as tocilizumab for IL6-driven inflammation. While computational, requiring biochemical validation, this study illuminates shared pathways, advancing prospects for precision medicine and multi-omics research in high-risk COVID-19 populations. Full article
(This article belongs to the Section Host Genetics and Susceptibility/Resistance)
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24 pages, 543 KiB  
Systematic Review
The Impact of Physical Activity on Suicide Attempt in Children: A Systematic Review
by Marissa Patel, Grace Branjerdporn and Sabine Woerwag-Mehta
Children 2025, 12(7), 890; https://doi.org/10.3390/children12070890 - 6 Jul 2025
Viewed by 360
Abstract
Suicide in children is a major global health crisis, with profound impacts on families, friends, and society. Understanding ways to ameliorate the rate of suicide attempt (SA) is critical given that it is a key factor in predicting future suicide risk. SA is [...] Read more.
Suicide in children is a major global health crisis, with profound impacts on families, friends, and society. Understanding ways to ameliorate the rate of suicide attempt (SA) is critical given that it is a key factor in predicting future suicide risk. SA is the deliberate act of causing physical injury to oneself with the intent of death. The incidence of SA may be influenced by physical activity (PA). PA includes bodily movement via skeletal muscles that results in energy expenditure and physical fitness. While there is evidence to suggest that PA improves dysregulation of the parasympathetic nervous system which underpins the physiology of suicidal behaviour, evaluating the impact of PA on SA in children is required. Objectives: This systematic review aims to determine the relationship between PA and SA in children to inform alternative preventative and interventional strategies. Methods: This systematic review was registered with PROSPERO: CRD42023389415. Eight electronic databases were systematically searched. References were transferred to Covidence software for title and abstract screening and full text review were performed based on eligibility criteria: (1) children aged 6–18 years old; (2) participated in PA (individual, group exercise, or team sports); and (3) examined SA as a dependent variable. The JBI Checklist was used to measure the quality and level of bias of included studies. Results: Of the 2322 studies identified, 21 were included in the final analysis of the review. Twenty studies were cross-sectional in design, and one implemented a prospective study design. Thirteen studies (61.9%) yielded statistically significant results, indicating that increased PA, particularly team sport, may be associated with reduced odds of SA. There was some evidence to suggest that certain intensities and frequencies of PA may be beneficial to some and detrimental to other subgroups. Conclusions: The results suggest that PA may reduce the risk of suicide attempts. Although PA may be associated with reduced SA in children, future research is required, which (1) uses standardised outcome variables; (2) adopts longitudinal and experimental study designs; (3) explores qualitative research to determine distinctive factors that influence participation in PA not captured by quantitative research; and (4) examines different target populations such as children with a broad range of mental health issues. Full article
(This article belongs to the Section Global Pediatric Health)
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