The rapid progress of multidrug-resistant (MDR) bacterial infections and the clinical aggressiveness of triple-negative breast cancer (TNBC) possess a great problem to human beings. It necessitates the discovery and development of multifunctional therapeutic biomaterials. Herein, we report two enzymatically stable short cationic peptide hydrogelators comprising of N-terminal lysine headgroups, non-coded amino acid spacers, aromatic phenylalanine residues, and dodecylamine tails. These amphiphilic peptides are rapidly self-assembled in Tris-HCl buffer (pH 7.4) to form hydrogels with nanofibrillar network. Remarkably, both of these hydrogelators exhibit potent antibacterial activity against several Gram-positive and Gram-negative drug-resistant strains, functioning through multitiered mechanism including membrane permeabilization, trans-membrane depolarization, and intracellular reactive oxygen species (ROS) generation. Moreover, one of these peptide amphiphiles demonstrates a significant anticancer efficacy (with IC50 value of 6.9 µM) against human TNBC cells by activating the extrinsic caspase-8/caspase-3-driven apoptotic pathway and reversing epithelial-to-mesenchymal transition (EMT). Interestingly, the peptide with centrally located amino acid residue with lesser number of methylene units than that of the other peptide shows better anticancer efficacy and less antimicrobial activity. This study vividly demonstrates a tunable class of proteolytically stable amphiphilic peptide gelators with potential antimicrobial as well as anticancer activities establishing a structure-function relationship of these bioactive peptide scaffolds suggesting a versatile blueprint for peptide-based next-generation soft bioactive materials.

Targeted therapy for BRAF V600E mutant papillary craniopharyngioma (PCP) has been rapidly accepted, though given the rarity of the tumor, there is limited guidance for appropriate use. Here, we retrospectively evaluated current practice patterns for the implementation of targeted therapeutics and their outcomes in the treatment of papillary craniopharyngioma (PCP).

Peritoneal metastases remain a major therapeutic challenge in gastric cancer. PERISCOPE II provided the first direct randomised comparison of an integrated operative strategy with continued systemic therapy in patients selected for limited peritoneal disease. Gastrectomy, cytoreductive surgery (CRS) and sequential heated oxaliplatin-normothermic docetaxel did not improve survival and caused substantial morbidity. The trial result should thus exclude routine adoption of that pathway, but it should not be interpreted as proof that every form of peritoneal-directed treatment is futile. Its multicomponent intervention was undertaken after brief systemic treatment, without mandatory laparoscopic confirmation of peritoneal response before randomisation, and frequently disrupted further systemic therapy. Meanwhile, DRAGON-01 has shown that repeated normothermic intraperitoneal paclitaxel can improve survival when added to systemic treatment, and STOPGAP has demonstrated the feasibility of serial laparoscopic reassessment and response-directed surgery in a Western pathway. Future trials should therefore separate two questions: whether intraperitoneal therapy adds benefit to contemporary biomarker-directed systemic treatment, and whether operative consolidation benefits the exceptional responders thereby identified. Surgery should become the consequence of demonstrated systemic and peritoneal response, not the intervention used to discover it.

Microsatellite instability (MSI) is a key biomarker for immunotherapy in gastric cancer (GC), but preoperative non-invasive prediction remains challenging. Radiomics is promising; however, a systematic evaluation of its diagnostic performance with explicit consideration of overfitting and model comparison is lacking.

Transformation of vestibular schwannoma (VS) into malignant peripheral nerve sheath tumor (MPNST) is rare and poorly characterized. We have synthesized available evidence from the literature to define clinical features, transformation patterns, management strategies, and survival outcomes in patients with MPNST after histologically confirmed transformation from VS.

Doxorubicin (Dox) remains a cornerstone chemotherapeutic for hepatocellular carcinoma (HCC), yet its efficacy is constrained by systemic toxicity and intrinsic chemoresistance. Nanocarrier systems are proposed to overcome these limitations. This study aimed to develop and evaluate a chitosan-silver nanoparticle (Cs-AgNPs) system as a Dox delivery vehicle in HepG2 cells. Cs-AgNPs+Dox nanoparticles were synthesized and characterized by FTIR, XRD, and SEM. Drug-loading efficiency, release kinetics, and cytotoxicity were assessed and compared with those of free Dox. The modulation of PI3K/AKT/mTOR, NF-κB, autophagy, and apoptosis pathways was investigated using RT-qPCR and Western blotting. The formulation produced spherical, stable nanoparticles with high encapsulation efficiency and sustained release. Unexpectedly, at sub-toxic concentrations (6.25-50 µg/mL), Cs-AgNPs+Dox exhibited significantly lower cytotoxicity than free Dox. Mechanistic studies revealed strong activation of the PI3K/AKT/mTOR and NF-κB signaling cascades, accompanied by upregulation of autophagy markers (LC3, Beclin1) and reduced Caspase-3 expression. These findings indicate that the nanocarrier itself induces a pro-survival, chemoresistant phenotype in HepG2 cells. Cs-AgNPs is not an inert carrier but an active biological modulator that can antagonize Dox-induced cytotoxicity by stimulating key survival and autophagy pathways. This work underscores the importance of assessing the intrinsic bioactivity of metallic polymer hybrid nanocarriers, as their inadvertent compromise of therapeutic efficacy is a concern. Future optimization should integrate pathway-specific inhibitors to mitigate nanocarrier-induced resistance.

Creating a frozen section slide and crafting an interpretation is a multistep process with multiple possible points of failure. Head and neck frozen section pathology presents particular technical and diagnostic challenges. The aim of our study was to identify discrepancies between head/neck intraoperative and final diagnoses, determine the site of process failure, and assess the potential causes.

Patients with AML have a poor prognosis due to recurrence and high-risk genetic factors. lncRNA OIP5-AS1 exhibits differential expression among AML patients with varying genetic risks. The aim of this study is to examine the clinical value and regulation mechanisms of OIP5-AS1 in AML. RT-qPCR was used to evaluate the OIP5-AS1, miR-15a-5p, and FOXO1 levels in patients with AML and cells, as well as the mRNA levels of Bcl-2, Bax, and Caspase-3 in AML cell. The CCK-8 test was employed to measure cell proliferation. Apoptosis rates were detected by flow cytometry. DLR experiments validated the interaction between OIP5-AS1, miR-15a-5p, and FOXO1. Compared with the controls, AML patients exhibited notably elevated levels of OIP5-AS1 and FOXO1, along with markedly reduced miR-15a-5p expression. Furthermore, OIP5-AS1 levels effectively differentiate patients with AML from controls. Patients in the high OIP5-AS1 level group exhibited lower 5-year survival rates. Knockdown of OIP5-AS1 elevated miR-15a-5p levels, reduced cell proliferation capacity, and notably increased apoptosis. Furthermore, FOXO1, as a target gene of miR-15a-5p, showed a positive correlation with OIP5-AS1 level and a negative correlation with miR-15a-5p level. OIP5-AS1 exhibits significant diagnostic and prognostic value in AML, showing promise as a novel clinical biomarker. Knockdown of OIP5-AS1 leads to upregulation of miR-15a-5p level, thereby influencing proliferation and apoptosis processes in AML cells. This mechanism may provide a new therapeutic target for improving the prognosis of AML patients.

Evidence regarding treatment intensity, tolerability, and outcomes of using trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BV) in older patients with metastatic colorectal cancer (mCRC) is limited. We compared relative dose intensity (RDI), toxicity, and survival between FTD/TPI monotherapy and FTD/TPI plus BV, and examined the relationship between RDI and overall survival (OS) in older patients.

Although cytarabine remains a cornerstone chemotherapeutic agent for Acute lymphoblastic leukemia (ALL), its clinical efficacy is frequently compromised by systemic toxicity and resistance mechanisms, notably telomerase activation via hTERT upregulation. This study investigates the synergistic potential of Zataria multiflora extract (ZME) combined with cytarabine to induce apoptosis in pre-B ALL cells (NALM-6) and explores the underlying molecular mechanisms.

Bladder cancer remains a major global health challenge, necessitating rigorous endoscopic surveillance and the precise identification of neoplastic lesions. While the detection of overt tumors is routine, achieving high specificity and distinguishing borderline tumor structures are critical for optimal clinical decision-making. This is especially vital given the rapid evolution of intravesical therapies for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Recent clinical advancements with novel agents-such as gemcitabine-releasing intravesical systems (TAR-200), nadofaragene firadenovec, and the IL-15 superagonist complex (N-803)-fundamentally require a clinically "tumor-free" state through complete resection to ensure maximum therapeutic efficacy. This study presents an advanced artificial intelligence (AI) system developed, utilizing a SE-ResNeXt-50 architecture to automate the classification of papillary bladder tumors from cystoscopic still images. To ensure transparency, Grad-CAM analysis was employed, revealing that the model prioritizes key morphological tumor features. Although background artifacts like air bubbles or mesh-like structures occasionally influence the signal, the system maintains high diagnostic reliability. Our findings suggest that this deep learning framework provides robust decision support, facilitating the rigorous complete resection necessary for successful intervention with next-generation intravesical agents.

PSA density (PSAD) may improve detection of clinically significant prostate cancer (csPCa) by normalizing PSA for prostate volume. Current practice applies a uniform PSAD threshold of 0.15 ng/ml/cm³; however, whether this approach performs adequately across prostate volumes remains unclear. This study evaluated the diagnostic performance of PSAD for csPCa and investigated the influence of age and prostate volume on its accuracy.

Acquired resistance to endocrine therapy poses a major limitation in the treatment of estrogen receptor (ER)-positive breast cancer (BC). Somatic mutations of the ESR1 gene, which encodes ERα, are one of the key resistance mechanisms. However, the effect of mutations and especially double mutations on the binding of novel drugs remains insufficiently understood. To evaluate the effect of the mutations at the molecular level, a comprehensive computational approach was employed, including molecular docking, binding free energy calculations (MM-GBSA), and molecular dynamics simulations. A comparative analysis revealed opposite effects of ESR1 mutations on affinities of various selective ER degraders (SERDs). Vepdegestrant and fulvestrant were found to bind far less efficiently with ERα mutants and especially double mutants (e.g., Y537C/D538G) than with the native ERα. In contrast, the SERD ZB716 demonstrated the same or even better binding with most mutants. A potential structural cause of its resilience to mutations was identified via a comprehensive analysis, which included the evaluation of individual amino acid residue mobility through root-mean-square fluctuation (RMSF) calculations and an assessment of intermolecular hydrogen bond stability. ZB716 was shown to maintain a stable hydrogen bond with Glu353, and the bond was preserved in the ERα mutants. A lower stability of this key interaction was observed with fulvestrant. The findings elucidate the molecular mechanism of ESR1 mutation-driven resistance and support the promise of ZB716 as a compound capable of overcoming resistance conferred by a subset of the most common somatic ESR1 mutations in BC patients. The results justify the targeted design of new SERDs aimed at interacting with ERα mutants and outline an avenue of further research in the field of personalized therapy for ER+ BC.

The degradation of intracellular proteins is a fundamental biological process necessary for maintaining cellular homeostasis, controlling the cell cycle, regulating signal transduction, and preventing the accumulation of toxic protein aggregates. Disorders of the proteolytic systems are implicated in the pathogenesis of numerous human diseases, including neurodegenerative diseases, lysosomal storage disorders, metabolic disorders, and certain types of cancer. The development of rudimentary and cost-effective models of these diseases for the purpose of evaluating novel pharmaceutical agents and elucidating the molecular mechanisms underlying disease pathogenesis constitutes a pivotal medical and biological undertaking. The proteolytic apparatus of the yeast species Saccharomyces cerevisiae has become a biochemical model organism of significant importance. This is due to its well-studied nature, low cost, ease of genetic manipulation, and evolutionary conservatism. The mechanisms of proteolytic system dysfunction can be studied in this organism. Furthermore, therapeutic approaches aimed at correcting these dysfunctional mechanisms can be sought.

The history of research on lactate is quite interesting. At first, it was considered an unnecessary product of glycolysis, which humans use only by converting it back into glucose (gluconeogenesis, Cori cycle). Then it turned out that it is a ready-made source of food for cells and, moreover, that some cells (neurons) may prefer it to glucose. Lactate receptors were discovered, and it became a regulator. Finally, in 2019 (after more than 200 years of study), the lactylation of histones and other proteins ( hundreds of targets) was discovered. Lactate became an epigenetic regulator. A single, very small molecule combines many functions. One of the main functions of interest to oncologists is that lactate, together with hypoxia, is a sign of supply dysfunction in the body and causes reactions aimed at normalization (angiogenesis, etc.). As a result, tumors, with the immune system silent, undergo "normalization," with blood vessels growing in them to reduce hypoxia and the lactate concentration. In addition, in the tumor microenvironment, where the concentration of lactate is dozens of times higher than normal, lactate acts as an immunosuppressant. In recent years, antitumor therapy has been reoriented from targeting tumor cells themselves to targeting immune cells (using "checkpoints"). Lactate has become one of the targets of such therapy. Various aspects of the molecular biology of lactate are covered in this review. Particular attention is paid to the role of lactate in antitumor therapy.

ObjectiveTo compare the clinical outcomes and hospitalization expenses of ligation-assisted endoscopic mucosal resection and endoscopic submucosal dissection for gastrointestinal deep-layer lesions measuring ≤1.0 cm.MethodsThis retrospective single-center cohort study included 486 patients with gastrointestinal deep-layer lesions detected using endoscopic ultrasonography. Eligible lesions measured ≤1.0 cm and were identified using endoscopic ultrasonography as originating from the muscularis mucosae, submucosa, or muscularis propria. Baseline characteristics and treatment outcomes were compared between the ligation-assisted endoscopic mucosal resection and endoscopic submucosal dissection groups before and after 1:1 propensity score matching. Multivariable ordinal logistic regression was performed to identify factors associated with hospitalization expense categories.ResultsAfter 1:1 propensity score matching, 336 patients were included in the matched cohort, with 168 patients in each group. No significant differences were observed in the en bloc resection rate, R0 resection status, incidence of procedure-related complications, duration of hemostatic drug use, and length of hospital stay between the ligation-assisted endoscopic mucosal resection and endoscopic submucosal dissection groups. Hospitalization expenses were significantly lower in the ligation-assisted endoscopic mucosal resection group than in the endoscopic submucosal dissection group after matching (renminbi 7900 (interquartile range, 6500-10,000) vs. 10,600 (interquartile range, 8700-13,200); p < 0.001). In adjusted ordinal logistic regression analyses, ligation-assisted endoscopic mucosal resection remained significantly associated with lower hospitalization expense categories in both primary adjusted model without actual length of hospital stay (adjusted odds ratio, 3.52; 95% confidence interval: 2.34-5.29; p < 0.001) and the sensitivity model further adjusted for actual length of hospital stay (adjusted odds ratio, 3.31; 95% confidence interval: 2.17-5.06; p < 0.001).ConclusionsLigation-assisted endoscopic mucosal resection was associated with comparable short-term clinical outcomes and lower observed hospitalization expenses compared with endoscopic submucosal dissection in selected patients with gastrointestinal deep-layer lesions measuring ≤1.0 cm. Prospective multicenter studies with long-term follow-up are needed to confirm these findings.

Purpose To evaluate the added value of a synthetic radiomics model (S-Radiomics) that integrates topologic and Hessian-based features with traditional radiomic features for predicting a pathologic complete response (pCR) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Materials and Methods Patients with HER2-positive breast cancer from three centers were retrospectively included between January 2018 and January 2024. Patients from centers 1 and 2 (n = 201) were randomly assigned to training (n = 150) and internal testing (n = 51) sets, whereas patients from center 3 (n = 82) constituted external testing set I. An additional genomic set (n = 64, I-SPY 2) and external testing set II (n = 57, I-SPY 1) were used for independent validation. Multivariable logistic regression with all clinical variables was used to identify independent predictors (P < .05) and develop the clinical model, adjusting for potential confounders. Traditional radiomics model (T-Radiomics) and S-Radiomics were constructed. Performance was evaluated using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification index, and survival analysis. Results A total of 404 female patients with HER2-positive breast cancer (mean age ± SD, 50 years ± 9) were included. The S-Radiomics outperformed the T-Radiomics on both the internal (AUC, 0.86 vs 0.78; P = .37) and external test (AUC, 0.84 vs 0.73; P = .11) sets, with improvements in the integrated discrimination improvement (P = .24 and .01) and net reclassification index (P = .21 and .01). Shapley additive explanations analysis revealed topologic features as the most important predictors. For center 1, survival analysis revealed longer disease-free survival in predicted responders (P = .02). Conclusion The S-Radiomics outperformed the T-Radiomics in predicting pathologic complete responses in patients with HER2-positive breast cancer. Keywords: Radiogenomics, MRI, Breast, Human Epidermal Growth Factor Receptor 2, Breast Cancer, Neoadjuvant Chemotherapy, Pathologic Complete Response, Radiomics Supplemental material is available for this article. © RSNA, 2026.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is biologically and prognostically distinct from HPV-negative disease, and staging directly impacts treatment. The American Joint Committee on Cancer (AJCC) and Union for International Cancer Control version 9 TNM staging system incorporates unequivocal imaging-detected and/or clinically detected extranodal extension (iENE) into clinical nodal staging and definitive pathologic extranodal extension into pathologic nodal staging. Additionally, it provides more explicit anatomic definitions for advanced local disease (clinical T4) while maintaining T and M category definitions from the eighth edition. Radiologists play a central role in the multidisciplinary team by evaluating endophytic tumor extent, regional nodal disease and iENE, and distant metastasis using CT, MRI, and PET. This article reviews clinically relevant oropharyngeal anatomy and proposes a practical radiologic approach to assigning T, N, and M categories in HPV-associated OPSCC. It emphasizes cautious interpretation of iENE because of interreader variability and imperfect diagnostic performance, with further high-grade evidence needed to establish its consistently reproducible, incremental prognostic value as a clinical N category modifier. It also highlights multidisciplinary factors that guide selection of surgical resection versus nonsurgical therapy. Posttreatment evaluation is discussed in the context of blood-based biomarkers such as tumor tissue-modified viral HPV DNA. The goal of this article is to provide a practical, staging-focused imaging framework for evaluation of HPV-associated OPSCC. Keywords: CT, MR Imaging, Head/Neck, Neck, Pharynx, Surgery, Human Papillomavirus, Squamous Cell Carcinoma, Oropharynx, Transoral Robotic Surgery, Oropharyngeal Carcinoma, TTMV HPV DNA © RSNA, 2026.

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with a poor prognosis. However, the molecular mechanisms underlying CCA and its treatment options remain unclear and limited.

Tertiary lymphoid structures (TLS) have emerged as critical modulators of antitumor immunity in non-small cell lung cancer (NSCLC), with growing evidence supporting their role as both prognostic biomarkers and functional targets in neoadjuvant chemoimmunotherapy. TLS are organized ectopic lymphoid aggregates that facilitate local antigen presentation, T and B cell activation, and memory immune responses within the tumor microenvironment. Their presence and maturation status correlate with favorable clinical outcomes and enhanced responsiveness to immune checkpoint inhibitors. Despite these insights, several obstacles hinder clinical translation. Current approaches remain limited in dynamically monitoring TLS evolution during treatment, and the underlying immunoregulatory mechanisms-particularly interactions among immune subsets, stromal components, and tumor cells-are not fully elucidated. Additionally, translation faces challenges including inter-institutional variability, lack of standardized assessment criteria, and the need for multi-center prospective validation. Integrating multimodal technologies-high-plex imaging, spatial transcriptomics, and digital pathology-with AI-based platforms holds promise for refined TLS characterization and real-time monitoring. Near-term priorities include optimizing dynamic monitoring techniques and establishing standardized scoring systems. Medium-to-long-term priorities encompass multi-center trials to validate TLS utility across diverse populations, identify novel drivers of TLS formation, and develop optimized combinatorial immunotherapy regimens that leverage TLS as both predictive biomarkers and therapeutic targets. By bridging basic immunology and clinical oncology, TLS are poised to emerge as key regulatory nodes in precision cancer immunotherapy, which may catalyze a paradigm shift in the neoadjuvant NSCLC landscape, enabling a closed-loop management framework encompassing prediction, intervention, and dynamic efficacy optimization across the entire continuum of patient care.