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关键词： Intrahepatic cholangiocarcinoma (ICC)   transarterial chemoembolization (TACE)   immune checkpoint inhibitors (ICIs)   single-cell analysis   prognostic factors  

摘要： Background: Mass-forming (MF) type is the most common, accounting for 57.1-83.6% of intrahepatic cholangiocarcinoma (ICC), with a poor prognosis. Transarterial chemoembolization (TACE) can induce necrosis of tumor cells, induce the release of tumor antigens, enhance the immune response of tumor-specific CD8+T cells, and regulate the proliferation of Treg cells. However, real-world data directly comparing TACE combined with programmed cell death protein-1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in MF-ICC are lacking. Therefore, we aimed to evaluate the efficacy and safety between the different immune checkpoint inhibitors (ICIs) (PD-1/PD-L1 inhibitors) in MF-ICC, and to explore prognosis-related clinical factors and preliminary immune mechanisms underlying this combined therapy. Methods: A total of 50 patients with MF-ICC who underwent TACE combined with ICIs at Beijing Friendship Hospital and Beijing Ditan Hospital from May 2020 to December 2024 were retrospectively enrolled. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the risk factors of overall survival (OS). Survival was estimated using the Kaplan-Meier method and compared by the log-rank test. Univariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between treatment regimen and survival. In parallel, we analyzed dynamic changes in immune cells before and after ICI treatment using the single-cell RNA sequencing dataset GSE208205 and further validated these findings by flow cytometry. Results: The median overall survival (mOS) and median progression-free survival (mPFS) for TACE-PD-L1 followed by therapy were 18 and 13 months, which were significantly longer than those with TACE-PD-1 sequential therapy (mOS: 12 months, HR: 0.42, 95% CI: 0.17-1.03, P=0.047;mPFS: 8 months, HR: 0.29, 95% CI: 0.12-0.7 3, P=0.006). In exploratory multivariable analysis, pre-treatment monocyte

关键词： Click chemistry   Iron sensor   Fluorescence spectroscopy   DFT study   Naphthalene  

摘要： Herein, synthesis, characterization and metal ion sensing of naphthalene linked 1,2,3-triazole chemosensor (5) synthesized by CuAAC approach is reported. The new molecule yielded a unique molecular architecture with potential applications as Fe2+ and Fe3+ ions sensor using fluorescence spectroscopy as well as naked eye detection. Ion sensing experiments revealed that, a prominent selective sensing of Fe2+ over Fe3+ ions by probe 5 without any interference from other cations was observed with 1:1 binding ratio for both probe 5-Fe2+ and probe 5-Fe3+ ions as determined by Job's plot method. The Limit of Detection (LOD) was calculated to be 82 nM and 1.8 nM for Fe2+ and Fe3+ ions, respectively. The DFT calculations were executed using B3LYP/6-311G++(d, p) for free probe and B3LYP/LANL2DZ for the associated metal complexes to elucidate binding interactions, confirming the metal-ligand interactions. The combined experimental and theoretical results provide an accurate detection framework for Fe2+/Fe3+ metal ions in environmental and biological samples.

关键词： HIV-1   protease inhibitors   drug resistance   CRF35-AD   molecular docking   molecular dynamics   saquinavir   amprenavir   treatment optimization  

摘要： Background: Drug resistance driven by protease (PR) gene mutations poses a major challenge to antiretroviral therapy (ART), particularly in regions such as Iran, where the HIV-1 CRF35-AD subtype predominates. Objectives: To characterize the prevalence, structural impact, and clinical associations of protease inhibitor (PI) resistance mutations in HIV-1 CRF35-AD among Iranian patients with virological failure. Methods: In this cross-sectional study, we analyzed 44 ART-experienced patients with viral loads > 1000 copies/mL in Hamadan, Iran (2020-2022). The PR gene was amplified using nested RT-PCR and subtyped via phylogenetic analysis. Drug resistance mutations (DRMs) were identified using Stanford HIVdb. Molecular docking and molecular dynamics (MD) simulations assessed structural effects on PI binding. Chi-square tests and logistic regression evaluated associations with clinical variables. Results: All sequences were confirmed as CRF35-AD. DRMs were detected in 93% of patients. Predominant mutations included R41K (95%), L89M (91%), L10I (36%), L19Q (36%), and L63V (27%). L19Q and L63V were significantly associated with resistance to atazanavir (P = 0.03) and darunavir (P = 0.04), respectively. Molecular docking showed reduced binding affinity to these PIs, while saquinavir and amprenavir retained strong interactions (Delta G: -9.5 to -10.2 kcal/mol). Molecular dynamics simulations further suggest that resistance-associated mutations promote increased conformational flexibility and reduced structural stability in protease-inhibitor complexes relative to the wild-type enzyme. Resistance was more common in younger women with mother-to-child transmission and prolonged ART exposure (P < 0.01). Conclusions: The high DRM burden in CRF35-AD highlights the need for routine genotypic resistance testing and subtype-tailored ART regimens. Saquinavir and amprenavir may remain viable options for patients with multi-PI resistance in CRF35-AD-endemic regions.

关键词： (1-0)-3 single crystal piezocomposite   Dual-piezo-charge mechanism   Hydrostatic figure of merit   Piezoelectric ultrasonic transducers   Acoustic sensitivity  

摘要： Piezoelectric ultrasonic transducers (PUTs) are extensively used in diverse technological fields, yet further enhancement in acoustic sensitivity and hydrostatic figure of merit d(h)g(h) have plateaued in conventional 1-3 piezocomposites, whose structures have remained largely unchanged for decades. Herein, we report a (1-0)-3 single-crystal piezocomposite (SCPC) based on the [011]-oriented Pb(In1/2Nb1/2)O-3-Pb(Mg1/3Nb2/3)O-3-PbTiO3 (PIN-PMN-PT) single-crystal, featuring a dual-piezo-charge (DPC) mechanism arising from the piezoelectric and piezoelectret synergy effect. The ordered and polar 0-phase microholes with aligned dipoles are intentionally introduced in 1-phase piezo-pillars, yielding a uniquely low effective dielectric constant, reduced acoustic impedance, and DPC properties unattainable in conventional SCPCs. Both Simulations and experiments confirm that this DPC mechanism in (1-0)-3 SCPC enables an ultrahigh d(h)g(h) of similar to 8089 x 10(-15) m(2) N-1, representing increases of 443.2% and 890.6% over commercial 1-3 SCPC and 1-3 piezoceramic composite, respectively. The engineered microhole structure and DPC strategy also significantly enhance underwater acoustic sensitivity while maintaining a broad - 3 dB bandwidth of 130 kHz, crucial for maritime safety and collision avoidance. Meanwhile, the long-term testing further verifies the PUT's operational stability. This design approach offers a promising pathway for next-generation piezocomposites and PUT technologies.

关键词： Non-small cell lung cancer (NSCLC)   neoadjuvant chemoimmunotherapy (NCIT)   tissue-resident memory T cells   spatial interaction   hypoxia-inducible factor-1 alpha (HIF-1 alpha)  

摘要： Background: Although neoadjuvant chemoimmunotherapy (NCIT) improves outcomes in resectable non-small cell lung cancer (NSCLC), traditional biomarkers like programmed death-ligand 1 (PD-L1) expression are insufficient for accurate patient selection. This study aimed to investigate the spatial interaction between specific T-cell subsets and PD-L1+ tumor cells using multiplex immunofluorescence (mIF), and to evaluate its value in predicting the efficacy of NCIT in NSCLC patients. Methods: We retrospectively recruited 44 patients with stage IIA-IIIB NSCLC who had NCIT at Shandong Cancer Hospital and Institute from January 2021 to June 2023. Pre-treatment specimens were subjected to multicolor immunofluorescence staining (panel 1: CK/PD-L1/PD-1/CD8/CD103/CD4/ FOXP3;panel 2: CK/CD8/CD4/alpha-SMA/CD31/HIF-1 alpha) to quantify PD-L1+ tumor cells and specific target T cells (CD4/conventional CD4/regulatory CD4, CD8/CD8+TRM/bystander CD8) and to delineate their spatial distribution. The Mann-Whitney U test, receiver operating characteristic (ROC) curves, and logistic regression were employed to examine the correlation between these indicators and treatment response. Spearman correlation analysis assessed their relationship with tumor microvasculature, cancer-associated fibroblasts (CAFs), and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Results: Among the 44 patients, 52.3% showed a response. Compared with non-responders, responders had closer distances between PD-L1+ tumor cells and CD8+ TRM, CD8, bystander CD8, conventional CD4, CD4, and regulatory CD4 prior to treatment, with decreasing area under the curve (AUC) values (0.728, 0.715, 0.680, 0.644, 0.643, 0.612). Further analysis of CD8+ TRM expressing programmed cell death 1 (PD-1) revealed that PD-1+ CD8+ TRM was the best predictor with an AUC of 0.743. Logistic regression analysis indicated that the closer PD-L1+ tumor cells were to CD8+ TRM, the better the treatment response [odds ratio (OR) =10.43, 95% confidence i

关键词： soil moisture estimation   hybrid physical-machine learning   Sentinel-1 SAR   Sentinel-2   ERA5-Land   perennial crops   citrus orchards   irrigation management   orchard-scale monitoring  

摘要： Accurate orchard-scale soil moisture information is a key requirement for efficient irrigation management in perennial crops such as citrus orchards, particularly in Mediterranean environments characterized by water scarcity and strong spatial and temporal variability in soil moisture, canopy structure, and irrigation scheduling. This study proposes a hybrid physical-machine learning methodology for soil moisture estimation that integrates in situ capacitance sensor measurements, Sentinel-1 SAR observations, Sentinel-2 optical imagery, and ERA5-Land agroclimatic variables. Physically based soil moisture estimates were first obtained through the inversion of Sentinel-1 backscatter using integral equation scattering models, a physically based soil dielectric model, and a simplified vegetation attenuation scheme. These physically derived estimates were subsequently incorporated as predictors within supervised machine learning models, together with multi-source remote sensing and meteorological variables. Several algorithms were evaluated, including regularized linear models, support vector regression, random forests, and gradient boosting methods. Model performance was assessed using a strict interannual validation strategy based on independent-year predictions to ensure robust generalization. Within this methodology, tree-based ensemble models achieved the highest and most consistent performance at the orchard scale, with coefficients of determination ranging from 0.55 to 0.76 and root mean square errors typically between 0.7 and 1.1% volumetric soil moisture in the best-performing cases. Benchmarking against a physical-only baseline demonstrated that the hybrid methodology consistently reduced prediction errors and improved temporal robustness under independent-year validation. Overall, the results demonstrate that hybrid physical-machine learning approaches provide a robust and scalable solution for orchard-scale soil moisture monitoring in irrigated citrus orchards

关键词： Colorectal cancer   Peroxiredoxin 1   Damage-associated molecular patterns   Pyroptosis   Gasdermin D  

摘要： This letter aims to comment on the paper by He et al, which investigated the role and mechanism of peroxiredoxin 1 (Prdx1) in colorectal cancer (CRC). In the original study, Prdx1 messenger RNA and protein levels were significantly increased in 60 clinical samples from CRC patients, in vitro cell experiments (RKO, SW480, HCT116 cells) and subcutaneous xenograft tumor mouse model. Recombinant Prdx1 (rPrdx1) inhibited the malignant behavior of RKO and SW480 cells, which was mechanistically shown to activate the NOD-like receptor thermal protein domain associated protein 3/caspase-1/gasdermin D (GSDMD) pathway to induce pyroptosis. Consequently, this pyroptosis-based anti-tumor activity effectively inhibited the growth of CRC xenografts in mice. We commend the study's scientific validity and innovation, the findings of which warrant further investigation into clinical translation, such as developing Prdx1/GSDMD co-expression markers and exploring rPrdx1-based combination therapies for advancing individualized CRC treatment.

摘要： The authors regret for any confusion that may have arisen for the reader. We recently discovered some errors in the transwell migration and invasion, when conducting a review of the original data and manuscripts. After a thorough review of the ori...

关键词： Q-fractional calculus   coupled system   implicit   controllability   Hyers-Ulam stability  

摘要： This paper deals with the controllability and Hyers-Ulam(HU) stability results of an implicit coupled fractional q-difference system with order alpha is an element of (1,2). By employing tools from fixed point theory, nonlinear functional analysis and the theory of q-calculus, we establish sufficient conditions for the existence and uniqueness of solutions, as well as controllability and stability criteria for the considered system. In particular, the Banach fixed point theorem is used to derive controllability results, while the Schauder fixed point theorem is applied to study the existence of at least one solution and HU stability. In the end, some illustrative examples are presented to demonstrate the applicability of the obtained theoretical results.