Preparation of surface molecularly imprinted polymers with Fe3O4/ZIF-8 as carrier for detection of Dimethoate in cabbage.

In this study, molecularly imprinted polymers (MIPs) were prepared for the specific recognition of organophosphorus pesticides and a rapid, efficient and simple method was established for the detection of dimethoate (DIT) in food samples. Fe3O4 magnetic nanoparticles were synthesized by co-precipitation, and Fe3O4/ZIF-8 complexes were prepared by a modified in-situ polymerization method, and then magnetic molecularly imprinted polymers (MMIPs) were prepared and synthetic route was optimized by applying density functional theory (DFT). The morphological characterization showed that the MMIPs were coarse porous spheres with an average particle size of 50 nm. The synthesized materials are highly selective for the organophosphorus pesticide dimethoate with an adsorption capacity of 461.50 mg·g-1 and are effective resistance to matrix effects. A novel method for the determination of DIT in cabbage was developed using the prepared MMIPs in combination with HPLC. The practical results showed that the method can meet the requirements for the determination of DIT in cabbage with recoveries of 85.6-121.1 % and detection limits of 0.033 µg·kg-1.

Stereo effects for efficient synthesis of orange-red multiple resonance emitters centered on a pyridine ring.

Despite theoretical difficulties, we herein demonstrate an effective strategy for the inaugural synthesis of an orange-red multiple resonance (MR) emitter centered on a pyridine ring via stereo effects. Compared to conventional benzene-centered materials, the pyridine moiety in the novel MR material acts as a co-acceptor. This results in a significant spectral redshift and a narrower spectrum, as well as an improved photoluminescence quantum yield (PLQY) due to the formation of intramolecular hydrogen bonds. As envisioned, the proof-of-concept emitter Py-Cz-BN exhibits bright orange-red emission peaking at 586 nm with a small full width at half maximum (FWHM) of 0.14 eV (40 nm), exceeding both the wavelength and FWHM achieved with benzene-centered BBCz-Y. Benefiting from high PLQYs (>92%) and suppressed chromophore interactions, the optimized organic light-emitting diodes achieved high maximum external quantum efficiencies of 25.3-29.6%, identical small FWHMs of 0.18 eV (54 nm), and long lifetimes over a wide range of dopant concentrations (1-15 wt%). The performance described above demonstrates the effectiveness of this molecular design and synthesis strategy in constructing high performance long-wavelength MR emitters.

CAEVR: Biosignals-Driven Context-Aware Empathy in Virtual Reality.

There is little research on how Virtual Reality (VR) applications can identify and respond meaningfully to users' emotional changes. In this paper, we investigate the impact of Context-Aware Empathic VR (CAEVR) on the emotional and cognitive aspects of user experience in VR. We developed a real-time emotion prediction model using electroencephalography (EEG), electrodermal activity (EDA), and heart rate variability (HRV) and used this in personalized and generalized models for emotion recognition. We then explored the application of this model in a context-aware empathic (CAE) virtual agent and an emotion-adaptive (EA) VR environment. We found a significant increase in positive emotions, cognitive load, and empathy toward the CAE agent, suggesting the potential of CAEVR environments to refine user-agent interactions. We identify lessons learned from this study and directions for future work.

Site-specific albumin tagging with NIR-II fluorogenic dye for high-performance and super-stable bioimaging.

Synthetic near-infrared-II (NIR-II) dyes are promising for deep tissue imaging, yet they are generally difficult to target a given biomolecule with high specificity. Furthermore, the interaction mechanism between albumin and cyanine molecules, which is usually regarded as uncertain "complexes" such as crosslinked nanoparticles, remains poorly understood. Methods: Here, we propose a new class of NIR-II fluorogenic dyes capable of site-specific albumin tagging for in situ albumin seeking/targeting or constructing high-performance cyanine@albumin probes. We further investigate the interaction mechanism between NIR-II fluorogenic dyes and albumin. Results: We identify CO-1080 as an optimal dye structure that produces a stable/bright NIR-II cyanine@albumin probe. CO-1080 exhibits maximum supramolecular binding affinity to albumin while catalyzing their covalent attachment. The probe shows exact binding sites located on Cys476 and Cys101, as identified by proteomic analysis and docking modeling. Conclusion: Our cyanine@albumin probe substantially improves the pharmacokinetics of its free dye counterpart, enabling high-performance NIR-II angiography and lymphography. Importantly, the site-specific labeling tags between NIR-II fluorogenic dyes and albumin occur under mild conditions, offering a specific and straightforward synthesis strategy for NIR-II fluorophores in the fields of targeting bioimaging and imaging-guided surgery.

Ultrasound-Base Radiomics for Discerning Lymph Node Metastasis in Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: Ultrasound is the imaging modality of choice for preoperative diagnosis of lymph node metastasis (LNM) in thyroid cancer (TC), yet its efficacy remains suboptimal. As radiomics gains traction in tumor diagnosis, its integration with ultrasound for LNM differentiation in TC has emerged, but its diagnostic merit is debated. This study assesses the accuracy of ultrasound-integrated radiomics in preoperatively diagnosing LNM in TC. METHODS: Literatures were searched in PubMed, Embase, Cochrane, and Web of Science until July 11, 2023. Quality of the studies was assessed by the radiomics quality score (RQS). A meta-analysis was executed using a bivariate mixed effects model, with a subgroup analysis based on modeling variables (clinical features, radiomics features, or their combination). RESULTS: Among 27 articles (16,410 TC patients, 6356 with LNM), the average RQS was 16.5 (SD:5.47). Sensitivity of the models based on clinical features, radiomics features, and radiomics features plus clinical features were 0.64, 0.76 and 0.69. Specificities were 0.77, 0.78 and 0.82. SROC values were 0.76, 0.84 and 0.81. CONCLUSION: Ultrasound-based radiomics effectively evaluates LNM in TC preoperatively. Adding clinical features does not notably enhance the model's performance. Some radiomics studies showed high bias, possibly due to the absence of standard application guidelines.

Mitochondria-targetable small molecule fluorescent probes for the detection of cancer-associated biomarkers: A review.

Cancer represents a global threat to human health, and effective strategies for improved cancer early diagnosis and treatment are urgently needed. The detection of tumor biomarkers has been one of the important auxiliary means for tumor screening and diagnosis. Mitochondria are crucial subcellular organelles that produce most chemical energy used by cells, control metabolic processes, and maintain cell function. Evidence suggests the close involvement of mitochondria with cancer development. As a consequence, the identification of cancer-associated biomarker expression levels in mitochondria holds significant importance in the diagnosis of early-stage diseases and the monitoring of therapy efficacy. Small-molecule fluorescent probes are effective for the identification and visualization of bioactive entities within biological systems, owing to their heightened sensitivity, expeditious non-invasive analysis and real-time detection capacities. The design principles and sensing mechanisms of mitochondrial targeted fluorescent probes are summarized in this review. Additionally, the biomedical applications of these probes for detecting cancer-associated biomarkers are highlighted. The limitations and challenges of fluorescent probes in vivo are also considered and some future perspectives are provided. This review is expected to provide valuable insights for the future development of novel fluorescent probes for clinical imaging, thereby contributing to the advancement of cancer diagnosis and treatment.

B-N Covalent Bond Embedded Double Hetero-[n]helicenes for Pure Red Narrowband Circularly Polarized Electroluminescence with High Efficiency and Stability.

Chiral B/N embedded multi-resonance (MR) emitters open a new paradigm of circularly polarized (CP) organic light-emitting diodes (OLEDs) owing to their unique narrowband spectra. However, pure-red CP-MR emitters and devices remain exclusive in literature. Herein, by introducing a B-N covalent bond to lower the electron-withdrawing ability of the para-positioned B-π-B motif, the first pair of pure-red double hetero-[n]helicenes (n = 6 and 7) CP-MR emitter peaking 617 nm with a small full-width at half-maximum of 38 nm and a high photoluminescence quantum yield of ≈100% in toluene is developed. The intense mirror-image CP light produced by the enantiomers is characterized by high photoluminescence dissymmetry factors (gPL ) of +1.40/-1.41 × 10-3 from their stable helicenes configuration. The corresponding devices using these enantiomers afford impressive CP electroluminescence dissymmetry factors (gEL ) of +1.91/-1.77 × 10-3 , maximum external quantum efficiencies of 36.6%/34.4% and Commission Internationale de I'Éclairage coordinates of (0.67, 0.33), exactly satisfying the red-color requirement specified by National Television Standards Committee (NTSC) standard. Notably a remarkable long LT95 (operational time to 95% of the initial luminance) of ≈400 h at an initial brightness of 10,000 cd m-2 is also observed for the same device, representing the most stable CP-OLED up to date.

Carbonyl- and Nitrogen-Embedded Multi-Resonance Emitter with Ultra-Pure Green Emission and High Electroluminescence Efficiencies.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters with narrow emission spectra have garnered significant attention in future organic light-emitting diode (OLED) displays. However, current C=O/N-embedded MR-TADF systems still lack satisfactory performance in terms of electroluminescence bandwidths and external quantum efficiencies (EQEs). In this study, a C=O/N-embedded green MR-TADF emitter, featuring two acridone units incorporated in a sterically protected 11-ring fused core skeleton, is successfully synthesized through finely controlling the reaction selectivity. The superior combination of multiple intramolecular fusion and steric wrapping strategies in the design of the emitter not only imparts an extremely narrow emission spectrum and a high fluorescence quantum yield to the emitter but also mitigates aggregation-induced spectral broadening and fluorescence quenching. Therefore, the emitter exhibits leading green OLED performance among C=O/N-based MR-TADF systems, achieving an EQE of up to 37.2 %, a full width at half maximum of merely 0.11 eV (24 nm), and a Commission Internationale de l'Éclairage coordinate of (0.20, 0.73). This study marks a significant advance in the realization of ideal C=O/N-based MR-TADF emitters and holds profound implications for the design and synthesis of other MR-TADF systems.

Comparing iodized oil with polyvinyl alcohol for portal vein embolization in promoting liver remnant increase before partial hepatectomy.

BACKGROUND: To compare the efficacy and safety of iodized oil versus polyvinyl alcohol (PVA) particles in portal vein embolization (PVE) before partial hepatectomy. METHODS: From October 2016 to December 2021, 86 patients who planned to undergo hepatectomy after PVE were enrolled, including 61 patients post-PVE with PVA particles + coils and 25 patients post-PVE with iodized oil + coils. All patients underwent CT examination before and 2-3 weeks after PVE to evaluate the future liver remnant (FLR). The intercohort comparison included the degree of liver volume growth, changes in laboratory data, and adverse events. RESULTS: There was no significant difference in the resection rate between the iodized oil group and the PVA particle group (68 % vs. 70 %, p = 0.822). In terms of the degree of hypertrophy (9.52 % ± 13.47 vs. 4.03 % ± 10.55, p = 0.047) and kinetic growth rate (4.07 % ± 5.4 vs. 1.55 % ± 4.63, p = 0.032), the iodized oil group was superior to the PVA group. The PVE operation time in the PVA particle group was shorter than that in the iodized oil group (121. 72 min ± 34.45 vs. 156. 2 min ± 71.58, p = 0.029). There was no significant difference in the degree of hypertrophy between the high bilirubin group and the control group (5.32 % ± 9.21 vs. 6.1 % ± 14.79, p = 0.764). Only 1 patient had a major complication. CONCLUSIONS: Compared with PVA particles, iodized oil PVE can significantly increase liver volume and the degree of hypertrophy without any significant difference in safety.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

An Ideal Molecular Construction Strategy for Ultra-Narrow-Band Deep-Blue Emitters: Balancing Bathochromic-Shift Emission, Spectral Narrowing, and Aggregation Suppression.

Narrowband emissive multiple resonance (MR) emitters promise high efficiency and stability in deep-blue organic light-emitting diodes (OLEDs). However, the construction of ideal ultra-narrow-band deep-blue MR emitters still faces formidable challenges, especially in balancing bathochromic-shift emission, spectral narrowing, and aggregation suppression. Here, DICz is chosen, which possesses the smallest full-width-at-half-maximum (FWHM) in MR structures, as the core and solved the above issue by tuning its peripheral substitution sites. The 1-substituted molecule Cz-DICz is able to show a bright deep-blue emission with a peak at 457 nm, an extremely small FWHM of 14 nm, and a CIE coordinate of (0.14, 0.08) in solution. The corresponding OLEDs exhibit high maximum external quantum efficiencies of 22.1%-25.6% and identical small FWHMs of 18 nm over the practical mass-production concentration range (1-4 wt.%). To the best of the knowledge, 14 and 18 nm are currently the smallest FWHM values for deep-blue MR emitters with similar emission maxima under photoluminescence and electroluminescence conditions, respectively. These discoveries will help drive the development of high-performance narrowband deep-blue emitters and bring about a revolution in OLED industry.

Precise Regulation of Multiple Resonance Distribution Regions of a B,N-Embedded Polycyclic Aromatic Hydrocarbon to Customize Its BT2020 Green Emission.

Recently, boron (B)/nitrogen (N)-embedded polycyclic aromatic hydrocarbons (PAHs), characterized by multiple resonances (MR), have attracted significant attention owing to their remarkable features of efficient narrowband emissions with small full width at half maxima (FWHMs). However, developing ultra-narrowband pure-green emitters that comply with the Broadcast Service Television 2020 (BT2020) standard remains challenging. Precise regulation of the MR distribution regions allows simultaneously achieving the emission maximum, FWHM value, and spectral shape that satisfy the BT2020 standard. The proof-of-concept molecule TPABO-DICz exhibited ultrapure green emission with a dominant peak at 515 nm, an extremely small FWHM of 17 nm, and Commission Internationale de l'Eclairage (CIE) coordinates of (0.17, 0.76). The corresponding bottom-emitting organic light-emitting diode (OLED) exhibited a remarkably high CIEy value (0.74) and maximum external quantum efficiency (25.8 %). Notably, the top-emitting OLED achieved nearly BT2020 green color (CIE: 0.14, 0.79) and exhibited a state-of-the-art maximum current efficiency of 226.4 cd A-1 , thus fully confirming the effectiveness of the above strategy.

Application of simple ultrasound Doppler hemodynamic parameters in the diagnosis of severe renal artery stenosis in routine clinical practice.

Background: Doppler ultrasound (DUS) is recommended in first-line imaging for the diagnosis of renal artery stenosis (RAS). However, the correct selection of Doppler direct or indirect parameters and their optimal thresholds remain controversial. This study explored simple ultrasound Doppler parameters to diagnose severe RAS (RAS ≥70%) in routine clinical practice. Methods: In this retrospective study, patients with clinically suspected renovascular hypertension who first underwent renal artery DUS and contrast-enhanced ultrasound (CEUS) and subsequent digital subtraction angiography (DSA) or computed tomography angiography (CTA) were consecutively included. Clinical characteristics and ultrasound Doppler hemodynamic parameters were collected, including peak systolic velocity (PSV), the ratio of the peak velocities in the renal artery and the aorta (RAR), the ratio of the peak velocities in the renal artery and the segmental artery (RSR), and the ratio of the peak velocities in the renal artery and the interlobar artery (RIR). All enrolled patients were divided into two groups based on the degree of diameter reduction: a severe stenosis group (diameter reduction ≥70%) and a non-severe stenosis group (diameter reduction <70%). Logistic regression analysis was performed to determine the independent predictors for severe stenosis. Receiver operating characteristic curves and areas under the curve were used to evaluate the diagnostic performance of the ultrasound Doppler parameters. Results: A total of 85 patients (106 renal arteries) with RAS were included in this study. The optimal thresholds of PSV in the main renal artery and the PSV ratios for diagnosing severe RAS obtained via receiver operating characteristic curves were 249.5 cm/s for PSV, 2.94 for RAR, 5.1 for RSR, and 7.5 for RIR. The areas under the curve of PSV and the ratios all exhibited good diagnostic efficiency (all >0.8). The combination of these four Doppler variables demonstrated a significant benefit to the overall diagnostic value compared with any factor alone [area under the curve (AUC) =0.962; 95% confidence interval (CI): 0.906-0.989; P<0.05]. The combination of PSV and RSR (AUC =0.925; 95% CI: 0.858-0.967) exhibited comparable diagnostic efficiency to the combination of four ultrasonographic variables (z statistic =1.882; P=0.06). Conclusions: This simple and accurate method to evaluate severe RAS based on the velocity obtained via basic DUS may facilitate the detection of severe RAS in the majority of medical institutions and provide a reliable basis for the selection of proper candidates for further angiography or revascularization.

How to More Effectively Obtain Ginsenoside Rg5: Understanding Pathways of Conversion.

Ginsenoside Rg5, a relatively uncommon secondary ginsenoside, exhibits notable pharmacological activity and is commonly hypothesized to originate from the dehydration of Rg3. In this work, we compared different conversion pathways using Rb1, R-Rg3 and S-Rg3 as the raw material under simple acid catalysis. Interestingly, the results indicate that the conversion follows this reaction activity order Rb1 > S-Rg3 > R-Rg3, which is contrary to the common understanding of Rg5 obtained from Rg3 by dehydration. Our experimental results have been fully confirmed by theoretical calculations and a NOESY analysis. The DFT analysis reveals that the free energies of S-Rg3 and R-Rg3 in generating carbocation are 7.56 mol/L and 7.57 mol/L, respectively, which are significantly higher than the free energy of 1.81 mol/L when Rb1 generates the same carbocation. This finding aligns with experimental evidence suggesting that Rb1 is more prone to generating Rg5 than Rg3. The findings from the nuclear magnetic resonance (NMR) analysis suggest that the fatty chains (C22-C27) in R-Rg3 and S-Rg3 adopt a Gauche conformation and an anti conformation with C16-C17 and C13-C17, respectively, due to the relatively weak repulsive van der Waals force. Therefore, the configuration of R-Rg3 is more conducive to the formation of intramolecular hydrogen bonds between 20C-OH and 12C-OH, whereas S-Rg3 lacks this capability. Consequently, this also explains the fact that S-Rg3 is more prone to dehydration to generate Rg5 than R-Rg3. Additionally, our research reveals that the synthetic route of Rg5 derived from protopanaxadiol (PPD)-type ginsenosides (including Rb1, Rb2, Rb3, Rc and Rd) exhibits notable advantages in terms of efficacy, purity and yield when compared to the pathway originating from Rg3. Moreover, this study presents a highly effective and practical approach for the extensive synthesis of Rg5, thereby facilitating the exploration of its pharmacological properties and potential application in drug discovery.

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study.

Aim: The purpose of this study is to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil and leucovorin (FOLFOX) plus lenvatinib and FOLFOX-HAIC alone in patients with unresectable cholangiocarcinoma. Patients & methods: Retrospective analysis of patients receiving FOLFOX-HAIC with or without lenvatinib. Results: Forty-one patients were included, with 22 patients receiving HAIC alone and 19 patients receiving HAIC plus lenvatinib. Combination treatment significantly prolonged overall survival and progression-free survival compared with HAIC alone. Grade 1-2 adverse events were more frequent in the combination group but manageable. No severe AEs or treatment-related deaths were reported. Conclusion: FOLFOX-HAIC plus lenvatinib has the potential to be a treatment option for unresectable cholangiocarcinoma.

This study compared the effectiveness and safety of two treatments for unresectable cholangiocarcinoma (CCA), a type of liver cancer. The first treatment involved a combination of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) and lenvatinib, a targeted therapy drug. The second treatment was FOLFOX-HAIC alone. The study included 41 patients with CCA, and the results showed that the group receiving FOLFOX-HAIC plus lenvatinib had significantly longer overall survival (32.0 months) and progression-free survival (20.0 months) compared with the group receiving FOLFOX-HAIC alone. The combination treatment had manageable side effects, although some mild adverse events were more common in the combination group. The study suggests that FOLFOX-HAIC plus lenvatinib could be a potential treatment option for unresectable CCA.

Site-specific albumin tagging with chloride-containing near-infrared cyanine dyes: molecular engineering, mechanism, and imaging applications.

Near-infrared dyes, particularly cyanine dyes, have shown great potential in biomedical imaging due to their deep tissue penetration, high resolution, and minimal tissue autofluorescence/scattering. These dyes can be adjusted in terms of absorption and emission wavelengths by modifying their chemical structures. The current issues with cyanine dyes include aggregation-induced quenching, poor photostability, and short in vivo circulation time. Encapsulating cyanine dyes with albumin, whether exogenous or endogenous, has been proven to be an effective strategy for improving their brightness and pharmacokinetics. In detail, the chloride-containing (Cl-containing) cyanine dyes have been found to selectively bind to albumin to achieve site-specific albumin tagging, resulting in enhanced optical properties and improved biosafety. This feature article provides an overview of the progress in the covalent binding of Cl-containing cyanine dyes with albumin, including molecular engineering methods, binding sites, and the selective binding mechanism. The improved optical properties of cyanine dyes and albumin complexes have led to cutting-edge applications in biological imaging, such as tumor imaging (diagnostics) and imaging-guided surgery.

Tailored Design of π-Extended Multi-Resonance Organoboron using Indolo[3,2-b]Indole as a Multi-Nitrogen Bridge.

Extending the π-skeletons of multi-resonance (MR) organoboron emitters can feasibly modulate their optoelectronic properties. Here, we first adopt the indolo[3,2-b]indole (32bID) segment as a multi-nitrogen bridge and develop a high-efficiency π-extended narrowband green emitter. This moiety establishes not only a high-yield one-shot multiple Bora-Friedel-Crafts reaction towards a π-extended MR skeleton, but a compact N-ethylene-N motif for a red-shifted narrowband emission. An emission peak at 524 nm, a small full width at half maximum of 25 nm and a high photoluminescence quantum yield of 96 % are concurrently obtained in dilute toluene. The extended molecular plane also results in a large horizontal emitting dipole orientation ratio of 87 %. A maximum external quantum efficiency (EQE) of 36.6 % and a maximum power efficiency of 135.2 lm/W are thereafter recorded for the corresponding device, also allowing a low efficiency roll-off with EQEs of 34.5 % and 28.1 % at luminance of 1,000 cd/m2 and 10,000 cd/m2 , respectively.

Hepatic arterial infusion chemotherapy plus lenvatinib with or without programmed cell death protein-1 inhibitors for advanced cholangiocarcinoma.

Background: New treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA. Methods: Between March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs). Results: Fifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5-42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia. Conclusion: HAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.

Ultra-Bright Heptamethine Dye Clusters Based on a Self-Adaptive Co-Assembly Strategy for NIR-IIb Biomedical Imaging.

Despite the wide range of applications of bright NIR-II polymethine scaffolds in biomedical imaging, their solvatochromism and aggregation-caused quenching (ACQ) effects in aqueous solutions limit their inherent brightness using traditional encapsulation methods, and effective hydrophilization strategies are still scarce. Here, a new set of Flav dyes is synthesized and PEGylated, followed by manufacturing DSPE@FlavP2000 nanoparticles using a self-adaptive co-assembly strategy to overcome these limitations. FlavP2000 can autonomously adjust its conformation when co-assembled with DSPE-PEG2000 , resulting in high-efficiency luminescence (≈44.9% fluorescence of Flav in DMSO). DSPE@FlavP2000 enables NIR-IIb (>1500 nm) angiography with high signal-to-noise ratios. Notably, this co-assembly can occur in situ between FlavP2000 with proteins in the living body based on a novel mechanism of brightness activation induced by disassembly (BAD), achieving consistent brightness as DSPE@FlavP2000 in blood or serum. The self-adaptive co-assembly strategy can be enhanced by incorporating an IPA moiety, which dynamically binds to albumin to prolong the dye's blood circulation time. Thus, the "enhanced" BAD is successfully applied to long-term vascular imaging and sciatic nerve imaging. Both the self-adaptive co-assembly strategy and BAD phenomenon improve the selectivity and availability of the hydrophilization methods, paving the way for efficient biological applications of polymethine dyes.