A universal strategy for constructing high-performance silica-based AIE materials for biomedical application.

As an emerging fluorophore, aggregation-induced emission luminogens (AIEgens) have received widespread attention in recent years, but the inherent drawbacks of AIEgens, such as the poor water-solubility and insufficient fluorescence stability in complex environments, restrict their performance in practical applications. Herein, we report a universal strategy based on hydrophobic dendritic mesoporous silica (HMSN) that can integrate different AIE molecules to construct multi-color fluorescent AIE materials. Specifically, HMSN with central radial pores was used as a powerful carrier for direct loading AIE molecules and restricting their intramolecular motions. Due to the pore-domain restriction effect and hydrophobic interaction, the obtained silica-based AIE materials have bright fluorescence with a maximum quantum yield of 68.38%, high colloidal/fluorescence stability, and excellent biosafety. Further, these silica-based AIE materials can be conjugated with functional antibodies to obtain probes with different targetability. After integration with immunomagnetic beads, the prepared detection probes achieved the quantitative detection of cardiac troponin I with the limit of detection (LOD) of 0.508 ng/mL. Overall, the targeting probes stemming from silica-based AIE materials can not only achieve cell-specific imaging, but quantify the number of Jurkat cells (LOD = 270 cells/mL) to further determine the specific etiology of the disease.

Foliar Application of Nanoparticles Reduced Cadmium Content in Wheat (Triticum aestivum L.) Grains via Long-Distance "Leaf-Root-Microorganism" Regulation.

Foliar application of beneficial nanoparticles (NPs) exhibits potential in reducing cadmium (Cd) uptake in crops, necessitating a systematic understanding of their leaf-root-microorganism process for sustainable development of efficient nano-enabled agrochemicals. Herein, wheat grown in Cd-contaminated soil (5.23 mg/kg) was sprayed with different rates of four commonly used NPs, including nano selenium (SeNPs)/silica (SiO2NPs)/zinc oxide/manganese dioxide. SeNPs and SiO2NPs most effectively reduced the Cd concentration in wheat grains. Compared to the control, Cd concentration in grains was significantly decreased by 35.0 and 33.3% by applying 0.96 mg/plant SeNPs and 2.4 mg/plant SiO2NPs, and the grain yield was significantly increased by 33.9% with SeNPs application. Down-regulated gene expression of Cd transport proteins (TaNramp5 and TaLCT1) and up-regulated gene expression of vacuolar Cd fixation proteins (TaHMA3 and TaTM20) were observed with foliar SeNPs and SiO2NPs use. SeNPs increased the levels of leaf antioxidant metabolites. Additionally, foliar spray of SeNPs resulted in lower abundances of rhizosphere organic acids and reduced Cd bioavailability in rhizosphere soil, and soil microorganisms related to carbon and nitrogen (Solirubrobacter and Pedomicrobium) were promoted. Our findings underscore the potential of the foliar application of SeNPs and SiO2NPs as a plant and rhizosphere soil metabolism-regulating approach to reduce Cd accumulation in wheat grains.

Expression of concern: Enhanced photocatalytic activity of g-C3N4/MnO composites for hydrogen evolution under visible light.

Expression of concern for 'Enhanced photocatalytic activity of g-C3N4/MnO composites for hydrogen evolution under visible light' by Na Mao et al., Dalton Trans., 2019, 48, 14864-14872, https://doi.org/10.1039/C9DT02748C.

Towards Durable and High-Rate Rechargeable Aluminum Dual-ion Batteries via a Crosslinked Diphenylphenazine-based Conjugated Polymer Cathode.

Rechargeable aluminum battery (RAB) is expected to be a promising energy storage technique for grid-scale energy storage. However, the development of RABs is seriously plagued by the lack of suitable cathode materials. Herein, we report two p-type conjugated polymers of L-PBPz and C-PBPz with the same building blocks of diphenylphenazine but different linkage patterns of linear and crosslinked structures as the cathode materials for Al dual-ion batteries. Compared to the linear polymer skeleton in L-PBPz, the crosslinked structure endows C-PBPz with amorphous nature and low dihedral angles of the polymer chains, which severally contribute to the fast diffusion of AlCl4 - with large size and the electron transfer during the redox reaction of diphenylphenazine. As a result, C-PBPz delivers a much better rate performance than L-PBPz. The crosslinked structure also leads to a stable cyclability with over 80000 cycles for C-PBPz. Benefiting from the fast kinetics, meanwhile, the C-PBPz cathode could realize a high redox activity of 117 mAh g-1 , corresponding to an areal capacity of 2.30 mAh cm-2 , even under a high mass loading of 19.7 mg cm-2 and a low content of 10 wt% conductive agent. These results might boost the development of polymer cathodes for RABs.

Machine learning-based risk models for procedural complications of radiofrequency ablation for atrial fibrillation.

BACKGROUND: Radiofrequency ablation (RFA) for atrial fibrillation (AF) is associated with a risk of complications. This study aimed to develop and validate risk models for predicting complications after radiofrequency ablation of atrial fibrillation patients. METHODS: This retrospective cohort study included 3365 procedures on 3187 patients with atrial fibrillation at a single medical center from 2018 to 2021. The outcome was the occurrence of postoperative procedural complications during hospitalization. Logistic regression, decision tree, random forest, gradient boosting machine, and extreme gradient boosting were used to develop risk models for any postoperative complications, cardiac effusion/tamponade, and hemorrhage, respectively. Patients' demographic characteristics, medical history, signs, symptoms at presentation, electrocardiographic features, procedural characteristics, laboratory values, and postoperative complications were collected from the medical record. The prediction results were evaluated by performance metrics (i.e., the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, F score, and Brier score) with repeated fivefold cross-validation. RESULTS: Of the 3365 RFA procedures, there were 62 procedural complications with a rate of 1.84% in the entire cohort. The most common complications were cardiac effusion/tamponade (28 cases, 0.83%), and hemorrhage (21 cases, 0.80%). There was no procedure-related mortality. The machine learning algorithms of random forest (RF) outperformed other models for any complication (AUC 0.721 vs 0.627 to 0.707), and hemorrhage (AUC 0.839 vs 0.649 to 0.794). The extreme gradient boosting (XGBoost) model outperformed other models for cardiac effusion/tamponade (AUC 0.696 vs 0.606 to 0.662). CONCLUSIONS: The developed risk models using machine learning algorithms showed good performance in predicting complications after RFA of AF patients. These models help identify patients at high risk of complications and guiding clinical decision-making.

Effectiveness comparison of third-generation EGFR-TKI as initial and sequential therapy in adjuvant treatment for EGFR mutation-sensitive stage IIIA non-small cell lung cancer after surgery.

Introduction: Although third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) Osimertinib has been approved as adjuvant therapy for resected stage IIIA non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, the optimal treatment sequencing of EGFR-TKIs, particularly whether Osimertinib should be the initial or sequential therapy following the first-generation EGFR-TKIs remains uncertain. Methods: A retrospective analysis was conducted on a cohort of patients with EGFR-mutated stage IIIA NSCLC who received treatment with either first-generation EGFR-TKIs or Osimertinib (third-generation) alone, or in sequential combination, at a single institution. The data analysis involved using the Kaplan-Meier method, log-rank test, and Cox regression. Results: Out of the total 148 patients with stage IIIA NSCLC included in the study, 76 individuals underwent treatment with either first-generation EGFR-TKIs (referred to as subgroup "1″) or exclusively Osimertinib (subgroup "0 + 3″), or a sequential combination of the two (subgroup "1 + 3″) following surgery. Both univariate and multivariate analyses demonstrated that there were no discernible disparities in terms of disease-free survival and overall survival between subgroup " 1″ and " 1 + 3," nor between subgroup " 0 + 3″ and "1 + 3". Conclusion: The findings from this study indicate that the introduction of third-generation EGFR-TKI Osimertinib did not yield enhanced survival benefits when compared to the first-generation drug in patients with stage IIIA completely resected NSCLC who were administered EGFR-TKIs as part of their postoperative adjuvant treatment. Additionally, within the observed sample size of this cohort, the sequential use of Osimertinib alongside first-generation EGFR-TKI did not demonstrate superiority over using either the first-generation EGFR-TKI or Osimertinib alone in terms of postoperative survival.

Foliar application of selenium nanoparticles alleviates cadmium toxicity in maize (Zea mays L.) seedlings: Evidence on antioxidant, gene expression, and metabolomics analysis.

The molecular and metabolic mechanisms of foliar selenium (Se) nanoparticles (SeNPs) application in mitigating cadmium (Cd) toxicity in crops have not been well studied. Herein, hydroponically cultured maize seedlings were exposed to Cd (20 µM) and treated without and with foliar SeNPs application. Effects of SeNPs on Cd transporter genes and plant metabolism were also explored. Results showed that compared to control plants without Cd exposure, Cd exposure decreased shoot height (16.8 %), root length (17.7 %), and fresh weight of root (24.2 %), stem (28.8 %), and foliar-applied leaves (Se-leaves) (15.0 %) via oxidative damage. Compared to Cd exposure alone, foliar SeNPs application at 20 mg/L (0.25 mg/plant) significantly alleviated the Cd toxicity by promoting photosynthesis and antioxidant capacity and fixing Cd in cell wall. Meanwhile, the mineral concentration of Ca (26.0 %), Fe (55.4 %), Mg (27.0 %), Na (28.6 %), and Zn (10.1 %) in Se-leaves was improved via foliar SeNPs application at 20 mg/L. QRT-PCR analysis further revealed that down- and up-regulation of the expression of ZmHMA2 and ZmHMA3 gene in Se-leaves contributed to reduced translocation of Cd in plants and enhanced Cd sequestration in the vacuole, respectively. Metabolomic results further indicated that metabolic pathways including carbohydrate metabolism, membrane transport, translation, amino acid metabolism, and energy metabolism were significantly affected by foliar SeNPs application. In conclusion, foliar SeNPs application at 20 mg/L could be a prospective strategy to mitigate Cd toxicity in maize.

Use of machine learning models to predict in-hospital mortality in patients with acute coronary syndrome.

BACKGROUND: Cardiovascular diseases are a significant health burden with the prevalence increasing worldwide. Thus, a highly accurate assessment and prediction of death risk are crucial to meet the clinical demand. This study sought to develop and validate a model to predict in-hospital mortality among patients with the acute coronary syndrome (ACS) using nonlinear algorithms. METHODS: A total of 2414 ACS patients were enrolled in this study. All samples were divided into five groups for cross-validation. The logistic regression (LR) model and XGboost model were applied to predict in-hospital mortality. The results of two models were compared between the variable set by the global registry of acute coronary events (GRACE) score and the selected variable set. RESULTS: The in-hospital mortality rate was 3.5% in the dataset. Model performance on the selected variable set was better than that on GRACE variables: a 3% increase in area under the receiver operating characteristic (ROC) curve (AUC) for LR and 1.3% for XGBoost. The AUC of XGBoost is 0.913 (95% confidence interval [CI]: 0.910-0.916), demonstrating a better discrimination ability than LR (AUC = 0.904, 95% CI: 0.902-0.905) on the selected variable set. Almost perfect calibration was found in XGBoost (slope of predicted to observed events, 1.08; intercept, -0.103; p < .001). CONCLUSIONS: XGboost modeling, an advanced machine learning algorithm, identifies new variables and provides high accuracy for the prediction of in-hospital mortality in ACS patients.

Meta-analysis of the effect and safety of recombinant human interferon α-2b combined with Baofukang suppository in the treatment of HPV infection.

Persistent infection of human papilloma virus (HPV) increases the risk of cervical precancerous lesions turning into cervical cancer, which seriously affects women's reproductive health and quality of life. This meta-analysis analyzed the effect and safety of recombinant human interferon α-2b (rhIFNα-2b) combined with Baofukang suppository in the treatment of HPV infection. Online databases were used to search for randomized clinical trials (RCTs) on the treatment of HPV infection with the deadline of January 2022 and the effects of treatment were analyzed by the odds ratio (OR) of treatment outcomes (total effective rate, HPV clearance rate and adverse reaction rate). The interval estimation was expressed by 95% confidence interval (CI). The searching results showed that there were 15 RCTs, including 1786 HPV-infected cases meeting the criteria for meta-analysis, of which 893 received combination therapy. In terms of total effective rate, combination therapy was superior to monotherapy (OR = 4.82, 95% CI 3.43-6.75, P < 0.001). In terms of increasing the HPV clearance rate and reducing the adverse reaction rate, combination therapy also showed obvious advantages over monotherapy (OR = 4.51, 95% CI 3.18-6.39, P < 0.001; OR = 0.60, 95% CI 0.40-0.91, P < 0.02). Our findings suggested that rhIFNα-2b combined with Baofukang suppository is safe and effective in the treatment of cervical HPV infection. Due to the limited quality of the included studies, the results need to be further studied and validated by more high quality RCTs.

Synthetic Control of Electronic Property and Porosity in Anthraquinone-Based Conjugated Polymer Cathodes for High-Rate and Long-Cycle-Life Na-Organic Batteries.

Redox-active carbonyl-containing compounds have received extensive attention as cathode materials for sodium-ion batteries (SIBs) because of their excellent attributes, including elemental sustainability, high theoretical capacity, diverse structures, and tunable properties. However, the storage of Na+ in most carbonyl-based cathode materials is plagued by the low capacity, unsatisfying rate performance, and short cycling life. Herein, we develop a series of anthraquinone-based conjugated polymer cathodes consisting of anthraquinone and benzene with different linking patterns. It reveals that the linkage sites on benzene ring could affect the electronic structures of the resulting polymers and thus their charge-storage capabilities. The 1,2,4,5-linkage on benzene leads to a high surface area, a narrow band gap, and the lowest unoccupied molecular orbital for the resulting polymer PBAQ-3. As a cathode for SIBs, it delivers a high capacity of around 200 mAh g-1 and excellent rate performance (105 mAh g-1 at 200 C) as well as stable cycling with a capacity retention of 95.8% after 1000 cycles at 0.05 A g-1 and 83.1% after 40000 cycles at 3 A g-1. Our findings highlight the influence of linking patterns of the building blocks on the electrochemical performance of organic electrodes.

Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors.

BACKGROUND: Regional lymph node (LN) acts as a pivotal organ for antitumor immunity. Paradoxically, tumor-draining LNs (TDLNs) are usually the first site of tumor metastasis in lung cancer. It is largely unknown about the association between the status of TDLNs and the response of primary tumor beds to immune checkpoint inhibitors (ICIs) in lung cancer patients. Also, studies characterizing the TDLNs in response to ICIs are scarce. METHODS: We characterized and compared the radiological, metabolic (18F-FDG) and pathologic responses between primary tumor beds and paired TDLNs (invaded/non-invaded) from 68 lung cancer patients who underwent neoadjuvant ICIs plus surgery. Additionally, we performed the spatial profiling of immune and non-immune cells within TDLNs using multiplexed immunofluorescence. Therapy responses (e.g., pathologic complete (pCR) or major response (MPR)) of primary lung tumor beds and paired TDLNs were investigated separately. FINDINGS: We observed that responses of TDLNs to ICIs markedly differ from their paired primary lung tumors regarding the radiological, metabolic (18F-FDG uptake), and pathologic alterations. Neoadjuvant ICIs therapy specifically decreased 18F-FDG-reflected metabolic activity in the primary tumor beds with pCR/MPR but not their TDLNs counterparts. Furthermore, the presence of invaded TDLNs was associated with poor pathologic responses in the matched primary tumor beds and predictive of rapid post-treatment tumor relapse. Spatial profiling demonstrated exclusion of T cell infiltrates within the metastatic lesions of invaded TDLNs, and diminished multiple immune and non-immune compositions in non-involved regions surrounding the metastatic lesions. INTERPRETATION: These results provide the first clinically-relevant evidence demonstrating unique response patterns of TDLNs under ICIs treatment and revealing the underappreciated association of TDLNs status with the response of their paired primary tumors to ICIs in lung cancer. FUNDING: This work was supported by the National Natural Science Foundation of China (82072570 to F. Yao; 82002941 to B. Sun), the excellent talent program of Shanghai Chest Hospital (to F.Y), the Basic Foundation Program for Youth of Shanghai Chest Hospital (2021YNJCQ2 to H.Yang), and the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212302 to F. Yao).

The improved success rate and reduced complications of a novel localization device vs. hookwire for thoracoscopic resection of small pulmonary nodules: a single-center, open-label, randomized clinical trial.

Background: In our previous study, we developed a 4-hook claw-suture localization device for pulmonary nodule resection, which acheived satifisfactory results. Following this, we conducted this single-center, open-label, randomized clinical trial to compare the success rate and complication rate of this novel localization device and currently widely-used hookwire. Methods: Patients with small pulmonary nodules (0.4-1 cm) who received preoperative localization and thoracoscopic resection at Shanghai Chest Hospital were randomly assigned (1:2 ratio, via computer-generated randomized numbers) to undergo localization using either a novel claw-suture system (claw group) or classical (hookwire group) localization device. The primary endpoint of this study was localization success rate, and the secondary endpoints included complications, localization-related time, and pain. Results: A total of 411 patients were randomly assigned to the claw group (n=136) or the hookwire group (n=275) before thoracoscopic resection of small pulmonary nodules and analyzed. Compared with the hookwire group, the claw group had a significantly higher success rate (133/136, 97.8% vs. 254/275, 92.4%, P=0.027), less asymptomatic hemorrhage (16.9% vs. 37.5%, P=0.003) and pleural reaction (0% vs. 5.1%, P=0.017), as well as better pain alleviation 10 min after localization (measured using the difference between two visual analog scale scores, 0.84±0.98 vs. 0.35±0.79, P<0.001). In contrast, the hookwire group was associated with a shorter localization procedure duration than the claw group (7.2±2.9 vs. 14.4±6.6 min, P<0.001). In the multiple localization subgroup, the claw group compared to the hookwire group also achieved higher success (32/33, 97.0% vs. 70/86, 81.4%) and less pleural reaction (0% vs. 16.3%). Conclusions: The new claw-suture localization device is superior to traditional hookwire, with a higher success rate, fewer complications, and better patient tolerance for preoperative localization of small pulmonary nodules. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027346.

[Structural Characteristics of Micro-nano Particle Size Biochar and Its Adsorption Mechanism for Cd2].

The aim of this study was to investigate the structural characteristics of biochar with different micro/nano particle sizes and its effect on the adsorption performance of Cd2+. Corn stalk biochar with different particle sizes (180-250 µm, 50-75 µm, and ≤ 20 µm, denoted as BC-1, BC-2, and BC-3, respectively) were prepared using the sieving and ball milling method. The structural properties of different particle sizes of biochar were analyzed via elemental analysis, laser particle size analysis, SEM, BET, FTIR, and XPS. Additionally, the adsorption mechanisms of Cd2+ by three particle sizes of biochar under initial Cd2+ concentrations, adsorption times, and pH conditions were comparatively studied using static adsorption experiments. The results showed that with the decrease in particle size, the pH and zeta potential of biochar were reduced; the aromaticity and polarity decreased; the specific surface area and pore volume increased; and the intensity of the characteristic peaks containing OH, C[FY=,1]C/C[FY=,1]O, and C-O groups increased. The adsorption kinetics of Cd2+ with different particle diameters of biochar were in accordance with the pseudo-secondary kinetic model, with chemisorption dominating. The equilibrium times were in the decreasing order of BC-1 (540 min)>BC-2 (360 min)>BC-3 (80 min). The Langmuir model could better fit the adsorption isotherm process of Cd2+ on biochar of different particle sizes (R2>0.97), and the maximum adsorption capacity of Cd2+ increased with the decrease in particle size, which was expressed as BC-3 (74.43 mg·g-1)>BC-2 (45.71 mg·g-1)>BC-1 (44.59 mg·g-1). The main mechanisms of Cd2+adsorption by biochar were electrostatic attraction, surface complexation, and cation-π interaction.

Multi-scale integrative analyses identify THBS2+ cancer-associated fibroblasts as a key orchestrator promoting aggressiveness in early-stage lung adenocarcinoma.

Rationale: Subsets of patients with early-stage lung adenocarcinoma (LUAD) have a poor post-surgical course after curative surgery. However, biomarkers stratifying this high-risk subset and molecular underpinnings underlying the aggressive phenotype remain unclear. Methods: We integrated bulk and single-cell transcriptomics, proteomics, secretome and spatial profiling of clinical early-stage LUAD samples to identify molecular underpinnings that promote the aggressive phenotype. Results: We identified and validated THBS2, at multi-omic levels, as a tumor size-independent biomarker that robustly predicted post-surgical survival in multiple independent clinical cohorts of early-stage LUAD. Furthermore, scRNA-seq data revealed that THBS2 is exclusively derived from a specific cancer-associated fibroblast (CAF) subset that is distinct from CAFs defined by classical markers. Interestingly, our data demonstrated that THBS2 was preferentially secreted via exosomes in early-stage LUAD tumors with high aggressiveness, and its levels in the peripheral plasma associated with short recurrence-free survival. Further characterization showed that THBS2-high early-stage LUAD was characterized by suppressed antitumor immunity. Specifically, beyond tumor cells, THBS2+ CAFs mainly interact with B and CD8+ T lymphocytes as well as macrophages within tumor microenvironment of early-stage LUAD, and THBS2-high LUAD was associated with decreased immune cell infiltrates but increased immune exhaustion marker. Clinically, high THBS2 expression predicted poor response to immunotherapies and short post-treatment survival of patients. Finally, THBS2 recombinant protein suppressed ex vivo T cells proliferation and promoted in vivo LUAD tumor growth and distant micro-metastasis. Conclusions: Our multi-level analyses uncovered tumor-specific THBS2+ CAFs as a key orchestrator promoting aggressiveness in early-stage LUAD.

Quinone-based conjugated polymer cathodes synthesized via direct arylation for high performance Li-organic batteries.

Direct arylation cross-coupling reaction was employed to prepare quinone-based conjugated polymer cathodes, which realize a high reversible capacity of 200 mA h g-1 at 0.05 A g-1, an excellent rate capability of 111 mA h g-1 at 30 A g-1 (150C), and a stable cycling performance for more than 3000 cycles.

In‒situ immobilization remediation, soil aggregate distribution, and microbial community composition in weakly alkaline Cd‒contaminated soils: A field study.

Biochar has advantages of a large specific surface area and micropore structure, which is beneficial for immobilization remediation of heavy metal‒contaminated soils. A field experiment was conducted to investigate the effects of rice husk biochar (BC) (7.5, 15, and 15 t hm-2) on Cd availability in soils and accumulation in maize (Zea mays L), soil aggregate structure, and microbial community abundance. The results show that BC treatment promoted the formation of large aggregates (5-8 and 2-5 mm) and enhanced aggregate stability, whereas it decreased the proportion of ≤0.25 mm soil aggregates. The geometric mean diameter and mean weight diameter under BC‒treated soils increased by 9.9%-40.5% and 3.6%-32.7%, respectively, indicating that the stability of soil aggregates increased. Moreover, BC facilitated the migration of Cd from large particles (>0.5 mm aggregates) to small particles (<0.25 mm aggregates). The application of BC decreased diethylenetriamine pentaacetic acid ‒extractable Cd by 17.6%-32.12% in contrast with the control. The amount of Cd in maize was reduced by 56.7%-81.1% for zhengdan958, 52.4%-85.9% for Sanbei218, and 73.7%-90.4% for Liyu16. When compared with the control groups, BC addition significantly (P < 0.05) increased the number of Ace observed, Shannon diversity indices, and the relative abundances of Proteobacteria, Acidobacteria, and Bacteroidetes. Therefore, rice husk BC exhibited a certain feasibility in immobilizing remediation of weakly alkaline Cd‒contaminated soils.

Smoking signature is superior to programmed death-ligand 1 expression in predicting pathological response to neoadjuvant immunotherapy in lung cancer patients.

BACKGROUND: There is a paucity of biomarkers that can predict the degree of pathological response [e.g., pathological complete response (pCR) or major response (pMR)] to immunotherapy. Neoadjuvant immunotherapy provides an ideal setting for exploring responsive biomarkers because the pathological responses can be directly and accurately evaluated. METHODS: We retrospectively collected the clinicopathological characteristics and treatment outcomes of non-small cell lung cancer (NSCLC) patients who received neoadjuvant immunotherapy or chemo-immunotherapy followed by surgery between 2018 and 2020 at a large academic thoracic cancer center. Clinicopathological factors associated with pathological response were analyzed. RESULTS: A total of 39 patients (35 males and 4 females) were included. The most common histological subtype was lung squamous cell carcinoma (LUSC) (n=28, 71.8%), followed by lung adenocarcinoma (LUAD) (n=11, 28.2%). After neoadjuvant treatment, computed tomography (CT) scan-based evaluation showed poor agreement with the postoperatively pathological examination (weighted kappa =0.0225; P=0.795), suggesting the poor performance of CT scans in evaluating the response to immunotherapy. Importantly, we found that the smoking signature displayed a better performance than programmed death-ligand 1 (PD-L1) expression in predicting the pathological response (area under the curve: 0.690 vs. 0.456; P=0.0259), which might have resulted from increased tumor mutational burden (TMB) and/or microsatellite instability (MSI) relating to smoking exposure. CONCLUSIONS: These findings suggest that CT scan-based evaluation is not able to accurately reflect the pathological response to immunotherapy and that smoking signature is a superior marker to PD-L1 expression in predicting the benefit of immunotherapy in NSCLC patients.

Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.

BACKGROUND: Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. EXPERIMENTAL: We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. RESULTS: In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response. CONCLUSION: These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response.

Carbon Dots-in-EuAPO-5 Zeolite: Triple-Emission for Multilevel Luminescence Anti-Counterfeiting.

Multilevel luminescence materials have aroused wide attention for their advanced anti-counterfeiting abilities. However, various complicated stimuli factors involved in multilevel luminescence anti-counterfeiting (MlLA) limit the practical applications of such materials. Herein, carbon dots (CDs) are in situ introduced into Eu-substituted AlPO4 -5 zeolite (named CDs@EuAPO-5) via a solvent-free thermal crystallization method, which exhibits triple emissions including pink fluorescence mainly associated with Eu3+ in the zeolite framework, blue fluorescence and green room temperature phosphorescence (RTP) associated with CDs. CDs are uniformly embedded in the EuAPO-5 zeolite matrix. Such composite displays excellent photo-, thermo-, and solvent resistance, as well as long-term storage-stability. Moreover, the triple emissions of the composite only need two kinds of common excitation lights to trigger, without involving other complicated stimuli. A triple-level luminescence anti-counterfeiting (TlLA) label has been built, realizing facile, quick, and advanced luminescence anti-counterfeiting that is hard to copy.