HTR3A Promotes Non-small Cell Lung Cancer Through the FOXH1/Wnt3A Signaling Pathway.

5-Hydroxytryptamine receptors (5-HTRs) are strongly correlated with tumor progression in various types of cancer. Despite this, the underlying mechanisms responsible for the role of 5-HTRs in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to investigate the relationship between 5-hydroxytryptamine receptor 3A (HTR3A) and NSCLC development. Our findings indicated a higher distribution of HTR3A expression in NSCLC tissues when compared with normal tissues, where patients with high HTR3A levels demonstrated shorter overall survival times. In vitro analyses revealed that overexpression of HTR3A facilitated the proliferation and migration of NSCLC cell lines (A549 and NCI-H3255). Similarly, a notable acceleration of tumor growth and enhanced pulmonary tumorigenic potential were observed in HTR3A-overexpressing tumor-bearing mice. Mechanistically, upregulation of Forkhead Box H1 (FOXH1) by HTR3A led to the activation of Wnt3A/ß-catenin signaling pathways, thereby promoting the development of NSCLC. Our report thus highlights the significance of the HTR3A/FOXH1 axis during tumor progression in NSCLC, proposing HTR3A as a possible diagnostic indicator and candidate target for clinical therapy.

Development and validation of a nomogram for predicting lymph node metastasis in early gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) significantly impacts the treatment and prognosis of early gastric cancer (EGC). Consequently, the precise prediction of LNM risk in EGC patients is essential to guide the selection of appropriate surgical approaches in clinical settings. AIM: To develop a novel nomogram risk model for predicting LNM in EGC patients, utilizing preoperative clinicopathological data. METHODS: Univariate and multivariate logistic regression analyses were performed to examine the correlation between clinicopathological factors and LNM in EGC patients. Additionally, univariate Kaplan-Meier and multivariate Cox regression analyses were used to assess the influence of clinical factors on EGC prognosis. A predictive model in the form of a nomogram was developed, and its discrimination ability and calibration were also assessed. RESULTS: The incidence of LNM in the study cohort was 19.6%. Multivariate logistic regression identified tumor size, location, degree of differentiation, and pathological type as independent risk factors for LNM in EGC patients. Both tumor pathological type and LNM independently affected the prognosis of EGC. The model's performance was reflected by an area under the curve of 0.750 [95% confidence interval (CI): 0.701-0.789] for the training group and 0.763 (95%CI: 0.687-0.838) for the validation group. CONCLUSION: A clinical prediction model was constructed (using tumor size, low differentiation, location in the middle-lower region, and signet ring cell carcinoma), with its score being a significant prognosis indicator.

Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022.

BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). METHOD: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. RESULT: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. CONCLUSION: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

Arbuscular mycorrhizal fungal interactions bridge the support of root-associated microbiota for slope multifunctionality in an erosion-prone ecosystem.

The role of diverse soil microbiota in restoring erosion-induced degraded lands is well recognized. Yet, the facilitative interactions among symbiotic arbuscular mycorrhizal (AM) fungi, rhizobia, and heterotrophic bacteria, which underpin multiple functions in eroded ecosystems, remain unclear. Here, we utilized quantitative microbiota profiling and ecological network analyses to explore the interplay between the diversity and biotic associations of root-associated microbiota and multifunctionality across an eroded slope of a Robinia pseudoacacia plantation on the Loess Plateau. We found explicit variations in slope multifunctionality across different slope positions, associated with shifts in limiting resources, including soil phosphorus (P) and moisture. To cope with P limitation, AM fungi were recruited by R. pseudoacacia, assuming pivotal roles as keystones and connectors within cross-kingdom networks. Furthermore, AM fungi facilitated the assembly and composition of bacterial and rhizobial communities, collectively driving slope multifunctionality. The symbiotic association among R. pseudoacacia, AM fungi, and rhizobia promoted slope multifunctionality through enhanced decomposition of recalcitrant compounds, improved P mineralization potential, and optimized microbial metabolism. Overall, our findings highlight the crucial role of AM fungal-centered microbiota associated with R. pseudoacacia in functional delivery within eroded landscapes, providing valuable insights for the sustainable restoration of degraded ecosystems in erosion-prone regions.

Inspection of Liner Wall Thinning and Interface Debonding in Bimetallic Lined Pipes Using Pulsed Eddy Current Testing.

Bimetallic lined pipe (BLP) has been increasingly used in offshore and subsea oil and gas structures, but how to identify the invisible inner defects such as liner wall thinning and interface debonding is a challenge for future development. A nondestructive testing (NDT) method based on pulsed eddy current testing (PECT) has been proposed to face these difficulties. The inspection of the BLP specimen (AISI1020 base tube and SS304 liner) is implemented from outside of the pipe by using a transmitter-receiver-type PECT probe consisting of two induction coils. By simplifying the BLP specimen to stratified conductive plates, the electromagnetic field interaction between the PECT probe and specimen is analytically modeled, and the probe inspection signals due to liner wall thinning and interface debonding are calculated. In order to highlight the weak response (in microvolts) from the liner, the inspection signals are subtracted by the signal, which is calculated in the case of only having a base tube, yielding differential PECT signals. The peak voltage of the differential signal is selected to characterize the liner wall thinning and interface debonding due to its distinguishable and linear variation. Experiment verification is also carried out on a double-walled specimen simulated by a combination of a Q235 casing pipe and SS304 tubes of different sizes. The experimental results basically agree with the analytical predictions. The peak value of the PECT signal has an ascending and descending variation with the increase in the remaining liner wall thickness and debonding gap, respectively, while the negative peak value shows opposite changes. The peak value exhibits a larger sensitivity than the negative peak value. The proposed method shows potential promise in practical applications for the evaluation of the inner defects in BLP lines.

Development and validation of a deep learning model for predicting gastric cancer recurrence based on CT Imaging: a multicenter study.

INTRODUCTION: The postoperative recurrence of gastric cancer has a significant impact on the overall prognosis of patients. Therefore, accurately predicting the postoperative recurrence of gastric cancer is crucial. METHODS: This retrospective study gathered data from 2,813 gastric cancer patients who underwent radical surgery between 2011 and 2017 at two medical centers. Follow-up was extended until May 2023, and cases were categorized as recurrent or non-recurrent based on postoperative outcomes. Clinical pathological information and imaging data were collected for all patients. A new deep learning signature (DLS) was generated using pretreatment CT images, based on a pre-trained baseline (a customized Resnet50), for predicting postoperative recurrence. The deep learning fusion signature (DLFS) was created by combining the score of DLS with the weighted values of identified clinical features. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. Survival curves were plotted to investigate the differences between DLFS and prognosis. RESULTS: In this study, 2813 patients with gastric cancer (GC) were recruited and allocated into training, internal validation, and external validation cohorts. The DLFS was developed and assessed for its capability in predicting the risk of postoperative recurrence. The DLFS exhibited excellent performance with AUCs of 0.833 (95% CI, 0.809-0.858) in the training set, 0.831 (95% CI, 0.792-0.871) in the internal validation set, and 0.859 (95% CI, 0.806-0.912) in the external validation set, along with satisfactory calibration across all cohorts (P>0.05). Furthermore, the DLFS model significantly outperformed both the clinical model and DLS (P<0.05). High-risk recurrent patients exhibit a significantly poorer prognosis compared to low-risk recurrent patients (P<0.05). CONCLUSIONS: The integrated model developed in this study, focusing on GC patients undergoing radical surgery, accurately identifies cases at high risk of postoperative recurrence and highlights the potential of DLFS as a prognostic factor for GC patients.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. METHODS: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. RESULTS: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. CONCLUSIONS: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Silver coordination-induced n-doping of PCBM for stable and efficient inverted perovskite solar cells.

The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.

Fungal composition associated with host tree identity mediates nutrient addition effects on wood microbial respiration.

Fungi are key decomposers of deadwood, but the impact of anthropogenic changes in nutrients and temperature on fungal community and its consequences for wood microbial respiration are not well understood. Here, we examined how nitrogen and phosphorus additions (field experiment) and warming (laboratory experiment) together influence fungal composition and microbial respiration from decomposing wood of angiosperms and gymnosperms in a subtropical forest. Nutrient additions significantly increased wood microbial respiration via fungal composition, but effects varied with nutrient types and taxonomic groups. Specifically, phosphorus addition significantly increased wood microbial respiration (65%) through decreased acid phosphatase activity and increased abundance of fast-decaying fungi (e.g., white rot), while nitrogen addition marginally increased it (30%). Phosphorus addition caused a greater increase in microbial respiration in gymnosperms than in angiosperms (83.3% vs. 46.9%), which was associated with an increase in Basidiomycota:Ascomycota operational taxonomic unit abundance in gymnosperms but a decrease in angiosperms. The temperature dependencies of microbial respiration were remarkably constant across nutrient levels, consistent with metabolic scaling theory hypotheses. This is because there was no significant interaction between temperature and wood phosphorus availability or fungal composition, or the interaction among the three factors. Our results highlight the key role of tree identity in regulating nutrient response of wood microbial respiration through controlling fungal composition. Given that the range of angiosperm species may expand under climate warming and forest management, our data suggest that expansion will decrease nutrient effects on forest carbon cycling in forests previously dominated by gymnosperm species.

Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure.

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

Atomically dispersed Iridium on Mo2C as an efficient and stable alkaline hydrogen oxidation reaction catalyst.

Hydroxide exchange membrane fuel cells (HEMFCs) have the advantages of using cost-effective materials, but hindered by the sluggish anodic hydrogen oxidation reaction (HOR) kinetics. Here, we report an atomically dispersed Ir on Mo2C nanoparticles supported on carbon (IrSA-Mo2C/C) as highly active and stable HOR catalysts. The specific exchange current density of IrSA-Mo2C/C is 4.1 mA cm-2ECSA, which is 10 times that of Ir/C. Negligible decay is observed after 30,000-cycle accelerated stability test. Theoretical calculations suggest the high HOR activity is attributed to the unique Mo2C substrate, which makes the Ir sites with optimized H binding and also provides enhanced OH binding sites. By using a low loading (0.05 mgIr cm-2) of IrSA-Mo2C/C as anode, the fabricated HEMFC can deliver a high peak power density of 1.64 W cm-2. This work illustrates that atomically dispersed precious metal on carbides may be a promising strategy for high performance HEMFCs.

Hydrothermally Assisted Conversion of Switchgrass into Hard Carbon as Anode Materials for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are emerging as a viable alternative to lithium-ion batteries, reducing the reliance on scarce transition metals. Converting agricultural biomass into SIB anodes can remarkably enhance sustainability in both the agriculture and battery industries. However, the complex and costly synthesis and unsatisfactory electrochemical performance of biomass-derived hard carbon have hindered its further development. Herein, we employed a hydrothermally assisted carbonization process that converts switchgrass to battery-grade hard carbon capable of efficient Na-ion storage. The hydrothermal pretreatment effectively removed hemicellulose and impurities (e.g., lipids and ashes), creating thermally stable precursors suitable to produce hard carbon via carbonization. The elimination of hemicellulose and impurities contributes to a reduced surface area and lower oxygen content. With the modifications, the initial Coulombic efficiency (ICE) and cycling stability are improved concurrently. The optimized hard carbon showcased a high reversible specific capacity of 313.4 mAh g-1 at 100 mA g-1, a commendable ICE of 84.8%, and excellent cycling stability with a capacity retention of 308.4 mAh g-1 after 100 cycles. In short, this research introduces a cost-effective method for producing anode materials for SIBs and highlights a sustainable pathway for biomass utilization, underscoring mutual benefits for the energy and agricultural sectors.

Stepwise Protonation of Three-Dimensional Covalent Organic Frameworks for Enhancing Hydrogen Peroxide Photosynthesis.

Three-dimensional covalent organic frameworks (3D COFs), recognized for their tailorable structures and accessible active sites, offer a promising platform for developing advanced photocatalysts. However, the difficulty in the synthesis and functionalization of 3D COFs hinders their further development. In this study, we present a series of 3D-bcu-COFs with 8 connected porphyrin units linked by linear linkers through imine bonds as a versatile platform for photocatalyst design. The photoresponse of 3D-bcu-COFs was initially modulated by functionalizing linear linkers with benzo-thiadiazole or benzo-selenadiazole groups. Furthermore, taking advantage of the well-exposed porphyrin and imine sites in 3D-bcu-COFs, their photocatalytic activity was optimized by stepwise protonation of imine bonds and porphyrin centers. The dual protonated COF with benzo-selenadiazole groups exhibited enhanced charge separation, leading to an increased photocatalytic H2O2 production under visible light. This enhancement demonstrates the combined benefits of linker functionalization and stepwise protonation on photocatalytic efficiency.

Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of Ostrinia furnacalis.

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.

A capillary-aided microfiber Bragg grating pH sensor for hydrovoltaic technology.

Hydrovoltaic is an emerging technology that aims to harvest energy from water flow and evaporation, in which the plasmonic hydrogen ions are generated by the interaction between water and hydrovoltaic device. However, the volume of the water sample for the interaction is usually ultra-small due to the compact size of hydrovoltaic device, making the quantification and characterization of the hydrogen ions in such water sample an elusive goal. To address this issue, a miniature fiber-optic pH probe is proposed using a unilaterally tapered-microfiber Bragg grating. The microfiber Bragg grating has an intrinsic Bragg reflection signal with a narrow linewidth. The fiber probe is functionalized by coating the sodium alginate, which can respond to the variation of pH mediated by the alteration of the hydrophilicity. The rigidity and robustness of microfiber Bragg grating facilitates the encapsulation of the sensor into a sampling capillary, allowing for the detection of trace aqueous sample less than 2 µL. The pH sensitivity of the tapered-µFBG-based sensor is 62.8 p.m./pH (R2 = 0.995) with a limit resolution of 0.096 pH. The sensor performed a practical application in the monitoring and characterization of the hydrovoltaic microdevice, which can generate microcurrent as soaked in the water. This work demonstrates a promising technology in the fields of materials, energy, biology and medicine, in which the detection of the microsamples is inevitable.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

RDFC-GAN: RGB-Depth Fusion CycleGAN for Indoor Depth Completion.

Raw depth images captured in indoor scenarios frequently exhibit extensive missing values due to the inherent limitations of the sensors and environments. For example, transparent materials frequently elude detection by depth sensors; surfaces may introduce measurement inaccuracies due to their polished textures, extended distances, and oblique incidence angles from the sensor. The presence of incomplete depth maps imposes significant challenges for subsequent vision applications, prompting the development of numerous depth completion techniques to mitigate this problem. Numerous methods excel at reconstructing dense depth maps from sparse samples, but they often falter when faced with extensive contiguous regions of missing depth values, a prevalent and critical challenge in indoor environments. To overcome these challenges, we design a novel two-branch end-to-end fusion network named RDFC-GAN, which takes a pair of RGB and incomplete depth images as input to predict a dense and completed depth map. The first branch employs an encoder-decoder structure, by adhering to the Manhattan world assumption and utilizing normal maps from RGB-D information as guidance, to regress the local dense depth values from the raw depth map. The other branch applies an RGB-depth fusion CycleGAN, adept at translating RGB imagery into detailed, textured depth maps while ensuring high fidelity through cycle consistency. We fuse the two branches via adaptive fusion modules named W-AdaIN and train the model with the help of pseudo depth maps. Comprehensive evaluations on NYU-Depth V2 and SUN RGB-D datasets show that our method significantly enhances depth completion performance particularly in realistic indoor settings.

Radiosensitization of Allogenic Subcutaneous C6 Glioma Model with Focused Ultrasound-Induced Mild Hyperthermia.

The radiosensitization potential of focused ultrasound (FUS)-induced mild hyperthermia was assessed in an allogenic subcutaneous C6 glioma tumor model in rats. Mild hyperthermia at 42 °C was induced in tumors using a single-element 350 kHz FUS transducer. Radiation was delivered with a small animal radiation research platform using a single-beam irradiation technique. The combined treatment involved 20 min of FUS hyperthermia immediately before radiation. Tumor growth changes were observed one week post-treatment. A radiation dose of 2 Gy alone showed limited tumor control (30% reduction). However, when combined with FUS hyperthermia, there was a significant reduction in tumor growth compared to other treatments (tumor volumes: control-1174 ± 554 mm3, FUS-HT-1483 ± 702 mm3, 2 Gy-609 ± 300 mm3, FUS-HT + 2 Gy-259 ± 186 mm3; ANOVA p < 0.00001). Immunohistological analysis suggested increased DNA damage as a short-term mechanism for tumor control in the combined treatment. In conclusion, FUS-induced mild hyperthermia can enhance the effectiveness of radiation in a glioma tumor model, potentially improving the outcome of standard radiation treatments for better tumor control.

Bimodal Oxidation Electrochemiluminescence Mechanism of Coreactant-Embedded Covalent Organic Frameworks via Postsynthetic Modification.

Electrochemiluminescence (ECL) efficiency is determined by charge transfer between coreactants and emitters in coreactant systems, which are usually limited by their slow intermolecular charge transfer. In this study, a covalent organic framework (COF) with aldehyde residue was synthesized, and then coreactants were covalently integrated into the skeleton through the postsynthetic modification strategy, resulting in a crystalline coreactant-embedded COF nanoemitter (C-COF). Compared to the pristine COF with an equivalent external coreactant, C-COF exhibited an extraordinary 1008-fold enhancement of ECL intensity due to the rapid intrareticular charge transfer. Significantly, with the pH increase, C-COF shows protonation-induced ECL enhancement for the first ECL peaked at +1.1 V and an opposite trend for the second ECL at +1.4 V, which were attributed to the antedating oxidation of coreactant in framework and COF self-oxidation, respectively. The resulting bimodal oxidation ECL mechanism was rationalized by spectral characterization and density functional theory calculations. The postsynthetic coreactant-embedded nanoemitters present innovative and universal avenues for advancing ECL systems.