Dual-mode detection of α-fetoprotein using the photothermal effect and peroxidase-like activity of Au@Cu/Cu2O-rGO.

α-Fetoprotein (AFP) is widely recognized as an important marker for monitoring hepatocellular carcinoma (HCC), and its monitoring using two different transduction mechanisms is an effective way to avoid the risk of false positives or false negatives. In this paper, Au@Cu/Cu2O-rGO was used as a photothermal converter as well as an actuator to promote the decomposition of hydrogen peroxide (H2O2), which was further designed as a probe for dual-mode detection to quantitatively assess AFP. The composite nanomaterials possessed photothermal conversion efficiencies (η) of up to 54.9 % and catalytically generated signals up to 1.6 times greater, relative to a single material. Based on the generated temperature and current signals, AFP has been sensitively detected in the range of 0.01-100 ng/mL, with limits of detection (LOD) of 5.62 pg/mL and 1.23 pg/mL, respectively. The dual-mode assay combines portability with high accuracy for the detection of human health systems.

Potential of gamma/delta T cells for solid tumor immunotherapy.

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy.

Smart modulation by bifunctional probes PNAI@Co3O4/Au NPs of the light/electric response of Au-Ag NCs to realize the dual-channel precise detection of AOH.

Mycotoxin contamination currently poses a significant concern and presents a major challenge to global food safety management. In this research, gold­silver nanoclusters (Au-AgNCs) were utilized as platforms for electrogenerated chemiluminescence (ECL) and electrochemical (EC) responses, while polyaniline-coated cobalt tetraoxide and gold (PANI@Co3O4/AuNPs) served as bifunctional probes with intelligently modulated light/electric signals to develop a dual mode adaptor sensor for sensitive detection of alternariol (AOH). The sensor's benefits are evident in three areas:(1) Bandgap modulation allows Au-Ag to exhibit enhanced light/electric response;(2) PANI@Co3O4/AuNPs exhibit both ECL quenching effects and the capability to activate KHSO5, along with improved electrical conductivity, which collectively improves the sensor's detection performance;(3) The dual-channel signal outputs significantly reduce the risk of false detections. Testing results indicated that the ECL and EC sensors performed exceptionally well across AOH concentration ranges of 0.001-100 ng/mL and 0.01-1000 ng/mL, with detection limit of 0.803 pg/mL and 0.378 pg/mL, respectively.

Ultrathin-N2C-Deficient Carbon Nitride for Stabilized Enhancement of Electrochemiluminescence.

In the realm of electrochemiluminescence (ECL), the issue of weak signal intensity and instability linked with pure graphitic carbon nitride (CN) is widely recognized. This study suggests a method to produce nitrogen-deficient (N2C) porous ultrathin CN (UACN) using ammonium acetate and ultrasonication. The ultrathin porous nature of UACN provides numerous N2C defects as catalytic sites, aiding in the decomposition of K2S2O8, a conclusion supported by density functional theory (DFT). Importantly, N2C defects serve as electron traps, assisting in electron localization and enhancing the recombination of electron-hole pairs, thereby achieving stable and intensified luminescence from UACN. In practical use, UACN, acting as an ECL emitter, is utilized in detecting the tumor marker carcinoembryonic antigen (CEA), effectively establishing a highly sensitive immunosensing platform. This study elucidates the correlation between UACN structure and ECL performance, offering crucial insights for comprehending ECL mechanisms and designing high-performance ECL materials.

Physiological Time-series Fusion with Hybrid Attention for Adaptive Recognition of Pain.

Automatic pain assessment is an application in healthcare serving personalized pain care, and patients cannot self-report pain. Pain at the present is inferred from physiological dynamics at the present and in the near past. However, heterogeneous pain responses cross-subject and cross-type hinder accurate recognition of pain. This work solves the adaptive pain recognition problem across pain types. We concrete the adaptivity problem into recognizing both phasic/short and tonic/long pain from the physiological sequences of the same length. The adaptivity of the proposed solution (TCAtt-PainNet) was ensured by hybrid temporal-channel attention when fusing multivariate time-series of electrocardiogram (ECG) and galvanic skin response (GSR) features. The attention was obtained by learning the dependencies between the point at present and the sequence in the near past, where sequence point temporal attention was constructed via modified self-attention, and the following feature channel attention was constructed by squeeze-and-excitation temporal attention weighted deep feature sequence. The proposed solution successfully enhanced recognition adaptivity by addressing relevant information only from long input sequences when testing with tonic and phasic pain databases, making progress towards automatic pain assessment for real application scenarios with attributes unknown pain.

Construction of a Three-Dimensional-Printed Immunosensing Platform Based on Smartphone Photothermal Signal Integration.

The combination of the photothermal effect and immunoassay serves as a potent tool for crafting cost-effective and user-friendly biosensing systems. To ensure efficient light-to-heat conversion, we integrated three-dimensional-printed (3D printed) technology to devise a novel design. This design functions as the structural support for both the cell phone and laser probe, as well as a means for sample handling. The main body features a three-way cavity structure, securing the test sample at a fixed position to maintain consistent light distance and angle, thereby minimizing testing errors. Card slot insert facilitates precise sample positioning to ensure the adequacy of receiving light. The sample holder's wide front and narrow back design enables the accommodation of fixed samples while providing a broad field of view, with intervals therein effectively preventing cascading heat. Our design employs MB@MOF235 (methylene blue adsorbed by iron terephthalate) as the photothermal reagent, successfully enabling the detection of α-fetoprotein (AFP). The detection range spans from 0.01 to 50 ng/mL, with a lower detection limit (LOD) of 0.032 pg/mL. The detection method, combining simplicity, portability, and visualization, offers a reliable reference for furthering precision medicine toward personalized medicine. Meanwhile, to verify the method's accuracy electrochemical testing was conducted to support the proof using the electro-oxidizing activity of MB.

A Chirped Characteristic-Tunable Terahertz Source for Terahertz Sensing.

In broadband terahertz waves generated by femtosecond lasers, spatial chirp will be simultaneously produced with the introduction of angular dispersion. The chirp characteristics of the terahertz wave will directly affect the frequency response, bandwidth response, and intensity response of the terahertz sensor. To enhance the capability of terahertz sensors, it is necessary to control and improve the chirped characteristics of broadband terahertz sources. We generate a chirped terahertz wave via optical rectification in a LiNbO3 prism using the technique of pulse front tilt. The effect of the pump-beam spot size on THz generation is systematically studied. The pump's spot size is manipulated using a telescope system. With a pump spot diameter of 1.8 mm, the scanning spectrum of the THz pulse is narrower and is divided into multiple distinct peaks. In contrast, using a pump spot diameter of 3.7 mm leads to increased efficiency in the generation of THz pulses. Also, we investigate the underlying properties governing the generation of chirped terahertz pulses using varying pump pulse spot diameters.

Dual-Mode Immunoassay Constructed by Water-Induced Perylene Diimide Supramolecular Self-Assembly and Enzymatic Biocatalytic Precipitation Strategy.

A water-induced electron-deficient dye, the supramolecule perylene diimide (PDI), has been identified recently. PDI possesses advantages such as easy reduction, nontoxicity, low cost, and simple preparation, making it a promising candidate for electrochemiluminescence (ECL) sensing platforms. In this study, a series of PDI supramolecular systems with morphological changes were prepared by utilizing water molecules to induce PDI self-assembly. This method improves the π-π stacking interactions between PDI molecules and effectively mitigates the aggregation-caused quenching (ACQ) effect on the luminous efficiency of the coplanar polycyclic aromatic hydrocarbon PDI. It is noteworthy that excellent ECL emission performance of the PDI supramolecular system was observed at -0.4 V. This low excitation potential aids in preserving antigen-antibody bioactivity and ensures accurate identification of the immune response. As a proof of concept, a dual-mode immunosensing platform for carcinoembryonic antigen (CEA) detection was constructed using an enzymatic biocatalytic precipitation (EBCP) strategy. The dual-mode immunosensor exhibited good detection performance in the concentration range of 0.001-80 ng·mL-1, presenting an advanced bioprotective analytical method for CEA detection.

Integrated Analysis of Clinical Outcome of Mesenchymal Stem Cell-related Genes in Pan-cancer.

Background: Although the application of mesenchymal stem cells (MSCs) in engineered medicine, such as tissue regeneration, is well known, new evidence is emerging that shows that MSCs can also promote cancer progression, metastasis, and drug resistance. However, no large-scale cohort analysis of MSCs has been conducted to reveal their impact on the prognosis of cancer patients. Objectives: We propose the MSC score as a novel surrogate for poor prognosis in pan-cancer. Methods: We used single sample gene set enrichment analysis to quantify MSC-related genes into a signature score and identify the signature score as a potential independent prognostic marker for cancer using multivariate Cox regression analysis. TIDE algorithm and neural network were utilized to assess the predictive accuracy of MSC-related genes for immunotherapy. Results: MSC-related gene expression significantly differed between normal and tumor samples across the 33 cancer types. Cox regression analysis suggested the MSC score as an independent prognostic marker for kidney renal papillary cell carcinoma, mesothelioma, glioma, and stomach adenocarcinoma. The abundance of fibroblasts was also more representative of the MSC score than the stromal score. Our findings supported the combined use of the TIDE algorithm and neural network to predict the accuracy of MSC-related genes for immunotherapy. Conclusion: We comprehensively characterized the transcriptome, genome, and epigenetics of MSCs in pan-cancer and revealed the crosstalk of MSCs in the tumor microenvironment, especially with cancer-related fibroblasts. It is suggested that this may be one of the key sources of resistance to cancer immunotherapy.

Trade shocks and trade diversion due to epidemic diseases: Evidence from 110 countries.

COVID-19 has been a massive trade shock that has disrupted global trade, making the last few years a special phase. Even during normal times, epidemic diseases have acted as trade shocks in specific countries, albeit not to the same extent as COVID-19. For some trade shocks, the situation normalizes after the disease transmission is over; for some, it does not. Thus, specific countries can sometimes lose their original trade ratio due to trade diversion; that is, an epidemic disease could lead to unexpected industry restructuring. To examine this, based on data on 110 WHO members from 1996 to 2018, we use a fixed-effect panel model supported by the Hausman Test to empirically identify whether epidemic diseases can cause trade shocks and trade diversion. We find: First, epidemic disease can lead to negative shocks to a country's trade growth and its ratio of worldwide trade. Second, with a longer epidemic, the probability of the trade diversion effect increases. Our results hold even after considering country heterogeneity. This presents a considerable concern about the shock of COVID-19 lasting further. Many countries are not just facing the problem of temporary trade shocks, but also the challenge of trade diversions. In particular, the probability of trade diversions is increasing rapidly, especially for late-developed countries due to their lack of epidemic containment and vaccine-producing capabilities. Even middle and high income countries cannot ignore global industry chain restructuring. Forward-looking policies should be implemented in advance; it may be too late when long-term trade damage is shown.

Quenching study of Cu2S-MPA/NGODs composites in electrochemiluminescence detection by modulating resonance energy transfer and adsorption process.

This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu2S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu2S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu2S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu+ ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples.

Evaluation of the learning state of online video courses based on functional near infrared spectroscopy.

Studying brain activity during online learning will help to improve research on brain function based on real online learning situations, and will also promote the scientific evaluation of online education. Existing research focuses on enhancing learning effects and evaluating the learning process associated with online learning from an attentional perspective. We aimed to comparatively analyze the differences in prefrontal cortex (PFC) activity during resting, studying, and question-answering states in online learning and to establish a classification model of the learning state that would be useful for the evaluation of online learning. Nineteen university students performed experiments using functional near-infrared spectroscopy (fNIRS) to monitor the prefrontal lobes. The resting time at the start of the experiment was the resting state, watching 13 videos was the learning state, and answering questions after the video was the answering state. Differences in student activity between these three states were analyzed using a general linear model, 1s fNIRS data clips, and features, including averages from the three states, were classified using machine learning classification models such as support vector machines and k-nearest neighbor. The results show that the resting state is more active than learning in the dorsolateral prefrontal cortex, while answering questions is the most active of the three states in the entire PFC, and k-nearest neighbor achieves 98.5% classification accuracy for 1s fNIRS data. The results clarify the differences in PFC activity between resting, learning, and question-answering states in online learning scenarios and support the feasibility of developing an online learning assessment system using fNIRS and machine learning techniques.

Two Birds with one Stone: Dual-mode immunoassay constructed using a novel emitter ethylene glycol-induced perylene diimide and a multifunctional ANS probe.

Perylene diimide (PDI) is a readily reducible electron-deficient dye that exhibits strong photoluminescent properties, providing new opportunities for synthesizing novel electrochemiluminescence (ECL) emitters. In this study, ethylene glycol (EG) was used to induce the self-assembly of PDI supramolecules for the preparation of ultrathin EG-PDI nanosheets characterized by low crystallinity and weak stacking interaction. Notably, EG-PDI integrates luminescent and catalytic functions into one device, accelerating the interfacial electron transfer and the faster charge transfer kinetics of EG-PDI with K2S2O8. Furthermore, the narrow band gap of EG-PDI facilitates its excitation at an ultra-low potential (-0.3 V). To improve the efficiency of tumor marker analysis, multifunctional Au nanostars (ANS) was introduced both as an energy acceptor of the ECL system and a probe for the photothermal system. Dual-mode immunoassay have demonstrated superior analytical performance in detecting alpha-fetoprotein (AFP), meeting the requirements of modern clinical diagnostics in resource-limited environments.

Alleviative effect of quercetin against reproductive toxicity induced by chronic exposure to the mixture of phthalates in male rats.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P < 0.05); Testicular histopathological observation showed that all seminiferous tubules were atrophy, leydig cells were hyperplasia, spermatogenic cells growth were arrested in MPEs group. Ultrastructural observation of testicular germ cells showed that the edges of the nuclear membranes were indistinct, and the mitochondria were severely damaged with the cristae disrupted, decreased or even disappeared in MPEs group. Immunohistochemistry and Western blot analysis showed that testicular CYP11A1, CYP17A1 and 17ß-HSD were up-regulated, while StAR, PIWIL1 and PIWIL2 were down-regulated in MPEs group (P < 0.05); However, the alterations of these parameters were restored in MPEs+Que group. The results indicated MPEs disturbed steroid hormone metabolism, and caused male reproductive injuries; whereas, Que could inhibit MPEs' male reproductive toxicity, which might relate to the restored regulation of steroid hormone metabolism.

A signal amplification electrochemiluminescence biosensor based on Ru(bpy)32+ and ß-cyclodextrin for detection of AFP.

By combining two different materials, metal-organic frameworks (MOF) and ß-cyclodextrins (ß-CD), a signal amplification electrochemical luminescence (ECL) immunosensor was constructed to realize the sensitive detection of AFP. The indium-based metal-organic framework (In-MOF) was used as the carrier of Ru(bpy)32+, and Ru(bpy)32+ was immobilized by In-MOF through suitable pore size and electrostatic interaction. At the same time, using host-guest recognition, ß-CD enriched TPA into the hydrophobic cavity for accelerating the electronic excitation of TPA, then, achieving the purpose of signal amplification. The signal amplification immunosensor structure is constructed among the primary antibody Ab1 connected to the Ru(bpy)32+@In-MOF modified electrode, AFP, BSA and the secondary antibody (Ab2) loaded with TPA-ß-CD. The immunosensor has a good linearity in the range of 10-5 ng/mL-50 ng/mL, and the low limit of detection (LOD) is 1.1 × 10-6 ng/mL. In addition, the electrochemiluminescence immunosensor that we designed has strong stability, good selectivity and repeatability, which provides a choice for the analysis of AFP.

Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.

Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.

Construction of a Dual-Mode Immune Platform Based on the Photothermal Effect of AgCo@NC NPs for the Detection of α-Fetoprotein.

Compared with the accuracy of a single signal and the limitation of environmental applicability, the application value of dual-mode detection is gradually increasing. To this end, based on the photothermal effect of Ag/Co embedded N-rich mesoporous carbon nanomaterials (AgCo@NC NPs), we designed a dual-mode signal response system for the detection of α-fetoprotein (AFP). First, AgCo@NC NPs act as a photothermal immunoprobe that converts light energy into heat driven by a near-infrared (NIR) laser and obtains temperature changes corresponding to the analyte concentration on a hand-held thermal imager. In addition, this temperature recognition system can significantly improve the efficiency of Fenton-like reactions. AgCo@NC NPs act as peroxidase mimics to initiate the generation of poly N-isopropylacrylamide (PNIPAM, resistance enhancer) by cascade catalysis and the degradation of methylene blue (MB), thus enabling electrochemical testing. The dual-mode assay ranges from 0.01 to 100 and 0.001-10 ng/mL, with lower limits of detection (LOD) of 3.2 and 0.089 pg/mL, respectively, and combines visualization, portability, and high efficiency, opening new avenues for future clinical diagnostics and inhibitor studies.

Current status and prospects of GREM1 research in cancer (Review).

GREM1 is a secreted protein that antagonizes bone morphogenetic proteins (BMPs) and participates in critical biological processes, including embryonic development, organogenesis and tissue differentiation. Gremlin 1 (GREM1) is also an inhibitor of TGF-ß and a ligand for vascular endothelial growth factor receptor 2. In addition, GREM1 can induce cells, participate in the process of epithelial-mesenchymal transition, and then participate in tumor development. GREM1 has a variety of biological functions and can participate in the malignant progression of a variety of tumors through the BMP signaling pathway. GREM1 also can inhibit TGF-ß in some tumors, thereby inhibiting tumors, and its involvement in tumor development varies in different types of cancer. The present review examines the role and function of GREM1 in tumors. GREM1 is expressed in a variety of tumor types. GREM1 expression can affect the epithelial-mesenchymal transformation of tumor cells. GREM1 has been studied in breast and colon cancer, and its potential role is to promote cancer. However, in pancreatic cancer, which was found to act differently from other cancer types, overexpression of GREM1 inhibits tumor metastasis. The present review suggests that GREM1 can be a diagnostic and prognostic indicator. In future studies, the study of GREM1 based on single-cell sequencing technology will further clarify its role and function in tumors.

Dual-functional Nanomaterials Polyo-phenylenediamine and Ru-Au Complement Each Other to Construct an Electrochemical and Electrochemiluminescent Dual-Mode Aptamer Sensor for Sensitive Detection of Alternariol.

To sensitively monitor trace amounts of alternariol (AOH) in fruits, a dual-mode aptamer sensor utilizing the dual-function nanomaterial PoPD/Ru-Au was developed. This sensor provides both electrochemical (EC) and electrochemiluminescence (ECL) signals, which can greatly avoid the potential false positive of the traditional single signal, thus enhancing the accuracy and reliability of detection results. Polyo-phenylenediamine (PoPD), known for its favorable EC response, can also assist in enhancing the ECL behavior of Ru-Au. Furthermore, Ru-Au demonstrates excellent ECL performance and effectively activates K2S2O8 to amplify the EC response of PoPD. The complementary effect of the two can effectively amplify the final detection signal. Additionally, the PoPD/Ru-Au nanomaterial exhibits excellent electrical conductivity, further enhancing the EC and ECL response signals. The experimental results demonstrate that the EC detection range of AOH was 0.01-100 ng/mL, while the ECL detection range was 0.001-100 ng/mL, both exhibiting a satisfactory linear relationship. Therefore, the mutual verification of the detection results can be highly realized, and the purpose of avoiding wrong detection can be achieved.

Construction of electrochemical and electrochemiluminescent dual-mode aptamer sensors based on ferrocene dual-functional signal probes for the sensitive detection of Alternariol.

In this study, a novel dual-mode aptamer sensor was developed using Fca-DNA2 as the quenching electrochemiluminescence (ECL) and electrochemical (EC) signal response probe, and Ru-MOF/Cu@Au NPs were used as the ECL substrate platform to detect Alternariol (AOH) via a competitive reaction between AOH and Fca-DNA2. Compared with the conventional aptamer sensor with a single detection signal, this dual-mode aptamer sensor has the following advantages: (1) Electrodeposition-based rapid synthesis Ru-MOF on the electrode surface. (2) The Signal amplification substance Cu@Au NPs can synergistically catalyze Triethanolamine (TEOA) to amplify ECL behavior. (3) The aptamer sensor employs the dual-functional material Fca, which can detect both ECL and EC signals, increasing the result accuracy. Both ECL and EC methods have excellent detection performance for AOH in the detection range of 0.1 pg/mL to 100 ng/mL, with detection limits of 0.014 and 0.083 pg/mL, respectively, and are expected to be used for sensitive AOH detection in real samples.