Steerable Structural Evolvement and Adsorption Behavior of Metastable Polyoxovanadate-Based Metal-Organic Polyhedra.

Promoting the advancement of the structure and function of metastable substances is challenging but worthwhile. In particular, how to harness the entangled state and evolution path of labile porous structures has been at the forefront of research in molecular self-assembly. In this work, the metastable structures of polyoxovanadate-based metal-organic polyhedra (VMOPs) can be manually regulated, including separation of the interlocked aggregate by a ligand-widening approach as well as transformation from a tetrahedral to capsule-like scaffold via a vertice-remodeling strategy. In these processes, intra- and intermolecular π···π and C-H···π interactions have been recognized as the primary driving forces. Besides being responsible for commanding the structural evolvement of VMOPs, such weak interactions were able to program their spatial arrangements and hence the adsorption performances for dye and iodine. The successful use of such a weak force-dominated design concept beacons a feasible route for customization of the function-oriented metastable structures. Separation and transformation of the interlocked metastable VMOPs have been achieved via the respective ligand-widening approach and vertice-remodeling strategy. Not only their structures but also adsorption features could be well regulated by such a weak force-dominated design concept.

Establishment of a method for detecting Trichinella spiralis in ovine muscle tissues using real-time fluorescence quantitative PCR.

Trichinellosis is caused by Trichinella spiralis, a meat-borne zoonotic disease transmitted to humans through the consumption of infected undercooked or raw meat. Surveillance using safe and precise diagnostic tools to diagnose T. spiralis in sheep is needed to assess the incidence and probability of transmission from sheep to humans. In this study, we developed a real-time PCR assay to detect T. spiralis DNA in ovine muscle samples that can be used as an alternative surveillance tool to ensure food safety using newly designed primers. The assay is specific for the Scfld4 gene of Trichinella (T1) and enables the detection of larvae in ovine muscle tissue samples with high sensitivity and specificity. Trichuris ovis, Oesophagostomum dentatum, Haemonchus contortus, and Bunostomum trigonocephalum showed no nonspecific amplification. The assay could detect Trichinella DNA concentrations as low as 0.0026 ng/µL, equivalent to 0.0064 larvae, indicating a high sensitivity for T. spiralis detection. We used this real-time PCR to detect 73 ovine muscle samples from an ovine abattoir, and five samples tested positive via real-time PCR but negative via microscopy. This assay may provide a more specific and sensitive method for rapidly detecting Trichinella larvae in ovine muscle tissues.

XGBoost-based machine learning test improves the accuracy of hemorrhage prediction among geriatric patients with long-term administration of rivaroxaban.

BACKGROUND: Hemorrhage is a potential and serious adverse drug reaction, especially for geriatric patients with long-term administration of rivaroxaban. It is essential to establish an effective model for predicting bleeding events, which could improve the safety of rivaroxaban use in clinical practice. METHODS: The hemorrhage information of 798 geriatric patients (over the age of 70 years) who needed long-term administration of rivaroxaban for anticoagulation therapy was constantly tracked and recorded through a well-established clinical follow-up system. Relying on the 27 collected clinical indicators of these patients, conventional logistic regression analysis, random forest and XGBoost-based machine learning approaches were applied to analyze the hemorrhagic risk factors and establish the corresponding prediction models. Furthermore, the performance of the models was tested and compared by the area under curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: A total of 112 patients (14.0%) had bleeding adverse events after treatment with rivaroxaban for more than 3 months. Among them, 96 patients had gastrointestinal and intracranial hemorrhage during treatment, which accounted for 83.18% of the total hemorrhagic events. The logistic regression, random forest and XGBoost models were established with AUCs of 0.679, 0.672 and 0.776, respectively. The XGBoost model showed the best predictive performance in terms of discrimination, accuracy and calibration among all the models. CONCLUSION: An XGBoost-based model with good discrimination and accuracy was built to predict the hemorrhage risk of rivaroxaban, which will facilitate individualized treatment for geriatric patients.

Piezotronic Effect-Assisted Photoelectrochemical Exosomal MicroRNA Monitoring Based on an Electron Donor Self-Supplying Strategy.

Exosomal microRNAs (miRNAs) as newly emerging reliable and noninvasive biomarkers have demonstrated a significant function in early cancer diagnosis. Photoelectrochemical (PEC) biosensing has attracted unprecedented attention in exosomal miRNA monitoring due to its inherent advantages of both electrochemical and optical techniques; however, the severe charge carrier recombination greatly restricts the PEC assay performance. Herein, a high-sensitive PEC strategy assisted by the piezoelectric effect is designed based on Bi2WO6/Cu2S heterojunctions and implemented for the monitoring of exosomal miRNAs. The introduction of the piezoelectric effect enables promoted electron-hole transfer and separation, thereby improving the analytical sensitivity. In addition, a target reprogramming metal-organic framework-capped CaO2 (MOF@CaO2) hybrids is prepared, in which MOF@CaO2 being responsive to exosomal miRNAs induces exposure of the capped CaO2 to H2O and then triggers self-supplying of H2O2, which effectively suppresses the electron-hole recombination, giving rise to an amplified photocurrent and a decrease in the cost of the reaction. Benefiting from the coupled sensitization strategy, the as-fabricated PEC strategy exhibits high sensitivity, specificity, low cost, and ease of use for real-time analysis of exosomal miRNAs within the effectiveness linear range of 0.1 fM-1 µM. The present work demonstrates promising external field coupling-enhanced PEC bioassay and offers innovative thoughts for applying this strategy in other fields.

Photoelectrochemical Detection of Exosomal miRNAs by Combining Target-Programmed Controllable Signal Quenching Engineering.

MicroRNAs extracted from exosomes (exosomal miRNAs) have recently emerged as promising biomarkers for early prognosis and diagnosis. Thus, the development of an effective approach for exosomal miRNA monitoring has triggered extensive attention. Herein, a sensitive photoelectrochemical (PEC) biosensing platform is demonstrated for exosomal miRNA assay via the target miRNA-powered λ-exonuclease for the amplification strategy. The metal-organic framework (MOF)-decorated WO3 nanoflakes heterostructure is constructed and implemented as the photoelectrode. Also, a target exosomal miRNA-activatable programmed release nanocarrier was fabricated, which is responsible for signal control. Hemin that acted as the electron acceptor was prior entrapped into the programmed control release nanocarriers. Once the target exosomal miRNAs-21 was introduced, the as-prepared programmed release nanocarriers were initiated to trigger the release of hemin, which enabled the quenching of the photocurrent. Under the optimized conditions, the level of exosomal miRNAs-21 could be accurately tracked ranging from 1 fM to 0.1 µM with a low detection limit of 0.5 fM. The discoveries illustrate the possibility for the rapid and efficient diagnosis and prognosis prediction of diseases based on the detection of exosomal miRNAs-21 and would provide feasible approaches for the fabrication of an efficient platform for clinical applications.

miR-31-5p promotes proliferation and inhibits apoptosis of goat hair follicle stem cells by targeting RASA1/MAP3K1 pathway.

The Yangtze River Delta white goat is a sole goat species that can naturally produce superior-quality brush hair. It's worth to mention that study the developmental mechanism of goat hair follicle stem cells is vital for future breed preservation and molecular breeding. In this study, we successfully isolated hair follicle stem cells from the skin tissue of fetal sheep neck spine, and harvested superior-quality and normal-quality brush hair goat tissue. The expression of miR-31-5p in goat hair follicle stem cells was verified by qPCR and Western blot. The effects of overexpression or inhibition of miR-31-5p on the proliferation and apoptosis of hair follicle stem cells were detected by EdU, CCK-8, flow cytometry, etc. miR-31-5p can significantly improve cell proliferation and inhibit cell apoptosis by targeting RASA1 and upregulating MAP3K1 level, whereas miR-31-5p knockdown led to an opposite effect. These results reveal a miR-31-5p-associated regulatory network between miR-31-5p and RASA1/MAP3K1 during the progression of superiorquality brush hair traits.

Integrative analysis of circRNAs from Yangtze River Delta white goat neck skin tissue by high-throughput sequencing (circRNA-seq).

The Yangtze River Delta white goat is a unique goat species that can produce superior-quality brush hair. The formation of this brush hair is controlled by a series of critical genes and related signaling pathways. Circular RNAs (circRNAs), are ubiquitous endogenous non-coding RNAs that regulate many biological and physiological processes in mammals. However, little is known about the potential regulatory role of circRNAs on superior-quality brush hair formation in Yangtze River Delta white goat. In this study, high-throughput sequencing technology was used to only detect circRNAs in the neck skin tissue of normal-quality goats (NHQs) and superior-quality goats (HQs). A total of 61 803 circRNAs were identified and 32 of them were differentially expressed in the NHQ group vs. the HQ group. Functional enrichment analysis showed that the source gene of differentially expressed circRNAs (DE-circRNAs) was enriched mostly in platelet activation and the focal adhesion signal pathway. Action mechanism analysis revealed that DE-circRNAs could sponge to many identified miRNAs, including miR-31, miR-125b, miR-let-7a and miR-149-5p, which have important roles in goat hair follicle stem cell growth, hair follicle development and morphogenesis. Altogether, our findings provide a valuable basis for studying circRNAs involved in superior-quality brush hair traits and meanwhile advance our understanding of circRNA complex regulation mechanisms in Yangtze River Delta white goat skin hair follicle development.

Paper-Based Constant Potential Electrochemiluminescence Sensing Platform with Black Phosphorus as a Luminophore Enabled by a Perovskite Solar Cell.

Exploring efficient luminophores in the electrochemiluminescence (ECL) system is highly desired to pursue a sensitive ECL sensing platform. Herein, the black phosphorus nanosheets (BP NSs) with excellent ECL properties are investigated and serve as the luminophore with the coreactant of peroxydisulfate (S2O82-) solution. Moreover, owing to the overlapping of emission and absorbance spectra, effective resonance energy transfer (RET) is realized between the BP NSs and the introduced Au nanoparticles. In order to achieve the portable and miniaturized developing trends for the paper-based ECL sensing platform, a paper-based perovskite solar cell (PSC) device is designed to act as the power source to replace the commonly utilized expensive and cumbersome electrochemical workstation. Benefiting from that, a PSC driven paper-based constant potential ECL-RET sensing platform is constructed, thereby realizing sensitive microRNAs (miRNAs) detection. What's more, to attain the preferable analytical performance, the duplex-specific nuclease (DSN) is also introduced to assist the target recycling signal amplification strategy. Based on this, highly sensitive detection of miRNA-107 with a range from 0.1 pM to 15 nM is achieved by this designed sensing platform. Most importantly, this work not only pioneers a precedent for developing a high-sensitivity PSC triggered ECL sensing platform but also explores the application prospect of BP nanomaterial in the field of bioanalysis.

Visual distance readout to display the level of energy generation in paper-based biofuel cells: application to enzymatic sensing of glucose.

Biofuel cells (BFCs) based on anodic oxidation and cathodic oxygen reduction represent an attractive alternative to self-powered devices. A glucose/oxygen BFC is described for monitoring glucose. It is making use of a piece of paper carrying a glucose oxidase (GOx) based bioanode, and a bilirubin oxidase (BilOx) based biocathode. The performance of the BFC is affected by the generation of H2O2, a byproduct of enzymatic glucose oxidation. Therefore, the removal of H2O2 is a crucial step in terms of BFC performance and stability. In addition, direct, unambiguous visual read-out is an ideal way to provide quantitative information. The colorimetric readout system described here is based on the consumption of undesired H2O2 and to convert the extent of energy generation into recognizable variations in color. As the H2O2 travels along the hydrophilic channel by capillary action, the formation of red gold nanoparticles from AuCl4- leads to the appearance of a red bar that provides distance-based information that can be read visually. The multiply readable information (maximum power density of BFC or visible distance) provides further choices for quantification. It also enhances reliability. The self-powered system based on the BFC exhibits excellent performance. Glucose can be determined by this method in the 1 to 50 mM concentration range. Graphical abstract Schematic presentation of a paper-supported biofuel cell equipped with a visual distance readout to display the level of energy generation in biofuel cells, and its application in sensing of glucose.

"On-Off-On" Photoelectrochemical/Visual Lab-on-Paper Sensing via Signal Amplification of CdS Quantum Dots@Leaf-Shape ZnO and Quenching of Au-Modified Prism-Anchored Octahedral CeO2 Nanoparticles.

An effective "on-off-on" photoelectrochemical (PEC)/visual sensing system based on cleaning-switchable lab-on-paper device was designed to achieve ultrasensitive detection of analytes. The first amplified "signal-on" PEC state was gained by CdS quantum dots sensitized leaf-shape ZnO (CdS QDs/leaf-shape ZnO) structure, which was assembled on reduced graphene oxide (rGO) modified paper electrode. Then Au-modified prism-anchored octahedral CeO2 nanoparticles (Au@PO-CeO2 NPs), as an efficient signal quencher, were immobilized on the CdS QDs/leaf-shape ZnO with the assistance of DNA hybridization, resulting in a noticeable photocurrent response decrement with the "signal-off" PEC state. With the addition of analytes, the quencher Au@PO-CeO2 NPs were immediately released from the sensing surface and robust PEC response was recovered to the signal-on state again. Meanwhile, the disengaged quencher in electrolyte solution flowed to the colorimetric detection area of lab-on-paper device and catalyzed oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine in the presence of H2O2 to form the colored product, making the analytes detection more convincing with the visual discrimination. Under optimal conditions, the proposed PEC/visual lab-on-paper device possessed the detection limits toward adenosine and potassium ion as low as 0.15 and 0.06 nM, respectively. With ingenious design of actuating conversion process between hydrophilicity and hydrophobicity by slipping paper tab to solve cleaning issue in the assay procedures, the cleaning-switchable lab-on-paper device was constructed for high-performance biosensing applications. It provides an unambiguous simplicity and portable operation for exploring high reliability and sensitivity of novel point-of-care diagnostic tool with dual-signal readout.

Electrochemiluminescence behavior of AgNCs and its application in immunosensors based on PANI/PPy-Ag dendrite-modified electrode.

In this study, hyperbranched polyethyleneimine-protected silver nanoclusters (hPEI-AgNCs) with excellent electrochemiluminescence (ECL) emission in the presence of coreactant K2S2O8 were prepared by chemical reduction of silver ions (silver nitrate) coordinated with dendrigraft polymer, and successfully used for the construction of an ECL immunosensor. Polyaniline (PANI)/polypyrrole (PPy)-silver (Ag) dendrites with good electrical conductivity and biocompatibility were electropolymerized on the surface of indium tin oxide (ITO) electrode as carriers. Porous ZnO sphere-loaded hPEI-AgNCs-induced signal amplification strategies were integrated exquisitely and applied sufficiently. Taking carcinoembryonic antigen (CEA) as an example, under optimal conditions, the CEA concentration was determined to be in the range of 10-3 ng mL-1-100 ng mL-1 and with a detection limit of 0.4 pg mL-1 using this method; it exhibited excellent selectivity, high stability, and acceptable fabrication reproducibility. It was anticipated that hPEI-AgNCs would have promising applications in green, selective, and sensitive detection of target analytes in the future.

MicroR-545 enhanced radiosensitivity via suppressing Ku70 expression in Lewis lung carcinoma xenograft model.

OBJECTIVE: Radiotherapy is an important therapeutic method for lung cancer. However, in clinical situations, cellular resistance to radiotherapy is a significant component of tumor treatment failure. Thus, clarification in cellular mechanism underlying radiosensitivity of cancer cell is urgently needed. In this study, we established a radiation model of Lewis lung carcinoma in C57BL/6 mice and investigated the possible signaling molecule involved in this process. METHODS: C57BL/6 mice were subcutaneously transplanted with Lewis lung carcinoma cells and locally irradiated followed by measurement in tumor volume. Levels of miR-545 and Ku70 mRNA expression were determined by using Quantitative Real-Time PCR. Expression of Ku70 was determined by using western blot assay. Cell viability was analyzed by MTT assay. Cell apoptosis was examined by using TUNEL assay. RESULTS: In mice bearing Lewis lung carcinoma tumor, local radiotherapy suppressed tumor growth as well as enhanced expression of miR-545 and downregulated Ku70 level. Inhibition of miR-545 expression reduced radiosensitivity of Lewis tumor. In vitro Lewis lung carcinoma cells experiment, we observed that miR-545 regulated Ku70 expression by targeting Ku70 3'UTR and this process was involved in radiotherapy. This was demonstrated by result of cell proliferation assay in which irradiation reduced apoptosis of cells was mediated by miR-545 inactivation which was reversed by Ku70 silence. CONCLUSION: miR-545 increased radiosensitivity of Lewis lung carcinoma via inhibiting Ku70 expression.

Self-powered and sensitive DNA detection in a three-dimensional origami-based biofuel cell based on a porous Pt-paper cathode.

In this work, a mediator-less and compartment-less glucose/air enzymatic biofuel cell (BFC) was introduced into microfluidic paper-based analytical devices (µ-PADs) with gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs)-modified paper electrode as the anodic and cathodic substrate, respectively, to implement self-powered, sensitive, low-cost and simple DNA detection. As a further development of the analytical equipment, an all-solid-state paper supercapacitor (PS) was designed and integrated into the BFC for current amplification, and a terminal digital multi-meter detector (DMM) was introduced for the current detection. A highly sensitive DNA sensor was fabricated by covalently immobilizing the capture DNA in the AuNPs-modified anode. The nanoporous gold conjugated with bienzymes, glucose oxidase and horseradish peroxidase, which were used as electrochemical labels. The electrons generated at the anode flow through an external circuit to the PtNPs-modified cathode that catalyzed the reduction of oxygen with the participation of protons. In addition, the generated current could be collected and stored by the PS. After that, the PS was automatically shorted under the control of a switch to output an instantaneously amplified current, which could be sensitively detected by the terminal DMM. At the optimal conditions, the paper-based analytical platform can detect DNA at the femtomole level. This approach also shows excellent specificity toward single nucleotide mismatches.

Incidence, prevalence, and mortality of schizophrenia from 2016 to 2020 in Shandong, China.

The epidemiology of schizophrenia has been reported in many countries. However, due to the limitations of those studies, the findings cannot be generalized to other parts of the world, especially in China. In this study, the incidence, prevalence, and mortality of schizophrenia in Shandong, China were calculated using data from the National Severe Mental Disorder Registration System collected between 2016 and 2020 and census data from 2010 to 2020. The overall incidence decreased from 9.61 per 100,000 in 2016 to 4.40 per 100,000 in 2020, the aggregate prevalence was approximately 3.20 per 1000, and the overall mortality ranged from 6.17 per 100,000 to 7.71 per 100,000. The evidence from this study indicated that the incidence, prevalence, and mortality of schizophrenia were higher in rural areas than in urban areas. Females had higher incidence, prevalence, and mortality than males. This study provided epidemiological information on schizophrenia and opened avenues for future research.

Construction of built-in correction photoelectrochemical sensing platform for diagnosis of Alzheimer's disease.

The occurrence of Alzheimer's disease (AD) is strongly associated with the progressive aggregation of a 42-amino-acid fragment derived from the amyloid-ß precursor protein (Aß1-42). Therefore, it is crucial to establish a versatile platform that can effectively detect Aß1-42 to aid in the early-stage preclinical diagnosis of AD. Herein, we introduce a specialized split-type analytical platform that enables sensitive and accurate monitoring of Aß1-42 based on a self-corrected photoelectrochemical (PEC) sensing system. To realize this design, gelatinized Ti3C2@Bi2WO6 Schottky heterojunctions were prepared and served as photoelectrodes for tackling the photoinduced charge carriers. Functionalized CaCO3@CuO2 nanocomposites were used as signal converters to detect Aß1-42 and amplify the signal further. Benefiting from the glucose oxidation induced acid microenvironment and H2O2 output, the nanocomposites are able to rapidly decompose, producing Ca2+ and Fenton-like catalyst Cu2+. The Cu2+-driven Fenton-like reaction generated ·OH, which accelerated the 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. Additionally, Ca2+ was cross-linked with alginate inducing gelation on the surface of Ti3C2@Bi2WO6 Schottky heterojunctions, influencing mass transfer and light absorption. Eventually results in the shift of photocurrent, allowing for precise quantification with a detection limit of 0.06 pg mL-1. The combination of colorimetric variation and the photoelectric effect provide a more accurate and reliable result. This research opens up new possibilities for constructing PEC platforms and beyond.

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment have shown promising results, multicentre randomised controlled phase II clinical trials remain uncommon. The primary aim of this trial is to assess the safety and efficacy of different MSCs treatment courses for ACLF. METHODS AND ANALYSIS: This is a multicentre, double-blind, two-stage, randomised and placebo-controlled clinical trial. In the first stage, 150 patients with ACLF will be enrolled and randomly assigned to either a control group (50 cases) or an MSCs treatment group (100 cases). They will receive either a placebo or umbilical cord-derived MSCs (UC-MSCs) treatment three times (at weeks 0, 1 and 2). In the second stage, 28 days after the first UC-MSCs infusion, surviving patients in the MSCs treatment group will be further randomly divided into MSCs-short and MSCs-prolonged groups at a 1:1 ratio. They will receive two additional rounds of placebo or UC-MSCs treatment at weeks 4 and 5. The primary endpoints are the transplant-free survival rate and the incidence of treatment-related adverse events. Secondary endpoints include international normalised ratio, total bilirubin, serum albumin, blood urea nitrogen, model for end-stage liver disease score and Child-Turcotte-Pugh score. ETHICS AND DISSEMINATION: Ethical approval of this study has been obtained from the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-3-19-1). All results of the study will be submitted to international journals and international conferences for publication on completion of the study. TRIAL REGISTRATION NUMBER: NCT05985863.

In Situ Wire + Powder Synchronous Arc Additive Manufacturing of Ti-Cu Alloys.

In this study, a new wire + powder synchronous arc additive manufacturing technique was used to manufacture Ti-Cu alloys. The microstructure and properties of the as-fabricated alloys were studied. The results showed that the prepared Ti-Cu alloys have good properties. The Cu with high growth restriction factor can increase the constitutional supercooling zone in the Ti-Cu alloys, which can override the negative effect of a high thermal gradient in the manufacturing process. Through the observation of the microstructure, the as-printed Ti-Cu alloy specimens have equiaxed fine-grained microstructure. Through corrosion performance analysis, the Cu can also make the passivation film of the alloy more compact and make the alloy more corrosion resistant.

Characteristics and functions of an atypical inflammation-associated GZMK+GZMB+CD8+ T subset in people living with HIV-1.

HIV-1 chronically infects host CD4+ T lymphocytes and further affects a variety of immune cells, including CD8+ T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK+CD8+ T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK+CD8+ T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK+CD8+ T cells, which could be further subdivided into a GZMK+GZMB- subset and a GZMK+GZMB+ subset, with the latter being significantly enriched in PLWHs. The GZMK+GZMB+ cells are a unique subset within CD8+ T cells, characterized by high proliferation, activation, inflammatory response, clone transition, etc., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αß T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK+GZMB- subset, the GZMK+GZMB+ subset exhibits differentiation at a later stage than the GZMK+GZMB- subset. We also observed that the frequency/count of GZMK+GZMB+CD8+ T cells was negatively correlated with CD4/CD8 ratio, and positively correlated with HIV DNA, IP-10, and MIG levels in PLWHs. In vitro experiments demonstrate that GZMK can potentiate the stimulatory effects of lipopolysaccharide (LPS) on THP-1 macrophages via the TLR-4 pathway, significantly enhancing the secretion of IP-10, MIG, and MCP-1, as well as increasing the proportion of TNF-α+ cells. In conclusion, in PLWHs, GZMK+GZMB+CD8+ T cells are a highly reactive and inflammatory-inducing subset that may be associated with systemic inflammation.

A visible light photoelectrochemical sensor for tumor marker detection using tin dioxide quantum dot-graphene as labels.

In this paper, a simple and sensitive sandwich-type photoelectrochemical (PEC) immunosensor for measurement of biomarkers on a gold nanoparticle-modified indium tin oxide (ITO) electrode through electrodeposition for point-of-care testing was developed by using a tin dioxide quantum dot-graphene nanocomposite (G-SnO2) as an excellent label with amplification techniques. The capture antibody (Ab1) was firstly immobilized on the gold nanoparticle-modified ITO electrode due to the covalent conjugation, then the antigen and the AuNP/PDDA-G-SnO2 nanocomposite nanoparticle labeled signal antibody (Ab2) were conjugated successively to form a sandwich-type immunocomplex through a specific interaction. Under irradiation with a common ultraviolet lamp (∼365 nm, price $50), the SnO2 NPs were excited and underwent charge-separation to yield electrons (e(-)) and holes (h(+)). As the holes were scavenged by ascorbic acid (AA), the electrons were transferred to the ITO electrode through RGO to generate a photocurrent. The photocurrents were proportional to the CEA concentrations, and the linear range of the developed immunosensor was from 0.005 to 10 ng mL(-1) with a detection limit of 0.036 pg mL(-1). The proposed sensor shows high sensitivity, stability, reproducibility, and can become a promising platform for other biomolecular detection.

DNAzyme-Mediated Biodeposition Coupling Adjustable Cascade Electric Fields for Photoelectrochemical Telomerase Activity Monitoring.

Telomerase, as a specialized reverse transcriptase, plays a vital role in early cancer diagnostics and prognosis; thus, developing efficient sensing technologies is of vital importance. Herein, an innovative "signal-on-off" photoelectrochemical (PEC) sensing platform was developed for ultrasensitive evaluation of telomerase activity based on an electron-transfer tunneling distance regulation strategy and DNAzyme-triggerable biocatalytic precipitation. Concretely, cascade internal electric fields between CuInS2 quantum dots (QDs), graphitic carbon nitride nanosheets (g-C3N4 NSs), and TiO2 nanorod arrays (NRAs) were developed to realize cascade electron extraction and hole transfer. Enabled by such a design, an effective "signal-on" state to gain a progressively enhanced PEC output was designed by suppressing the photogenerated electron-hole pair recombination. With the introduction of hairpin probe H2 and the subsequent extension of the primer sequence driven by the target telomerase, the CuInS2 QDs labeled with hairpin probe H1 were programmatically unfolded, resulting in CuInS2 QDs' close proximity to the working electrode away from the cascade interface, accompanied by the formation of G-quadruplex/hemin complexes. The gradual undermining of tunneling distance and implantation of DNAzyme-initiating biocatalytic precipitation tremendously induced the sluggish migration kinetics of the photoinduced charge, accompanied by the photocurrent intensity decrement, leading to the "signal-off" state. Under optimized conditions, the as-prepared PEC biosensor realizes ultrasensitive detection of telomerase activity from 10 to 105 cell·mL-1 with a detection limitation of 3 cells·mL-1. As a proof of concept, this well-designed method provides new insights into signal amplification for telomerase activity evaluation and also presents promising potential for further development in drug screening, healthcare diagnostics, and biological assays.