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Thanks to its structural characteristics and signal patterns similar to those of human brain synapses, memristors are widely believed to be applicable for neuromorphic computing. However, to our knowledge, memristors have not been effectively applied in the biomedical field, especially in disease diagnosis and health monitoring. In this work, a blood-based biomemristor was prepared for in vitro detection of hyperglycemia and hyperlipidemia. It was found that the device exhibits excellent resistance switching (RS) behavior at lower voltage biases. Through mechanism analysis, it has been confirmed that the RS behavior is driven by Ohmic conduction and ion rearrangement. Furthermore, the hyperglycemia and hyperlipidemia detection devices were constructed for the first time based on memristor logic circuits, and circuit simulations were conducted. These results confirm the feasibility of blood-based biomemristors in detecting hyperglycemia and hyperlipidemia, providing new prospects for the important application of memristors in the biomedical field.

The memristor, characterized by its resistive switching (RS) behavior, has garnered significant interest within the scientific community, particularly because of its vast potential applications in the fields of artificial intelligence (AI) and information storage. This is attributed to its unique properties, which align well with the requirements of advanced computational and memory systems. Ferroelectric memristors are currently a thriving area of research, and this study uses Sm-doped Pb(Mg1/3Nb2/3)O3–PbTiO3 (Sm-PMN-PT) and polyvinylidene difluoride (PVDF) as the functional layer. A multi-factor responsive memristor based on a Ag/Sm-PMN-PT:PVDF/ITO sandwich structure is fabricated, for which the RS behavior of the memristor can be adjusted by multi-factors such as voltage scanning rate, bias voltage amplitude, temperature and environmental humidity. Specifically, this device is sensitive to changes in environmental humidity and exhibits the properties of an artificial neural synapse. These advantageous characteristics endow this device with great potential for use in environmental sensors and artificial neural network (ANN) systems.

Conventional implantable electronics based on von Neumann architectures encounter significant limitations in computing and processing vast biological information due to computational bottlenecks. The memristor with integrated memory-computing and low power consumption offer a promising solution to overcome the computational bottleneck and Moore's law limitations of traditional silicon-based implantable devices, making them the most promising candidates for next-generation implantable devices. In this work, a highly stable memristor with an Ag/BaTiO3/MnO2/FTO structure was fabricated, demonstrating retention characteristics exceeding 1200 cycles and endurance above 1000 s. The device successfully exhibited three-stage responses to biological signals after implantation in SD (Sprague-Dawley) rats. Importantly, the memristor perform remarkable reversibility, maintaining over 100 cycles of stable repetition even after extraction from the rat. This study provides a new perspective on the biomedical application of memristors, expanding the potential of implantable memristive devices in intelligent medical fields such as health monitoring and auxiliary diagnostics.

Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed bulk RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, providing a reference for the scientific use of BMP4 and bFGF/BMP4-induced qNSCs models.

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The application of PARP inhibitors has revolutionized cancer treatment and has achieved significant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efficacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efficiency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efficacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic.

Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

To elucidate the impact of decision-makers’ risk preferences on the perishable-goods supply chain system during demand fluctuations, this study utilizes prospect theory and system dynamics to develop a simulation model that incorporates decision-makers’ risk attitudes. By solving this model with different parameter settings, the Lyapunov exponent is obtained to determine the system’s stability domain under different scenarios. Retailer losses are evaluated using spoilage conversion rates and fresh product stockouts, shedding light on the relationship between system stability and retailer losses. The research aims to explore the optimal ordering strategy under demand fluctuations. The findings indicate that inappropriate inventory strategies, coupled with decision-makers’ risk attitudes, can lead to system oscillations and substantial losses. Conversely, an appropriate inventory strategy coupled with moderate risk aversion can help mitigate retailer losses. [ABSTRACT FROM AUTHOR]

IntroductionOvarian cancer (OV) is a highly lethal gynecological malignancy with a poor prognosis. Lactate metabolism is crucial for tumor cell survival, proliferation, and immune evasion. Our study aims to investigate the role of lactate metabolism-related genes (LMRGs) in OV and their potential as biomarkers for prognosis, immune microenvironment, and immunotherapy response.MethodsOvarian samples were collected from the TCGA cohort. And 12 lactate-related pathways were identified from the MsigDB database. Differentially expressed genes within these pathways were designated as LMRGs, which undergo unsupervised clustering to identify distinct clusters based on LMRGs. Subsequently, we assessed survival outcomes, immune cell infiltration levels, Hallmaker pathway activation patterns, and chemotaxis among different subtypes. After conducting additional unsupervised clustering based on differentially expressed genes (DEGs), significant differences in the expression of LMRGs between the two clusters were observed. The differentially expressed genes were subjected to subsequent functional enrichment analysis. Furthermore, we construct a model incorporating LMRGs. Subsequently, the lactate score for each tumor sample was calculated based on this model, facilitating the classification of samples into high and low groups according to their respective lactate scores. Distinct groups examined disparities in survival prognosis, copy number variation (CNV), single nucleotide variation (SNV), and immune infiltration. The lactate score served as a quantitative measure of OV's lactate metabolism pattern and an independent prognostic factor.ResultsThis study investigated the potential role of LMRGs in tumor microenvironment diversity and prognosis in OV, suggesting that LMRGs play a crucial role in OV progression and the tumor microenvironment, thus serving as novel indicators for prognosis, immune microenvironment status, and response to immunotherapy.