Halide Perovskite Inducing Anomalous Nonvolatile Polarization in Poly(vinylidene fluoride)-based Flexible Nanocomposites.

Ferroelectric materials have important applications in transduction, data storage, and nonlinear optics. Inorganic ferroelectrics such as lead zirconate titanate possess large polarization, though they are rigid and brittle. Ferroelectric polymers are light weight and flexible, yet their polarization is low, bottlenecked at 10 µC cm-2. Here we show poly(vinylidene fluoride) nanocomposite with only 0.94% of self-nucleated CH3NH3PbBr3 nanocrystals exhibits anomalously large polarization (~19.6 µC cm-2) while retaining superior stretchability and photoluminance, resulting in unprecedented electromechanical figures of merit among ferroelectrics. Comprehensive analysis suggests the enhancement is accomplished via delicate defect engineering, with field-induced Frenkel pairs in halide perovskite stabilized by the poled ferroelectric polymer through interfacial coupling. The strategy is general, working in poly(vinylidene fluoride-co-hexafluoropropylene) as well, and the nanocomposite is stable. The study thus presents a solution for overcoming the electromechanical dilemma of ferroelectrics while enabling additional optic-activity, ideal for multifunctional flexible electronics applications.

Methotrexate and the Risk of Dementia: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. METHODS: We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. RESULTS: Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. CONCLUSION: The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

High-Efficiency Circularly Polarized Light-Emitting Diodes Based on Chiral Metal Nanoclusters.

Circularly polarized light-emitting diodes (CP-LEDs) are critical for next-generation optical technologies, ranging from holography to quantum information processing. Currently deployed chiral luminescent materials, with their intricate synthesis and processing and limited efficiency, are the main bottleneck for CP-LEDs. Chiral metal nanoclusters (MNCs) are potential CP-LED materials, given their ease of synthesis and processability as well as diverse structures and excited states. However, their films are usually plagued by inferior electronic quality and aggregation-caused photoluminescence quenching, necessitating their incorporation into host materials; without such a scheme, MNC-based LEDs exhibit external quantum efficiencies (EQEs) < 10%. Herein, we achieve an efficiency leap for both CP-LEDs and cluster-based LEDs by using novel chiral MNCs with aggregation-induced emission enhancement. CP-LEDs using enantiopure MNC films attain EQEs of up to 23.5%. Furthermore, by incorporating host materials, the devices yield record EQEs of up to 36.5% for both CP-LEDs and cluster-based LEDs, along with electroluminescence dissymmetry factors (|gEL|) of around 1.0 × 10-3. These findings open a new avenue for advancing chiral light sources for next-generation optoelectronics.

A bibliometric analysis of the research status and trends in studies on polymyositis and dermatomyositis with interstitial lung disease from 2000 to 2022 using Web of Science.

BACKGROUND: The main subtypes of idiopathic inflammatory myopathies (IIMs)-polymyositis (PM) and dermatomyositis (DM)-are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. METHODS: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. RESULTS: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. CONCLUSION: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.

An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Recent progress in biosensor regeneration techniques.

Biosensors are widely used in various applications, from medical diagnostics to environmental monitoring. Their widespread and continuous use necessitates regeneration methods to ensure cost-effectiveness and sustainability. In the realm of advancing human-centric bioelectronics for continuous monitoring, employing these sensors for real-time, in situ detection of biomarkers presents a considerable challenge. This mini-review examines diverse strategies utilized for the regeneration of biosensors, categorizing them based on their underlying mechanisms and discussing representative works. We explore methods ranging from surface engineering/re-functionalization, chemical treatments, allosteric regulation of bioreceptors, to manipulations of electric/magnetic fields, highlighting their working principles and exemplary studies. The advantages of each method, such as simplicity, high regeneration efficiency, and versatility, are discussed alongside their challenges, including degradation over cycles, limited applicability, and potential damage to sensors. As the demand for continuous and real-time biosensing escalates, the development of efficient and reliable regeneration strategies becomes essential. This mini-review offers an overview of the current landscape of biosensor regeneration, aiming to guide future research and innovations in this area.

Electrically and mechanically driven rotation of polar spirals in a relaxor ferroelectric polymer.

Topology created by quasi-continuous spatial variations of a local polarization direction represents an exotic state of matter, but field-driven manipulation has been hitherto limited to creation and destruction. Here we report that relatively small electric or mechanical fields can drive the non-volatile rotation of polar spirals in discretized microregions of the relaxor ferroelectric polymer poly(vinylidene fluoride-ran-trifluoroethylene). These polar spirals arise from the asymmetric Coulomb interaction between vertically aligned helical polymer chains, and can be rotated in-plane through various angles with robust retention. Given also that our manipulation of topological order can be detected via infrared absorption, our work suggests a new direction for the application of complex materials.

Ni Single-Atom Bual Catalytic Electrodes for Long Life and High Energy Efficiency Zinc-Iodine Batteries.

Zinc-iodine batteries (Zn-I2) are extremely attractive as the safe and cost-effective scalable energy storage system in the stationary applications. However, the inefficient redox kinetics and "shuttling effect" of iodine species result in unsatisfactory energy efficiency and short cycle life, hindering their commercialization. In this work, Ni single atoms highly dispersed on carbon fibers is designed and synthesized as iodine anchoring sites and dual catalysts for Zn-I2 batteries, and successfully inhibit the iodine species shuttling and boost dual reaction kinetics. Theoretical calculations indicate that the reinforced d-p orbital hybridization and charge interaction between Ni single-atoms and iodine species effectively enhance the confinement of iodine species. Ni single-atoms also accelerate the iodine conversion reactions with tailored bonding structure of I─I bonds and reduced energy barrier for the dual conversion of iodine species. Consequently, the high-rate performance (180 mAh g-1 at 3 A g-1 ), cycling stability (capacity retention of 74% after 5900 cycles) and high energy efficiency (90% at 3 A g-1 ) are achieved. The work provides an effective strategy for the development of iodine hosts with high catalytic activity for Zn-I2 batteries.

A novel model for predicting prognosis and response to immunotherapy in nasopharyngeal carcinoma patients.

Blood-based biomarkers of immune checkpoint inhibitors (ICIs) response in patients with nasopharyngeal carcinoma (NPC) are lacking, so it is necessary to identify biomarkers to select NPC patients who will benefit most or least from ICIs. The absolute values of lymphocyte subpopulations, biochemical indexes, and blood routine tests were determined before ICIs-based treatments in the training cohort (n = 130). Then, the least absolute shrinkage and selection operator (Lasso) Cox regression analysis was developed to construct a prediction model. The performances of the prediction model were compared to TNM stage, treatment, and Epstein-Barr virus (EBV) DNA using the concordance index (C-index). Progression-free survival (PFS) was estimated by Kaplan-Meier (K-M) survival curve. Other 63 patients were used for validation cohort. The novel model composed of histologic subtypes, CD19+ B cells, natural killer (NK) cells, regulatory T cells, red blood cells (RBC), AST/ALT ratio (SLR), apolipoprotein B (Apo B), and lactic dehydrogenase (LDH). The C-index of this model was 0.784 in the training cohort and 0.735 in the validation cohort. K-M survival curve showed patients with high-risk scores had shorter PFS compared to the low-risk groups. For predicting immune therapy responses, the receiver operating characteristic (ROC), decision curve analysis (DCA), net reclassifcation improvement index (NRI) and integrated discrimination improvement index (IDI) of this model showed better predictive ability compared to EBV DNA. In this study, we constructed a novel model for prognostic prediction and immunotherapeutic response prediction in NPC patients, which may provide clinical assistance in selecting those patients who are likely to gain long-lasting clinical benefits to anti-PD-1 therapy.

Understanding the intention and behavior of psychological help-seeking among Chinese college students using theory of planned behavior: a three-month follow-up study.

Underutilization of mental health services is common and associated with substantial suffering, mental disorders and death. The present study aimed to explore factors significantly affecting the professional psychological help-seeking behavior based on the Theory of Planned Behavior (TPB). A sample of 597 Chinese college students recruited online completed the questionnaires, which measured four constructs of TPB including help-seeking intention, attitude, subjective norm and perceived behavioral control in December 2020. Help-seeking behaviors were evaluated three months later in March 2021. A two-step structural equation modeling procedure was used to test the TPB model. Findings show that partially consistent with TPB, more positive attitudes about seeking professional help (Β = .258, p = .001) and higher perceived behavioral control (Β = .504, p < .001) directly predicted higher intention to seek mental health services, and perceived behavioral control (Β = .230, p = .006) directly predicted help-seeking behavior. However, behavioral intention (Β = -.017, p = .830) did not statistically significantly predict help-seeking behavior, while subjective norm (Β = .047, p = .356) did not predict help-seeking intention as well. The model accounted for 49.9% of the variance modeling help-seeking intention and 12.4% of the variance modeling help-seeking behavior. The results revealed the importance of attitude and perceived behavioral control in predicting help-seeking intention and behavior among Chinese college students and indicated that there existed a gap between intention and actual help-seeking behavior.

Partial wet oxidation of dairy manure as a pretreatment process to produce acetic acid 'a Source Growth of Methanogens'.

Wet oxidation can be an effective process for the pretreatment of complex biomass such as lignocellulose. However, studies on the use of wet oxidation for treating solid waste such as dairy manure are limited. The use of partial wet oxidation to convert dairy manure into low molecular weight carboxylic acids as final products were investigated. This work focuses on the performance of the sub-critical wet oxidation treatment of dairy cattle manure as a conversion/pretreatment process to release matter from the lignocellulosic fraction rather than a destructive process. The operating conditions were controlled at the short residence time and optimal temperature in the presence of oxygen under a pressure of 120 psi. The thermal hydrolysis under wet oxidation significantly affected conversion manure slurry into organic acids. The concentration of acetic acid reached 1778 mg L-1, achieved at 190°C (60 minutes reaction time) as the reaction temperature increased within the range of 150°C-200°C, total organic carbon was reduced and monomers in the process liquids decreased. On the other hand, soluble COD in process liquids increased with an increment in reaction temperature. The results provide insights into technical options to pretreat dairy manure to improve biochemical conversion yield.

Leonurine alleviates rheumatoid arthritis by regulating the Hippo signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.

Understanding the Workplace-Violence-Related Perceptions and Coping Strategies of Nurses in Emergency Rooms.

BACKGROUND: Workplace violence (WPV) is a well-known and serious issue in most countries, and WPV against healthcare providers is of particular concern, especially among nurses working in emergency rooms (ERs). PURPOSE: We aimed to develop a deeper understanding of nurses' perceptions and coping strategies related to WPV that took place over a 1-year period from the perspective of nursing victims still working in ERs in southern Taiwan. METHODS: This is a qualitative study with in-depth and semistructured interviews. Nineteen ER nurse victims were recruited from six hospitals in southern Taiwan from June 2015 to April 2016. All of the interview recordings were analyzed using content analysis. RESULTS: The content analysis identified two themes of perceptions and two themes of coping strategies toward WPV. The two themes of perceptions were "adversity" and "dilemma," with the former covering the three subthemes of "misunderstanding of health policy," "unsafe environment," and "nursing shortage" and the latter covering the two subthemes of "burnout" and "keeping or quitting the job." The two themes of coping strategies were "adjustment" and "resilience," with the former covering the three subthemes of "acceptance of the reality of WPV," "self-regulation," and "culture and belief" and the latter covering the two subthemes of "living with WPV" and "problem solving." CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings revealed that ER nurse victims of WPV experienced a complicated journey after encountering WPV. Their coping strategies may be referenced by other ER nurses to better prevent and manage violent events in ERs. To prevent and manage violence in ERs, hospital managers should create a safe working environment through, for example, assigning sufficient security personnel and staff; provide relevant training to ER nurses in communications and other skills; and implement support systems to strengthen nurse resilience.

Effectiveness on Quality of Life and Life Satisfaction for Older Adults: A Systematic Review and Meta-Analysis of Life Review and Reminiscence Therapy across Settings.

BACKGROUND: With the growing trend of ageing, there is an urgent need for effective interventions that enhance positive psychological functions among older adults. OBJECTIVE: (1) To evaluate the effectiveness of life review and reminiscence therapy in enhancing the quality of life and life satisfaction among older adults. (2) To discover efficacious variables during interventions, such as form of intervention and number of sessions. METHODS: Relevant randomized controlled trials in both English and Chinese languages were searched across eight databases. The meta-analysis was conducted by a random effects model using STATA 17. The registration number of this review is CRD42023424085. RESULTS: Thirty-two studies with 2353 participants were included. Experimental groups of older adults significantly improved their quality of life (SMD 1.07; 95% CI 0.48 to 1.66; p < 0.001) and life satisfaction (SMD 1.12; 95% CI 0.63 to 1.60; p < 0.001). Subgroup analyses revealed that individual sessions of life review and reminiscence therapy had a more significant impact on improving quality of life and six to eight intervention sessions could enhance life satisfaction more effectively. CONCLUSIONS: Life review and reminiscence therapy hold promise for application in medical and nursing care for older adults, suggesting the potential benefits of implementing intervention designs with effective settings for positive psychological functions.

Age and sex-specific differences of mindfulness traits with measurement invariance controlled in Chinese adult population: A pilot study.

Objectives: To examine the relationships of age and sex with mindfulness traits among Chinese adults with controlling for measurement invariance. Methods: A total of 1777 participants completing the Five-Facet Mindfulness Questionnaire were included for analysis. Their age and sex information were also collected. Descriptive analysis, Pearson's Chi-Square test and analysis of variance were performed to test the age- and sex-specific differences, measurement invariance was examined by confirmatory factor analysis. Results: Excellent data fit to the model indicated configural, metric, and scalar invariance across age and sex. Participants aged 60 or above scored significantly higher in dimensions of acting with awareness, nonjudging of inner experience, nonreactivity to inner experience, and the total scores than younger individuals, who had higher scores in the observing domain. In addition, females scored higher in describing and observing than males, while the latter had higher score in nonreactivity to inner experience. Conclusions: The Five-Facet Mindfulness Questionnaire Mindfulness showed acceptable measurement invariance across age and sex in Chinese adult population. The old and the young differs in the traits of awareness, observing, nonjudging of inner experience, nonreactivity to inner experience and the total mindfulness level, while males and females varied in describing, observing and nonreactivity to inner experience. Individual differences should be considered and well addressed in future studies on mindfulness.

Achieving highly reversible zinc metal anode via surface termination chemistry.

An oxidation layer on a Zn surface is considered to play a negative role in hindering the practical applications of aqueous zinc ion batteries (AZBs). Herein, we demonstrate the importance of Zn-surface termination on the overall electrochemical behavior of AZBs by revisiting the well-known bottleneck issues. Experimental characterizations in conjugation with theoretical calculations reveal that the formation of a dense Zn4(OH)6SO4·xH2O (ZSH) layer from the well-designed surface-oxide termination layer improves the interface stability of the Zn anode and reduces the dehydration energy of Zn(H2O)62+, thereby accelerating the interface transport kinetics of Zn2+. Moreover, instead of directly diffusing over the ZSH layer, a new "edge dehydration-along edge transfer" mechanism of Zn2+ is discovered. Owing to the presence of a Zn anode with a ZnO-derived ZSH layer, an ultrahigh stability of over 1200 h with a high cumulative-plated capacity of 6.24mAh cm-2 is achieved with a symmetrical cell. Furthermore, high cycling stability (over 1000 cycles) and Coulombic efficiency (99.07%) are obtained in the entire AZBs with a MnO2 cathode. An understanding of the oxygen surface termination mechanism is beneficial to Zn-anode protection and is a timely forward step toward the long-pursued practical application of AZBs.

Integrated proteomics and phosphoproteomics analyses of esophageal cancer cells with different invasive abilities.

AIMS: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive and lethal malignancies with an extremely poor prognosis. It is necessary to explore the molecular mechanisms of ESCC invasion. MAIN METHODS: We utilized high-throughput mass spectrometry to analyze the proteomes and phosphorylation profiles of two ESCC cell lines with differing invasion capacities (HK vs TE10). Differentially expressed proteins and phosphorites were identified, followed by comprehensive bioinformatics analyses encompassing function and pathway enrichment, protein-protein interaction (PPI) network analysis, hub gene identification, co-expression analysis, kinase-substrate prediction, and drug-target network analysis. CCK-8 assay, transwell examination, wound-healing assay, and western blot was used to validate the effects of fostamatinib on ESCC cells proliferation, invasion, migration, and LYN expression. KEY FINDINGS: The Q4 cluster of differentially phosphorylated proteins was primarily associated with functions and pathways relevant to tumor metastasis. Phosphorylated hub proteins including ARHGAP35, CTNNA1, and SHC1 were identified through the analysis of PPI network, and their respective regulated kinases were predicted. Among the predicted kinases, LYN was validated to be associated with lymph node metastasis (N0 vs. N1-3) and prognosis in ESCC patients at mRNA levels using TGGA data and protein levels in ESCC tissues (p < 0.05). Validation experiments confirmed the inhibitory effects of fostamatinib on ESCC cells proliferation, migration, invasion, and LYN expression. SIGNIFICANCE: Our multi-omics analysis offers deeper perspectives on ESCC invasiveness and unveils new phosphorylated hub proteins with their regulatory kinase. This study also suggests that fostamatinib may be a potential agent for treating ESCC.

The pear genomics database (PGDB): a comprehensive multi-omics research platform for Pyrus spp.

BACKGROUND: Pears are among the most important temperate fruit trees in the world, with significant research efforts increasing over the last years. However, available omics data for pear cannot be easily and quickly retrieved to enable further studies using these biological data. DESCRIPTION: Here, we present a publicly accessible multi-omics pear resource platform, the Pear Genomics Database (PGDB). We collected and collated data on genomic sequences, genome structure, functional annotation, transcription factor predictions, comparative genomics, and transcriptomics. We provide user-friendly functional modules to facilitate querying, browsing and usage of these data. The platform also includes basic and useful tools, including JBrowse, BLAST, phylogenetic tree building, and additional resources providing the possibility for bulk data download and quick usage guide services. CONCLUSIONS: The Pear Genomics Database (PGDB, http://pyrusgdb.sdau.edu.cn ) is an online data analysis and query resource that integrates comprehensive multi-omics data for pear. This database is equipped with user-friendly interactive functional modules and data visualization tools, and constitutes a convenient platform for integrated research on pear.

Flexible, Miniaturized Sensing Probes Inspired by Biofuel Cells for Monitoring Synaptically Released Glutamate in the Mouse Brain.

Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 µm, can detect real-time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.

Multiple TMA-aided CRISPR/Cas13a platform for highly sensitive detection of IL-15 to predict immunotherapeutic response in nasopharyngeal carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs)-based treatments have been recommended as the first line for refractory recurrent and/or metastatic nasopharyngeal carcinoma (NPC) patients, yet responses vary, and predictive biomarkers are urgently needed. We selected serum interleukin-15 (sIL-15) out of four interleukins as a candidate biomarker, while most patients' sIL-15 levels were too low to be detected by conventional methods, so it was necessary to construct a highly sensitive method to detect sIL-15 in order to select NPC patients who would benefit most or least from ICIs. METHODS: Combining a primer exchange reaction (PER), transcription-mediated amplification (TMA), and a immuno-PER-TMA-CRISPR/Cas13a system, we developed a novel multiple signal amplification platform with a detection limit of 32 fg/mL, making it 153-fold more sensitive than ELISA. RESULTS: This platform demonstrated high specificity, repeatability, and versatility. When applied to two independent cohorts of 130 NPC sera, the predictive value of sIL-15 was accurate in both cohorts (area under the curve: training, 0.882; validation, 0.898). Additionally, lower sIL-15 levels were correlated with poorer progression-free survival (training, HR: 0.080, p<0.0001; validation, HR: 0.053, p<0.0001). CONCLUSION: This work proposes a simple and sensitive approach for sIL-15 detection to provide insights for personalized immunotherapy of NPC patients.