Generative Large Language Models in Electronic Health Records for Patient Care Since 2023: A Systematic Review.

Background: Generative Large language models (LLMs) represent a significant advancement in natural language processing, achieving state-of-the-art performance across various tasks. However, their application in clinical settings using real electronic health records (EHRs) is still rare and presents numerous challenges. Objective: This study aims to systematically review the use of generative LLMs, and the effectiveness of relevant techniques in patient care-related topics involving EHRs, summarize the challenges faced, and suggest future directions. Methods: A Boolean search for peer-reviewed articles was conducted on May 19th, 2024 using PubMed and Web of Science to include research articles published since 2023, which was one month after the release of ChatGPT. The search results were deduplicated. Multiple reviewers, including biomedical informaticians, computer scientists, and a physician, screened the publications for eligibility and conducted data extraction. Only studies utilizing generative LLMs to analyze real EHR data were included. We summarized the use of prompt engineering, fine-tuning, multimodal EHR data, and evaluation matrices. Additionally, we identified current challenges in applying LLMs in clinical settings as reported by the included studies and proposed future directions. Results: The initial search identified 6,328 unique studies, with 76 studies included after eligibility screening. Of these, 67 studies (88.2%) employed zero-shot prompting, five of them reported 100% accuracy on five specific clinical tasks. Nine studies used advanced prompting strategies; four tested these strategies experimentally, finding that prompt engineering improved performance, with one study noting a non-linear relationship between the number of examples in a prompt and performance improvement. Eight studies explored fine-tuning generative LLMs, all reported performance improvements on specific tasks, but three of them noted potential performance degradation after fine-tuning on certain tasks. Only two studies utilized multimodal data, which improved LLM-based decision-making and enabled accurate rare disease diagnosis and prognosis. The studies employed 55 different evaluation metrics for 22 purposes, such as correctness, completeness, and conciseness. Two studies investigated LLM bias, with one detecting no bias and the other finding that male patients received more appropriate clinical decision-making suggestions. Six studies identified hallucinations, such as fabricating patient names in structured thyroid ultrasound reports. Additional challenges included but were not limited to the impersonal tone of LLM consultations, which made patients uncomfortable, and the difficulty patients had in understanding LLM responses. Conclusion: Our review indicates that few studies have employed advanced computational techniques to enhance LLM performance. The diverse evaluation metrics used highlight the need for standardization. LLMs currently cannot replace physicians due to challenges such as bias, hallucinations, and impersonal responses.

Carrier-phonon decoupling in perovskite thermoelectrics via entropy engineering.

Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m-1 K-1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V-1 s-1. Such carrier-phonon decoupling behaviors enable the greatly enhanced µW/κL of ~5.2 × 103 cm3 K J-1 V-1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations.

The ability to generate multiple RNA transcript isoforms from the same gene is a general phenomenon in eukaryotes. However, the complexity and diversity of alternative isoforms in natural populations remain largely unexplored. Using a newly developed full-length transcripts enrichment protocol with 5' CAP selection, we sequenced full-length RNA transcripts of 48 individuals from outbred populations and subspecies of Mus musculus, and from the closely related sister species Mus spretus and Mus spicilegus as outgroups. The dataset represents the most extensive full-length high-quality isoform catalog at the population level to date. In total, we reliably identified 117,728 distinct isoforms, of which only 51% were previously annotated. We show that the population-specific distribution pattern of isoforms is phylogenetically informative and reflects the segregating SNP diversity between the populations. We find that ancient housekeeping genes are a major source of the overall isoform diversity, and that the generation of alternative first exons plays a major role in generating new isoforms. Given that our data allow us to distinguish between population-specific isoforms and isoforms that are conserved across multiple populations, it is possible to refine the annotation of the reference mouse genome to a set of about 40,000 isoforms that should be most relevant for comparative functional analysis across species.

Screening of serum markers in patients with resistant hypertension.

Background: This study delves into the intricacies of resistant hypertension (RH), a prevalent yet enigmatic chronic cardiovascular ailment that is linked to a myriad of complications. Although its full pathogenesis is still shrouded in mystery, the field of proteomics offers a beacon of hope, with its potential to shed light on the proteins that orchestrate the tapestry of life. Harnessing the power of proteomics is essential for demystifying the pathogenesis of RH, enabling more precise diagnostics and treatments, and ultimately improving prognostic outcomes. Methods: Our approach was to employ rigorous statistical analyses to home in on proteins with significant expression variances between our two cohorts. We complemented this with bioinformatics tools to unravel the intricate functions and pathways of these proteins. By synthesizing these insights with the clinical profiles of our patients, we were able to distill a set of definitive biomarkers with diagnostic potential. In our quest for clarity, we also embarked on a retrospective journey, amassing and scrutinizing clinical data from both RH and hypertension (HTN) patients. We crafted and rigorously assessed risk factor models to evaluate their diagnostic prowess. Results: Our exploration spanned across 30 blood samples from RH patients and 20 from those grappling with HTN. Our inquiry yielded some compelling revelations: (1) RH patients showcased 29 unique proteins, in contrast to the 59 unique proteins found in HTN patients. A deeper dive into the proteomic data unveiled molecular functions predominantly tied to lipid metabolism, protein networking, and oxidative stress, with a spotlight on pathways such as cholesterol metabolism, coagulation, and the complement cascade. (2) By charting receiver operating characteristic curves and rigorously analyzing the proteomic data, we surfaced 11 proteins with notable diagnostic potential, tightly interwoven with clinical metrics. Conclusion: Our research has pinpointed 11 proteins that stand as promising serum biomarkers, endowed with significant diagnostic value. This discovery marks a stride towards a more nuanced understanding and management of resistant hypertension.

Biomimetic Iron-Based Nanoparticles Remodel Immunosuppressive Tumor Microenvironment for Metabolic Immunotherapy.

Introduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses. Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME). Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response. Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy.

HDAC7 is a potential therapeutic target in acute erythroid leukemia.

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance. The established mouse AEL cells expressing Cas9 can be cultured in vitro, induce AEL in vivo even in unirradiated recipient mice, and enable efficient gene ablation using the CRISPR/Cas9 system. We also confirmed the cooperation between ERG overexpression and TP53 inactivation in promoting the growth of immature erythroid cells in human cord blood cells. Mechanistically, ERG antagonizes KLF1 and inhibits erythroid maturation, whereas TP53 deficiency promotes proliferation of erythroid progenitors. Furthermore, we identified HDAC7 as a specific susceptibility in AEL by the DepMap-based two-group comparison analysis. HDAC7 promotes the growth of human and mouse AEL cells both in vitro and in vivo through its non-enzymatic functions. Our study provides experimental evidence that TP53 deficiency and ERG overexpression are necessary and sufficient for the development of AEL and highlights HDAC7 as a promising therapeutic target for this disease.

Subject-Independent Wearable P300 Brain-Computer Interface Based on Convolutional Neural Network and Metric Learning.

OBJECTIVE: The calibration procedure for a wearable P300 brain-computer interface (BCI) greatly impact the user experience of the system. Each user needs to spend additional time establishing a decoder adapted to their own brainwaves. Therefore, achieving subject independent is an urgent issue for wearable P300 BCI needs to be addressed. METHODS: A dataset of electroencephalogram (EEG) signals was constructed from 100 individuals by conducting a P300 speller task with a wearable EEG amplifier. A framework is proposed that initially improves cross-subject consistency of EEG features through a common feature extractor. Subsequently, a simple and compact convolutional neural network (CNN) architecture is employed to learn an embedding sub-space, where the mapped EEG features are maximally separated, while pursuing the minimum distance within the same class and the maximum distance between different classes. Finally, the model's generalization capability was further optimized through fine-tuning. RESULTS: The proposed method significantly boosts the average accuracy of wearable P300 BCI to 73.23 ±7.62% without calibration and 78.75±6.37% with fine-tuning. CONCLUSION: The results demonstrate the feasibility and excellent performance of our dataset and framework. SIGNIFICANCE: A calibration-free wearable P300 BCI system is feasible, suggesting significant potential for practical applications of the wearable P300 BCI system.

Phosphoenolpyruvate carboxykinase 2-mediated metabolism promotes lung tumorigenesis by inhibiting mitochondrial-associated apoptotic cell death.

Background: It is unknown how cancer cells override apoptosis and maintain progression under nutrition-deprived conditions within the tumor microenvironment. Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting reaction in gluconeogenesis, which is an essential metabolic alteration that is required for the proliferation of cancer cells under glucose-limited conditions. However, if PCK-mediated gluconeogenesis affects apoptotic cell death of non small cell lung cancer (NSCLC) and its potential mechanisms remain unknown. Methods: RNA-seq, Western blot and RT-PCR were performed in A549 cell lines cultured in medium containing low or high concentrations of glucose (1 mM vs. 20 mM) to gain insight into how cancer cells rewire their metabolism under glucose-restriction conditions. Stable isotope tracing metabolomics technology (LC-MS) was employed to allow precise quantification of metabolic fluxes of the TCA cycle regulated by PCK2. Flow Cytometry was used to assess the rates of early and later apoptosis and mitochondrial ROS in NSCLC cells. Transwell assays and luciferase-based in vivo imaging were used to determine the role of PCK2 in migration and invasion of NSCLC cells. Xenotransplants on BALB/c nude mice to evaluate the effects of PCK2 on tumor growth in vivo. Western blot, Immunohistochemistry and TUNEL assays to evaluate the protein levels of mitochondrial apoptosis. Results: This study report that the mitochondrial resident PCK (PCK2) is upregulated in dependent of endoplasmic reticulum stress-induced expression of activating transcription factor 4 (ATF4) upon glucose deprivation in NSCLC cells. Further, the study finds that PCK2-mediated metabolism is required to decrease the burden of the TCA cycles and oxidative phosphorylation as well as the production of mitochondrial reactive oxygen species. These metabolic alterations in turn reduce the activation of Caspase9-Caspase3-PARP signal pathway which drives apoptotic cell death. Importantly, silencing PCK2 increases apoptosis of NSCLC cells under low glucose condition and inhibits tumor growth both in vitro and in vivo. Conclusion: In summary, PCK2-mediated metabolism is an important metabolic adaptation for NSCLC cells to acquire resistance to apoptosis under glucose deprivation.

SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity. Mechanistically, SETDB1 depletion upregulates interferon-stimulated genes and NKG2D ligands through the demethylation of histone H3 Lys9 at the enhancer regions, thereby enhancing their immunogenicity to NK cells and intrinsic apoptosis. Importantly, these effects are not observed in non-monocytic leukemia cells. We also identified the expression of myeloid cell nuclear differentiation antigen (MNDA) and its murine counterpart Ifi203 as biomarkers to predict the sensitivity of AML to SETDB1 depletion. Our study highlights the critical and selective role of SETDB1 in AML with granulo-monocytic differentiation and underscores its potential as a therapeutic target for current unmet needs.

Different neural correlates of deception: Crafting high and low creative scams.

Deception is a complex social behavior that manifests in various forms, including scams. To successfully deceive victims, liars have to continually devise novel scams. This ability to create novel scams represents one kind of malevolent creativity, referred to as lying. This study aimed to explore different neural substrates involved in the generation of high and low creative scams. A total of 40 participants were required to design several creative scams, and their cortical activity was recorded by functional near-infrared spectroscopy. The results revealed that the right frontopolar cortex (FPC) was significantly active in scam generation. This region associated with theory of mind may be a key region for creating novel and complex scams. Moreover, creativity-related regions were positively involved in creative scams, while morality-related areas showed negative involvement. This suggests that individuals might attempt to use malevolent creativity while simultaneously minimizing the influence of moral considerations. The right FPC exhibited increased coupling with the right precentral gyrus during the design of high-harmfulness scams, suggesting a diminished control over immoral thoughts in the generation of harmful scams. Additionally, the perception of the victim's emotions (related to right pre-motor cortex) might diminish the quality of highly original scams. Furthermore, an efficient and cohesive neural coupling state appears to be a key factor in generating high-creativity scams. These findings suggest that the right FPC was crucial in scam creation, highlighting a neural basis for balancing malevolent creativity against moral considerations in high-creativity deception.

Electrochemical Dehydrogenative [3 + 2]/[5 + 2] Annulation of N-Arylacrylamides with γ,σ-Unsaturated Malonates via Direct C(sp3)-H/C(sp2)-H Functionalization.

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available N-arylacrylamides with γ,σ-unsaturated malonates through C(sp3)-H/C(sp2)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[b]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp3)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp2)-H functionalization cascades.

Oxophilic gallium single atoms bridged ruthenium clusters for practical anion-exchange membrane electrolyzer.

The development of highly efficient and durable alkaline hydrogen evolution reaction (HER) catalysts is crucial for achieving high-performance practical anion exchange membrane water electrolyzer (AEMWE) at ampere-level current density. Herein, we report a design concept by employing Ga single atoms as an electronic bridge to stabilize the Ru clusters for boosting alkaline HER performance in practical AEMWE. Experimental and theoretical results collectively reveal that the bridged Ga sites trigger strong metal-support interaction for the homogeneous distribution of Ru clusters with high density, as well as optimize the Ru-H bond strength due to the electron transfer between Ru and Ga for enhanced intrinsic HER activity. Moreover, the oxophilic Ga sites near the Ru clusters tend to adsorb the hydroxyl species and accelerate the water dissociation for sufficient proton supplement in an alkaline medium. The Ru-GaSA/N-C catalyst exhibits a low overpotential of 4 ± 1 mV (10 mA cm-2) and high mass activity of 9.3 ± 0.5 A mg-1Ru at -0.05 V vs RHE. In particular, the Ru-GaSA/N-C-based AEMWE in 1 M KOH delivers a voltage of only 1.74 V to reach an industrial current density of 1 A cm-2, and can steadily operate at 1 A cm-2 for more than 170 h.

The relationship between anger and creative performance: a three-level meta-analysis.

A substantial body of empirical research has focused on the interaction between creativity and mood, yet the results regarding the impact of anger on creative performance are notably varied. To clarify the overall relationship between the two, a three-level meta-analysis employing a random effects model was conducted. This analysis reviewed 115 effect sizes from 2,413 participants, revealing that anger is significantly positively correlated with creative performance (r = 0.184, 95% CI [0.111, 0.254]). The strength of this correlation was found to be moderated by the general and malevolent facets of creativity, as well as the procedures used for mood induction. Specifically, anger appears to enhance creative performance, particularly when it is elicited through imaginative processes and directed towards malevolent facet of creativity. However, the link between anger and creative performance was not influenced by the type of creative task used, the reported creative outcome, or the time limitation of the task. These findings contribute to refining the theoretical frameworks of mood and creativity and highlight the practical implications of utilising anger to moderate creative performance.

Enhanced Hydrogen Peroxide Decomposition in a Continuous-Flow Reactor over Immobilized Catalase with PAES-C.

Due to the specificity, high efficiency, and gentleness of enzyme catalysis, the industrial utilization of enzymes has attracted more and more attention. Immobilized enzymes can be recovered/recycled easily compared to their free forms. The primary benefit of immobilization is protection of the enzymes from harsh environmental conditions (e.g., elevated temperatures, extreme pH values, etc.). In this paper, catalase was successfully immobilized in a poly(aryl ether sulfone) carrier (PAES-C) with tunable pore structure as well as carboxylic acid side chains. Moreover, immobilization factors like temperature, time, and free-enzyme dosage were optimized to maximize the value of the carrier and enzyme. Compared with free enzyme, the immobilized-enzyme exhibited higher enzymatic activity (188.75 U g-1, at 30 °C and pH 7) and better thermal stability (at 60 °C). The adsorption capacity of enzyme protein per unit mass carrier was 4.685 mg. Hydrogen peroxide decomposition carried out in a continuous-flow reactor was selected as a model reaction to investigate the performance of immobilized catalase. Immobilized-enzymes showed a higher conversion rate (90% at 8 mL/min, 1 h and 0.2 g) compared to intermittent operation. In addition, PAES-C has been synthesized using dichlorodiphenyl sulfone and the renewable resource bisphenolic acid, which meets the requirements of green chemistry. These results suggest that PAES-C as a carrier for immobilized catalase could improve the catalytic activity and stability of catalase, simplify the separation of enzymes, and exhibit good stability and reusability.

Effect of luteolin on oxidative stress and inflammation in the human osteoblast cell line hFOB1.19 in an inflammatory microenvironment.

BACKGROUND: Periapical lesions are characterized by periapical inflammation and damage to periapical tissues and eventually lead to bone resorption and even tooth loss. H2O2 is widely used in root canal therapy for patients with periapical inflammation. Luteolin possesses high anti-inflammatory, antioxidant, and anticancer potential. However, the underlying mechanism of the efficacy of H2O2 and luteolin on oxidative stress and inflammatory tissue has not been previously addressed. We aimed to investigate the anti-inflammatory and antioxidative effects of luteolin on H2O2-induced cellular oxidative inflammation. METHODS: After human osteoblasts (hFOB1.19) were treated with lipopolysaccharide (LPS), luteolin, or H2O2, cell proliferation was analysed by using a cell counting kit-8 (CCK-8), cell apoptosis was measured by using flow cytometry, the production of reactive oxygen species (ROS) was evaluated by using an oxidation-sensitive probe DCFH-DA ROS assay kit, and the expression of genes and proteins was detected by using reverse transcription quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). RESULTS: We demonstrated that inflammation is closely related to oxidative stress and that the oxidative stress level in the inflammatory environment is increased. Luteolin inhibited the H2O2-induced increase in the expression of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor α (TNF-α) and significantly repressed the H2O2-induced increase in ROS, as well as markedly strengthened superoxide dismutase (SOD) activity in hFOB1.19 cells. Moreover, we detected that luteolin may inhibit H2O2-induced hFOB1.19 cell injury by suppressing the NF-κB pathway. CONCLUSION: We elucidated that luteolin protected human osteoblasts (hFOB1.19) from H2O2-induced cell injury and inhibited the production of proinflammatory cytokines by suppressing the NF-κB signalling pathway. Our findings provide a potential drug for treating H2O2-induced periodontitis and cell injury.

Plasma Biomarker Screening Based on Proteomic Signature of Patients with Resistant Hypertension.

Resistant hypertension (RH) poses a significant health challenge, yet its underlying pathogenesis remains unclear. This study employs untargeted proteomic techniques to analyze the plasma of patients with RH and controlled hypertension (CH), identifying 157 differentially expressed proteins, with TGFB1 emerging as a key candidate. Through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Protein-Protein Interaction Networks (PPI) topological analysis, TGFB1's differential regulation in RH is established. ELISA verification solidifies TGFB1's role, marking it as a potential biological target for early RH diagnosis and treatment. The study underscores the importance of proteomic approaches in enhancing our understanding of RH and improving therapeutic strategies. These findings carry implications for advancing RH diagnostics and treatment modalities, addressing a critical gap in current knowledge.

Realizing Efficient Activity and High Conductivity of Perovskite Symmetrical Electrode by Vanadium Doping for CO2 Electrolysis.

Solid oxide electrolysis cells (SOECs) show significant promise in converting CO2 to valuable fuels and chemicals, yet exploiting efficient electrode materials poses a great challenge. Perovskite oxides, known for their stability as SOEC electrodes, require improvements in electrocatalytic activity and conductivity. Herein, vanadium(V) cation is newly introduced into the B-site of Sr2Fe1.5Mo0.5O6-δ perovskite to promote its electrochemical performance. The substitution of variable valence V5+ for Mo6+ along with the creation of oxygen vacancies contribute to improved electronic conductivity and enhanced electrocatalytic activity for CO2 reduction. Notably, the Sr2Fe1.5Mo0.4V0.1O6-δ based symmetrical SOEC achieves a current density of 1.56 A cm-2 at 1.5 V and 800 °C, maintaining outstanding durability over 300 h. Theoretical analysis unveils that V-doping facilitates the formation of oxygen vacancies, resulting in high intrinsic electrocatalytic activity for CO2 reduction. These findings present a viable and facile strategy for advancing electrocatalysts in CO2 conversion technologies.

Nanozymes in Alzheimer's disease diagnostics and therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative condition that has become an important public health problem of global concern, and the early diagnosis and etiological treatment of AD are currently the focus of research. In the course of clinical treatment, approved clinical drugs mainly serve to slow down the disease process by relieving patients' clinical symptoms. However, these drugs do not target the cause of the disease, and the lack of specificity of these drugs has led to undesirable side effects in treatment. Meanwhile, AD is mainly diagnosed by clinical symptoms and imaging, which does not have the advantage of early diagnosis. Nanozymes have been extensively investigated for the diagnosis and treatment of AD with high stability and specificity. Therefore, this review summarizes the recent advances in various nanozymes for AD diagnosis and therapy, including with peroxidase-like-activity gold nanozymes, iron nanozymes, superoxide dismutase-like- and catalase-like-activity selenium dioxide nanozymes, platinum nanozymes, and peroxidase-like palladium nanozymes, among others. A comprehensive analysis was conducted on the diagnostic and therapeutic characteristics of nanozyme therapy for AD, as well as the prospects and challenges of its clinical application. Our goal is to advance this emerging topic by building on our own work and the new insights we have learned from others. This review will assist researchers to quickly understand relevant nanozymes' therapeutic and diagnostic information and further advance the field of nanozymes in AD.

Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.

Wound healing is an intensely studied topic involved in many relevant pathophysiological processes, including fibrosis. Despite the large interest in fibrosis, the network that is related to commensal microbiota and skin fibrosis remains mysterious. Here, we pay attention to keloid, a classical yet intractable skin fibrotic disease to establish the association between commensal microbiota to scaring tissue. Our histological data reveal the presence of microbiota in the keloids. 16S rRNA sequencing characterizes microbial composition and divergence between the pathological and normal skin tissues. Moreover, the data show elevation of interleukin-8 (IL-8) in both the circulation and keloid tissue, which elicited the collagen accumulation and migratory program of dermal fibroblasts via CXCR1/2 receptor. Our research provides insights into the pathology of human fibrotic diseases, advocating commensal bacteria and IL-8 signaling as useful targets in future interventions of recurrent keloid disease.

Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury.

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.