Can cadmium-contaminated rice be used to produce food additive sodium erythorbate?

Cadmium (Cd) in rice is a significant concern for its quality and safety. Currently, there is a crucial need to develop cost-effective and efficient ways to remove Cd or re-utilize Cd-contaminated rice. The food additive sodium erythorbate is produced via 2-ketogluconic acid (2KGA) fermentation by Pseudomonas plecoglossicida and lactonization using starch-rich raw materials, such as rice. We aimed to determine whether cadmium-contaminated rice can be used to produce sodium erythorbate. To achieve this aim, the migration of cadmium during the production of sodium erythorbate from Cd-contaminated rice was studied. Five rice varieties with different Cd contents from 0.10 to 0.68 mg/kg were used as raw materials. The results indicated the presence of Cd in rice and CaCO3 did not have a notable impact on the fermentation performance of 2KGA. The acidification of 2KGA fermentation broth, the addition of K4Fe(CN)6·3H2O and ZnSO4, and 2KGA purification using cation exchange effectively removed >98% of the Cd in the fermentation broth, but the 2KGA yield remained high at approximately 94%. The sodium erythorbate synthesized from Cd-contaminated rice was of high quality and free from Cd, meeting the requirements of the Chinese National Standard, GB 1886.28-2016. The study provided a safe and effective strategy for comprehensively utilizing Cd-contaminated rice to produce high value-added food additive.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective. MATERIALS AND METHODS: The Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors. RESULT: Using scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB. CONCLUSION: The results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

Effects of fermentation conditions on molecular weight, production, and physicochemical properties of gellan gum.

Gellan gum has been widely used in many industries due to its excellent physical properties. In this study, the effects of different fermentation conditions on molecular weight and production of gellan gum were analyzed, and the optimized fermentation conditions for a high molecular weight gellan gum (H-GG: 6.42 × 105 Da) were obtained, which increased the molecular weight and yield of gellan gum by 201.4 % and 44.9 % respectively. Fourier transform infrared spectroscopy (FT-IR) and x-ray diffraction (XRD) analysis indicated that H-GG has similar characteristic absorption and semi-crystalline structures with the initial gellan gum (I-GG), and it was composed of glucose, rhamnose, and glucuronic acid showing no obvious changes in the molecular structure. Scanning electron microscope (SEM) observation revealed that the filaments of H-GG were slender, longer, and looser with larger pores. Importantly, gel properties analysis showed that the gel strength, viscoelasticity, and water-holding capacity of H-GG were better than those of I-GG, and the rheological results revealed that the H-GG is a pseudoplastic fluid with higher apparent viscosity and stable viscoelasticity at 20-70 °C. Therefore, the molecular weight and yield of gellan gum are significantly affected by fermentation conditions, and the obtained H-GG demonstrates improved gel and rheological properties.

Impact of dry eye disease on psychological symptoms among Chinese doctoral students studying abroad.

This study aimed to evaluate the impact of dry eye disease (DED) on depression, anxiety, and stress among Chinese doctoral students studying abroad. This is a cross-sectional study. This study enrolled 185 Chinese doctoral students pursuing education in the Philippines. DED was assessed using the Ocular Surface Disease Index, while psychological symptoms were evaluated using the abbreviated version of the Depression, Anxiety, and Stress Scale-21 questionnaire. A survey encompassing demographic information, potential DED risk factors, and individual habits was also administered. Of the 185 students, 129 completed the survey, of which 40 (31.0%) were male and 89 (69.0%) were female. The average age was 36.3 ±â€…7.0 (mean ±â€…SD; range, 22-57) years. The prevalence of DED, depression, anxiety, and stress was 73.6% (95/129), 43.4% (56/129), 50.4% (65/129), and 22.5% (29/129), respectively. Univariate analysis revealed that aging (P < .001), prolonged visual display terminal (VDT) use (P = .004), extended paperwork time (P < .001), higher depression score (P = .006), higher anxiety score (P < .001), and higher stress score (P < .001) were associated with increased influence of DED. After adjusting for age, duration of VDT use, duration of paperwork, and depression score, age (P = .030) had significant association with DED. Additionally, after adjusting for age, duration of VDT use, duration of paperwork, and anxiety score, age (P = .026) and anxiety score (P = .047) were significantly associated with DED. Moreover, after adjusting for age, duration of VDT use, duration of paperwork, and stress score, age (P = .035) and stress score (P = .028) showed significant associations with DED. In the multivariate analysis of variance, there was a significant impact of DED severity classification on psychological distress (V = 0.19, F(9, 375) = 2.83, P = .003). Univariate analysis of variances indicated that DED severity had a significant impact on anxiety F(3, 125) = 6.06, P = .001 and stress F(3, 125) = 3.00, P = .033. A higher influence of DED was related to stress and anxiety. Anxiety and stress levels increase with the severity of DED.

A novel visible light-driven oxygen doped C3N4/Bi12O17Cl2/ferrate(VI) system for Bisphenol A degradation: Radical and nonradical pathways.

In this study, visible light-activated photocatalyst oxygen-doped C3N4@Bi12O17Cl2 (OCN@BOC) and Fe(VI) coupling system was proposed for the efficient degradation of bisphenol A (BPA). The comprehensive characterization of the OCN@BOC photocatalyst revealed its excellent photogenerated carrier separation rate in heterogeneous structures. The OCN@BOC/Fe(VI)/Vis system exhibited a remarkable BPA removal efficiency of over 84% within 5 min. Comparatively, only 37% and 59% of BPA were degraded by single OCN@BOC and Fe(VI) in 5 min, respectively. Reactive species scavenging experiments, phenyl sulfoxide transformation experiments, and electron paramagnetic resonance experiments confirmed the involvement of superoxide radicals (⋅O2-), singlet oxygen (1O2), as well as iron(V)/iron(IV) (Fe(V)/Fe(IV)) species in the degradation process of BPA. Furthermore, density functional theoretical calculations and identification of intermediates provided insights into the potential degradation mechanism of BPA during these reactions. Additionally, simulation evaluations using an ecological structure activity relationship model demonstrated that the toxicity of BPA to the ecological environment was mitigated during its degradation process. This study presented a novel strategy for removing BPA utilizing visible light photocatalysts, highlighting promising applications for practical water environment remediation with the OCN@BOC/Fe(VI)/Vis system.

Phosphoproteomic Analysis Indicates Phosphorylated Proteins in Response to Postharvest Blueberries Fruit Softening during Shelf Life.

Postharvest blueberry fruit is prone to softening. Protein phosphorylation is an important post-translational modification that was involved in fruit softening. However, little is known about protein phosphorylation in postharvest blueberry fruit softening. The firmness, the apparent morphology, and cell structures of blueberry fruit were changed. As the decay rate of postharvest blueberry fruit increased, the soluble solid and titrable acid contents decreased significantly. Phosphoproteomic sequencing results showed that there were 4100 phosphorylated peptides, 5635 phosphorylated sites, and 1437 phosphorylated proteins and showed significant differences on 0 and 8 d. The GO database and KEGG pathway results indicated that these phosphorylated proteins were mainly involved in "biological process", "molecular function", "plant hormone signal transduction", and "metabolic pathways". Besides, a number of phosphorylated proteins were found in cell wall metabolism, plant hormone signaling, primary metabolism, energy metabolism, membrane and transport, ubiquitination-based proteins, and other metabolisms.

Prevalence and risk factors of significant Fibrosis in CHB patients with concurrent MASLD.

INTRODUCTION AND OBJECTIVES: Significant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB. PATIENTS AND METHODS: This retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n=844) and CHB + MASLD (n=974) group. METAVIR values of F≥2 were used to categorize significant fibrosis. RESULTS: Patients with CHB + MASLD had more significant fibrosis (35.5% vs. 23.5%, p<0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95% confidence interval (CI) 1.635-2.584; p<0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis:(25.7% in CMRF1 subgroup v.s. 34.9% in CMRF2 subgroup v.s. 53.7% in CMRF≥ 3 subgroup, p<0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF. CONCLUSIONS: MASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

Simultaneous Focused Ultrasound Neuromodulation and Fiber Photometry Recording in Free-Moving Mouse.

Focused ultrasound neuromodulation (FUN) represents a promising approach for non-invasive perturbation of neuronal circuits at deep brain regions. It is compatible with most of the existing modalities for monitoring brain functions in vivo. Integration with brain function recording modalities not only enables us to address orders and disorders of specific brain functions with closed-loop feedback but also provides us with mechanistic insights about FUN itself. Here, we provide a modified, simple, dependable, and robust protocol for the simultaneous application of FUN and fiber photometry GCaMP6s fluorescence recording in free-moving mice. This involves the fabrication of a well-sized single transducer and its temporary placement on the mice, along with the secure fixation of a fiber optical implant to facilitate the smooth passage of the transducer. The combination of FUN and fiber photometry provides for the optical recording of neural circuitry responses upon FUN in real-time in deep brain regions. To demonstrate the efficiency of this protocol, Thy1-GCaMP6s mice were used as an example to record the neuroactivity in the anterior thalamic nucleus during FUN while the mice are freely moving. We believe that this protocol can promote the widespread use of FUN in both the neuroscience field and the biomedical ultrasound field.

Regulatory science promotes the translation of transcatheter tricuspid valve repair/replacement devices.

For patients with symptomatic and severe tricuspid regurgitation but inoperable with open surgery, transcatheter tricuspid valve intervention (TTVI) is a procedure of great clinical value. TTVI products include repair and replacement devices. TTVI products are one of the hotspots of investigation now, with different innovative biomaterials and structural designs in trials to satisfy divergent indications and reduce complications. With the emerging biomaterials, the technical difficulty of structural design will be greatly reduced, spurring further product innovation and development. The innovativeness and complexity of TTVI products have brought challenges to academia, industry, and regulatory agencies. Regulatory science provides a bridge to address these difficulties and challenges. This perspective article introduces the latest development of the TTVI products. With traditional methods, regulatory agencies face challenges in evaluating the safety and efficacy of TTVr/TTVR devices given the uncertainty of clinical use and the diversity of innovative structural design. This perspective article analyzes the regulatory challenges and discusses regulatory science that can be developed to assess the safety, efficacy, quality and performance of such products: including new approaches for innovative devices, pre-review path, computer modeling and simulation, accelerated wear testing methods for transcatheter heart valves and evidence-based research. This article reveals for the first time how to apply regulatory science systematically to TTVI products, which is of great relevance to their development and translation.

Research progress of traditional Chinese medicine in the treatment of ischemic stroke by regulating mitochondrial dysfunction.

Ischemic stroke (IS) is a severe cerebrovascular disease with increasing incidence and mortality rates in recent years. The pathogenesis of IS is highly complex, with mitochondrial dysfunction playing a critical role in its onset and progression. Thus, preserving mitochondrial function is a pivotal aspect of treating ischemic brain injury. In response, there has been growing interest among scholars in the regulation of mitochondrial function through traditional Chinese medicine (TCM), including herb-derived compounds, individual herbs, and herbal prescriptions. This article reviews recent research on the mechanisms of mitochondrial dysfunction in IS and explores the potential of TCM in treating this condition by targeting mitochondrial dysfunction.

BA-CLM: A Globally Consistent 3D LiDAR Mapping Based on Bundle Adjustment Cost Factors.

Constructing a globally consistent high-precision map is essential for the application of mobile robots. Existing optimization-based mapping methods typically constrain robot states in pose space during the graph optimization process, without directly optimizing the structure of the scene, thereby causing the map to be inconsistent. To address the above issues, this paper presents a three-dimensional (3D) LiDAR mapping framework (i.e., BA-CLM) based on LiDAR bundle adjustment (LBA) cost factors. We propose a multivariate LBA cost factor, which is built from a multi-resolution voxel map, to uniformly constrain the robot poses within a submap. The framework proposed in this paper applies the LBA cost factors for both local and global map optimization. Experimental results on several public 3D LiDAR datasets and a self-collected 32-line LiDAR dataset demonstrate that the proposed method achieves accurate trajectory estimation and consistent mapping.

Metformin reprograms tryptophan metabolism via gut Microbiome-Derived bile acid metabolites to ameliorate Depression-Like behaviors in mice.

As an adjunct therapy, metformin enhances the efficacy of conventional antidepressant medications. However, its mode of action remains unclear. Here, metformin was found to ameliorate depression-like behaviors in mice exposed to chronic restraint stress (CRS) by normalizing the dysbiotic gut microbiome. Fecal transplants from metformin-treated mice ameliorated depressive behaviors in stressed mice. Microbiome profiling revealed that Akkermansia muciniphila (A. muciniphila), in particular, was markedly increased in the gut by metformin and that oral administration of this species alone was sufficient to reverse CRS-induced depressive behaviors and normalize aberrant stress-induced 5-hydroxytryptamine (5-HT) metabolism in the brain and gut. Untargeted metabolomic profiling further identified the bile acid metabolites taurocholate and deoxycholic acid as direct A. muciniphila-derived molecules that are, individually, sufficient to rescue the CRS-induced impaired 5-HT metabolism and depression-like behaviors. Thus, we report metformin reprograms 5-HT metabolism via microbiome-brain interactions to mitigate depressive syndromes, providing novel insights into gut microbiota-derived bile acids as potential therapeutic candidates for depressive mood disorders from bench to bedside.

4D printing of biological macromolecules employing handheld bioprinters for in situ wound healing applications.

In situ bioprinting may be preferred over standard in vitro bioprinting in specific cases when de novo tissues are to be created directly on the appropriate anatomical region in the live organism, employing the body as a bioreactor. So far, few efforts have been made to create in situ tissues that can be safely halted and immobilized during printing in preclinical live animals. However, the technique has to be improved significantly in order to manufacture complex tissues in situ, which may be attainable in the future thanks to multidisciplinary advances in tissue engineering. Thanks to the biological macromolecules, natural and synthetic hydrogels and polymers are among the most used biomaterials in in situ bioprinting procedure. Bioprinters, which encounter multiple challenges, including cross-linking the printed structure, adjusting the rheology parameters, and printing various constructs. The introduction of handheld 3D and 4D bioprinters might potentially overcome the difficulties and problems associated with using traditional bioprinters. Studies showed that this technique could be efficient in wound healing and skin tissue regeneration. This study aims to analyze the benefits and difficulties associated with materials in situ 4D printing via handheld bioprinters.

Relationship between abdominal fat volume and bone base material pairs from dual-energy spectral computed tomography in young and middle-aged patients with metabolic syndrome.

Background: Metabolic syndrome (MetS) has complex effects on bone health, and dual-energy spectral computed tomography (CT) has become increasingly valuable for bone quantification. However, the relationship between bone base material pairs (BMPs) and abdominal fat volume in patients with MetS remains underexplored. This study thus aimed to analyze the relationship between abdominal fat volume and various bone BMPs using dual-energy spectral CT in young and middle-aged patients with MetS. Methods: Patients with MetS who underwent sleeve gastrectomy at the Center of Obesity and Metabolic Diseases, Beijing Shijitan Hospital, Capital Medical University, from June to November 2021 were retrospectively collected. The abdominal fat measurements and BMPs were acquired using dual-energy spectral CT imaging. These included the volumes of total abdominal fat (TAF), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF), as well as bone densities based on hydroxyapatite (water), i.e., HAP (water), and calcium (water), i.e., Ca (water), BMPs. After grouping the patients by sex, we analyzed the differences in clinical and imaging features. The correlation between the clinical and imaging parameters of patients with MetS was evaluated with Pearson correlation coefficients. Age- and sex-adjusted partial correlation analysis between fat volume and bone BMPs was conducted for patients of different sexes. Additionally, multiple linear regression analyses were performed with age, sex, and TAF volume as the independent variables and with Ca (water) and HAP (water) as dependent variables. Results: A total of 112 young and middle-aged patients with MetS were included in this study, including 85 females and 27 males. Compared to male patients with MetS, the females with MetS exhibited higher lumbar Ca (water) and HAP (water) BMPs, with lower volumes of TAF and AVF and a smaller abdominal circumference (P<0.01). The volumes of TAF, AVF, and ASF were negatively correlated with the average Ca (water) and HAP (water) BMPs in the first to third lumbar vertebrae (L1-L3) (P<0.05). Ca (water) and HAP (water) BMPs decreased with age and increasing TAF volume (P<0.001). The fitted equations for the relationship between bone BMPs with age, sex, and TAF volume were as follows: (I) bone Ca (water) BMP = 76.469 - 0.500 age + 6.762 sex - 0.002 TAF volume; (II) bone HAP (water) BMP =171.704 - 1.138 age + 11.825 sex - 0.004 TAF volume. Conclusions: In young and middle-aged patients with MetS, the abdominal fat volume was negatively correlated with lumbar bone Ca (water) and HAP (water) BMPs, implying that increased abdominal fat volume may play a crucial role in the pathogenesis of osteopenia among those with MetS. The reduction of bone Ca (water) and HAP (water) with high abdominal fat volume may hold clinical significance for fracture risk in individuals with MetS.

Haplotype-based pangenomes reveal genetic variations and climate adaptations in moso bamboo populations.

Moso bamboo (Phyllostachys edulis), an ecologically and economically important forest species in East Asia, plays vital roles in carbon sequestration and climate change mitigation. However, intensifying climate change threatens moso bamboo survival. Here we generate high-quality haplotype-based pangenome assemblies for 16 representative moso bamboo accessions and integrated these assemblies with 427 previously resequenced accessions. Characterization of the haplotype-based pangenome reveals extensive genetic variation, predominantly between haplotypes rather than within accessions. Many genes with allele-specific expression patterns are implicated in climate responses. Integrating spatiotemporal climate data reveals more than 1050 variations associated with pivotal climate factors, including temperature and precipitation. Climate-associated variations enable the prediction of increased genetic risk across the northern and western regions of China under future emissions scenarios, underscoring the threats posed by rising temperatures. Our integrated haplotype-based pangenome elucidates moso bamboo's local climate adaptation mechanisms and provides critical genomic resources for addressing intensifying climate pressures on this essential bamboo. More broadly, this study demonstrates the power of long-read sequencing in dissecting adaptive traits in climate-sensitive species, advancing evolutionary knowledge to support conservation.

Carboxymethyl cellulose-coated iron-doped hollow silica carriers with erythrocyte-like structure for improved foliar adhesion and responsive pesticide delivery.

The development of nanopestcide carriers with high foliage adhesion remains a challenging task. Erythrocytes are double concave disc structure with thinner center and thicker rim and erythrocyte-like carriers would present enhanced foliar affinity. In this study, we fabricated novel rough-surfaced erythrocyte-like carriers for pesticide delivery. Firstly, erythrocyte-like silica (ES) nanoparticles were prepared by sol-gel method. Subsequently, the ES nanoparticles were further hydrothermal treated to obtain rough-surfaced iron-doped hollow ES (Fe-EHS) nanocarriers. The Fe-EHS nanocarriers could increase contact area and form a topological effect between the pesticide carriers and the micro/nanostructures on plant foliage, effectively enhancing the retention and rain fastness on foliage. Fe-EHS nanocarriers presented a loading capacity of 38.1 % for imidacloprid (IMI). After loading IMI, carboxymethyl cellulose (CMC) was encapsulated to generate nanopesticide delivery system (IMI@Fe-EHS-CMC). The obtained IMI@Fe-EHS-CMC exhibited good foliar adhesion, biosafety, and excellent UV shielding. Additionally, the IMI@Fe-EHS-CMC system possessed pH/cellulase responsive release behavior and could be bidirectionally transported through vascular bundles in tobacco plants. Furthermore, the IMI@Fe-EHS-CMC system showed potent insecticidal activity. This work offers valuable insights for enhancing the effective utilization of pesticides.

Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia.

BACKGROUND: Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia. METHODS: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis. RESULTS: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice. LIMITATIONS: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia. CONCLUSION: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.

Neuronal Membrane-Derived Nanodiscs for Broad-Spectrum Neurotoxin Detoxification.

Neurotoxins pose significant challenges in defense and healthcare due to their disruptive effects on nervous tissues. Their extreme potency and enormous structural diversity have hindered the development of effective antidotes. Motivated by the properties of cell membrane-derived nanodiscs, such as their ultrasmall size, disc shape, and inherent cell membrane functions, here, we develop neuronal membrane-derived nanodiscs (denoted "Neuron-NDs") as a countermeasure nanomedicine for broad-spectrum neurotoxin detoxification. We fabricate Neuron-NDs using the plasma membrane of human SH-SY5Y neurons and demonstrate their effectiveness in detoxifying tetrodotoxin (TTX) and botulinum toxin (BoNT), two model toxins with distinct mechanisms of action. Cell-based assays confirm the ability of Neuron-NDs to inhibit TTX-induced ion channel blockage and BoNT-mediated inhibition of synaptic vesicle recycling. In mouse models of TTX and BoNT intoxication, treatment with Neuron-NDs effectively improves survival rates in both therapeutic and preventative settings. Importantly, high-dose administration of Neuron-NDs shows no observable acute toxicity in mice, indicating its safety profile. Overall, our study highlights the facile fabrication of Neuron-NDs and their broad-spectrum detoxification capabilities, offering promising solutions for neurotoxin-related challenges in biodefense and therapeutic applications.

The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation.

Psoriasis is a chronic, proliferative, and inflammatory skin disease closely associated with inflammatory cytokine production. Cyclophilin A (CypA) is an important proinflammatory factor; however, its role in psoriasis remains unclear. The present data indicate that CypA levels are increased in the lesion skin and serum of patients with psoriasis, which is positively correlated with the psoriasis area severity index. Furthermore, extracellular CypA (eCypA) triggered psoriasis-like inflammatory responses in keratinocytes. Moreover, anti-CypA mAb significantly reduced pathological injury, keratinocyte proliferation, cytokine expression in imiquimod-induced mice. Notably, the therapeutic effect of anti-CypA mAb was better than that of the clinically used anti-IL-17A mAb and methotrexate. Mechanistically, eCypA binds to ACE2 and CD147 and is blocked by anti-CypA mAb. eCypA not only induces the dimerization and phosphorylation of ACE2 to trigger the JAK1/STAT3 signaling pathway for cytokine expression but also interacts with CD147 to promote PI3K/AKT/mTOR signaling-mediated keratinocyte proliferation. These findings demonstrate that the binding of eCypA to ACE2 and CD147 cooperatively triggers psoriasis-like inflammation and anti-CypA mAb is a promising candidate for the treatment of psoriasis.