Repeated platelet-rich plasma injections improve erectile dysfunction in a rat model of hyperhomocysteinemia.

ABSTRACT: Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze‒thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans.

Computed Tomography-Based Intratumor Heterogeneity Predicts Response to Immunotherapy Plus Chemotherapy in Esophageal Squamous Cell Carcinoma.

RATIONALE AND OBJECTIVES: This study explored the intratumor heterogeneity (ITH) of esophageal squamous cell carcinoma (ESCC) using computed tomography (CT) and investigated the value of CT-based ITH in predicting the response to immune checkpoint inhibitor (ICI) plus chemotherapy in patients with ESCC. MATERIALS AND METHODS: This retrospective study included 416 patients with ESCC who received ICI plus chemotherapy at two independent hospitals between January 2019 and July 2022. Multiparametric CT features were extracted from ESCC lesions and screened using hierarchical clustering and dimensionality reduction algorithms. Logistic regression and machine learning models based on selected features were developed to predict treatment response and validated in separate datasets. ITH was quantified using the score calculated by the best-performing model and visualized through feature clustering and feature contribution heatmaps. A gene set enrichment analysis (GSEA) was performed to identify the biological pathways underlying the CT-based ITH. RESULTS: The extreme gradient boosting model based on CT-derived ITH had higher discriminative power, with areas under the receiver operating characteristic curve of 0.864 (95% confidence interval [CI]: 0.774-0.954) and 0.796 (95% CI: 0.698-0.893) in the internal and external validation sets. The CT-based ITH pattern differed significantly between responding and non-responding patients. The GSEA indicated that CT-based ITH was associated with immunity-, keratinization-, and epidermal cell differentiation-related pathways. CONCLUSION: CT-based ITH is an effective biomarker for identifying patients with ESCC who could benefit from ICI plus chemotherapy. Immunity-, keratinization-, and epidermal cell differentiation-related pathways may influence the patient's response to ICI plus chemotherapy.

[Applications of high performance liquid chromatography-mass spectrometry in proteomics].

Proteomics profiling plays an important role in biomedical studies. Proteomics studies are much more complicated than genome research, mainly because of the complexity and diversity of proteomic samples. High performance liquid chromatography-mass spectrometry (HPLC-MS) is a fundamental tool in proteomics research owing to its high speed, resolution, and sensitivity. Proteomics research targets from the peptides and individual proteins to larger protein complexes, the molecular weight of which gradually increases, leading to sustained increases in structural and compositional complexity and alterations in molecular properties. Therefore, the selection of various separation strategies and stationary-phase parameters is crucial when dealing with the different targets in proteomics research for in-depth proteomics analysis. This article provides an overview of commonly used chromatographic-separation strategies in the laboratory, including reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), hydrophobic interaction chromatography (HIC), ion-exchange chromatography (IEC), and size-exclusion chromatography (SEC), as well as their applications and selectivity in the context of various biomacromolecules. At present, no single chromatographic or electrophoretic technology features the peak capacity required to resolve such complex mixtures into individual components. Multidimensional liquid chromatography (MDLC), which combines different orthogonal separation modes with MS, plays an important role in proteomics research. In the MDLC strategy, IEC, together with RPLC, remains the most widely used separation mode in proteomics analysis; other chromatographic methods are also frequently used for peptide/protein fractionation. MDLC technologies and their applications in a variety of proteomics analyses have undergone great development. Two strategies in MDLC separation systems are mainly used in proteomics profiling: the "bottom-up" approach and the "top-down" approach. The "shotgun" method is a typical "bottom-up" strategy that is based on the RPLC or MDLC separation of whole-protein-sample digests coupled with MS; it is an excellent technique for identifying a large number of proteins. "Top-down" analysis is based on the separation of intact proteins and provides their detailed molecular information; thus, this technique may be advantageous for analyzing the post-translational modifications (PTMs) of proteins. In this paper, the "bottom-up" "top-down" and protein-protein interaction (PPI) analyses of proteome samples are briefly reviewed. The diverse combinations of different chromatographic modes used to set up MDLC systems are described, and compatibility issues between mobile phases and analytes, between mobile phases and MS, and between mobile phases in different separation modes in multidimensional chromatography are analyzed. Novel developments in MDLC techniques, such as high-abundance protein depletion and chromatography arrays, are further discussed. In this review, the solutions proposed by researchers when encountering compatibility issues are emphasized. Moreover, the applications of HPLC-MS combined with various sample pretreatment methods in the study of exosomal and single-cell proteomics are examined. During exosome isolation, the combined use of ultracentrifugation and SEC can yield exosomes of higher purity. The use of SEC with ultra-large-pore-size packing materials (200 nm) enables the isolation of exosomal subgroups, and proteomics studies have revealed significant differences in protein composition and function between these subgroups. In the field of single-cell proteomics, researchers have addressed challenges related to reducing sample processing volumes, preventing sample loss, and avoiding contamination during sample preparation. Innovative methods and improvements, such as the utilization of capillaries for sample processing and microchips as platforms to minimize the contact area of the droplets, have been proposed. The integration of these techniques with HPLC-MS shows some progress. In summary, this article focuses on the recent advances in HPLC-MS technology for proteomics analysis and provides a comprehensive reference for future research in the field of proteomics.

A Biphasic Strategy to Synergistically Accelerate Activation and CO Spillover in Formic Acid Oxidation Catalysis.

Developing highly efficient and carbon monoxide (CO)-tolerant platinum (Pt) catalysts for the formic acid oxidation reaction (FAOR) is vital for direct formic acid fuel cells (DFAFCs), yet it is challenging due to the high energy barrier of direct intermediates (HCOO* and COOH*) as well as the CO poisoning issues associated with Pt alloy catalysts. Here we present a versatile biphasic strategy by creating a hexagonal/cubic crystalline-phase-synergistic PtPb/C (h/c-PtPb/C) catalyst to tackle the aforementioned issues. Detailed investigations reveal that h/c-PtPb/C can simultaneously facilitate the adsorption of direct intermediates while inhibiting CO adsorption, thereby significantly improving the activation and CO spillover. As a result, h/c-PtPb/C showcases an outstanding FAOR activity of 8.1 A mgPt-1, which is 64.5 times higher than that of commercial Pt/C and significantly surpasses monophasic PtPb. Moreover, the h/c-PtPb/C-based membrane electrode assembly exhibits an exceptional peak power density of 258.7 mW cm-2 for practical DFAFC applications.

Construction of early warning classification of risk in bladder spasm and its intervention plans guided by the rate adjustment card of continuous bladder irrigation after transurethral resection of the prostate (TURP): development and usability study.

Background: Benign prostatic hyperplasia (BPH) is the most common benign disease causing voiding dysfunction in middle-aged and elderly men. the current "gold standard" for surgical treatment is transurethral resection of the prostate (TURP). Continuous bladder irrigation (CBI) is routinely given for 3 to 5 days after operation. However, this may induce bladder spasm. Bladder spasm not only brings physical and mental pain to patients, delaying the postoperative recovery process, but it also increases the medical economic burden. Therefore, it is important to take active measures to effectively warn and deal with bladder spasm. The color of the drainage fluid is an important indicator and requires close observation during CBI, as it can reflect real-time postoperative bleeding. When the color of drainage fluid is abnormal, effective measures should be undertaken. Grading nursing intervention divides patients into different conditions according to their possible changes, and then recommends targeted nursing intervention. Existing studies have formulated CBI programs from the perspective of quantifying the relationship between drainage fluid color and irrigation speed, but have yet to incorporate bladder spasm prevention and control levels or design corresponding grading nursing intervention programs according to different drainage fluid colors. This study aimed to construct the risk warning classification and intervention plan of bladder spasm under the guidance of CBI speed adjusting card after TURP. Methods: Based on the rate adjustment card of CBI after TURP, we formulated the first draft of an early warning classification of risk in bladder spasm and its intervention plans by combining methods suggested from a literature search with semi-structured interviews and results from 2 rounds of correspondence inquiries with 28 experts by the Delphi method. We further screened and revised grading standards and measures. Results: The positive coefficients of experts in 2 rounds of correspondence inquiries were both 100%, the authority coefficients were both 0.952, and the Kendall harmony coefficients were 0.238 and 0.326, respectively (P<0.01). In the second round of correspondence inquiries, the coefficient of variation of expert opinions was 0.000-0.154, and the coefficient of variation of all items was <0.25. Finally, a 3-level risk warning classification standard and 23 nursing measures for CBI complicated by bladder spasm was constructed. Conclusions: The early warning classification of risk in bladder spasm and its intervention plans guided by rate adjustment card of CBI after TURP are scientific and feasible, and can provide a basis and guidance for effective and standardized CBI in patients after TURP.

Histone methyltransferase MLL4 protects against pressure overload-induced heart failure via a THBS4-mediated protection in ER stress.

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.

Immunohistochemical co-expression of PAX2 and CAIX predicts better prognosis in clear cell renal cell carcinoma after nephrectomy: A retrospective observational study.

Clear cell renal cell carcinoma (ccRCC) is a lethal malignancy with high metastatic probability. Paired box 2 gene product (PAX2) carbonic anhydrase IX were biomolecules closely linked with ccRCC development and outcomes of multiple malignancies. We aim to explore the role of immunohistochemical staining of PAX2 and CAIX to predict ccRCC prognosis after nephrectomy. Surgical specimens of patients who were pathologically diagnosed as ccRCC were reviewed. Expression levels of PAX2 and CAIX were assessed via immunohistochemical staining. Recurrence-free survival (RFS) and overall survival were compared among different phenotypes. Inverse probability of treatment weighting (IPTW) was used for adjustment of confounding factors. 56 patients were included. Patients with PAX2 and CAIX high-expression (the two-high group, n=8) had significantly longer RFS and OS than those of simultaneously down-expression (the two-low group, n=31). Median RFS was 38.4 (95% CI: 32.3-NA) for the two-high group and 14.8 (95% CI: 13.4-39.0) months for the two-low group (P=0.043). IPTW confirmed PAX2 and CAIX co-expression is associated with less recurrence risk HR: 0.39, 95% CI: 0.17-0.92, P=0.031). Co-expression of PAX2 and CAIX is associated better prognosis of ccRCC. We are looking for validation by large cohort studies.

Source localization comparison and combination of OPM-MEG and fMRI to detect sensorimotor cortex responses.

BACKGROUND AND OBJECTIVES: The exploration of various neuroimaging techniques have become focal points within the field of neuroscience research. Magnetoencephalography based on optically pumped magnetometers (OPM-MEG) has shown significant potential to be the next generation of functional neuroimaging with the advantages of high signal intensity and flexible sensor arrangement. In this study, we constructed a 31-channel OPM-MEG system and performed a preliminary comparison of the temporal and spatial relationship between magnetic responses measured by OPM-MEG and blood-oxygen-level-dependent signals detected by functional magnetic resonance imaging (fMRI) during a grasping task. METHODS: For OPM-MEG, the ß-band (15-30 Hz) oscillatory activities can be reliably detected across multiple subjects and multiple session runs. To effectively localize the inhibitory oscillatory activities, a source power-spectrum ratio-based imaging method was proposed. This approach was compared with conventional source imaging methods, such as minimum norm-type and beamformer methods, and was applied in OPM-MEG source analysis. Subsequently, the spatial and temporal responses at the source-level between OPM-MEG and fMRI were analyzed. RESULTS: The effectiveness of the proposed method was confirmed through simulations compared to benchmark methods. Our demonstration revealed an average spatial separation of 10.57 ± 4.41 mm between the localization results of OPM-MEG and fMRI across four subjects. Furthermore, the fMRI-constrained OPM-MEG localization results indicated a more focused imaging extent. CONCLUSIONS: Taken together, the performance exhibited by OPM-MEG positions it as a potential instrument for functional surgery assessment.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

Precision medicine for severe asthma - Biological targeted therapy.

Severe asthma is a complex and heterogeneous chronic airway inflammatory disease. Current treatment strategies are increasingly focused on disease classification, facilitating the transition towards personalized medicine by integrating biomarkers and monoclonal antibodies for tailored therapeutic approaches. Several approved biological agents, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-4, anti-IL-5, and anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, have demonstrated significant efficacy in reducing asthma exacerbations, eosinophil counts, improving lung function, minimizing oral corticosteroid usage, and enhancing patients' quality of life. The utilization of these biological agents has brought about profound transformations in the management of severe asthma. This article provides a comprehensive review on biomarkers and biological agents for severe asthma while emphasizing the increasing importance of further research into its pathogenesis and novel treatment modalities.

[Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99， r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.

Effects of Thermal Exposure on the Microstructure and Mechanical Properties of a Ti-48Al-3Nb-1.5Ta Alloy via Powder Hot Isostatic Pressing.

Research on how thermal exposure affects the microstructure and mechanical properties of the Ti-48Al-3Nb-1.5Ta (at. %) alloy, which is prepared via powder hot isostatic pressing (P-HIP), is essential since this low-density alloy shows promise for use in high-temperature applications, particularly for aero-engines, which require long-term stable service. In this study, a P-HIP Ti-48Al-3Nb-1.5Ta (at. %) alloy was exposed to high temperatures for long durations. The phase, microstructure and mechanical properties of the P-HIP Ti-48Al-3Nb-1.5Ta alloy after thermal exposure under different conditions were analyzed using XRD, SEM, EBSD, EPMA, TEM, nanomechanical testing and tensile testing. The surface scale is composed of oxides and nitrides, primarily Al2O3, TiO2, and TiN, among which Al2O3 is preferentially generated and then covered by rapidly growing TiO2 as the thermal exposure duration increases. The nitrides appear later than the oxides and exist between the oxides and the substrate. With increasing exposure temperature and duration, the surface scale becomes more continuous, TiO2 particles grow larger, and the oxide layer thickens or even falls off. The addition of Ta and Nb can improve the oxidation resistance because Ta5+ and Nb5+ replace Ti4+ in the rutile lattice and weaken O diffusion. Compared with the P-HIP Ti-48Al-3Nb-1.5Ta alloy, after thermal exposure, the grain size does not increase significantly, and the γ phase increases slightly (by less than 3%) with the decomposition of the α2 phase. With increasing thermal exposure duration, the γ phase exhibits discontinuous coarsening (DC). Compared with the P-HIP Ti-48Al-3Nb-1.5Ta alloy, the hardness increases by about 2 GPa, the tensile strength increases by more than 50 MPa, and the fracture strain decreases by about 0.1% after thermal exposure. When the depth extends from the edge of the thermally exposed specimens, the hardness decreases overall.

Transcriptomic analysis of bovine endometrial epithelial cells in response to interferon tau and hormone stimulation.

The embryonic loss during early stage of gestation is one of the major causes of infertility for domestic ruminants, causing huge economic losses to pasture. Maternal recognition of pregnancy and implantation are the crucial process for determining the successful establishment and development of pregnancy in cattle. The research on molecular mechanisms of pregnancy recognition will facilitate illustrating the complex process of pregnancy establishment and help to improve pregnancy outcomes. In this study, we performed transcriptomic analysis of primary bovine endometrial epithelial cells (BEND) with or without IFNT and hormones intervention through RNA sequencing. We eventually identified 608 differentially expressed genes (DEGs) including 409 up-regulated genes and 199 down-regulated genes in IFNT and hormones-treated group compared with control group. Gene Ontology (GO) enrichment analysis demonstrated that the majority of DEGs were implicated in immune system process, response to external stimulus, response to cytokine, regulation of response to stress. Results from KEGG analysis showed a significant enrichment of NOD-like receptor signaling pathway, antigen processing and presentation, necroptosis, oxidative phosphorylation, RIG-I-like receptor signaling pathway. Additionally, a set of promising candidate genes, including (USP18, STAT1, PSMB8, IFIH1, MX2, IFI44, DHX58, CASP8, DRAM1, CXCR4), were characterized by constructing an integrated interaction network. Specifically, the mRNA expression of HOXA11, PTGS1 and PTGS2 were remarkably suppressed by silencing DRAM1 under IFNT and hormone administration, thus speculating that DRAM1 might play a crucial role in early pregnancy by regulating endometrial function. The results of this study depicted a relatively comprehensive transcriptional profiles of BEND in response to IFNT and hormones, which contributes to a better understanding of gene interaction network and underlying regulatory mechanisms in endometrium of ruminants during early pregnancy.

Exploration of anti­osteosarcoma activity of asiatic acid based on network pharmacology and in vitro experiments.

Osteosarcomas are malignant bone tumors that typically originate in the epiphyses of the long bones of the extremities in adolescents. Asiatic acid has been reported to possess anti­inflammatory, neuroprotective, antidiabetic, antitumor and antimicrobial activities. The present study used a combination of network pharmacological prediction and in vitro experimental validation to explore the potential pharmacological mechanism of asiatic acid against osteosarcoma. A total of 78 potential asiatic acid targets in osteosarcoma were identified using databases. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/AKT and MAPK signaling pathways are essential in the treatment of osteosarcoma with asiatic acid. Molecular docking revealed binding of asiatic acid to EGFR, Caspase­3, ESR1, HSP90AA1, IL­6 and SRC proteins. asiatic acid inhibited proliferation through G2/M cell cycle arrest in osteosarcoma cells. In addition, asiatic acid induced mitochondria­dependent apoptosis as demonstrated by increases in Bax and VDAC1 expression, and a decrease in Bcl­2 protein expression. The increased autophagosomes, increased LC3­II/I ratios and decreased p62 expression in the treatment group indicated that asiatic acid triggered autophagy. In addition, asiatic acid decreased the levels of phosphorylated (p­)PI3K/PI3K and p­AKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of p­ERK1/2/ERK1/2, p­p38/p38 and p­JNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.

Current progression in application of extracellular vesicles in central nervous system diseases.

Early diagnosis and pharmacological treatment of central nervous system (CNS) diseases has been a long-standing challenge for clinical research due to the presence of the blood-brain barrier. Specific proteins and RNAs in brain-derived extracellular vesicles (EVs) usually reflect the corresponding state of brain disease, and therefore, EVs can be used as diagnostic biomarkers for CNS diseases. In addition, EVs can be engineered and fused to target cells for delivery of cargo, demonstrating the great potential of EVs as a nanocarrier platform. We review the progress of EVs as markers and drug carriers in the diagnosis and treatment of neurological diseases. The main areas include visual imaging, biomarker diagnosis and drug loading therapy for different types of CNS diseases. It is hoped that increased knowledge of EVs will facilitate their clinical translation in CNS diseases.

Amorphization Activated Multimetallic Pd Alloys for Boosting Oxygen Reduction Catalysis.

Amorphous nanomaterials have drawn extensive attention owing to their unique features, while amorphization on noble metal nanomaterials still remains formidably challenging. Herein, we demonstrate a universal strategy to synthesize amorphous Pd-based nanomaterials from unary to quinary metals through the introduction of phosphorus (P). The amorphous Pd-based nanoparticles (NPs) exhibit generally promoted oxygen reduction reaction (ORR) activity and durability compared with their crystalline counterparts. Significantly, the quinary P-PdCuNiInSn NPs, benefiting from the amorphous structure and multimetallic component effect, exhibit mass activities as high as 1.04 A mgPd-1 and negligible activity decays of 1.8% among the stability tests, which are much better than values for original Pd NPs (0.134 A mgPd-1 and 28.4%). Experimental and theoretical analyses collectively reveal that the synergy of P-induced amorphization and the expansion of metallic components can considerably lower the free energy changes in the rate-determined step, thereby explaining the positive correlation with the catalytic activity.

Epithelial Tight Junction Anomalies in Nasal Inverted Papilloma.

OBJECTIVES: As a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP. METHODS: We assessed the expression of ZO-1, occludin, claudin-1, claudin-3, and claudin-7 in healthy controls and NIP by real-time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, TH 1/TH 2/TH 17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated. RESULTS: Upregulation of ZO-1, occludin, claudin-1, and claudin-7, along with downregulation of claudin-3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin-3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO-1, but positively with claudin-3 (all p < 0.05). Furthermore, FOXP3, IL-10, TGF-ß1, IL-5, IL-13, and IL-22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL-10, IL-5, IL-13, and IL-22, whereas ZO-1 was positively with TGF-ß1 (all p < 0.05). CONCLUSION: Nasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP. LEVEL OF EVIDENCE: NA Laryngoscope, 134:552-561, 2024.