Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Therapeutic Implication of Targeting Mitochondrial Drugs Designed for Efferocytosis Dysfunction.

Efferocytosis refers to the process by which phagocytes remove apoptotic cells and related apoptotic products. It is essential for the growth and development of the body, the repair of damaged or inflamed tissues, and the balance of the immune system. Damaged efferocytosis will cause a variety of chronic inflammation and immune system diseases. Many studies show that efferocytosis is a process mediated by mitochondria. Mitochondrial metabolism, mitochondrial dynamics, and communication between mitochondria and other organelles can all affect phagocytes' clearance of apoptotic cells. Therefore, targeting mitochondria to modulate phagocyte efferocytosis is an anticipated strategy to prevent and treat chronic inflammatory diseases and autoimmune diseases. In this review, we introduced the mechanism of efferocytosis and the pivoted role of mitochondria in efferocytosis. In addition, we focused on the therapeutic implication of drugs targeting mitochondria in diseases related to efferocytosis dysfunction.

CsMIKC1 regulates inflorescence development and grain production in Cannabis sativa plants.

Female inflorescence is the primary output of medical Cannabis. It contains hundreds of cannabinoids that accumulate in the glandular trichomes. However, little is known about the genetic mechanisms governing Cannabis inflorescence development. In this study, we reported the map-based cloning of a gene determining the number of inflorescences per branch. We named this gene CsMIKC1 since it encodes a transcription factor that belongs to the MIKC-type MADS subfamily. Constitutive overexpression of CsMIKC1 increases inflorescence number per branch, thereby promoting flower production as well as grain yield in transgenic Cannabis plants. We further identified a plant-specific transcription factor, CsBPC2, promoting the expression of CsMIKC1. CsBPC2 mutants and CsMIKC1 mutants were successfully created using the CRISPR-Cas9 system; they exhibited similar inflorescence degeneration and grain reduction. We also validated the interaction of CsMIKC1 with CsVIP3, which suppressed expression of four inflorescence development-related genes in Cannabis. Our findings establish important roles for CsMIKC1 in Cannabis, which could represent a previously unrecognized mechanism of inflorescence development regulated by ethylene.

Pretreatment pulmonary tumor necrosis is a promising prognostic imaging biomarker for first-line anti-PD-1/PD-L1 therapy in advanced lung squamous cell carcinoma: a multi-institutional, propensity score-matching cohort analysis.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.

Interactions of graphene oxide with the microbial community of biologically active filters from a water treatment plant.

With widespread occurrence and increasing concern of emerging contaminants (CECs) in source water, biologically active filters (BAF) have been gaining acceptance in water treatment. Both BAFs and graphene oxide (GO) have been shown to be effective in treating CECs. However, studies to date have not addressed interactions between GO and microbial communities in water treatment processes such as BAFs. Therefore, in the present study, we investigated the effect of GO on the properties and microbial growth rate in a BAF system. Synthesized GO was characterized with a number of tools, including scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Raman spectrometry. GO exhibited the characteristic surface functional groups (i.e., C-OH, C=O, C-O-C, and COOH), crystalline structure, and sheet-like morphology. To address the potential toxicity of GO on the microbial community, reactive oxygen species (ROS) generation was measured using nitro blue tetrazolium (NBT) assay. Results revealed that during the exponential growth phase, ROS generation was not observed in the presence of GO compared to the control batch. In fact, the adenosine triphosphate (ATP) concentrations increased in the presence of GO (25 µg/L - 1000 µg/L) compared to the control without GO. The growth rate in systems with GO exceeded the control by 20 % to 46 %. SEM images showed that GO sheets can form an effective scaffold to promote bacterial adhesion, proliferation, and biofilm formation, demonstrating its biocompatibility. Next-generation sequencing (Illumina MiSeq) was used to characterize the BAF microbial community, and high-throughput sequencing analysis confirmed the greater richness and more diverse microbial communities compared to systems without GO. This study is the first to report the effect of GO on the microbial community of BAF from a water treatment plant, which provides new insights into the potential of utilizing a bio-optimized BAF for advanced and sustainable water treatment or reuse strategies.

Usefulness of estimated glucose disposal rate in detecting heart failure: results from national health and nutrition examination survey 1999-2018.

BACKGROUND: Estimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population. METHODS: 25,450 subjects from the National Health and Nutrition Examination Survey 1999-2018 were included. HF was recorded according to the subjects' reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF. RESULTS: The prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P < 0.001) risk reduction for prevalent HF. In the quartile analysis, the top quartile had a 31.1% (P < 0.001) risk of prevalent HF compared to the bottom quartile in the full model. Smooth curve fitting demonstrated that the association was linear in the whole range of eGDR (P for non-linearity = 0.313). Subgroup analysis revealed that the association was robust in age, sex, race, diabetes, and hypertension subgroups (All P for interaction > 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P < 0.001). CONCLUSION: Our study indicates that eGDR, a costless surrogate of insulin resistance, may have a linear and robust association with the prevalent HF. Furthermore, our findings implicate the potential value of eGDR in refining the detection of prevalent HF in the general population.

Risk factors for arrhythmias occurred in cancer patients after chemotherapy: An evidence-based systematic review and meta-analysis.

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), P＜0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients (P = 0.52; P = 0.19). Disease-related factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), P＜0.00001; OR = 1.30, 95%CI (1.10, 2.52), P = 0.002; OR = 1.76, 95%CI (1.51, 2.05), P＜0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), P＜0.00001]. Chemotherapy-related factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), P＜0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), P＜0.00001; OR = 3.35, 95%CI (2.20, 5.10), P＜0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P = 0.0001]. Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Machine learning identifies key cells and therapeutic targets during ferroptosis after spinal cord injury.

Ferroptosis, a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation, is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury. Thus, in this study, bulk RNA sequencing data (GSE47681 and GSE5296) and single-cell RNA sequencing data (GSE162610) were acquired from gene expression databases. We then conducted differential analysis and immune infiltration analysis. Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms. Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes. Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells, confirming the high expression of Atf3 and Piezo1 in these cells. Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide. In a mouse model of T8 spinal cord injury, low-dose cycloheximide treatment was found to improve neurological function, decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase, and increase levels of the anti-inflammatory cytokine arginase 1. Correspondingly, the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia, while the expression of Acsl4 decreased. Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury, identify the key cell types and genes involved in ferroptosis after spinal cord injury, and validate the efficacy of potential drug therapies, pointing to new directions in the treatment of spinal cord injury.

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.

This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.

Probing charge redistribution at the interface of self-assembled cyclo-P5 pentamers on Ag(111).

Phosphorus pentamers (cyclo-P5) are unstable in nature but can be synthesized at the Ag(111) surface. Unlike monolayer black phosphorous, little is known about their electronic properties when in contact with metal electrodes, although this is crucial for future applications. Here, we characterize the atomic structure of cyclo-P5 assembled on Ag(111) using atomic force microscopy with functionalized tips and density functional theory. Combining force and tunneling spectroscopy, we find that a strong charge transfer induces an inward dipole moment at the cyclo-P5/Ag interface as well as the formation of an interface state. We probe the image potential states by field-effect resonant tunneling and quantify the increase of the local change of work function of 0.46 eV at the cyclo-P5 assembly. Our experimental approach suggest that the cyclo-P5/Ag interface has the characteristic ingredients of a p-type semiconductor-metal Schottky junction with potential applications in field-effect transistors, diodes, or solar cells.

Photochemically Driven Peptide Formation in Supersaturated Aerosol Droplets.

The condensation of amino acids into peptides plays a crucial role in protein synthesis and is thus essential for understanding the origins of life. However, the spontaneous formation of peptides from amino acids in bulk aqueous media is energetically unfavorable, posing a challenge for elucidating plausible abiotic mechanisms. In this study, we investigate the formation of amide bonds between amino acids within highly supersaturated aerosol droplets containing dicyandiamide (DCD), a cyanide derivative potentially present on primordial Earth. Metastable states, i.e. supersaturation, within individual micron-sized droplets are studied using both an optical trap and a linear quadrupole electrodynamic balance. When irradiated with intense visible light, amide bond formation is observed to occur and can be monitored using vibrational bands in Raman spectra. The reaction rate is found to be strongly influenced by droplet size and kinetic modelling suggests that it is driven by the photochemical product of a DCD self-reaction. Our results highlight the potential of atmospheric aerosol particles as reaction environments for peptide synthesis and have potential implications for the prebiotic chemistry of early Earth.

Multi-omics analysis and experimental validation of the value of monocyte-associated features in prostate cancer prognosis and immunotherapy.

Background: Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD. Method: Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. Result: Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis. Conclusion: Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

BACKGROUND: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. METHODS: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. RESULTS: Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. CONCLUSIONS: Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

The Epidemiological Characteristics of Mpox Cases - China, 2023.

What is already known about this topic?: Since May 2022, a global outbreak of mpox has emerged in more than 100 non-endemic countries. As of December 2023, over 90,000 cases had been reported. The outbreak has predominantly affected men who have sex with men (MSM), with sexual contact identified as the principal mode of transmission. What is added by this report?: Since June 2023, China has faced an occurrence of mpox, predominantly affecting the MSM population. Approximately 90% of those affected reported engaging in homosexual behavior within 21 days prior to symptom onset, a trend that aligns with the global outbreak pattern. The prompt identification of cases, diligent tracing of close contacts, and the implementation of appropriate management strategies have successfully mitigated the spread of mpox virus in China. What are the implications for public health practice?: We propose that mpox is transmitted locally within China. Drawing from our experiences in controlling the virus spread, it is crucial to investigate and formulate effective surveillance and educational strategies. Importantly, we must encourage high-risk populations to promptly seek medical care upon the onset of symptoms.

Prognostic Assessment in Patients With Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Using MRI-Based Radiomics.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) carries a poor prognosis. Radiomics may hold potential value in prognostic assessment. PURPOSE: To develop and validate an MRI-based radiomics model and combine it with clinical factors to assess progression-free survival (PFS) and overall survival (OS) of patients with PCNSL. STUDY TYPE: Retrospective and prospective. POPULATION: Three hundred seventy-nine patients (179 female, 53 ± 7 years) from 2014 to 2022. FIELD STRENGTH/SEQUENCE: T2/fluid-attenuated inversion recovery, contrast-enhanced T1WI and diffusion-weighted echo-planar imaging sequences on 3.0 T. ASSESSMENT: Radiomics features were extracted from enhanced tumor regions on preoperative multi-sequence MRI. Using a least absolute shrinkage and selection operator (LASSO) Cox regression model to select radiomic signatures in training cohort (N = 169). Cox proportional hazards models were constructed for clinical, radiomics, and combined models, with internal (N = 72) and external (N = 32) cohorts validating model performance. STATISTICAL TESTS: Chi-squared, Mann-Whitney, Kaplan-Meier, log-rank, LASSO, Cox, decision curve analysis, time-dependent Receiver Operating Characteristic, area under the curve (AUC), and likelihood ratio test. P-value <0.05 was considered significant. RESULTS: Follow-up duration was 28.79 ± 22.59 months (median: 25). High-risk patients, determined by the median radiomics score, showed significantly lower survival rates than low-risk patients. Compared with NCCN-IPI, conventional imaging and clinical models, the combined model achieved the highest C-index for both PFS (0.660 internal, 0.802 external) and OS (0.733 internal, 0.781 external) in validation. Net benefit was greater with radiomics than with clinical alone. The combined model exhibited performance with AUCs of 0.680, 0.752, and 0.830 for predicting 1-year, 3-year, and 5-year PFS, and 0.770, 0.789, and 0.863 for OS in internal validation, with PFS AUCs of 0.860 and 0.826 and OS AUCs of 0.859 and 0.748 for 1-year and 3-year survival in external validation. DATA CONCLUSION: Incorporating a multi-sequence MR-based radiomics model into clinical models enhances the assess accuracy for the prognosis of PCNSL. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Racism and Health Among Aotearoa New Zealand Young People Aged 15-24 years: Analysis of Multiple National Surveys.

PURPOSE: This Aotearoa New Zealand-based study addresses a gap in literature focusing on individual experiences of racism among adolescents and young adults and its links to health. METHODS: This cross-sectional study uses data from multiple instances of the New Zealand Health Survey (2002/03, 2006/07, 2011/12, 2016/17) and General Social Survey (2008-2016) restricted to participants aged 15-24 years. Prevalence of reported experiences of racism are estimated. Meta-analytic techniques to pool data and multiple regression analyses are used to examine associations between experiences of racism and outcomes measures (mental and physical health, general health and well-being, life satisfaction, inability to access health care, and identity). The study used an ethical co-design process between university researchers and a rangatahi Maori (Maori young people) partnership group. RESULTS: Racism was higher among Maori, Pacific, and Asian young people compared to European young people. Racism was associated with all negative health and well-being measures examined for young people, including negative mental and physical health measures (12-Item Short Form Survey, Kessler Psychological Distress Scale), lower self-rated health, negative life satisfaction, higher unmet need for primary care, and identity measures (feelings of not belonging in New Zealand, less able to express their identity). DISCUSSION: The results of this study are concerning. Non-European young people disproportionately bear the burden of racism in Aotearoa New Zealand with a potentially substantial impact on their health and well-being. This is a breach of Indigenous (for Maori) and other international human rights and should be motivation to act to eliminate racism in all its forms.

Interplay between Intermediate Anionic and Cationic Species and the Reflection to Voltage Hysteresis of Oxygen-Redox Battery Electrodes: A Holistic Picture.

Ligand-to-metal charge transfer (LMCT) is conceived as a universal theory to account for voltage hysteresis in oxygen-redox battery electrodes. However, the influence of oxygen anionic species on mediating LMCT and its reflection to voltage hysteresis remain poorly understood. Herein, we demonstrate a close interplay between the chemical states of oxidized oxygen species, the cationic species, and the kinetics of LMCT and forcefully identify their influence on the magnitude of voltage hysteresis. Combining electrochemical/spectroscopic evidence and first-principles calculations, we clarify two distinct kinds of dynamic LMCT processes─that is, the formation of trapped molecular O2 accompanied by the reduction of Ni4+/Ni3+ to Ni2+ (fast LMCT) during relaxation in Li-rich cation-disordered rock-salt (DRX) Li1.3Ni0.27Ta0.43O2 with extremely large voltage hysteresis, the formation of O-O dimers, and the partial reduction of Mn4+ to Mn3+ (slow LMCT) in DRX-Li1.3Mn0.4Ta0.3O2 with medium hysteresis. We further validate the maintenance of both cationic (Mn4+) and anionic (O-•) species during relaxation in Na2Mn3O7, reconciling its nonhysteretic behavior to the absence of LMCT. This study highlights the critical role of intermediate anionic species in mediating LMCT and provides a causal explanation of various voltage hysteresis signatures of oxygen-redox materials.

Racial Disparities in Plasma Cytokine and Microbiome Profiles.

BACKGROUND: Many health issues prevalent in African American (AA) populations are associated with chronic inflammation and related health conditions, including autoimmune diseases, infectious diseases, neurologic disorders, metabolic syndromes, and others. The current study aims to understand plasma microbiome translocation as a potential trigger for chronic inflammation. METHODS: In this study, 16 Caucasian American (CA) and 22 African American (AA) healthy individuals were recruited. Microbial DNA was isolated from the plasma samples and sequenced via microbial 16S rRNA V3-4 sequencing. The plasma levels of 33 cytokines and chemokines were evaluated. The proinflammatory microbiomes were verified using human THP-1 cells in vitro. RESULTS: The plasma levels of IL-6, IL-15, MIP-1α, MIP-1ß, and MIP-3α were higher in the AA people, whereas IL-1α and IL-27 were elevated in the CA people. The plasma microbiomes exhibited eight bacterial genera/phyla differentially enriched in the CA and AA people. Given the critical role of IL-6 in chronic inflammation and associated diseases, we identified five bacteria genera significantly associated with IL-6. The abundance of Actinomyces was positively correlated with the plasma IL-6 level (r = 0.41, p = 0.01), while the abundance of Kurthia (r = -0.34, p = 0.04), Noviherbaspirillum (r = -0.34, p = 0.04), Candidatus Protochlamydia (r = -0.36, p = 0.03), and Reyranella (r = -0.39, p = 0.02) was negatively correlated with this. Finally, the THP-1 cells treated with heat-killed bacteria produced higher levels of IL-6 in vitro in response to the Actinomyces species compared to the species in the genus either uncorrelated or negatively correlated with IL-6. CONCLUSIONS: This is the first study to report potential blood microbiome translocation as a driver for persistently elevated IL-6 levels in the periphery in healthy AA versus CA people. Understanding the plasma microbiome linked to the IL-6 levels in people with different racial backgrounds is essential to unraveling the therapeutic approaches to improve precision medicine.