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This study aimed to assess the predictive role of blood markers in neuromyelitis optica spectrum disorders (NMOSD). Data from patients with NMOSD, multiple sclerosis (MS), and healthy individuals were retrospectively collected in a 1:1:1 ratio. The expanded disability status scale (EDSS) score was used to assess the severity of the NMOSD upon admission. Receiver operating characteristic (ROC) curve analysis was used to distinguish NMOSD patients from healthy individuals, and active NMOSD from remitting NMOSD patients. Binary logistic regression analysis was used to evaluate risk factors that could be used to predict disease recurrence. Finally, Wilcoxon signed-rank test or matched-sample -test was used to analyze the differences between the indicators in the remission and active phases in the same NMOSD patient. Among the 54 NMOSD patients, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) (platelet × NLR) were significantly higher than those of MS patients and healthy individuals and positively correlated with the EDSS score of NMOSD patients at admission. PLR can be used to simultaneously distinguish between NMOSD patients in the active and remission phase. Eleven (20.4%) of the 54 patients had recurrence within 12 months. We found that monocyte-to-lymphocyte ratio (MLR) (AUC = 0.76, cut-off value = 0.34) could effectively predict NMOSD recurrence. Binary logistic regression analysis showed that a higher MLR at first admission was the only risk factor for recurrence (  = 0.027; OR = 1.173; 95% CI = 1.018-1.351). In patients in the relapsing phase, no significant changes in monocyte and lymphocyte count was observed from the first admission, whereas patients in remission had significantly higher levels than when they were first admitted. High PLR is a characteristic marker of active NMOSD, while high MLR is a risk factor for disease recurrence. These inexpensive indicators should be widely used in the diagnosis, prognosis, and judgment of treatment efficacy in NMOSD.

Background/Aims: Estradiol (EST) reduces the risk of stroke and decreases the incidence and progression of the disease because of its neuroprotective roles in inhibiting cell death that occurs in response to a variety of neuronal stimuli such as inflammation and oxidative stress. In this study, we determined the role played by autophagy and Nrf2-ARE signal pathways in the hippocampus regions in modulating cerebral ischemia under different EST conditions. Methods: Western blot analysis and ELISA were used to determine the protein expression of autophagy and Nrf2-ARE pathways; and the levels of pro-inflammatory cytokines (PICs) and a key marker of oxidative stress. Results: Lacking of EST amplifies autophagy and attenuates Nrf2-ARE pathway in the hippocampus CA1 region. Blocking autophagy alleviates neurological deficits following cerebral ischemia with lacking of EST levels and the effects of autophagy are associated with PIC and oxidative stress. Conclusions: EST influences the protein expression of autophagy and Nrf2-ARE signaling in the brain, which is linked to the pathophysiological processes of PICs and oxidative stress. Moreover, inhibition of autophagy plays a beneficial role in modulating neurological deficits after cerebral ischemia observed under conditions of a lower level of EST.

Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using KKAy mice. Here, we find that the combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combined administration enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR. Additionally, BBR with Sta significantly reduces the concentrations of fecal short-chain fatty acids compared to BBR. Collectively, these results indicate that the combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and short-chain fatty acids, thereby providing a novel approach for the treatment of type 2 diabetes mellitus.

To explore atrophy patterns in thalamic nuclei at different phases of amyotrophic lateral sclerosis (ALS) and determine any correlations between thalamic nucleus volume and either cognitive impairments or motor disabilities. We used the King's clinical staging system for ALS to divide 76 consecutive patients with ALS by disease stage. We investigated patterns of thalamic atrophy in the patients and in 94 healthy controls (HCs). Cognitive functions were evaluated with the Mini-Mental State Examination (MMSE), Frontal Assessment Battery, Boston Naming Test, and Auditory Verbal Learning Test. Considering all ALS patients, no significant differences were observed in the volume of any thalamic nuclei between the ALS group and HCs. Thalamic nucleus volumes remained normal in ALS patients at King's Stage 2 and Stage 3. However, atrophy was detected in the bilateral anteroventral nucleus, bilateral pulvinar-limitans, bilateral mediodorsal-paratenial-reuniens, bilateral motor hub, bilateral sensory hub, and bilateral intralaminar nucleus in patients who had reached King's Stage 3. In these patients, the volume of the bilateral motor nuclei was associated with the revised ALS Functional Rating Scale scores, and that of the right pulvinar-limitans independently correlated with MMSE scores. Our study provides a comprehensive profile of thalamic atrophy in ALS patients. The thalamic atrophy patterns in these patients extremely differs at different King's Stages, and we suggest that these alterations might result largely from sequential, regional patterns of TDP-43 pathology in ALS. Furthermore, thalamic atrophy might play important roles in motor disability and global cognitive impairments observed in patients with ALS.

Background Using in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients. Methods In this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup. Results We found that compared with HCs, ALS patients had a significantly higher CP volume ( p  < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction ( p  = 0.006 and p  < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score ( r = -0.226; p  = 0.005) and the Qalb ( r  = 0.479; p  < 0.001) in ALS patients. Conclusion Our study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.

In recent years, the large-scale integration of renewable energy sources represented by wind power and the widespread application of power electronic devices in power systems have led to the emergence of multi-frequency oscillation problems covering multiple frequency segments, which seriously threaten system stability and restrict the accommodation of renewable energy. The oscillation problems related to renewable energy integration have become one of the most popular topics in the field of wind power integration and power system stability research. It has received extensive attention from both academia and industries with many promising research results achieved to date. This paper first analyzes several typical multi-frequency oscillation events caused by large-scale wind power integration in domestic and foreign projects, then studies the multi-frequency oscillation problems, including wind turbine's shafting torsional oscillation, sub/super-synchronous oscillation and high frequency resonance. The state of the art is systematically summarized from the aspects of oscillation mechanism, analysis methods and mitigation measures, and the future research directions are explored.

Background: Hepatocellular carcinoma (HCC) is a prevalent and highly lethal form of liver cancer, with limited effective treatment options, particularly in the advanced stages. Immunotherapy using PD-1 inhibitors has emerged as a promising treatment modality, yet a substantial proportion of patients exhibit resistance or fail to respond to such therapies. This study aimed to elucidate the role of G0/G1 Switch 2 (G0S2) in regulating PD-L1 expression in monocytes within the HCC tumor microenvironment and to investigate its impact on the efficacy of PD-1 inhibitors. Methods: Gene expression data among HCC patients treated with PD-1 inhibitors were obtained from the HCC single-cell sequencing database; immunohistochemistry was performed to detect G0S2 expression in liver cancer tissues and adjacent non-tumorous tissues of HCC patients; flow cytometry was utilized to analyze the expression of G0S2, PD-L1, CD206, and CD14 in PBMCs from HCC patients; and CD8+T cell proliferation and IFN-γ secretion were used to evaluate the impact of G0S2 knockdown. Results: Utilizing single-cell sequencing data from HCC patients, we identified that G0S2 expression was significantly elevated in the non-responders (NR) compared to responders (R) to PD-1 inhibitor therapy. The immunohistochemical analysis confirmed higher levels of G0S2 in HCC tumor tissues and adjacent non-tumorous tissues, while the flow cytometry revealed the increased expression of G0S2, PD-L1, and CD206 in peripheral blood mononuclear cells (PBMCs) from NR patients compared to R patients and healthy controls. The functional experiments involving the knockdown of G0S2 in the THP-1 monocyte cell line resulted in a significant reduction in PD-L1 expression and a concomitant increase in CD8+T cell proliferation and IFN-γ production. Conclusions: These findings indicate that G0S2 facilitates the upregulation of PD-L1 in monocytes, thereby suppressing T cell activity and contributing to resistance against PD-1 inhibitors in HCC. The high expression of G0S2 in peripheral blood monocytes offers a non-invasive and easily detectable biomarker for predicting the efficacy of PD-1 inhibitor therapy. Consequently, targeting G0S2 may enhance the responsiveness to immunotherapy in HCC patients, providing a new avenue for optimizing treatment strategies and improving patient outcomes.

Background and purpose Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood–brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion. Methods To verify our hypothesis, rat model of IR was established, then the change of activated microglia/macrophage (M/M) and permeability of BBB at 1, 7, 14, and 21 days could be clearly observed post IR. And the activated M/M still can be observed during the whole experiment. Results The Evans blue extravasation of BBB gradually declined from day 1 to day 21. Compared to the control group, microbubbles containing PS were taken up more by activated M/M (approximately twofold) both in vitro and in vivo. Conclusions PS-MBs combined with ultrasound (US) exposure could safely open BBB, and the resulting PS nanoparticles (PS-NPs) could further target activated M/M in the neuroinflammation.

Background Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts. Methods Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed. Results CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients ( r  = 0.462 ∼ 0.636, p <  0.001). Conclusion Our study is the first to reveal a consistent and replicable contribution of peripheral inflammation to CP enlargement in vivo in sporadic ALS patients. Given that CP enlargement has been recently detected in other brain diseases, these findings should consider extending to other disease conditions with a peripheral inflammatory component.

Lung macrophages, as key components of the pulmonary immune system, exert multiple key functions in maintaining pulmonary homeostasis and immune defense by eliminating pathogens (such as bacteria and viruses), modulating inflammatory responses, participating in antigen presentation, and promoting tissue repair. This review summarizes the fundamental biological functions of lung macro- phages and explores their mechanisms of action in diseases such as acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD), influenza, tuberculosis (TB) and lung cancer. Mounting evidence highlights the crucial link between macrophage dysfunction and disease progression. With the advent of advanced technologies such as single-cell transcriptomics, CRISPR gene editing, and proteomics, our understanding of lung macrophage heterogeneity, developmental origins, and functional landscapes has significantly expanded. However, challenges remain in the field, and future research requires interdisciplinary efforts to unravel the molecular mechanisms of macrophages in disease and to develop novel therapeutic targets and strategies for the prevention and treatment of lung diseases.