T Cells Immune Imbalance Present in Patients With Multiple Intracranial Aneurysms.

Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs.

Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm.

BACKGROUND: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. METHODS: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRß, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. RESULTS: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. CONCLUSION: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study.

BACKGROUND: The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD). METHODS: This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups. RESULTS: A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031-362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259-92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005). CONCLUSION: NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.

CTC, ctDNA, and Exosome in Thyroid Cancers: A Review.

Thyroid cancer has become more common in recent years all around the world. Many issues still need to be urgently addressed in the diagnosis, treatment, and prognosis of thyroid cancer. Liquid biopsy (mainly circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating exosomes) may provide a novel and ideal approach to solve these issues, allows us to assess the features of diseases more comprehensively, and has a function in a variety of malignancies. Recently, liquid biopsy has been shown to be critical in thyroid cancer diagnosis, treatment, and prognosis in numerous previous studies. In this review, by testing CTCs, ctDNA, and exosomes, we focus on the possible clinical role of liquid biopsy in thyroid cancer, including diagnostic and prognostic biomarkers and response to therapy. We briefly review how liquid biopsy components have progressed in thyroid cancer by consulting the existing public information. We also discuss the clinical potential of liquid biopsy in thyroid cancer and provide a reference for liquid biopsy research. Liquid biopsy has the potential to be a useful tool in the early detection, monitoring, or prediction of response to therapies and prognosis in thyroid cancer, with promising clinical applications.

Heterogeneous Copper-Catalyzed Cross-Coupling for Sustainable Synthesis of Chiral Allenes: Application to the Synthesis of Allenic Natural Products.

Classical Crabbé type SN 2' substitutions of propargylic substrates has served as one of the standard methods for the synthesis of allenes. However, the stereospecific version of this transformation often requires either stoichiometric amounts of organocopper reagents or special functional groups on the substrates, and the chirality transfer efficiency is also capricious. Herein, we report a sustainable methodology for the synthesis of diverse 1,3-di and tri-substituted allenes by using a simple and cheap cellulose supported heterogeneous nanocopper catalyst (MCC-Amp-Cu(I/II)). This approach represents the first example of heterogeneous catalysis for the synthesis of chiral allenes. High yields and excellent enantiospecificity (up to 97 % yield, 99 % ee) were achieved for a wide range of di- and tri-substituted allenes bearing various functional groups. It is worth noting that the applied heterogeneous catalyst could be recycled at least 5 times without any reduced reactivity. To demonstrate the synthetic utility of the developed protocol, we have applied it to the total synthesis of several chiral allenic natural products.

Association of morning hypertension with chronic kidney disease progression and cardiovascular events in patients with chronic kidney disease and hypertension.

BACKGROUND AND AIM: Associations of morning hypertension with chronic kidney disease are rarely investigated in prospective studies. We aim to investigate the predictive value of uncontrolled morning hypertension (UMH) to chronic kidney disease (CKD) progression and cardiovascular (CV) events in patients with CKD and hypertension. METHODS AND RESULTS: In this prospective two-center observational study, 304 hypertensive patients with CKD were enrolled. Time to total mortality, CKD progression and CV events was recorded; Kaplan-Meier survival function estimates and Multivariable Cox proportional hazard model were used to investigate associations between UMH and outcomes. The study protocol was approved by the Institutional Review Board (http://www.thaiclinicaltrials.org; TCTR20180313004). After a follow-up for median 30 months, 23 (7.6%) patients died, 34 (11.2%) had CKD progression, and 95 (31.3%) occurred new-onset CV events, respectively. UMH was shown to be a strong predictor of CKD progression [hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.22-4.94] and CV events (HR 1.69, 95% CI 1.12-2.53). When morning hypertension was analyzed as a continuous variable, morning systolic blood pressure (per 10 mmHg) was also shown to be predictive to CKD progression (HR 1.28, 95% CI 1.07-1.53, P < 0.01) and CV events (HR 1.15, 95% CI 1.03-1.28, P < 0.01). CONCLUSIONS: UMH is strongly associated with CKD progression and CV events in patients with CKD and hypertension. UMH in CKD patients deserves further attentions.

High-performance flexible UV photodetector based on self-supporting ZnO nano-networks fabricated by substrate-free chemical vapor deposition.

Self-supporting ZnO nano-networks have been demonstrated by a substrate-free chemical vapor deposition process for the application as flexible ultraviolet (UV) photodetector. The device shows a responsivity of ∼300 mA W-1over a wide wavelength range from 254 to 365 nm and a high UV/visible rejection ratio of more than 104. More interestingly, a short 90%-10% decay time of <0.12 s can be observed in the air atmosphere, and the current can fully recover to its original dark value within 1 s after switching off the light. The quick response speed should be associated with the wire-wire junction barriers and the adsorption/desorption process of oxygen molecules on the oxygen vacancies near the surface of the ZnO. In addition, the photocurrent, the dark current and the response speed of the ZnO nano-networks flexible UV photodetector nearly stay the same under different bending conditions, suggesting the excellent photoelectric stability and repeatability. Such a simple and cheap way for fabricating self-supporting ZnO-based devices has broad application prospects in the fields of flexible and wearable electronic devices.

[Carbon Monoxide and Pain Regulation: A Review].

Carbon monoxide (CO) is an endogenous gasotransmitter produced by the degradation of heme in the presence of heme oxygenase (HO) in mammals. It has been demonstrated that CO participates in a variety of physiological activities and pathological processes, and is closely related to cell protection and homeostasis maintenance in organ tissues. It has been shown by a growing number of studies that CO may play a regulatory and interventional role in the process of the occurrence and development of pain through a variety of mechanisms of action. However, its mechanism of action is still not fully understood and the uncontrollable factors concerning CO administration also placed considerable limitation to its application. This paper reviews the potential targets and pathways of CO in pain regulation and discusses the challenges and opportunities in the clinical application of CO in order to provide suggestions for further exploration and development of CO analgesics.

Probiotic characteristics of Lactobacillus plantarum E680 and its effect on Hypercholesterolemic mice.

BACKGROUND: Probiotics have been reported to reduce total cholesterol levels in vitro, but more evidence is needed to determine the clinical relevance of this activity. Chinese traditional fermented pickles are a good source of lactic acid bacteria. Therefore, pickle samples were collected for screening lactic acid bacteria based on their ability to survive stresses encountered during gastrointestinal passage and cholesterol reducing potency. RESULTS: Seventy five lactic acid bacteria strains were isolated from 22 fermented pickles. From these bacteria, Lactobacillus plantarum E680, showed the highest acid (85.25%) and bile tolerance (80.79%). It was sensitive to five of the eight antibiotics tested, inhibited the growth of four pathogenic bacteria, and reduced the total cholesterol level by 66.84% in broth culture. In vivo testing using hypercholesterolemic mice fed high-fat emulsion, independent of food intake, found that L. plantarum E680 suppressed body weight gain and reduced total cholesterol and low-density lipoprotein cholesterol levels, with no effect on high-density lipoprotein cholesterol. CONCLUSIONS: Chinese traditional fermented pickles are a good source for probiotics. L. plantarum E680, isolated from pickles, was acid and bile tolerant, sensitive to antibiotics, and reduced cholesterol levels both in vitro and in vivo. Based on these results, L. plantarum E680 may have potential as a novel probiotic for the development of cholesterol-lowering functional food.

Development of Chiral Spiro Phosphoramidites for Rhodium-Catalyzed Enantioselective Reactions.

A series of 1,1'-spirobiindane-7,7'-diol (SPINOL) analogues bearing a 2,2'-dimethyl-, cyclopentyl-, or cyclohexyl-fused ring were synthesized, and their distinct structural features were elucidated by X-ray crystallography. On the basis of these scaffolds, chiral monophosphoramidite ligands 6 a-m were synthesized, which demonstrated excellent enantioselectivity in RhI -catalyzed asymmetric hydrogenation of a dehydro amino acid methyl ester. Ligands 6 a-m were also successfully applied in the RhI -catalyzed enantioselective [4+2] cycloaddition of α,ß-unsaturated imines with isocyanates, which afforded the corresponding pyrimidinones in good yields (60-92 %) with high enantioselectivities (75-92 % ee).

Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis.

1,1'-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1'-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α'-bis(arylidene)ketones and TiCl4 promoted asymmetric spiroannulation of the hydrogenated chiral ketones. The protocol can be performed in one pot and is readily scalable, and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused spirobiindanediol (1 S,2 S,2' S)-5, in >99% ee and 67% overall yield for four steps without chromatographic purification. Facile derivations of (1 S,2 S,2' S)-5 provided straightforward access to chiral monodentate phosphoramidites 6a-c and a tridentate phosphorus-amidopyridine 11, which were evaluated as chiral ligands in several benchmark enantioselective reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed by transition metal (Rh, Au, or Ir). Preliminary results from comparative studies showcased the excellent catalytic performances of these ligands, with a competency essentially equal to the corresponding well-established privileged ligands bearing a regular spirobiindane backbone. X-ray crystallography revealed a close resemblance between the structures of the precatalysts 20 and 21 and their analogues, which ultimately help to rationalize the almost identical stereochemical outcomes of reactions catalyzed by metal complexes of spirobiindane-derived ligands with or without a fused cyclohexyl ring on the backbone. This work is expected to stimulate further applications of this type of readily accessible skeletons in development of chiral ligands and functional molecules.

Rhodium-Complex-Catalyzed Hydroformylation of Olefins with CO2 and Hydrosilane.

A rhodium-catalyzed one-pot hydroformylation of olefins with CO2 , hydrosilane, and H2 has been developed that affords the aldehydes in good chemoselectivities at low catalyst loading. Mechanistic studies indicate that the transformation is likely to proceed through a tandem sequence of poly(methylhydrosiloxane) (PMHS) mediated CO2 reduction to CO and a conventional rhodium-catalyzed hydroformylation with CO/H2 . The hydrosilylane-mediated reduction of CO2 in preference to aldehydes was found to be crucial for the selective formation of aldehydes under the reaction conditions.

Prophylactic effects of supplementation of a combination of Lactobacillus lactis WHH2078 and saffron on depressive-like behaviors in mice exposed to chronic stress.

Depression is one of the most common psychiatric conditions worldwide, with an annual escalation in prevalence. The serotonin (5-Hydroxytryptamine [5-HT]) metabolism through the gut-brain axis has been revealed to be related to the development of depression. Our previous study demonstrated that Lactococcus lactis WHH2078 alleviated depression in mice by shaping the gut microbiome composition and 5-HT metabolism. However, little research has explored the synergistic effects of probiotics and natural mental health-improving products. In this study, three natural products (saffron, l-theanine, and phosphatidylserine), either individually or in combination, were orally administrated for 4 weeks in chronic restraint stress (CRS)-induced mice, and their depressive behaviors, hippocampal 5-HT, and serum corticosterone were assessed. Saffron demonstrated improvement of the depressive-like behaviors via multiple behavioral tests and reversed the declined concentration of 5-HT and increased concentration of corticosterone. Following an initial screening, saffron was chosen to be combined with WHH2078, referred to as WHHMOOD™. Furthermore, the effects of WHHMOOD were evaluated in mice with depressive-like behaviors. WHHMOOD reduced immobility time in the forced swimming test and tail suspension test, increased the time spent in the central area in open field test, and reduced the serum corticosterone level. Besides, WHHMOOD improved the CRS-induced gut microbial dysbiosis by reversing gut microbial diversity and the abundances of Ligilactobacillus, Candidatus Arthromitus, and Erysipelatoclostridium. Compared to WHH2078, WHHMOOD treatment significantly increased the travel distance and hippocampal 5-HT level in mice. In conclusion, WHHMOOD exhibited prophylactic effects on depressive-like in CRS mice, which may act as a promising agent for improving the symptoms of depression.

Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.

This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.

Lactococcus strains with psychobiotic properties improve cognitive and mood alterations in aged mice.

Aging often accompanies cognitive and mood disturbances. Emerging evidence indicates that specific probiotics mitigate cognitive and mood dysfunctions. Strains within Lactococcus, a subgroup of probiotics, including Lactococcus lactis and Lactococcus cremoris are shown beneficial effects on brain functions via the gut microbiota-brain axis (GBA). Our previous study identified two Lactococcus strains (L. lactis WHH2078 and L. cremoris WHH2080) with the ability to promote the secretion of gut 5-hydroxytryptophan (5-HTP), the precursor of the GBA mediator 5-hydroxytryptamine (5-HT). In this study, the modulatory effects of WHH2078 and WHH2080 on cognitive and mood alternations were investigated in aged mice. Oral administration of WHH2078 and WHH2080 (1 × 109 CFU/mL/day) in aged mice (12-month-old) for 12 weeks significantly improved cognitive and depressive-and anxiety-like behaviors. The neuronal loss, the 5-HT metabolism dysfunction, and the neuroinflammation in the hippocampus of aged mice were restored by WHH2078 and WHH2080. the disturbances in the serum tryptophan metabolism in aged mice were unveiled by metabolomics, notably with decreased levels of 5-HT and 5-HTP, and increased levels of kynurenine, 3-hydroxykynurenine, and indolelactic acid, which were reversed by WHH2078 and WHH2080. Regarding the gut microbial community, WHH2078 and WHH2080 restored the increased abundance of Firmicutes, Desulfobacterota, and Deferribacterota and the decreased abundance of Bacteroidota and Actinobacteriota in aged mice. The beneficial effects of the two strains were linked to the modulation of 5-HT metabolism and gut microbiota. Our findings point to the potential role of Lactococcus strains with 5-HTP-promoting abilities as therapeutic approaches for age-related cognitive and mood disorders.

Comprehensive Analysis and In Vitro Verification of Endothelial-Mesenchymal Transition-Related Genes in Moyamoya Disease.

Moyamoya disease (MMD) is a rare, chronic, and progressive cerebrovascular disorder with unclear underlying causes and mechanisms. Previous studies suggest a potential involvement of endothelial-mesenchymal transition (EndMT) in the pathogenesis of MMD. This study aimed to explore the contribution of EndMT-related genes (ERGs) in MMD. Two datasets, GSE141022 and GSE157628, were integrated as the training set after batch effects removal. Differentially expressed ERGs were identified between MMD and control groups. Functional enrichment analysis and immune infiltration analysis were further performed. LASSO regression was used for hub MMD-related ERG selection. Consensus clustering was used for MMD subtype classification based on these hub MMD-related ERGs. Molecular characteristics between MMD subtypes were analyzed using WGCNA. PPI network was used to illuminate the genetic relationship. The hub MMD-related ERGs were validated in an independent testing set, GSE189993. The nomogram model was constructed and evaluated using ROC curves and calibration plots. Additionally, CCK-8, EdU, wound healing, and western blot were performed to confirm the function of the hub MMD-related ERGs. A total of 107 DE-ERGs were identified. Functional enrichment analysis showed these genes were associated with EndMT and immune response. The infiltrating levels of immune cells were commonly higher in the MMD group. LASSO regression identified 12 hub MMD-related ERGs, leading to the identification of two MMD subtypes. Four ERGs emerged as the final hub MMD-related ERGs after validation in the testing set, including CCL21, CEBPA, KRT18, and TNFRSF11A. The nomogram model exhibited excellent discrimination ability. In vitro experiments showed that CCL21, CEBPA, KRT18, and TNFRSF11A could promote proliferation, migration, and EndMT. This study investigated the potential role of EndMT in MMD and identified four hub MMD-related ERGs, providing potential therapeutic targets for MMD treatment.

Single-Cell Atlas of Atherosclerosis Patients by Cytof: Circulatory and Local Immune Disorders.

Atherosclerosis (AS) is a common underlying pathology of coronary artery disease, peripheral artery disease, and stroke. The characteristics of immune cells within plaques and their functional relationships with blood are crucial in AS. In this study, Mass cytometry (CyTOF), RNA-sequencing and immunofluorescence were combined to comprehensively analyze plaque tissues and peripheral blood from 25 AS patients (22 for Mass cytometry and 3 for RNA-sequencing), as well as blood from 20 healthy individuals. The study identified a complexity of leukocytes in the plaque, including both defined anti-inflammatory and pro-inflammatory subsets such as M2-like CD163+ macrophages, Natural killer T cells (NKT), CD11b+ CD4+ T effector memory cells (Tem), and CD8+ terminally differentiated effector memory cells (TEMRA). Functionally activated cell subsets were also found in peripheral blood in AS patients, highlighting the vivid interactions between leukocytes in plaque and blood. The study provides an atlas of the immune landscape in atherosclerotic patients, where pro-inflammatory activation was found to be a major feature of peripheral blood. The study identified NKT, CD11b+ CD4+ Tem, CD8+ TEMRA and CD163+ macrophages as key players in the local immune environment.

Single-cell atlas of peripheral blood by CyTOF revealed peripheral blood immune cells metabolic alterations and neutrophil changes in intracranial aneurysm rupture.

Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single-cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate-limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti-inflammatory polymorphonuclear myeloid-derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.

Mass cytometry revealed the circulating immune cell landscape across different Suzuki stages of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disorder marked by progressive arterial narrowing, categorized into six stages known as Suzuki stages based on angiographic features. Growing evidence indicates a pivotal role of systemic immune and inflammatory responses in the initiation and advancement of MMD. This study employs high-dimensional mass cytometry to reveal the immunophenotypic characteristics of peripheral blood immune cells (PBMCs) at various Suzuki stages, offering insights into the progression of MMD. PBMC samples from eight patients with early-stage MMD (Suzuki stages II and III) and eight patients with later-stage MMD (Suzuki stages IV, V, and VI) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. We identified 15 cell clusters and found that the immunological features of early-stage MMD and later-stage MMD are composed of cluster variations. In this study, we confirmed that, compared to later-stage MMD, the early-stage MMD group exhibits an increase in non-classical monocytes. As the Suzuki stage level increases, the proportions of plasmacytoid DCs and monocyte-derived DCs decrease. Furthermore, T cells, monocytes, DCs, and PMN-MDSCs in the early-stage MMD group show activation of the canonical NF-κB signaling pathway. We summarized and compared the similarities and differences between early-stage MMD patients and later-stage MMD patients. There is a potential role of circulating immune dysfunction and inflammatory responses in the onset and development of MMD.

Circulating immune cell landscape and T-cell abnormalities in patients with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. METHODS: In this study, we employed a combination of single-cell RNA sequencing (scRNA-seq), mass cytometry and RNA-sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age-matched healthy controls. RESULTS: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T-cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA-DR and p-STAT3. CONCLUSIONS: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T-cell populations, including a decrease in effector T-cells and an increase in regulatory T-cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.