Intensive mannitol slow infusion post-stenting may attenuate stenting-related early adverse effects in patients with cerebral venous sinus stenosis.

AIMS: To analyze intensive slow mannitol poststenting on attenuating stenting-related early adverse effects in cerebral venous sinus stenosis (CVSS). METHODS: This real-world study enrolled subacute or chronic CVSS patients from January 2017 through March 2022 and divided them into DSA only and stenting post-DSA groups. The later group was subdivided into control (without extra mannitol use) and intensive slow mannitol subgroup (immediate extra mannitol 250-500 mL, 2 mL/min infusion post-stenting) after signed informed consent. All data were compared. RESULTS: A total of 95 eligible patients entered into final analysis, in which 37 cases underwent DSA only and 58 cases underwent stenting post-DSA. Finally, 28 patients were entered into intensive slow mannitol subgroup and 30 in control. Stenting group vs. DSA group, HIT-6 scores and WBC counts were higher in the former (both p < 0.001). Intensive slow mannitol subgroup vs. control on the third day post-stenting, a statistically significant reductions were noticed in the former on WBC counts (6.19 ± 1.86 × 109 /L vs. 9.59 ± 2.05 × 109 /L); HIT-6 scores (degree of headache) (40.00 (38.00-40.00) vs. 49.00 (41.75-55.25)) and brain edema surrounding the stent on CT maps (17.86% vs.96.67%), all p < 0.001. CONCLUSIONS: Stenting-related severe headache, inflammatory biomarkers elevation, and brain edema aggravation can be attenuated by intensive slow mannitol infusion.

Dural Arteriovenous Fistulas With or Without Cerebral Venous Thrombosis: A Cross-Sectional Analysis of 511 Patients.

BACKGROUND AND OBJECTIVES: Recent studies suggest a bidirectional relationship of dural arteriovenous fistula (DAVF) with cerebral venous thrombosis (CVT). We aimed to compare the characteristics of patients with DAVF with or without CVT and to analyze the risk factors for the coexistence of CVT in a DAVF population. METHODS: A total of 511 adult patients with DAVF were enrolled consecutively in our hospital from February 2019 through November 2022. Demographic data, clinical manifestations, and imaging characteristics were reviewed in detail. The patients with DAVF were divided into two groups: DAVF with CVT (DAVF-CVT) group and without CVT (DAVF alone) group. Univariate logistic regression and multivariate logistic regression were used to analyze the risk factors for the coexistence of CVT and DAVF. RESULTS: CVT was found in 19.8% of patients with DAVF. In univariate analysis, compared with the DAVF-alone group, the DAVF-CVT group was more likely to have tinnitus ( P = .001), blurred vision ( P < .001), visual field loss ( P = .001), focal neurological deficits ( P = .002), seizures ( P = .008), and cognitive impairment ( P = .046) and less likely to have spinal cord/brain stem dysfunction ( P = .004). In addition, there were significant differences in age ( P = .009), sex ( P = .019), the occurrence of venous cerebral infarction ( P = .001), and DAVF location ( P < .001) between the two groups. Furthermore, multivariate analysis showed that blurred vision, venous cerebral infarction, large sinus DAVF, and multiple DAVF were risk factors for the coexistence of CVT in patients with DAVF, with the odds ratio of 2.416 (95% CI 1.267-4.606, P = .007), 6.018 (95% CI 1.289-28.100, P = .022), 5.801 (95% CI 2.494-13.496, P < .001), and 5.640 (95% CI 2.122-14.989, P = .001), respectively. CONCLUSION: CVT occurred in approximately one fifth of patients with DAVF. Blurred vision, venous cerebral infarction, large sinus DAVF, and multiple DAVF may be the risk factors for predicting the coexistence of CVT in patients with DAVF.

Identification of necroptosis-related features in diabetic nephropathy and analysis of their immune microenvironent and inflammatory response.

Background: Diabetic nephropathy (DN) was considered a severe microvascular complication of diabetes, which was recognized as the second leading cause of end-stage renal diseases. Therefore, identifying several effective biomarkers and models to diagnosis and subtype DN is imminent. Necroptosis, a distinct form of programmed cell death, has been established to play a critical role in various inflammatory diseases. Herein, we described the novel landscape of necroptosis in DN and exploit a powerful necroptosis-mediated model for the diagnosis of DN. Methods: We obtained three datasets (GSE96804, GSE30122, and GSE30528) from the Gene Expression Omnibus (GEO) database and necroptosis-related genes (NRGs) from the GeneCards website. Via differential expression analysis and machine learning, significant NRGs were identified. And different necroptosis-related DN subtypes were divided using consensus cluster analysis. The principal component analysis (PCA) algorithm was utilized to calculate the necroptosis score. Finally, the logistic multivariate analysis were performed to construct the necroptosis-mediated diagnostic model for DN. Results: According to several public transcriptomic datasets in GEO, we obtained eight significant necroptosis-related regulators in the occurrence and progress of DN, including CFLAR, FMR1, GSDMD, IKBKB, MAP3K7, NFKBIA, PTGES3, and SFTPA1 via diversified machine learning methods. Subsequently, employing consensus cluster analysis and PCA algorithm, the DN samples in our training set were stratified into two diverse necroptosis-related subtypes based on our eight regulators' expression levels. These subtypes exhibited varying necroptosis scores. Then, we used various functional enrichment analysis and immune infiltration analysis to explore the biological background, immune landscape and inflammatory status of the above subtypes. Finally, a necroptosis-mediated diagnostic model was exploited based on the two subtypes and validated in several external verification datasets. Moreover, the expression level of our eight regulators were verified in the singe-cell level and glomerulus samples. And we further explored the relationship between the expression of eight regulators and the kidney function of DN. Conclusion: In summary, our necroptosis scoring model and necroptosis-mediated diagnostic model fill in the blank of the relationship between necroptosis and DN in the field of bioinformatics, which may provide novel diagnostic insights and therapy strategies for DN.

Ketone Body ß-Hydroxybutyric Acid Ameliorates Dopaminergic Neuron Injury Through Modulating Zinc Finger Protein 36/Acyl-CoA Synthetase Long-Chain Family Member Four Signaling Axis-Mediated Ferroptosis.

ß-hydroxybutyrate (BHB) is one of main component of ketone body, which plays an important protective role in various tissues and organs. Whereas, its exact regulatory roles and mechanisms in Parkinson's disease (PD) have not been full elucidated. In this study, SN4741 cells and C57BL/6 mice were treated with 1-methyl-4-phenylpyridinium ion (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish the PD model in vitro and in vivo. Cell viability and damage to dopaminergic neurons were measured by cell counting kit 8, Calcein-AM/PI staining, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and hematoxylin & eosin staining. Corresponding assay kits and BODIPY 581/591 C11 probe evaluated oxidative stress and intracellular iron levels. Western blot examined the ferroptosis-related proteins. MPTP/MPP+-treatment reduced cell viability but triggered oxidative stress and ferroptosis in SNA4741 cells and brain tissues of mice. However, these effects were dramatically reversed by BHB and Fer-1 treatment. Mechanistically, Zinc finger protein 36 (ZFP36) was a target of BHB, and its depletion could reverse the anti-oxidative stress and anti-ferroptosis roles of BHB. Moreover, ZFP36 could directly bound to acyl-CoA synthetase long-chain family member 4 (ACSL4) mRNA to decay its expression, thus negatively modulating ACSL4-mediated oxidative stress and ferroptosis. Summary, BHB alleviated oxidative stress and ferroptosis of dopaminergic neurons in PD via modulating ZFP36/ACSL4 axis, which provided some new understanding for PD prevention and treatment.

Plasma inflammatory biomarkers in cerebral small vessel disease: A review.

Cerebral small vessel disease (CSVD) is a group of pathological processes affecting small arteries, arterioles, capillaries, and small veins of the brain. It is one of the most common subtypes of cerebrovascular diseases, especially highly prevalent in elderly populations, and is associated with stroke occurrence and recurrence, cognitive impairment, gait disorders, psychological disturbance, and dysuria. Its diagnosis mainly depends on MRI, characterized by recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy. While the pathophysiological processes of CSVD are not fully understood at present, inflammation is noticed as playing an important role. Herein, we aimed to review the relationship between plasma inflammatory biomarkers and the MRI features of CSVD, to provide background for further research.

Monitoring Tritrophic Biocontrol Interactions Between Bacillus spp., Fusarium oxysporum f. sp. cubense, Tropical Race 4, and Banana Plants in vivo Based on Fluorescent Transformation System.

Bacillus spp. is effective biocontrol agents for Fusarium wilt of banana (FWB), tropical race 4 (TR4). This study explores the colonization by Bacillus subtilis, Bacillus velezensis, and Bacillus amyloliquefaciens of host banana plants and elucidates the mechanism of antagonistic TR4 biocontrol. The authors selected one B. subtilis strain, three B. velezensis strains, and three B. amyloliquefaciens strains that are proven to significantly inhibit TR4 in vitro, optimized the genetic transformation conditions and explored their colonization process in banana plants. The results showed that we successfully constructed an optimized fluorescent electro-transformation system (OD600 of bacteria concentration=0.7, plasmid concentration=50ng/µl, plasmid volume=2µl, transformation voltage=1.8kV, and transformation capacitance=400Ω) of TR4-inhibitory Bacillus spp. strains. The red fluorescent protein (RFP)-labeled strains were shown to have high stability with a plasmid-retention frequency above 98%, where bacterial growth rates and TR4 inhibition are unaffected by fluorescent plasmid insertion. In vivo colonizing observation by Laser Scanning Confocal Microscopy (LSCM) and Scanning Electron Microscopy (SEM) showed that Bacillus spp. can colonize the internal cells of banana plantlets roots. Further, fluorescent observation by LSCM showed these RFP-labeled bacteria exhibit chemotaxis (chemotaxis ratio was 1.85±0.04) toward green fluorescent protein (GFP)-labeled TR4 hyphae in banana plants. We conclude that B. subtilis, B. velezensis, and B. amyloliquefaciens can successfully colonize banana plants and interact with TR4. Monitoring its dynamic interaction with TR4 and its biocontrol mechanism is under further study.

Identification of miRNAs Contributing to the Broad-Spectrum and Durable Blast Resistance in the Yunnan Local Rice Germplasm.

MicroRNAs are 20-24 nucleotide non-coding RNAs and play important roles in plant-environment interactions. In recent years, many microRNAs (miRNAs) have been found to regulate rice immunity against rice blast fungus. However, there are limited studies about miRNAs that directly target resistance (R) genes to regulate rice immunity. In this study, by deep sequencing, small RNA libraries were constructed from four-leaf stage seedlings of the resistant variety Ziyu44 and susceptible variety Jiangnanxiangnuo (JNXN) upon Magnaporthe oryzae infection, we found that much more miRNAs were significantly differentially expressed in Ziyu44 than in JNXN. Among these miRNAs, we focused on miR9664, a newly identified rice miRNA in our sequencing, which was upregulated lightly in Ziyu44 and drastically in JNXN at 24-48 h post-inoculation (hpi). The transgenic plants overexpressing miR9664 (miR9664-oe) displayed reduced defense responses to M. oryzae, while those knocking down miR9664 (miR9664-m) displayed enhanced defense responses to M. oryzae. Most of the detected miR9664 predicted target genes were reduced in the miR9664-oe lines while increased in the miR9664-m lines. The cleavage site of LOC_Os08g07774 was confirmed by RLM-RACE. Meanwhile, after being inoculated with M. oryzae, the genes were expressed differently between Ziyu44 and JNXN. The results suggest that miR9664-mediated R gene turnover contributes to Ziyu44 broad-spectrum resistance to rice blast fungus. Taken together, our research identified a new rice miRNA that directly targets R genes to regulate rice immunity against rice blast fungus, adding significant information to the study of rice-M. oryzae interaction.

Reinforcing Increase of ΔTc in MgB2 Smart Meta-Superconductors by Adjusting the Concentration of Inhomogeneous Phases.

Incorporating with inhomogeneous phases with high electroluminescence (EL) intensity to prepare smart meta-superconductors (SMSCs) is an effective method for increasing the superconducting transition temperature (Tc) and has been confirmed in both MgB2 and Bi(Pb)SrCaCuO systems. However, the increase of ΔTc (ΔTc = Tc ‒ Tcpure) has been quite small because of the low optimal concentrations of inhomogeneous phases. In this work, three kinds of MgB2 raw materials, namely, aMgB2, bMgB2, and cMgB2, were prepared with particle sizes decreasing in order. Inhomogeneous phases, Y2O3:Eu3+ and Y2O3:Eu3+/Ag, were also prepared and doped into MgB2 to study the influence of doping concentration on the ΔTc of MgB2 with different particle sizes. Results show that reducing the MgB2 particle size increases the optimal doping concentration of inhomogeneous phases, thereby increasing ΔTc. The optimal doping concentrations for aMgB2, bMgB2, and cMgB2 are 0.5%, 0.8%, and 1.2%, respectively. The corresponding ΔTc values are 0.4, 0.9, and 1.2 K, respectively. This work open a new approach to reinforcing increase of ΔTc in MgB2 SMSCs.

MAPK-RAP1A Signaling Enriched in Hepatocellular Carcinoma Is Associated With Favorable Tumor-Infiltrating Immune Cells and Clinical Prognosis.

BACKGROUND: MAPK-RAP1A signaling, which is involved in cancer progression, remains to be defined. Upregulation of MAPK-RAP1A signaling accounts for most cancers that harbor high incident rate, such as non-small cell lung cancer (NSCLC) and pancreatic cancer, especially in hepatocellular carcinoma (HCC). MAPK-RAP1A signaling plays an important function as clinical diagnosis and prognostic value in cancers, and the role of MAPK-RAP1A signaling related with immune infiltration for HCC should be elucidated. METHODS: Microarray data and patient cohort information from The Cancer Genome Atlas (TCGA; n = 425) and International Cancer Genome Consortium (ICGC; n = 405) were selected for validation. The Cox regression and least absolute shrinkage and selection operator (LASSO) were used to construct a clinical prognostic model in this analysis and validation study. We also tested the area under the curve (AUC) of the risk signature that could reflect the status of predictive power by determining model. MAPK-RAP1A signaling is also associated with tumor-infiltrating immune cells (TICs) as well as clinical parameters in HCC. The GSEA and CIBERSORT were used to calculate the proportion of TICs, which should be beneficial for the clinical characteristics (clinical stage, distant metastasis) and positively correlated with the survival of HCC patients. RESULTS: HCC patients with enrichment of MAPK-RAP1A signaling were associated with clinical characteristics and favorable T cell gamma delta (Vδ T cells), and STMN1, RAP1A, FLT3, HSPA8, ANGPT2, and PGF were used as candidate biomarkers for risk scores of HCC. To determine the molecular mechanism of this signature gene association, Gene Set Enrichment Analysis (GSEA) was proposed. Cytokine-cytokine receptor interaction, TGF-ß signaling pathway, and Intestinal immune network for IgA production gene sets were closely related in MAPK-RAP1A gene sets. Thus, we established a novel prognostic prediction of HCC to deepen learning of MAPK-RAP1A signaling pathways. CONCLUSION: Our findings demonstrated that HCC patients with enrichment of MAPK-RAP1A signaling were associated with clinical characteristics and favorable T cell gamma delta (Vδ T cells), which may be a novel prognostic prediction of HCC.

The Crosstalks Between Jasmonic Acid and Other Plant Hormone Signaling Highlight the Involvement of Jasmonic Acid as a Core Component in Plant Response to Biotic and Abiotic Stresses.

Plant hormones play central roles in plant growth, developmental processes, and plant response to biotic and abiotic stresses. On the one hand, plant hormones may allocate limited resources to the most serious stresses; on the other hand, the crosstalks among multiple plant hormone signaling regulate the balance between plant growth and defense. Many studies have reported the mechanism of crosstalks between jasmonic acid (JA) and other plant hormones in plant growth and stress responses. Based on these studies, this paper mainly reviews the crosstalks between JA and other plant hormone signaling in regulating the balance between plant growth and defense response. The suppressor proteins JASMONATE ZIM DOMAIN PROTEIN (JAZ) and MYC2 as the key components in the crosstalks are also highlighted in the review. We conclude that JA interacts with other hormone signaling pathways [such as auxin, ethylene (ET), abscisic acid (ABA), salicylic acid (SA), brassinosteroids (BRs), and gibberellin (GA)] to regulate plant growth, abiotic stress tolerance, and defense resistance against hemibiotrophic pathogens such as Magnaporthe oryzae and Pseudomonas syringae. Notably, JA may act as a core signal in the phytohormone signaling network.