Fe7S8 coupled with VS4 heterogeneous interface engineering driven by FeV bimetallic MOFs: An efficient all-pH and durable hydrogen evolution.

Rational design and preparation of a multiphase electrocatalyst for hydrogen evolution reaction (HER) has become a hot research topic, while applicable and pH versatility of vanadium tetrasulfide (VS4) and heptairon octasulfide (Fe7S8) composites have rarely been reported. Here, the facile topological sulfide self-template sacrifice method using FeV bimetallic MOFs is designed to obtain Fe7S8 coupled with VS4 heterostructures, enhancing the electron precipitation in the catalysts and attracts electrons to migrate. According to DFT simulations, the electronic coupling at the atomic orbital level and the modulation of interfacial electrons among various interfaces play a crucial role in enhancing the intermediate state process of the hydrogen evolution reaction (HER) across the entire pH range, promoting the optimal d-band centroid value (εd). Reassuringly, the prepared 3D Fe7S8/VS4 electrodes possessed excellent performances of η10 = 53 mV, η10 = 135 mV and η10 = 38 mV in a conventional three-electrode configuration in a 1 M KOH, 1 M Na2SO4, and 0.5 M H2SO4, and the stabilized currents can all be maintained for 48 h. This innovative design of in situ heterostructured materials constructed from dual transition metal sulfides provides inspiring ideas for the preparation of all-pH catalysts.

Acid-mediated strategies designed for stretchable and durable polyacrylamide/sodium alginate dual-network hydrogels toward flexible capacitors and wearable sensors.

The utilization of acid as a synthesis assistant provides an effective means to regulate the structure of hydrogels, thereby simplifying the design and preparation process of multifunctional hydrogels. However, there remains a dearth of discourse concerning the utilization of this convenient acid-mediated strategy, which possesses the potential to directly govern molecular interactions within gel networks for rational structure and property design. Herein, we describe the preparation of flexible dual-network conductive hydrogels using polyacrylamide (PAM) and sodium alginate (SA) as substrates, driven by the strategy of acid-mediated (HCI, H2SO4, and H2C2O4) in detail for the first time. Especially, the structure-activity relationship of hydrogels was elucidated through a comparative analysis of molecular dynamics (MD) simulations and empirical properties, thereby enhancing the understanding of this field. Furthermore, extensive investigations have been conducted to explore the distinct impacts of acid ions and concentrations. The acid-mediated method exhibits superior versatility and operability compared to the filler modification method, thereby enabling a more convenient acquisition of conductive and robust hydrogels suitable for flexible capacitors and wearable sensors. Consequently, this study presents a straightforward, efficient, and cost-effective universal strategy for targeted functional hydrogel design.

Nrf2 deficiency exacerbated pulmonary pyroptosis in maternal hypoxia-induced intrauterine growth restriction offspring mice.

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5% O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

[Different levels and clinical significance of growth differentiation factor-15 in patients with atrial fibrillation].

OBJECTIVE: To measure the concentration of growth differentiation factor-15 (GDF-15) in the serum of patients with atrial fibrillation (AF), to study the correlations between the levels of GDF-15 and different factors including basic clinical information, biochemical examinations, and atrial structure, and further to explore the association between GDF-15 and AF types and structural remodeling. METHODS: AF patients who were admitted to the ward of the Department of Cardiology at Peking University Third Hospital between October 2017 and October 2019 were prospectively enrolled. Patients admitted to the ward at the same time with sinus rhythm and no prior AF history were enrolled in the control group. Clinical information and blood samples of the patients were collected. Enzyme-linked immunosorbent assay was used to measure the concentration of GDF-15. SPSS 23.0 was used for statistical analysis. RESULTS: In the study, 156 AF patients (64 persistent AF and 92 paroxysmal AF) and 38 patients of the control group were included. Serum GDF-15 levels in the AF group were significantly higher than in the control group [1 112 (723, 1 525) ng/L vs. 697 (499, 825) ng/L, P < 0.001]. Serum GDF-15 levels in the persistent AF group were significantly higher than in the paroxysmal AF group [1 140 (858, 1 708) ng/L vs. 1 090 (662, 1 374) ng/L, P=0.047]. The area under the curve (AUC) of serum GDF-15 levels for prediction of AF was 0.736 (95%CI: 0.651-0.822, P < 0.001). The cut-off value was 843.2 ng/L with a sensitivity of 68.2% and a specificity of 78.9%. The AUC of serum GDF-15 levels for prediction of persistent AF was 0.594 (95%CI: 0.504-0.684, P=0.047). The cut-off va-lue was 771.5 ng/L with a sensitivity of 82.8% and a specificity of 35.9%. Spearman rank correlation analysis showed that the serum GDF-15 levels were positively correlated with age (r=0.480, P < 0.001), left atrial pressure (LAP, r=0.300, P < 0.001), and also negatively correlated with left atrial appendage flow velocity (LAAV, r=-0.252, P=0.002). Multiple linear regression analysis showed that age and LAP affected the GDF-15 levels significantly (P < 0.05). Logistic regression analysis suggested GDF-15 (OR=1.002, 95%CI: 1.001-1.003, P=0.004) and left atrial diameter (LAD, OR=1.400, 95%CI: 1.214-1.616, P < 0.001) were independent predictors of AF. CONCLUSIONS: Serum GDF-15 levels are higher in AF patients. Meanwhile, serum GDF-15 levels are higher in persistent AF patients than paroxysmal AF patients. GDF-15 is associated with AF and atrial structural remodeling.

Recombination of variable and host range regions of glycoprotein gp85 in different avian leukosis virus subgroup K isolates.

Given the high prevalence of avian leukosis virus subgroup K (ALV-K) in chickens in China, the positive rate of ALV-K in local chickens in Henan province was investigated, and the genetic region encoding the glycoprotein gp85 of isolates from positive chickens was analyzed. The positive rate of ALV-K in local chickens in Henan was found to be 87.2% (41/47). Phylogenetic analysis of gp85 sequences revealed six clusters that differed in their host range regions (hr1 and hr2) and variable regions (vr1, vr2, and vr3). Evidence of recombination of hr1, hr2, vr1, vr2, and vr3 was observed between the different clusters. The isolate HN23LS02 appears to have obtained its hr1 and hr2 regions from separate lineages via recombination but without having a significant affect on the replication capacity of the virus.

A fibroblast-dependent TGFß1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGFß1 signaling inhibitor, epigallocatechin gallate (EGCG), to Interstitial Lung Disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA sequencing on spare tissue. Biopsies from untreated patients showed higher fibroblast TGFß1 signaling compared to non-disease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGFß1 signaling and several pro-inflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzle-like receptor protein 2 (sFRP2), an unrecognized TGFß1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision cut lung slices (PCLS) from non-diseased donors, we found TGFß1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature Krt5+ basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGFß1 signaling in ILD, the therapeutic potential of EGCG in reducing IPF-related transcriptional changes, and identify TGFß1-non-canonical Wnt pathway crosstalk via sFRP2 as a novel mechanism for dysfunctional epithelial signaling in Idiopathic Pulmonary Fibrosis/ILD.

Copper-Catalyzed Dual Remote Asymmetric Vinylogous Alkynylallylic Substitution of Yne-Allylic Esters with Coumarins.

Chiral coumarins and their derivatives are ubiquitous structural motifs found in an array of biologically and therapeutically active natural products and drugs. Herein, a highly enantioselective dual remote copper-catalyzed vinylogous alkynylallylic substitution of yne-allylic esters with coumarins has been developed. The practicality of this method is exemplified by the use of readily available starting materials; mild reaction conditions; excellent regio-, enantio-, and stereoselectivities; and the very broad substrate scope (67 examples), while the scalability and further applications of this method are illustrated by the gram-scale reaction and the series of derivations of the products.

Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments.

BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.

Hepatic insulin resistance affects the efficacy of metformin in patients with newly diagnosed type 2 diabetes: A Sub-Analysis of the MARCH trial.

AIM: Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients. METHODS: We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment. RESULTS: Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of ß cell function (HOMA-ß), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI. CONCLUSIONS: Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-ß, IR, and lower Matsuda index were indicators of better hepatic IR improvement.

HBXIP induces PARP1 via WTAP-mediated m6A modification and CEBPA-activated transcription in cisplatin resistance to hepatoma.

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Atomic-Scale Insights into the Effects of the Foaming Degree on the Glass-Ceramic Matrix Derived from Waste Glass and Incineration Bottom Ash.

Precise management of the inverse correlation between the total porosity and compressive strength is crucial for the progress of foaming glass-ceramics (FGCs). To deeply understand this relationship, we investigated the atomic-level transformations of five CO2-foaming FGC samples using molecular dynamics simulation. The short-range and intermediate-range structures of the FGCs with varying total porosities (36.68%, 66.28%, 66.96%, 72.21%, and 79.88%) in the system were elucidated. Na cations were observed to exhibit a strong interaction with CO2, accumulating at the surface of the pore wall and influencing the oxygen species. Therefore, the change in the atomic structure of the matrix was accompanied by an increase in the total porosity with an increasing CO2 content. Specifically, as the total porosity increased, the bridging oxygen content within the FGCs rose accordingly. However, once the total porosity exceeded 66.96%, the bridging oxygen content began to decline. This observation was significant considering the role of the bridging oxygen content in forming a continuous cross-linked network of chemical bonds, which contributed to the enhanced mechanical strength. Consequently, the influence of the total porosity on the oxygen species resulted in a two-stage reduction in the compressive strength. This study offers valuable insights for the development of high-strength lightweight FGCs.

C-H-activated Csp2-Csp3 diastereoselective gridization enables ultraviolet-emitting stereo-molecular nanohydrocarbons with mulitple H···H interactions.

Gridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh3-cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H…H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|gPL | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications.

Withdrawn: The altered dynamic community structure for adaptive adjustment in stroke patients with multidomain cognitive impairments: A multilayer network analysis.

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Blue valorization of lignin-derived monomers via reprogramming marine bacterium Roseovarius nubinhibens.

Biological valorization of lignin, the second most abundant biopolymer on Earth, is an indispensable sector to build a circular economy and net-zero future. However, lignin is recalcitrant to bioupcycling, demanding innovative solutions. We report here the biological valorization of lignin-derived aromatic carbon to value-added chemicals without requesting extra organic carbon and freshwater via reprogramming the marine Roseobacter clade bacterium Roseovarius nubinhibens. We discovered the unusual advantages of this strain for the oxidation of lignin monomers and implemented a CRISPR interference (CRISPRi) system with the lacI-Ptrc inducible module, nuclease-deactivated Cas9, and programmable gRNAs. This is the first CRISPR-based regulatory system in R. nubinhibens, enabling precise and efficient repression of genes of interest. By deploying the customized CRISPRi, we reprogrammed the carbon flux from a lignin monomer, 4-hydroxybenzoate, to achieve the maximum production of protocatechuate, a pharmaceutical compound with antibacterial, antioxidant, and anticancer properties, with minimal carbon to maintain cell growth and drive biocatalysis. As a result, we achieved a 4.89-fold increase in protocatechuate yield with a dual-targeting CRISPRi system, and the system was demonstrated with real seawater. Our work underscores the power of CRISPRi in exploiting novel microbial chassis and will accelerate the development of marine synthetic biology. Meanwhile, the introduction of a new-to-the-field lineage of marine bacteria unveils the potential of blue biotechnology leveraging resources from the ocean.IMPORTANCEOne often overlooked sector in carbon-conservative biotechnology is the water resource that sustains these enabling technologies. Similar to the "food-versus-fuel" debate, the competition of freshwater between human demands and bioproduction is another controversial issue, especially under global water scarcity. Here, we bring a new-to-the-field lineage of marine bacteria with unusual advantages to the stage of engineering biology for simultaneous carbon and water conservation. We report the valorization of lignin monomers to pharmaceutical compounds without requesting extra organic substrate (e.g., glucose) or freshwater by reprogramming the marine bacterium Roseovarius nubinhibens with a multiplex CRISPR interference system. Beyond the blue lignin valorization, we present a proof-of-principle of leveraging marine bacteria and engineering biology for a sustainable future.

Relationship between human serum metabolites and angina pectoris: a Mendelian randomization study.

PURPOSE: We aimed to explore the causal relationship between human serum metabolites and angina pectoris. METHODS: This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform. RESULTS: In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism. CONCLUSION: We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris.

Safety and Efficacy of 90Y Selective Internal Radiation Therapy Using Glass Microspheres in Hepatocellular Carcinoma: A Southeast Asian Single-Institution Initial Experience.

Our objective was to demonstrate primarily the safety and secondarily the efficacy of 90Y glass microspheres in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC) in a local Southeast Asian hospital. Methods: Eleven consecutive patients with small, unresectable, nonmetastatic HCC and referred for locoregional therapy with SIRT with a curative intention were followed up for 6 mo after the procedure by way of interviews, blood tests, and anatomic scans. Results: Although 5 patients had deranged liver function tests after the procedure, in only 1 patient did this constitute a grade 1 toxicity (in alkaline phosphatase) by the Common Terminology Criteria for Adverse Events. Half the patients showed a reduction in serum α-fetoprotein measurements, and 6 of 11 patients demonstrated an objective response (complete or partial) on imaging. Conclusion: SIRT with 90Y glass microspheres is a safe and efficacious locoregional therapy for unresectable HCC. There are similar articles published in the West; however, the patient population there comprises far fewer Asians and the underlying cause for HCC is different from that in the Asian population. Despite these differences, SIRT is an equally effective and safe option for such patients.

Unraveling the Predictors of Enlarged Perivascular Spaces: A Comprehensive Logistic Regression Approach in Cerebral Small Vessel Disease.

Background: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders. Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses. Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis. Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings.

Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia.

We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40-18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings.