Topologically Localized Vibronic Excitations in Second-Layer Graphene Nanoribbons.

It is of fundamental importance to characterize the intrinsic properties, like the topological end states, in the on-surface synthesized graphene nanoribbons (GNRs), but the strong electronic interaction with the metal substrate usually smears out their characteristic features. Here, we report our approach to investigate the vibronic excitations of the topological end states in self-decoupled second-layer GNRs, which are grown using an on-surface squeezing-induced spillover strategy. The vibronic progressions show highly spatially localized distributions at the second-layer GNR ends, which can be ascribed to the decoupling-extended lifetime of charging through resonant electron tunneling at the topological end states. In combination with theoretical calculations, we assign the vibronic progressions to specific vibrational modes that mediate the vibronic excitations. The spatial distribution of each resolved excitation shows evident characteristics beyond the conventional Franck-Condon picture. Our work by direct growth of second-layer GNRs provides an effective way to explore the interplay between the intrinsic electronic, vibrational, and topological properties.

Improved Nitrate-to-Ammonia Electrocatalysis through Hydrogen Poisoning Effects.

Electrochemical conversion from nitrate to ammonia is a key step in sustainable ammonia production. However, it suffers from low productive efficiency or high energy consumption due to a lack of desired electrocatalysts. Here we report nickel cobalt phosphide (NiCoP) catalysts for nitrate-to-ammonia electrocatalysis that display a record-high catalytic current density of -702±7 mA cm-2, ammonia production rate of 5415±26 mmol gcat-1 h-1 and Faraday efficiency of 99.7±0.2 % at -0.3 V vs. RHE, affording the estimated energy consumption as low as 22.7 kWh kgammonia-1. Theoretical and experimental results reveal that these catalysts benefit from hydrogen poisoning effects under low overpotentials, which leave behind catalytically inert adsorbed hydrogen species (HI*) at Co-hollow sites and thereupon enable ideally reactive HII* at secondary Co-P sites. The dimerization between HI* and HII* for H2 evolution is blocked due to the catalytic inertia of HI* thereby the HII* drives nitrate hydrogenation timely. With these catalysts, the continuous ammonia production is further shown in an electrolyser with a real energy consumption of 18.9 kWh kgammonia-1.

Multiscale simulations reveal the driving forces of p53C phase separation accelerated by oncogenic mutations.

Liquid-Liquid phase separation (LLPS) of p53 to form liquid condensates has been implicated in cellular functions and dysfunctions. The p53 condensates may serve as amyloid fibril precursors to initiate p53 aggregation, which is associated with oncogenic gain-of-function and various human cancers. M237I and R249S mutations located in p53 core domain (p53C) have been detected respectively in glioblastomas and hepatocellular carcinoma. Interestingly, these p53C mutants can also undergo LLPS and liquid-to-solid phase transition, which are faster than wild type p53C. However, the underlying molecular basis governing the accelerated LLPS and liquid-to-solid transition of p53C remain poorly understood. Herein, we explore the M237I/R249S mutation-induced structural alterations and phase separation behavior of p53C by employing multiscale molecular dynamics simulations. All-atom simulations revealed conformational disruptions in the zinc-binding domain of the M237I mutant and in both loop3 and zinc-binding domain of the R249S mutant. The two mutations enhance hydrophobic exposure of those regions and attenuate intramolecular interactions, which may hasten the LLPS and aggregation of p53C. Martini 3 coarse-grained simulations demonstrated spontaneous phase separation of p53C and accelerated effects of M237I/R249S mutations on the phase separation of p53C. Importantly, we find that the regions with enhanced intermolecular interactions observed in coarse-grained simulations coincide with the disrupted regions with weakened intramolecular interactions observed in all-atom simulations, indicating that M237I/R249S mutation-induced local structural disruptions expedite the LLPS of p53C. This study unveils the molecular mechanisms underlying the two cancer-associated mutation-accelerated LLPS and aggregation of p53C, providing avenues for anticancer therapy by targeting the phase separation process.

Key quality parameter comparison of mesenchymal stem cell product cryopreserved in different cryopreservation solutions for clinical applications.

Introduction: Cryopreservation is a critical process of cell products for achieving a commercial viability through wide scale adoption. By preserving cells in a lower temperature, cryopreservation enables a product to be off-the-shelf and ready for infusion. An optimized cryopreservation strategy can maintain the viability, phenotype, and potency of thawed mesenchymal stromal/stem cells (MSCs) while being regulatory compliant. We compared three clinical-ready formulations with one research cryopreservation solutions and evaluated key quality parameters of post thawed MSCs. Method and result: MSCs were cryopreserved at 3, 6, and 9 million cells/mL (M/mL) in four different cryopreservation solutions: NutriFreez (10% dimethyl sulfoxide [DMSO]), Plasmalyte A (PLA)/5% human albumin (HA)/10% DMSO (PHD10), CryoStor CS5 (5% DMSO), and CryoStor CS10 (10% DMSO). To establish post thaw viability, cells were evaluated with no dilution of DMSO (from 3 M/mL), 1:1 dilution (from 6 M/mL), or 1:2 dilution (from 9 M/mL) with PLA/5% HA, to achieve uniform concentration at 3 M/mL. Cell viability was measured at 0-, 2-, 4-, and 6-h post thaw with Trypan blue exclusion and Annexin V/PI staining. Dilution (1:2) of final cell products from 9M/mL resulted in an improvement of cell viability over 6 h but showed a trend of decreased recovery. MSCs cryopreserved in solutions with 10% DMSO displayed comparable viabilities and recoveries up to 6 h after thawing, whereas a decreasing trend was noted in cell viability and recovery with CS5. Cells from all groups exhibited surface marker characteristics of MSCs. We further evaluated cell proliferation after 6-day recovery in culture. While cells cryopreserved in NutriFreez and PHD10 presented similar cell growth post thaw, MSCs cryopreserved in CS5 and CS10 at 3 M/mL and 6M/mL showed 10-fold less proliferative capacity. No significant differences were observed between MSCs cryopreserved in NutriFreez and PHD10 in their potency to inhibit T cell proliferation and improve monocytic phagocytosis. Conclusion: MSCs can be cryopreserved up to 9 M/mL without losing notable viability and recovery, while exhibiting comparable post thaw potency with NutriFreez and PHD10. These results highlight the importance of key parameter testing for selecting the optimal cryopreservation solution for MSC-based therapy.

Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy.

Probing σ-Aromaticity-Driven Ring Contraction of Metallabenzocyclobutadiene to Metallabenzocyclopropene.

Ring contraction of metallacyclobutadiene to metallacyclopropene is rare because of the increasing strain from a four-membered ring to a three-membered one. Here we demonstrate a new series of reactions of metallabenzocyclobutadiene to metallabenzocyclopropene via density functional theory calculations. The results suggest that these reactions are thermodynamically favorable ranging from -17.4 to -29.4 kcal mol-1, and a low reaction barrier (10.3 kcal mol-1) is achieved when the metal center is Ru and the ligands are one cyanide and one chloride. Further analysis suggests that a strengthened binding energy helps stabilize the transition state in the protonation process. The aromaticity during the reaction was investigated using the electron density of delocalized bonds (EDDB), isomerization stabilization energy, and isodesmic reactions. The EDDB shows that the π-conjugation is disrupted in the intermediate, and then σ-aromaticity is generated and dominant in the products. Our findings could be helpful for experimentalists in developing novel ring contraction reactions driven by aromaticity.

Au-Based Bimetallic Catalysts for Aerobic Oxidation of 5-Hydroxymethylfurfural to 2,5-Furandicarboxylic Acid under Base-Free Reaction Conditions.

The aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) plays a pivotal role in the synthesis of renewable, biodegradable plastics and sustainable chemicals. Although supported gold nanoclusters (NCs) exhibit significant potential in this process, they often suffer from low selectivity. To address this challenge, a series of gold-M (M means Ni, Fe, Cu, and Pd) bimetallic NCs catalysts were designed and synthesized to facilitate the selective oxidation of HMF to FDCA. Our findings indicate that the introduction of doped metals, particularly Ni and Pd, not only improves the reaction rates for HMF tandem oxidation but also promotes high yields of FDCA. Various characterizations techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), in situ diffuse reflectance infrared Fourier transform spectroscopy of CO adsorption (CO-DRIFTS), and temperature-programmed desorption of oxygen (O2-TPD), were employed to scrutinize the structural and electronic properties of the prepared catalysts. Notably, an electronic effect was observed across the Au-based bimetallic catalysts, facilitating the activation of reactant molecules and enhancing the catalytic performance. This study provides valuable insights into the alloy effects, aiding in the development of highly efficient Au-based bimetallic catalysts for biomass conversions.

Bulk T-cell receptor sequencing confirms clonality in obstetric antiphospholipid syndrome and may as a potential biomarker.

The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRß repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.

Correction: Contrast of oropharyngeal leak pressure and clinical performance of I-gel™ and LMA ProSeal™ in patients: A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0278871.].

YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) is a heterogeneous GC subtype characterized by the overexpression of HER2. To date, few specific targeted therapies have demonstrated durable efficacy in HER2-positive GC patients, with resistance to trastuzumab typically emerging within 1 year. However, the mechanisms of resistance to trastuzumab remain incompletely understood, presenting a significant challenge to clinical practice. METHODS: In this study, we integrated genetic screening and bulk transcriptome and epigenomic profiling to define the mechanisms mediating adaptive resistance to HER2 inhibitors and identify potential effective therapeutic strategies for treating HER2-positive GCs. RESULTS: We revealed a potential association between adaptive resistance to trastuzumab in HER2-positive GC and the expression of YES-associated protein (YAP). Notably, our investigation revealed that long-term administration of trastuzumab triggers extensive chromatin remodeling and initiates YAP gene transcription in HER2-positive cells characterized by the initial inhibition and subsequent reactivation. Furthermore, treatment of HER2-positive GC cells and cell line-derived xenografts (CDX) models with YAP inhibitors in combination with trastuzumab was found to induce synergistic effects through the AKT/mTOR and ERK/mTOR pathways. CONCLUSION: These findings underscore the pivotal role of reactivated YAP and mTOR signaling pathways in the development of adaptive resistance to trastuzumab and may serve as a promising joint target to overcome resistance to trastuzumab.

Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis-Associated Acute Kidney Injury.

Histone lactylation is a metabolic stress-related histone modification. However, the role of histone lactylation in the development of sepsis-associated acute kidney injury (SA-AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA-AKI, which is reported in this study. Furthermore, this lactate-dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho-associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor-κB (NF-κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA-AKI and reportes a novel post-translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA-AKI.

Association Between Preoperative Ocular Parameters and Myopic Shift in Children Undergoing Primary Intraocular Lens Implantation.

Purpose: To evaluate the association between preoperative ocular parameters and myopic shift following primary intraocular lens (IOL) implantation in pediatric cataracts. Methods: Eyes from pediatric patients undergoing bilateral cataract surgery with primary IOL implantation were included. Eyes were grouped by age at surgery and subdivided into three axial length (AL) subgroups and three keratometry subgroups. Mixed-effects linear regression was utilized to assess the trend in myopic shift among subgroups. Multivariable analysis was performed to determine factors associated with myopic shift. Results: A total of 222 eyes were included. The median age at surgery was 4.36 years (interquartile range [IQR], 3.16-6.00 years) and the median follow-up was 4.18 years (IQR, 3.48-4.64 years). As preoperative AL increased, a decreased trend was observed in myopic shift and rate of myopic shift (P = 0.008 and P = 0.003, respectively, in the 4 to <6 years old group; P = 0.002 and P < 0.001, respectively, in the ≥6 years old group). Greater myopic shift and rate of myopic shift were associated with younger age at surgery (P = 0.008 and P = 0.008, respectively). Both myopic shift and rate of myopic shift were negatively associated with AL. Conclusions: Age at surgery and preoperative AL were associated with myopic shift in pediatric cataracts following primary IOL implantation. Adjusting the target refraction based on preoperative AL could potentially improve patients' long-term refractive outcome. Translational Relevance: This study may help to guide the selection of postoperative target refraction according to age at surgery and preoperative ocular parameters for pediatric cataracts.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

Evaluation of systemic medications associated with diabetic retinopathy: a nested case-control study from the UK Biobank.

AIMS: This study aims to investigate the associations between commonly used systemic medications and diabetic retinopathy (DR). METHODS: Individuals with linked primary care prescription data from the UK Biobank were included. Cases were defined as individuals with a Hospital Episode Statistics-coded or primary care recorded diagnosis of DR or self-reported DR. Controls were matched for age, sex, glycosylated haemoglobin, duration of diabetes mellitus (DM), hypertension status and cardiovascular disease status. ORs and 95% CIs were calculated using conditional univariate and multivariable logistic regression models. RESULTS: A total of 3377 case subjects with DR were included in the study and matched with 3377 control subjects. In multivariable logistic regression, increased odds of incident DR were observed for exposure to short-acting insulins (OR 1.63; 95% CI 1.22 to 2.18), medium-acting insulins (OR 2.10; 95% CI 1.60 to 2.75), sulfonylureas (OR 1.30; 95% CI 1.16 to 1.46). Instead, the use of fibrates (OR 0.71; 95% CI 0.53 to 0.94) and Cox-2 inhibitors (OR 0.68; 95% CI 0.58 to 0.79) was associated with decreased odds of incident DR. Dose-response relationships were observed for all five drug categories (all p<0.05). CONCLUSIONS: This study comprehensively investigated the associations between systemic medication use and DR and found significant associations between the use of short-acting insulins, medium-acting insulins and sulfonylureas with increased odds of incident DR. In contrast, fibrates and Cox-2 inhibitors were associated with decreased odds of incident DR. These findings may provide valuable insights into DM medication management and serve as a reference for the prevention of DR in patients with DM.

Artificial kagome lattices of Shockley surface states patterned by halogen hydrogen-bonded organic frameworks.

Artificial electronic kagome lattices may emerge from electronic potential landscapes using customized structures with exotic supersymmetries, benefiting from the confinement of Shockley surface-state electrons on coinage metals, which offers a flexible approach to realizing intriguing quantum phases of matter that are highly desired but scarce in available kagome materials. Here, we devise a general strategy to construct varieties of electronic kagome lattices by utilizing the on-surface synthesis of halogen hydrogen-bonded organic frameworks (XHOFs). As a proof of concept, we demonstrate three XHOFs on Ag(111) and Au(111) surfaces, which correspondingly deliver regular, breathing, and chiral breathing diatomic-kagome lattices with patterned potential landscapes, showing evident topological edge states at the interfaces. The combination of scanning tunnelling microscopy and noncontact atomic force microscopy, complemented by density functional theory and tight-binding calculations, directly substantiates our method as a reliable and effective way to achieve electronic kagome lattices for engineering quantum states.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Proteomics analysis of plasm exosomes in early pregnancy among normal pregnant women and those with antiphospholipid syndrome.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombosis and adverse obstetric outcomes. Early diagnosis and intervention can improve pregnancy outcomes to some extent, but current results are unsatisfactory. Exosomes, containing biomacromolecules relevant to reproduction, play essential roles in pregnancy. However, research progress on their involvement in APS remains limited. Objectives: This study aims to investigate protein profile changes in plasma exosomes and identify potential biomarkers for obstetric APS. Methods: We employed tandem mass tag (TMT) markers to analyze exosome protein profiles from 6 healthy early pregnant women and 6 early-stage APS patients. Quantitative proteomics analysis was conducted using the Maxquant search engine. Results: Differential expression analysis identified 51 upregulated and 22 downregulated proteins in plasma exosomes from early pregnant women with APS, such as serpin peptidase inhibitor C1/A1/A7, apolipoprotein 1/2, orosomucoid 1/2 and apolipoprotein H. Kyoto Encyclopedia of Genes and Genomes analysis shows that differentially expressed proteins are enriched in the PPAR signaling pathway and staphylococcus aureus infection pathway. Enrichment analysis indicated associations with glycerolipid biosynthesis, vitamin transport, and negative regulation of very-low-density lipoprotein particle remodeling. Conclusion: Our study highlights alterations in the protein profiles of plasma exosomes in APS pregnant patients and proposes potential biomarkers, offering insights for early diagnosis and treatment and improving reproductive outcomes.

H3K4me3-Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in ß2GPI/Anti-ß2GPI-Treated Monocytes.

Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3-related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC-seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with ß2GPI/anti-ß2GPI, which mimics APS, and decreases after OICR-9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple-positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF-κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF-κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via ß2GPI intraperitoneal injection, and the results suggest that OICR-9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3-mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR-9429 is a promising candidate drug for APS therapy.

Optimized Intermediates Adsorption Configuration on Co-Doped Fe2P@NiP2 Heterojunction Interface for Enhanced Electrocatalytic Nitrate-To-Ammonia Conversion.

The extraction of ammonia (NH3) through electrocatalytic nitrate reduction reaction (NO3 -RR) represents a sustainable avenue in NH3 generation and utilization. However, the catalytic efficiency of the NO3 -RR is hindered by the sluggish kinetics. This study first theoretically found that phosphide-based heterostructure can alter the adsorption structure of intermediates in the nitrate-to-ammonia process, thereby achieving precise regulation of the energy barrier in the rate-determining step. Based on theoretical design, a novel Co-doped Fe2P@NiP2 heterojunction catalyst is successfully synthesized, which deliver a notable NH3 yield rate of 0.395 mmol h-1 cm-2 at -0.7 V versus RHE, as well as a remarkable ammonia Faraday efficiency of 97.2% at -0.6 V versus RHE. Experimental and theoretical results further confirm that redistributing electrons and shifting the center of the d-band upwards through interfacial doping modulate intermediates adsorption strength and inhibition of hydrogen evolution, leading to excellent performance in NO3 --to-NH3. Further integrating the Co-Fe2P@NiP2 catalyst into a Zn-nitrate battery exhibits a substantial voltage output of 1.49 V and a commendable power density of 13.2 mW cm-2. The heteroatom-doped heterojunction strategy provides a versatile route for developing advanced catalysts, thereby broadening the horizons of electrocatalytic methodologies for nitrate reduction and ammonia synthesis.

Helical Nanographenes Bearing Pentagon-Heptagon Pairs by Stepwise Dehydrocyclization.

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.