Linear polydichlorophosphazene and Ti3C2Tx MXene nanohybrids: Synthesis and application to epoxy resin to improve the fire safety and mechanical properties.

Enhancing the fire safety of epoxy resins (EPs) typically requires a significant amount of flame retardants, which often results in considerable degradation of their mechanical properties. To address this issue, a novel flame retardant known as PDCP@DPA@MXene was synthesized and integrated into EP to achieve notable improvements in flame retardancy, smoke suppression, and mechanical strength. By incorporating 1.5 wt% PDCP@DPA@MXene, the impact strength, tensile strength, and elongation at break of the resulting PDM-1.5 %/EP composite reached 12.1 kJ/m2, 57.4 MPa, and 13.0, respectively, reflecting enhancements of 63.5 %, 18.4 %, and 17.1 % compared to the pure EP. The enhancement in tensile strength may be attributed to the high rigidity of Ti3C2Tx MXene, which reinforces the EP matrix. Additionally, the intertwined structure of PDCP@DPA@MXene chains effectively mitigates material fracturing and absorbs impact forces, thus toughening the EP. The presence of phosphorus, nitrogen, and titanate in PDCP@DPA@MXene contributes to the formation of a more compact char layer. The PDM-1.5 %/EP sample achieved a V-0 rating in the vertical UL-94 test and exhibited a high limiting oxygen index of 32.0. Furthermore, the sample containing 2 wt% PDCP@DPA@MXene showed a significant reduction in peak heat release rate (p-HRR) and total heat release (THR), recording values of 689 kW/m2 and 71.9 MJ/m2, which are decreases of 45.1 % and 26.9 %, respectively, compared to pure EP. Additionally, the incorporation of PDCP@DPA@MXene led to a reduction in CO production. These flame-retarded EPs demonstrate strong potential for various applications due to their elevated glass transition temperature and robust thermal stability.

Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp3)-H Bonds with CO2: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids.

Direct carboxylation of C-H bonds with CO2 represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp3)-H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp3)-H bonds with CO2 via visible-light photoredox catalysis. Various all-carbon quaternary carboxylic acids, which are of significant importance in medicinal chemistry, are successfully obtained with high yields. This direct carboxylation is characterized by good functional group tolerance, broad substrate scope, and mild operational conditions. Furthermore, our methodology enables the efficient and rapid synthesis of key drug or bioactive molecules, such as carbetapentane, caramiphen, and PRE-084 (σ1 receptor agonist), and facilitates various functionalizations of C(sp2)-H bonds using the directing ability of target carboxylic acids, thus highlighting its practical applications. Mechanistic studies indicate that a carbanion, which serves as the key intermediate to react with CO2, is catalytically generated via a single electron reduction of a benzylic radical through a consecutive photoinduced electron transfer process.

The p. S178L mutation in Tbc1d24 disrupts endosome-mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice.

The ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle resupply to enable fast and sustained release rates. However, the molecular mechanisms of these physiological activities remain unelucidated. Previous studies showed that the RAB-specific GTPase-activating protein TBC1D24 controls the endosomal trafficking of the synaptic vesicles (SVs) in Drosophila and mammalian neurons, and mutations in TBC1D24 may lead to non-syndromic hearing loss or hearing loss associated with the DOORS syndrome in humans. In this study, we generated a knock-in mouse model for the p. S178L mutation in TBC1D24, which leads to autosomal dominant non-syndromic hearing loss (DFNA65). The p.S178L mutant mice show mild hearing loss and progressively declined wave I amplitude of the auditory brainstem responses. Despite the normal gross and cellular morphology of the cochlea, transmission electron microscopy reveals accumulation of endosome-like vacuoles and a lower-than-normal number of SVs directly associated with the ribbons in the IHCs. Consistently, patch clamp of the IHCs shows reduced exocytosis under prolonged stimulus. ARF6, a TBC1D24-interacting protein also involved in endosomal membrane trafficking, was underexpressed in the cochleae of the mutant mouse and has weakened in vitro interaction with the p.S178L mutant TBC1D24. Our results suggest an important role of TBC1D24 in maintaining endosomal-mediated vesicle recycling and sustained exocytosis of hair cell ribbon synapses.

A unique cell division protein critical for the assembly of the bacterial divisome.

Identification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here, we report a previously unrecognized core component of the Acinetobacter baumannii divisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202K and FtsBE65A mutants effectively bypassed the need of Aeg1 by A. baumannii, as did the activation variants FtsWM254I and FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.

Hybrid versus catheter ablation for Hypertrophic CardioMyopathy with Atrial Fibrillation (HCM-AF): study protocol for a randomised controlled trial.

INTRODUCTION: Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF. METHODS/ANALYSIS: This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments. ETHICS AND DISSEMINATIONAPPROVAL: The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05610215.

Cardiovascular prognosis in patients with type 2 diabetes mellitus mediated by the functional completeness after revascularization.

BACKGROUND: Functional complete revascularization (CR) after percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. METHODS: A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial. Functional CR was defined as rFSS=0, while anatomic CR was defined as residual SYNTAX score (rSS) = 0. Structural equation modeling was used to analysis whether functional CR explained the relationship between T2DM (Type 2 diabetes mellitus) and the risk of 2-year rates of major adverse cardiac events (including all-cause death, all myocardial infarction, or any ischemia-driven revascularization). RESULTS: Multiple cox regression revealed that T2DM was associated with MACE (P=0.007), but not after adding functional CR to the model (P=0.05), suggesting a mediation effect. Structural equation modeling analysis revealed a significant indirect effect of T2DM on MACE through functional CR (P=0.006, Mediated [%] = 27.3), suggesting a partial mediation effect. CONCLUSION: The degree of functional revascularization may emerge as a central mechanism pivotal in elucidating the association between T2DM and the risk of MACE. Cardiologists should prioritize functional complete revascularization during the initial PCI procedure for patients with diabetes mellitus.

Ionically assembled hemostatic powders with rapid self-gelation, strong acid resistance, and on-demand removability for upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is bleeding in the upper part of the gastrointestinal tract with an acidic and dynamic environment that limits the application of conventional hemostatic materials. This study focuses on the development of N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride/phytic acid (HTCC/PA, HP) powders with fast hemostatic capability and strong acid resistance, for potential applications in managing UGIB. Upon contact with liquids within 5 seconds, HP powders rapidly transform into hydrogels, forming ionic networks through electrostatic interactions. The ionic crosslinking process facilitates the HP powders with high blood absorption (3.4 times of self-weight), sufficient tissue adhesion (5.2 and 6.1 kPa on porcine skin and stomach, respectively), and hemostasis (within 15 seconds for in vitro clotting). Interestingly, the PA imparts the HP powders with strong acid resistance (69.8% mass remaining after 10 days of incubation at pH 1) and on-demand removable sealing while HTCC contributes to fast hemostasis and good wet adhesion. Moreover, the HP powders show good biocompatibility and promote wound healing. Therefore, these characteristics highlight the promising clinical potential of HP powders for effectively managing UGIB.

Inhibition of cGAS attenuates neonatal hypoxic-ischemic encephalopathy via regulating microglia polarization and pyroptosis.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition causing brain injury in newborns with unclear pathogenesis. Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and NOD-like receptor protein 3 (NLRP3) mediated pyroptosis are thought to be involved in the pathological process of HIE, but whether these two mechanisms act independently is still unknown. Therefore, we aim to clarify whether there is any interaction between these two pathways and thus synergistically affects the progression of HIE. Methods: The HIE model of neonatal rats was established using the Rice-Vannucci method. The potential therapeutic effect of RU.521 targeting cGAS on HIE was explored through rescue experiment. Twenty-four hours after modeling was selected as observation point, sham + vehicle group, HIE + vehicle group and HIE + RU.521 group were established. A complete medium of BV2 cells was adjusted to a glucose-free medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 4 hours and reoxygenation for 12 to 24 hours. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining was used to observe tissue injury. Immunofluorescence was applied to monitor the expression of cGAS. Real-time quantitative polymerase chain reaction and western blot were utilized to detect the expression of messenger RNA and protein. Results: cGAS expression was increased in brain tissues of neonatal rats with HIE, and mainly localized in microglia. RU.521 administration reduced infarct size and pathological damage in rat HIE. Moreover, blocking cGAS with RU.521 significantly reduced inflammatory conditions in the brain by down-regulating STING expression, decreasing NLRP3 inflammasome activation and reducing microglial pyroptosis both in vivo and in vitro. Besides, RU.521 promoted the switching of BV2 cells towards the M2 phenotype. Conclusions: This study revealed a link between the cGAS/STING pathway and the NLRP3/GSDMD/pyroptosis pathway in neonatal HIE. Furthermore, the small molecule compound RU.521 can negatively regulate cGAS/STING/NLRP3/pyroptosis axis and promote M2 polarization in microglia, which provides a potential therapeutic strategy for the treatment of neuroinflammation in HIE.

The role of residual inflammatory risk and LDL cholesterol in patients with in-stent restenosis undergoing percutaneous coronary intervention.

BACKGROUND: To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. METHODS: Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. RESULTS: During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95 % CI, 1.39-2.59]; P < 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95 % CI, 0.71- 1.22]; P = 0.59). Compared with patients without residual risk (hsCRP <2 mg/L and LDL-C < 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95 % CI, 1.06-1.83]; P = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C < 70 mg/dL) (aHR, 1.34 [95 % CI, 1.01-1.72]; P = 0.04) had significantly higher risks of MACE. CONCLUSIONS: In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis.

Insights into the role of legionella effectors on host metabolic perturbations.

Legionella infection, the causative agent of Legionnaires' disease, represents a significant threat to human health. The pathogenesis of this infection is intricately linked to the complex interactions between the bacterium and its host, resulting in profound metabolic perturbations. Central to these metabolic shifts is the bacterium's modulation of lipid metabolism, with changes in lipid synthesis and breakdown modifying membrane composition and function. These alterations can influence cellular signaling and immune responses, further contributing to disease progression. It also disrupts glucose utilization and lipid metabolism, altering cellular energy production and immune responses. Additionally, Legionella infection perturbs amino acid and protein metabolism, affecting protein synthesis and degradation, leading to changes in cellular functions and immune responses. This mini-review underscores the complexity of metabolic perturbations in Legionella infection and their significance in host-pathogen interactions. Understanding these metabolic shifts provides valuable insights into the pathogenesis of Legionnaires' disease and could lead to the development of novel therapeutic strategies.

Unlocking epoxy thermal management capability via hierarchical Ce-MOF@MoS2 hybrid constructed by in-situ growth method.

This study demonstrates the preparation of needle-like Ce-MOF crystals on molybdenum disulfide (MoS2) nanosheets using in-situ growth technology. This hybrid structure significantly enhances the thermal management and mechanical properties of thermosetting epoxy resin (EP). Specifically, EP/Ce-MOF@MoS2-3 exhibits a notable increase in tensile strength (TS) to 50.87 MPa and elongation at break (EB) to 10.84 %. Moreover, Ce-MOF@MoS2 provides synergistic flame retardant benefits, reducing the peak heat release rate (pHRR) and total heat release (THR) of EP/Ce-MOF@MoS2-3 by 38 % and 12.64 %, respectively, compared to EP-0. Additionally, Ce-MOF@MoS2 suppresses smoke and reduces toxic emissions; at a 3 % loading, it decreases CO and CO2 production in EP nanocomposites by 48.8 % and 38.7 %, respectively. Thus, this Ce-MOF@MoS2 hybrid, synthesized via in-situ growth, offers a novel approach for developing EP nanocomposites with superior thermal management and mechanical properties, along with effective flame retardancy and reduced hazardous emissions during thermal events.

Purtscher-Like Retinopathy Secondary to Febrile Illnesses in Pediatric Patients: A Case Series.

PURPOSE: Purtscher-like retinopathy is a rare microvascular occlusive disease that has been reported in few literature especially in pediatric patients. The ocular manifestation is associated with various systemic disorders, though its distinct pathophysiology and appropriate therapies remain unclear. This research presents three cases of Purtscher-like retinopathy secondary to febrile illnesses in pediatric patients. METHODS: Medical history and clinical findings were retrospectively collected. RESULTS: We report a series of three pediatric patients (age range, 7-13 years) who developed Purtscher-like retinopathy, secondary to febrile illnesses, including systemic juvenile idiopathic arthritis, thrombotic microangiopathy, and COVID-19 infection. All patients received steroidal therapy to control underlying conditions and ocular disease, with visual improvement in different degrees. CONCLUSIONS: Clinician awareness of Purtscher-like retinopathy is crucial for the prompt diagnosis and treatment of pediatric patients with protracted high fevers and febrile viral illnesses.

Anti-flammable, anti-fouling, anti-bacterial treatment of cotton fabrics with MOF-based hybrid coatings for highly efficient oil-water separation.

A flame-retardant and hydrophobic coating was deposited on the surface of the cotton fabric via a two-step spray deposition technique. Specifically, the coating was composed of flame-retardant component (guanidine phosphate) and hydrophobic components (Ti-MOF and bis(3-aminopropyl)-terminated poly(dimethylsiloxane) (PDMS)) and crosslinked with glutaraldehyde. The limiting oxygen index (LOI) of the coated cotton fabrics increased from 18.0 % to 32.0 % (15#) and 26.5 % (15#-Ti-PDMS) relative to that of the original cotton fabric, and the coated cotton fabrics also self-extinguished in the UL-94 flammability test. Compared with that of the original cotton fabric, the PHRR of the coated fabrics was significantly lower, reaching 80 %. The coated cotton fabrics (15# and 15#-Ti-PDMS) had good antibacterial properties against Staphylococcus aureus (S. aureus). In addition, 15#-Ti-PDMS had high hydrophobicity, good washing and abrasion resistance and good water-oil separation performance. Its water contact angle was 146°. The water contact angle remained above 130° after 10 laundering cycles and 50 scratch cycles. Even under strongly acidic and strongly basic conditions, the water-oil separation efficiency of 15#-Ti-PDMS was greater than 99 %, and it was still greater than 90 % after 10 cycles. Therefore, a simple and effective method for preparing flame-retardant, hydrophobic and antibacterial cotton fabric was developed.

Multivalent Weak Protections Ultimately Enable Customizable DNA Grafting on Pristine Ag Colloids for Nanoplasmonics.

Silver nanoparticles (AgNPs) have superior plasmonic properties surpassing other metals. However, a long-standing difficulty in valence/density-tunable DNA grafting of AgNPs disfavors their use in DNA-directed nanoplasmonics. Herein a close-to-ideal surface protection of pristine AgNPs against various notorious stability issues of Ag is achieved based on multidentate weak nucleobase bindings of non-programming FSDNA (fish sperm DNA). This further allows grafting of thiolated DNA with tunable valence/density on AgNPs. The end-on format of the thiolated DNA grafts and the very thin FSDNA layer benefit DNA hybridization and plasmon coupling, respectively. Significantly promoted optical coupling and Raman enhancing are achieved. The compatibility of FSDNA-capped AgNPs with Au enables DNA-bonded symmetry-broken Au-Ag heterodimers with strong near-field coupling and an easily seen Fano-induced feature. Our work provides a treasured freedom of using AgNPs in DNA-programmed, better-behaving plasmonic devices.

Impact of nitroglycerin on machine-learning fractional flow reserve in coronary computed tomography (CT)-angiography.

Background: Nitroglycerin administration prior to examination improves stenosis assessment of coronary computed tomography (CT) angiography (CCTA). However, whether nitroglycerin influences CT-derived fractional flow reserve (FFR, CT-FFR) evaluation remains unclear. This study aimed to investigate the effect of nitroglycerin on diagnostic performance of CT-FFR. Methods: In this single-center retrospective study, 107 consecutive patients suspected of coronary artery disease (CAD) with nitroglycerin administration prior to CCTA in 2019 were matched to 107 patients without nitroglycerin in 2016 from Fuwai Hospital. All patients underwent CCTA and invasive FFR in a month. Vessel-based and patient-based accuracy and diagnostic performance of CT-FFR were compared between the two groups, as well as image quality, coronary artery diameter and evaluability. Quantitative variables were compared by Kruskal-Wallis H test. Categorical variables and rates were compared by χ2 test or Fisher exact test. Results: A total of 214 patients (56.1±8.9 years, 155 male) with 237 target lesion vessels were analyzed, including 120 vessels in nitroglycerin and 117 vessels in non-nitroglycerin group. Per-vessel based accuracy of CT-FFR was higher in nitroglycerin group {80.0% [95% confidence interval (CI): 71.7-86.7%] vs. 68.4% (59.1-76.7%), P=0.041}. On a per-patient basis, nitroglycerin administration improved the accuracy [83.2% (74.7-89.7%) vs. 68.2% (58.5-76.9%), P=0.01], specificity [82.7% (69.7-91.8%) vs. 61.9% (48.8-73.9%), P=0.01], positive predictive value (PPV) [83.6% (73.6-90.4%) vs. 58.6% (50.0-66.9%), P=0.004], and area under the curve (AUC) [0.83 (0.75-0.89) vs. 0.71 (0.61-0.79), P=0.03] of CT-FFR. Vessel diameters (left main arteries: 4.3 vs. 3.8 mm, P<0.001; left anterior descending arteries: 3.1 vs. 2.9 mm, P=0.001; left circumflex arteries: 2.9 vs. 2.7 mm, P=0.01; right coronary arteries: 3.7 vs. 3.4 mm, P=0.001) and number of evaluable coronary arteries (11.0 vs. 8.0, P<0.001) were larger in nitroglycerin group. Conclusions: Nitroglycerin administration prior to CCTA has positive effects on diagnostic performance of CT-FFR.

Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer.

Microsatellite stable (MSS) colorectal cancers (CRCs) are often resistant to anti-programmed death-1 (PD-1) therapy. Here, we show that a CRC pathogen, Fusobacterium nucleatum (Fn), paradoxically sensitizes MSS CRC to anti-PD-1. Fecal microbiota transplantation (FMT) from patients with Fn-high MSS CRC to germ-free mice bearing MSS CRC confers sensitivity to anti-PD-1 compared to FMT from Fn-low counterparts. Single Fn administration also potentiates anti-PD-1 efficacy in murine allografts and CD34+-humanized mice bearing MSS CRC. Mechanistically, we demonstrate that intratumoral Fn generates abundant butyric acid, which inhibits histone deacetylase (HDAC) 3/8 in CD8+ T cells, inducing Tbx21 promoter H3K27 acetylation and expression. TBX21 transcriptionally represses PD-1, alleviating CD8+ T cell exhaustion and promoting effector function. Supporting this notion, knockout of a butyric acid-producing gene in Fn abolishes its anti-PD-1 boosting effect. In patients with MSS CRC, high intratumoral Fn predicts favorable response to anti-PD-1 therapy, indicating Fn as a potential biomarker of immunotherapy response in MSS CRC.