Isoindoline-based fluorogenic probes bearing a self-immolative linker for the sensitive and selective detection of O-GlcNAcase activity.

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

Euphorbia factor L2 alleviated gouty inflammation by specifically suppressing both the priming and activation of NLRP3 inflammasome.

Euphorbia L. is a traditionally used herb and contains many newly identified compounds with novel chemical structures. Euphorbia factor L2 (EFL2), a diterpenoid derived from Euphorbia seeds, is reported to alleviate acute lung injury and arthritis by exerting anti-inflammatory effects. In this study, we aimed to test the therapeutic benefit and mechanisms of EFL2 in NLRP3 inflammasome-mediated gouty models and identified the potential molecular mechanism. A cell-based system was used to test the specific inhibitory effect of EFL2 on NLRP3-related inflammation. The gouty arthritis model and an air pouch inflammation model induced by monosodium urate monohydrate (MSU) crystals were used for in vivo experiments. Nlrp3-/- mice and in vitro studies were used for mechanistic exploration. Virtual molecular docking and biophysical assays were performed to identify the direct binding and regulatory target of EFL2. The inhibitory effect of EFL2 on inflammatory cell infiltration was determined by flow cytometry in vivo. The mechanism by which EFL2 activates the NLRP3 inflammasome signaling pathway was evaluated by immunological experiment and transmission electron microscopy. In vitro, EFL2 specifically reduced NLRP3 inflammasome-mediated IL-1ß production and alleviated MSU crystal-induced arthritis, as well as inflammatory cell infiltration. EFL2 downregulated NF-κB phosphorylation and NLRP3 inflammasome expression by binding to glucocorticoid receptors. Moreover, EFL2 could specifically suppress the lysosome damage-mediated NLRP3 inflammasome activation process. It is expected that this work may be useful to accelerate the development of anti-inflammatory drugs originated from traditional herbs and improve therapeutics in gout and its complications.

Combining the novel FLT3 and MERTK dual inhibitor MRX-2843 with venetoclax results in promising antileukemic activity against FLT3-ITD AML.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately one third of acute myeloid leukemia (AML) patients. FLT3-Internal tandem duplication (FLT3-ITD) mutations are the most common FLT3 mutations and are associated with a poor prognosis. Gilteritinib is a FLT3 inhibitor that is US FDA approved for treating adult patients with relapsed/refractory AML and a FLT3 mutation. While gilteritinib monotherapy has improved patient outcome, few patients achieve durable responses. Combining gilteritinib with venetoclax (VEN) appears to make further improvements, though early results suggest that patients with prior exposure to VEN fair much worse than those without prior exposure. MRX-2843 is a promising inhibitor of FLT3 and MERTK. We recently demonstrated that MRX-2843 is equally potent as gilteritinib in FLT3-ITD AML cell lines in vitro and primary patient samples ex vivo. In this study, we investigated the combination of VEN and MRX-2843 against FLT3-ITD AML cells. We found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-mutated AML cell lines and primary patient samples. Importantly, we found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-ITD AML cells with acquired resistance to cytarabine (AraC) or VEN+AraC. VEN and MRX-2843 significantly reduce colony-forming capacity of FLT3-ITD primary AML cells. Mechanistic studies show that MRX-2843 decreases Mcl-1 and c-Myc protein levels via transcriptional regulation and combined MRX-2843 and VEN significantly decreases oxidative phosphorylation in FLT3-ITD AML cells. Our findings highlight a promising combination therapy against FLT3-ITD AML, supporting further in vitro and in vivo testing.

High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Hybrid fiber-based time synchronization and vibration detection system.

We propose a hybrid fiber-based time synchronization and vibration detection system. The vibration is detected by exploring the idle light of the time synchronization system, i.e., the Rayleigh backscattering of the timing pulse disseminated in the fiber link. The addition of a sensing function does not affect the performance of time synchronization. In the multiuser experimental demonstration, time deviation results are 3.6 ps at τ = 1 s and 1.4 ps at τ = 104 s on the 40-km fiber link. Meanwhile, the hybrid system can accurately detect and locate vibrations occurring on the link. This method enables multiple functions of the optical fiber network without occupying extra optical channels. Moreover, it gives a possible solution for enhancing the security of the time synchronization network through vibration detection.

Clinical characteristics and risk factors for poor outcomes of invasive pneumococcal disease in pediatric patients in China.

BACKGROUND: Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou. METHODS: A retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically. RESULTS: A total of 178 IPD patients were included in the study. The majority of the IPD children were 2-10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62-8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO2) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80-0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD. CONCLUSION: Pediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies.

A machine learning-based approach for improving plasmid DNA production in Escherichia coli fed-batch fermentations.

Artificial Intelligence (AI) technology is spearheading a new industrial revolution, which provides ample opportunities for the transformational development of traditional fermentation processes. During plasmid fermentation, traditional subjective process control leads to highly unstable plasmid yields. In this study, a multi-parameter correlation analysis was first performed to discover a dynamic metabolic balance among the oxygen uptake rate, temperature, and plasmid yield, whilst revealing the heating rate and timing as the most important optimization factor for balanced cell growth and plasmid production. Then, based on the acquired on-line parameters as well as outputs of kinetic models constructed for describing process dynamics of biomass concentration, plasmid yield, and substrate concentration, a machine learning (ML) model with Random Forest (RF) as the best machine learning algorithm was established to predict the optimal heating strategy. Finally, the highest plasmid yield and specific productivity of 1167.74 mg L-1 and 8.87 mg L-1/OD600 were achieved with the optimal heating strategy predicted by the RF model in the 50 L bioreactor, respectively, which was 71% and 21% higher than those obtained in the control cultures where a traditional one-step temperature upshift strategy was applied. In addition, this study transformed empirical fermentation process optimization into a more efficient and rational self-optimization method. The methodology employed in this study is equally applicable to predict the regulation of process dynamics for other products, thereby facilitating the potential for furthering the intelligent automation of fermentation processes.

[Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4+ T cells, the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients. METHODS: The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4+ T cells, the proportion of CD4+ T cell subsets and the cytokines secreted by CD4+ T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate. RESULTS: The serum lactate level in the RA patients (n=66) was significantly higher than that in the HC (n=60, P < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (r=0.273, P=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL vs. 29.30 (0.00, 102.60) IU/mL, P < 0.01], CRP [37.40 (11.30, 72.60) mg/L vs. 5.83 (2.36, 12.45) mg/L, P < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h, P>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL, P>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% vs. 41.67%±9.98%, P < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% vs. 18.65%±7.94%, P < 0.01) and CD25 (25.89%±5.80% vs. 22.25%±4.59%, P < 0.01) on the surface of CD4+ T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% vs. 2.93%±1.92%, P < 0.05) and Tph (28.02%±6.28% vs. 20.32%±5.82%, P < 0.01) cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% vs. 4.75%±1.71%, P < 0.05) in CD4+T cells was up-regulated in the RA patients treated with sodium lactate. CONCLUSION: The level of serum lactate in RA patients is increased, which promotes the activation of CD4+T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

Research on Foot Contact State Detection Technology of Wheel-Legged Robot.

The accurate perception of external environment information through the robot foot is crucial for the mobile robot to evaluate its ability to traverse terrain. Adequate foot-end contact signals can provide robust support for robot motion control and decision-making processes. The shape and uncertain rotation of the wheel-legged robot foot end represent a significant challenge to sensing the robot foot-end contact state, which current foot-end sensing schemes cannot solve. This paper presents a sensing method for the tire stress field of wheel-legged robots. A finite element analysis was conducted to study the deformation characteristics of the foot-end tire under force. Based on this analysis, a heuristic contact position estimator was designed that utilizes symmetrical deformation characteristics. Strain sensors, arranged in an array, extract the deformation information on the inner surface of the tire at a frequency of 200 Hz. The contact position estimator reduces the dimensionality of the data and fits the eigenvalues to the estimated contact position. Using support vector regression, the force estimator utilizes the estimated contact position and sensor signal to estimate the normal reaction force, designated as FZ. The sensing system is capable of detecting the contact position on the wheel circumference (with a root mean square error of 1.150°), as well as the normal force of 160 N on the Z axis (with a root mean square error of 6.04%). To validate the efficacy of the sensor detection method, a series of randomized and repeated experiments were conducted on a self-constructed test platform. This novel approach offers a promising avenue for perceiving contact states in wheel-legged robots.

The Effect of Process Parameters on the Microstructure, Stability, and Sensorial Properties of an Emulsion Cream Formulation.

A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for the effect of process parameters on drug product quality and performance attributes. The Initial Design of Experiment (DoE) suggested that an oil phase above 15%, coupled with less than 10% emulsifying wax, resulted in less stable emulsions. Different processing parameters such as homogenization speed, duration, cooling rate, and final temperature showed minimal influence on properties and failed to improve stability. The final DoE suggested that the optimal emulsion stability was achieved by introducing a holding period midway through the cooling stage after solvent addition. Within the studied holding temperature range (25-35 °C), a higher holding temperature correlated with increased emulsion stability. However, the application of shear during the holding period, using a paddle mixer, adversely affected stability by disrupting the emulsion microstructure. IVRT studies revealed that the release of lidocaine was higher in the most stable emulsion produced at a holding temperature of 35 °C compared to the least stable emulsion produced at a holding temperature of 25 °C. This suggests that a holding temperature of 35 °C improves both the stability and active release performance. It appears that a slightly higher holding temperature, 35 °C, allows a more flexible and stable emulsifying agent film around the droplets facilitating stabilization of the emulsion. This study offers valuable insights into the relationship between process parameters at various stages of manufacture, microstructure, and various quality attributes of emulsion cream systems. The knowledge gained will facilitate improved design and optimization of robust manufacturing processes, ensuring the production of the formulations with the desired critical quality attributes.

Electrosynthesis of an Improbable Directly Bonded Phosphorene-Fullerene Heterodimensional Hybrid toward Boosted Photocatalytic Hydrogen Evolution.

Phosphorene and fullerene are representative two-dimensional (2D) and zero-dimensional (0D) nanomaterials respectively, constructing their heterodimensional hybrid not only complements their physiochemical properties but also extends their applications via synergistic interactions. This is however challenging because of their diversities in dimension and chemical reactivity, and theoretical studies predicted that it is improbable to directly bond C60 onto the surface of phosphorene due to their strong repulsion. Here, we develop a facile electrosynthesis method to synthesize the first phosphorene-fullerene hybrid featuring fullerene surface bonding via P-C bonds. Few-layer black phosphorus nanosheets (BPNSs) obtained from electrochemical exfoliation react with C602- dianion prepared by electroreduction of C60, fulfilling formation of the "improbable" phosphorene-fullerene hybrid (BPNS-s-C60). Theoretical results reveal that the energy barrier for formation of [BPNS-s-C60]2- intermediate is significantly decreased by 1.88 eV, followed by an oxidization reaction to generate neutral BPNS-s-C60 hybrid. Surface bonding of C60 molecules not only improves significantly the ambient stability of BPNSs, but also boosts dramatically the visible light and near-infrared (NIR) photocatalytic hydrogen evolution rates, reaching 1466 and 1039 µmol h-1 g-1 respectively, which are both the highest values among all reported BP-based metal-free photocatalysts.

Native Characterization of Noncanonical Nucleic Acid Thermodynamics via Programmable Dynamic DNA Chemistry.

Folding thermodynamics, quantitatively described using parameters such as ΔGfold°, ΔHfold°, and ΔSfold°, is essential for characterizing the stability and functionality of noncanonical nucleic acid structures but remains difficult to measure at the molecular level. Leveraging the programmability of dynamic deoxyribonucleic acid (DNA) chemistry, we introduce a DNA-based molecular tool capable of performing a free energy shift assay (FESA) that directly characterizes the thermodynamics of noncanonical DNA structures in their native environments. FESA operates by the rational design of a reference DNA probe that is energetically equivalent to a target noncanonical nucleic acid structure in a series of toehold-exchange reactions, yet is structurally incapable of folding. As a result, a free energy shift (ΔΔGrxn°) is observed when plotting the reaction yield against the free energy of each toehold-exchange. We mathematically demonstrated that ΔGfold°, ΔHfold°, and ΔSfold° of the analyte can be calculated based on ΔΔGrxn°. After validating FESA using six DNA hairpins by comparing the measured ΔGfold°, ΔHfold°, and ΔSfold° values against predictions made by NUPACK software, we adapted FESA to characterize noncanonical nucleic acid structures, encompassing DNA triplexes, G-quadruplexes, and aptamers. This adaptation enabled the successful characterization of the folding thermodynamics for these complex structures under various experimental conditions. The successful development of FESA marks a paradigm shift and a technical advancement in characterizing the thermodynamics of noncanonical DNA structures through molecular tools. It also opens new avenues for probing fundamental chemical and biophysical questions through the lens of molecular engineering and dynamic DNA chemistry.

Coronary artery wall contrast enhancement imaging impact on disease activity assessment in IgG4-RD: a direct marker of coronary involvement.

BACKGROUND: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. METHODS: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. RESULTS: Coronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001). CONCLUSIONS: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.

Evaluation of atmospheric particulate matter pollution characteristics in Shanghai based on biomagnetic monitoring technology.

Atmospheric particulate matter (PM) pollution is one of the world's most serious environmental challenges, and it poses a significant threat to environmental quality and human health. Biomagnetic monitoring of PM has great potential to improve spatial resolution and provide alternative indicators for large area measurements, with respect and complementary to standard air quality monitoring stations. In this study, 160 samples of evergreen plant leaves were collected from park green spaces within five different functional areas of Shanghai. Magnetic properties were investigated to understand the extent and nature of particulate pollution and the possible sources, and to assess the suitability of various plant leaves for urban particulate pollution monitoring. The results showed that magnetic particles of the plant leaf-adherent PM were predominantly composed of pseudo-single domain (PSD) and multi-domain (MD) ferrimagnetic particles. Magnolia grandiflora, as a large evergreen arbor with robust PM retention capabilities, proved to be a more suitable candidate for monitoring urban particulate pollution compared to Osmanthus fragrans, a small evergreen arbor, and Aucuba japonica Thunb. var. variegata and Photinia serratifolia, evergreen shrubs. Meanwhile, there were significant differences in the spatial distribution of the magnetic particle content and heavy metal enrichment of the samples, mainly showing regional variations of industrial area > traffic area > commercial area > residential area > clean area. Additionally, the combination with the results of scanning electron microscopy, shows that industrial production (metal smelting, coal burning), transport and other activities are the main sources of particulate pollution. Plant leaves can be used as an effective tool for urban particulate pollution monitoring and assessment of atmospheric particulate pollution characteristics, and the technique provided useful information on particle size, mineralogy and possible sources.

[Hydrochemical and Stable Isotopic Characteristics and Transformation Relationship of Water Bodies in the Guohe River Basin, Anhui Province].

The Guohe River Basin in Anhui Province was selected as the research area for this study. By collecting surface water, shallow groundwater, and middle-deep groundwater samples, various hydrochemical parameters and stable isotopes of water in different water bodies were analyzed using methods such as the Gibbs diagram, ion ratios, and MixSIAR model to reveal and quantify the transformation relationships between these water bodies. The results indicated that both surface water and groundwater in the study area were predominantly neutral to weakly alkaline. The hydrochemical types of surface water were mainly characterized by Cl·SO4·HCO3-Na and Cl·SO4-Na types, whereas the shallow groundwater exhibited HCO3-Ca·Mg and HCO3-Mg·Na types, and the middle-deep groundwater was of the Cl·HCO3-Na type. The hydrochemical characteristics of various water bodies were influenced by multiple factors such as rock weathering, evaporation concentration, and positive cation exchange. The distribution characteristics of δ18O and δ2H values in surface water and groundwater indicated that atmospheric precipitation was the main water source. The δ18O and δ2H in groundwater were significantly correlated with K+, Na+, Cl-, SO42-, and NO3-. According to the analysis using the MixSIAR model, the contribution of atmospheric precipitation to surface water was 46.5 %, whereas the contribution from shallow groundwater was 53.5 %. The sources of shallow groundwater were identified as atmospheric precipitation (57.4 %) and surface water (42.6 %), and the main source of supply for middle-deep groundwater was lateral flow from upstream groundwater.

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Synthesis of [60]Fullerene-Fused Lactones via Carboxylic Acid Group-Directed C-H Bond Activation and Further Retro Baeyer-Villiger Reaction.

An efficient palladium-catalyzed reaction of [60]fullerene with benzoic acids via carboxylic acid group-directed C-H bond activation is achieved. The obtained [60]fullerene-fused lactones can undergo a retro Baeyer-Villiger reaction to provide [60]fullerene-fused ketones via apparent reduction in the presence of triflic acid. A representative ketone product obtained by the reduction reaction can be employed as an overcoating layer for the electron-transporting layer in an n-type perovskite solar cell.

Finding influential nodes in complex networks based on Kullback-Leibler model within the neighborhood.

As a research hot topic in the field of network security, the implementation of machine learning, such as federated learning, involves information interactions among a large number of distributed network devices. If we regard these distributed network devices and connection relationships as a complex network, we can identify the influential nodes to find the crucial points for optimizing the imbalance of the reliability of devices in federated learning system. This paper will analyze the advantages and disadvantages of existing algorithms for identifying influential nodes in complex networks, and propose a method from the perspective of information dissemination for finding influential nodes based on Kullback-Leibler divergence model within the neighborhood (KLN). Firstly, the KLN algorithm removes a node to simulate the scenario of node failure in the information dissemination process. Secondly, KLN evaluates the loss of information entropy within the neighborhood after node removal by establishing the KL divergence model. Finally, it assesses the damage influence of the removed node by integrating the network attributes and KL divergence model, thus achieving the evaluation of node importance. To validate the performance of KLN, this paper conducts an analysis and comparison of its results with those of 11 other algorithms on 10 networks, using SIR model as a reference. Additionally, a case study was undertaken on a real epidemic propagation network, leading to the proposal of management and control strategies for daily protection based on the influential nodes. The experimental results indicate that KLN effectively evaluates the importance of the removed node using KL model within the neighborhood, and demonstrate better accuracy and applicability across networks of different scales.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.