Manipulating d-Band Center of Nickel by Single-Iodine-Atom Strategy for Boosted Alkaline Hydrogen Evolution Reaction.

Ni-based electrocatalysts have been predicted as highly potential candidates for hydrogen evolution reaction (HER); however, their applicability is hindered by an unfavorable d-band energy level (Ed). Moreover, precise d-band structural engineering of Ni-based materials is deterred by appropriative synthesis methods and experimental characterization. Herein, we meticulously synthesize a special single-iodine-atom structure (I-Ni@C) and characterize the Ed manipulation via resonant inelastic X-ray scattering (RIXS) spectroscopy to fill this gap. The complex catalytic mechanism has been elucidated via synchrotron radiation-based multitechniques (SRMS) including X-ray absorption fine structure (XAFS), in situ synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy, and near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS). In particular, RIXS is innovatively applied to reveal the precise regulation of Ni Ed of I-Ni@C. Consequently, the role of such single-iodine-atom strategy is confirmed to not only facilitate the moderate Ed of the Ni site for balancing the adsorption/desorption capacities of key intermediates but also act as a bridge to enhance the electronic interaction between Ni and the carbon shell for forming a localized polarized electric field conducive to H2O dissociation. As a result, I-Ni@C exhibits an enhanced alkaline hydrogen evolution performance with an overpotential of 78 mV at 10 mA/cm2 and superior stability, surpassing the majority of the reported Ni-based catalysts. Overall, this study has managed to successfully tailor the d-band center of materials from the SRMS perspective, which has crucial implications for nanotechnology, chemistry, catalysis, and other fields.

Dynamics of epitranscriptomes uncover translational reprogramming directed by ac4C in rice during pathogen infection.

Messenger RNA modifications play pivotal roles in RNA biology, but comprehensive landscape changes of epitranscriptomes remain largely unknown in plant immune response. Here we report translational reprogramming directed by ac4C mRNA modification upon pathogen challenge. We first investigate the dynamics of translatomes and epitranscriptomes and uncover that the change in ac4C at single-base resolution promotes translational reprogramming upon Magnaporthe oryzae infection. Then by characterizing the specific distributions of m1A, 2'O-Nm, ac4C, m5C, m6A and m7G, we find that ac4Cs, unlike other modifications, are enriched at the 3rd position of codons, which stabilizes the Watson-Crick base pairing. Importantly, we demonstrate that upon pathogen infection, the increased expression of the ac4C writer OsNAT10/OsACYR (N-ACETYLTRANSFERASE FOR CYTIDINE IN RNA) promotes translation to facilitate rapid activation of immune responses, including the enhancement of jasmonic acid biosynthesis. Our study provides an atlas of mRNA modifications and insights into ac4C function in plant immunity.

ß-Cyclodextrin-optimized supramolecular nanovesicles enhance the droplet/foliage interface interactions and inhibition of succinate dehydrogenase (SDH) for efficient treatment of fungal diseases.

BACKGROUND: Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. RESULTS: To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@ß-CD), driven by the host-guest recognition principle between AoH25 and ß-cyclodextrin (ß-CD). Intriguingly, AoH25@ß-CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@ß-CD exhibited significantly higher inhibition of SDH (IC50 = 1.56 µM) compared to fluopyram (IC50 = 244.41 µM) and AoH25 alone (IC50 = 2.29 µM). Additionally, AoH25@ß-CD increased the permeability of cell membranes in Botryosphaeria dothidea, facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@ß-CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µg mL-1, outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@ß-CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). CONCLUSION: This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@ß-CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management.

Investigation of risk factors for invasive pulmonary aspergillosis among patients with COVID-19.

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA.

The relationship between semen quality in male infertility clinic patients and bisphenol A：A Chinese cross-sectional study.

Bisphenol A (BPA) is a growing concern as an endocrine-disrupting chemical due to its adverse health effects. However, the association between BPA and sperm quality in adult human males remains unclear. The aim of this study was to assess the daily life exposure level of BPA and analyze its correlation with sperm quality in males. Patients who sought treatment in Chinese infertility clinics between May and October 2023 were selected as study subjects. We determined participants' serum BPA content using high-performance liquid chromatography. Sperm count and motility were assessed using a computer-aided sperm analysis system, while sperm morphology was analyzed using an improved Papanicolaou stain. A total of 405 participants, averaging 33.01 ± 5.44 years old, were included. We observed low semen quality among participants in infertility clinics. Principal component analysis was performed for each semen quality index, and three principal components reflecting sperm motility, count, and morphology were extracted. The participants' mean serum BPA level was 6.96 ng/mL. Negative correlations were observed between serum BPA content and total sperm count, sperm density, forward motility rate, and non-forward motility rate. A positive correlation was found between the non-motile sperm rate and the head deformity rate. Morphological abnormalities were the predominant adverse effects observed. Despite low daily life BPA exposure, long-term low-dose exposure in the general population may damage semen quality. This study provides a scientific basis for managing health risks associated with BPA exposure.

A new tetrahydroxybenzophenone from a marine-associated fungus of penicillium sp. and its potential antibacterial activity.

Penicillium species are renowned for their ability to produce a wide range of secondary metabolites with medicinal properties. In this study, compounds 1-10 were isolated from Penicillium sp. Z-16, of which compound 1 is a new benzophenone derivative named methyl 2-(2,6-dihydroxy-4-methylbenzoyl)-4,5-dihydroxy-3-methoxybenzoate. The chemical structure of 1 was determined through comprehensive spectroscopic analysis, including 1D, 2D NMR (HMBC, HSQC) and HRESIMS. In addition, six other known compounds (11-16) were isolated and identified from Penicillium sp. T-5-1. The antimicrobial activity tests demonstrated that compound 1 was moderately active against Candida albicans with a MIC value of 125 µg/mL, while compound 2 showed a MIC value of 62.5 µg/mL against Staphylococcus aureus.

Spin Manipulation of Heterogeneous Molecular Electrocatalysts by an Integrated Magnetic Field for Efficient Oxygen Redox Reactions.

Understanding the spin-dependent activity of nitrogen-coordinated single metal atom (M-N-C) electrocatalysts for oxygen reduction and evolution reactions (ORR and OER) remains challenging due to the lack of structure-defined catalysts and effective spin manipulation tools. Herein, both challenges using a magnetic field integrated heterogeneous molecular electrocatalyst prepared by anchoring cobalt phthalocyanine (CoPc) deposited carbon black on polymer-protected magnet nanoparticles, are addressed. The built-in magnetic field can shift the Co center from low- to high-spin (HS) state without atomic structure modification, affording one-order higher turnover frequency, a 50% increased H2O2 selectivity for ORR, and a ≈4000% magnetocurrent enhancement for OER. This catalyst can significantly minimize magnet usage, enabling safe and continuous production of a pure H2O2 solution for 100 h from a 100 cm2 electrolyzer. The new strategy demonstrated here also applies to other metal phthalocyanine-based catalysts, offering a universal platform for studying spin-related electrochemical processes.

Light-Driven Reverse Water Gas Shift Reaction with 1000-H Stability on High-Entropy Alloy Catalysts.

Highly stable and active catalysts are of significant importance and a longstanding challenge for a number of industrial chemical transformations. Here, motivated by the principle of the high entropy-stabilized structure, high-entropy alloy-loaded porous TiO2 as an efficient and sintering-resistant catalyst for the light-driven reverse water gas‒shift reaction without external heating is synthesized. The optimized CoNiCuPdRu/TiO2 catalyst exhibits a long-term stability of 1000 h (1.23 mol gmetal -1 h-1 CO production rate, >99% high selectivity). In situ characterizations confirm that the slow diffusion effect of high-entropy alloys endows the catalyst with excellent structural stability. The CO adsorption measurements and theoretical calculations consolidate that the hydrogen surface coverage weakens CO adsorption on the catalyst surface. Two major problems of catalyst deactivation - sintering and poisoning, are handled in one case, which synergistically enable unparalleled stability. This work provides new guidance for the rational design of ultradurable harsh-condition operation catalysts for industrial catalysis.

Fine-tuning of IPA1 transactivation activity by E3 ligase IPI7-mediated non-proteolytic K29-ubiquitination during Magnaporthe oryzae infection.

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Comparison between CFR-PEEK and titanium plate for proximal humeral fracture: A meta-analysis.

OBJECTIVES: The aim of the present meta-analysis was to compare the efficacy and safety of the carbon fiber-reinforced polyetheretherketone (CFR-PEEK) and titanium plate for the treatment of proximal humeral fractures (PHFs) from clinical comparative trials. MATERIALS AND METHODS: A comprehensive search of English databases was carried out, such as PubMed, Web of Science, ScienceDirect, Springer and Cochrane Library databases. The RevMan version 5.1 software was applied for statistical analysis, and the mean difference (MD) and risk difference (RD) as the combined variables, and "95%" as the confidence interval (CIs). RESULTS: One randomized-controlled trial and five retrospective controlled studies including 282 PHFs were considered eligible and finally included. Meta-analysis demonstrated that there were significant differences in Constant score (CS) (MD=9.23; 95% CI: 5.02, 13.44; p<0.0001), anterior elevation (MD=18.83; 95% CI: 6.27, 31.38; p=0.003), lateral elevation (MD=18.42; 95% CI: 3.64, 33.19; p=0.01) and adduction (MD=3.53; 95% CI: 0.22, 6.84; p=0.04). No significant differences were observed regarding Constant score compared to the contralateral shoulder, Oxford Shoulder Score, internal rotation, external rotation, screw perforation and cutout, varus/valgus malalignment, humeral head collapse/necrosis, implant removal, and revision surgery between the two groups. CONCLUSION: Compared to titanium plate, CFR-PEEK plate showed better Constant score, anterior elevation, lateral elevation and adduction in treating PHFs. The complications are comparable to those achieved with conventional titanium plates.

Molecular Iridium Catalyzed Electrochemical Formic Acid Oxidation: Mechanistic Insights.

Electrochemical formic acid oxidation reaction (FAOR) is a pivotal model for understanding organic fuel oxidation and advancing sustainable energy technologies. Here, we present mechanistic insights into a novel molecular-like iridium catalyst (Ir-N4-C) for FAOR. Our studies reveal that isolated sites facilitate a preferential dehydrogenation pathway, circumventing catalyst poisoning and exhibiting high inherent activity. In-situ spectroscopic analyses elucidate that weakly adsorbed intermediates mediate the FAOR and are dynamically regulated by potential-dependent redox transitions. Theoretical and experimental investigations demonstrate a parallel mechanism involving two key intermediates with distinct pH and potential sensitivities. The rate-determining step is identified as the adsorption of formate via coupled or sequential proton-electron transfer, which aligns well with the observed kinetic properties, pH dependence, and hydrogen/deuterium isotope effects in experiments. These findings provide valuable insights into the reaction mechanism of FAOR, advancing our understanding at the molecular level and potentially guiding the design of efficient catalysts for fuel cells and electrolyzers.

Analysis of the thermal insulation performance of cement with waste glass powder in geothermal well.

To improve the heat extraction efficiency from the wellbore fluids to the stratum in the geothermal well, thermal insulation cement, which contains of waste glass powder as a heat-insulating material, is proposed to apply in geothermal well's middle and upper sections in the paper. Effect of such glass powers on mechanic and thermal property of thermal insulation cement was then investigated. Various tests were carried out to measure compressive strength, thermal conductivity, microstructure porosity etc. parameters of the thermal insulation cement. Results showed that the waste glass powder would enhance its the compressive strength and improve its the thermal insulation performance. Correlation study between contents of the added waste glass powder in geothermal cements and its mechanic and thermal property was conducted. It was found that thermal insulation cement exhibited its optimum performance when the added content of glass powers was 20% in weight. Analysis of the microstructure porosity with SEM found that the pores in thermal insulation cement with added waste glass powders were mostly closed, tiny and even, and therefore contributed to the compressive strength of the thermal insulation cement; such pores would be also beneficial to improving its thermal insulation performance.

A pan-cancer gamma delta T cell repertoire.

This report presents the largest collection of gamma-delta T cell receptor (γδ TCR) reads in human cancer to date, analyzing about 11,000 patient tumor samples across 33 cancer types using the TRUST4 algorithm. Despite γδ T cells being a small fraction of the T cell population, they play a key role in both innate and adaptive immunity. Our comprehensive analysis reveals their significant presence across all cancer types, specifically highlighting the diverse spectrum and clonality patterns of their γδ receptors. This research highlights the complex roles of γδ T cells in tumor tissues and their potential as prognostic biomarkers. We also demonstrate the utility of T cell receptor gamma (TRG) and delta (TRD) gene expression values from standard RNA-seq data. Ultimately, our work establishes a fundamental resource for future tumor-infiltrating γδ T cell research and may facilitate the development of novel γδ-T-cell-based therapeutic strategies. Together, we demonstrate the strong diversity and prognostic potential of γδ T cells in multiple cancer types.

High-throughput arousing interconnected interfaces for excellent sodium storage chemistry.

Heterostructures endow electrochemical hybrids with promising energy storage properties owing to synergistic effects and interfacial interaction. However, developing a facile but effective approach to maximize interface effects is crucial but challenging. Herein, a bimetallic sulfide/carbon heterostructure is realized in a confined carbon network via a high-throughput template-assisted strategy to induce highly active and stable electrode architecture. The designed heterostructures not only yield abundant interconnected Co9S8/MoS2/N-doped carbon (Co9S8/MoS2/NC) heterojunctions with continuous channels for ion/electron transfer but maintain excellent conversion reversibility. Serving as anode for sodium storage, the Co9S8/MoS2/NC framework displayed excellent sodium storage properties (reversible capacity of 480 mAh/g after 100 cycles at 0.2 A/g and 286.2 mAh/g after 500 cycles at 2 A/g). Given this, this study can guide future design protocols for interface engineering by forming dynamic channels of conversion reaction kinetics for potential applications in high-performance electrodes.

Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting ß2-adrenergic receptor.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be reduced by nonselective ß1/ß2-adrenergic receptor (ß1/ß2-AR) blocker. However, several side effects were identified. Thus, it is extremely warranted to explore more effective and better-tolerated ß2-AR blocker. Currently, we demonstrated that baicalin (BA), a major bioactive component of Scutellaria baicalensis Georgi, could significantly attenuate stress hormones especially epinephrine (Epi)-induced breast cancer cell migration and invasion in vitro. Mechanistically, we identified that ß2-AR was a direct target of BA via the drug affinity responsive target stability (DARTS) combined with mass spectrum assay, and BA photoaffinity probe with pull-down assay, which was further confirmed by a couple of biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of ß2-AR, subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase (cAMP-PKA-FAK) pathway, and thus impede epithelial-mesenchymal transition (EMT), thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model. These findings firstly identify BA as a potential ß2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Impact of Carotid Siphon Calcification on the Course and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.

Analysis of Serum Exosome Metabolites Identifies Potential Biomarkers for Human Hepatocellular Carcinoma.

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. A comprehensive untargeted metabolomics study was conducted using exosome samples extracted from the serum of 48 subjects (36 HCC patients and 12 healthy controls) via a commercial kit. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) strategy was used to identify the metabolic compounds. A total of 18 differential metabolites were identified using the non-targeted metabolomics approach of UPLC-QTOF-MS/MS. Pathway analysis revealed significant alterations in the arachidonic acid metabolism, linoleic acid metabolism, and unsaturated fatty acid metabolism pathways. ROC analysis indicated that three metabolites with AUC values exceeding 0.900 were selected as potential biomarkers: caprylic acid and linoleic acid were upregulated in the HCC group, whereas pentadecanoic acid was downregulated. Linoleic acid, caprylic acid, and pentadecanoic acid are potential biomarkers for diagnosing HCC. The significant alterations in these three metabolic pathways offer new insights into the mechanisms underlying HCC formation and progression.

Fluid-Induced Piezoelectric Field Enhancing Photo-Assisted Zn-Air Batteries Based on a Fe@P(V-T) Microhelical Cathode.

Photo-assisted Zn-air batteries can accelerate the kinetics of oxygen reduction and oxygen evolution reactions (ORR/OER); however, challenges such as rapid charge carrier recombination and continuous electrolyte evaporation remain. Herein, for the first time, piezoelectric catalysis is introduced in a photo-assisted Zn-air battery to improve carrier separation capability and accelerate the ORR/OER kinetics of the photoelectric cathode. The designed microhelical catalyst exploits simple harmonic vibrations to regenerate the built-in electric field continuously. Specifically, in the presence of the low-frequency kinetic energy that occurs during water flow, the piezoelectric-photocoupling catalyst of poly(vinylidene fluoride-co-trifluoroethylene)@ferric oxide(Fe@P(V-T)) is periodically deformed, generating a constant reconfiguration of the built-in electric field that separates photogenerated electrons and holes continuously. Further, on exposure to microvibrations, the gap between the charge and discharge potentials of the Fe@P(V-T)-based photo-assisted Zn-air battery is reduced by 1.7 times compared to that without piezoelectric assistance, indicating that piezoelectric catalysis is highly effective for enhancing photocatalytic efficiency. This study provides a thorough understanding of coupling piezoelectric polarization and photo-assisted strategy in the field of energy storage and opens a fresh perspective for the investigation of multi-field coupling-assisted Zn-air batteries.

Environment-responsive dopamine nanoplatform for tumor synergistic therapy.

Nanoparticle-based photothermal therapy (PTT) has emerged as a promising approach in tumor treatment due to its high selectivity and low invasiveness. However, the penetration of near-infrared light (NIR) is limited, leading it fails to induce damage to the deep-seated tumor cells within the tumor tissue. Additionally, inefficient uptake of photothermal nanoparticles by tumor cells results in suboptimal outcomes for PTT. In this study, we utilized the adhesive properties of photothermal material, polydopamine (PDA), which can successfully load the photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) to achieve photothermal and chemotherapy synergy treatment (PDA/DOX&ICG), aiming to compensate the defects of single tumor treatment. To extending the blood circulation time of PDA/DOX&ICG nanoparticles, evading clearance by the body immune system and achieving targeted delivery to tumor tissues, a protective envelopment was created using erythrocyte membranes modified with folate acid (FA-EM). After reaching the tumor tissue, the obtained FA-EM@PDA/DOX&ICG nanoparticles can specific bind with folate acid receptors on the surface of tumor cells, which can improve the uptake behavior of FA-EM@PDA/DOX&ICG nanoparticles by tumor cells, and leading to the release of loaded DOX and ICG in response to the unique tumor microenvironment. ICG, as a typical photosensitizer, significantly enhances the photothermal conversion performance of FA-EM@PDA/DOX&ICG nanoparticles, thus inducing tumor cells damage. In vitro and in vivo experimental results demonstrated that the coordinated NIR treatment with FA-EM@PDA/DOX&ICG not only effectively inhibits tumor growth, but also exhibits superior biocompatibility, effectively mitigating DOX-induced tissue damage.

Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury.

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury.