Remediation mechanism of high concentrations of multiple heavy metals in contaminated soil by Sedum alfredii and native microorganisms.

Pollution accident of nonferrous metallurgy industry often lead to serious heavy metal pollution of the surrounding soil. Phytoremediation of contaminated soil is an environmental and sustainable technology, and soil native microorganisms in the process of phytoremediation also participate in the remediation of heavy metals. However, the effects of high concentrations of multiple heavy metals (HCMHMs) on plants and native soil microorganisms remain uncertain. Thus, further clarification of the mechanism of phytoremediation of HCMHMs soil by plants and native soil microorganisms is required. Using the plant Sedum alfredii (S. alfredii) to restore HCMHM-contaminated soil, we further explored the mechanism of S. alfredii and native soil microorganisms in the remediation of HCMHM soils. The results showed that (i) S. alfredii can promote heavy metals from non-rhizosphere soil to rhizosphere soil, which is conducive to the effect of plants on heavy metals. In addition, it can also enrich the absorbed heavy metals in its roots and leaves; (ii) native soil bacteria can increase the abundance of signal molecule-synthesizing enzymes, such as trpE, trpG, bjaI, rpfF, ACSL, and yidC, and promote the expression of the pathway that converts serine to cysteine, then synthesize substances to chelate heavy metals. In addition, we speculated that genes such as K19703, K07891, K09711, K19703, K07891, and K09711 in native bacteria may be involved in the stabilization or absorption of heavy metals. The results provide scientific basis for S. alfredii to remediate heavy metals contaminated soils, and confirm the potential of phytoremediation of HCMHM contaminated soil.

Multifunctional Porous Bilayer Artificial Skin for Enhanced Wound Healing.

Meeting the exacting demands of wound healing encompasses rapid coagulation, superior exudate absorption, high antibacterial efficacy, and imperative support for cell growth. In this study, by emulating the intricate structure of natural skin, we prepare a multifunctional porous bilayer artificial skin to address these critical requirements. The bottom layer, mimicking the dermis, is crafted through freeze-drying a gel network comprising carboxymethyl chitosan (CMCs) and gelatin (GL), while the top layer, emulating the epidermis, is prepared via electrospinning poly(l-lactic acid) (PLLA) nanofibers. With protocatechuic aldehyde and gallium ion complexation (PA@Ga) as cross-linking agents, the bottom PA@Ga-CMCs/GL layer featured an adjustable pore size (78-138 µm), high hemostatic performance (67s), and excellent bacterial inhibition rate (99.9%), complemented by an impressive liquid-absorbing capacity (2000% swelling rate). The top PLLA layer, with dense micronanostructure and hydrophobic properties, worked as a shield to effectively thwarted liquid or bacterial penetration. Furthermore, accelerated wound closure, reduced inflammatory responses, and enhanced formation of hair follicles and blood vessels are achieved by the porous artificial skin covered on the surface of wound. Bilayer artificial skin integrates the advantages of nanofibers and freeze-drying porous materials to effectively replicate the protective properties of the epidermal layer of the skin, as well as the cell migration and tissue regeneration of the dermis. This bioabsorbable artificial skin demonstrates structural and functional comparability to real skin, which would advance the field of wound care through its multifaceted capabilities.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

Destabilization mechanisms of Semi-aerobic aged refuse biofilters under harsh treatment conditions: Evidence from fluorescence and microbial characteristics.

Semi-aerobic aged refuse biofilters (SAARB) are commonly-used biotechnologies for treating landfill leachate. In actual operation, SAARB often faces harsh conditions characterized by high concentrations of chemical oxygen demand (COD) and Cl-, as well as a low carbon-to-nitrogen ratio (C/N), which can disrupt the microbial community within SAARB, leading to operational instability. Maintaining the stable operation of SAARB is crucial for the efficient treatment of landfill leachate. However, the destabilization mechanism of SAARB under harsh conditions remains unclear. To address this, the study simulated the operation of SAARB under three harsh conditions, namely, high COD loading (H-COD), high chloride ion (Cl-) concentration environment (H-Cl-), and low C/N ratio environment (L-C/N). The aim is to reveal the destabilization mechanism of SAARB under harsh conditions by analyzing the fluorescence characteristics of effluent DOM and the microbial community in aged refuse. The results indicate that three harsh conditions have different effects on SAARB. H-COD leads to the accumulation of proteins; H-Cl- impedes the reduction of nitrite nitrogen; L-C/N inhibits the degradation of humic substances. These outcomes are attributed to the specific effects of different factors on the microbial communities in different zones of SAARB. H-COD and L-C/N mainly affect the degradation of organic matter in aerobic zone, while H-Cl- primarily impedes the denitrification process in the anaerobic zone. The abnormal enrichment of Corynebacterium, Castellaniella, and Sporosarcina can indicate the instability of SAARB under three harsh conditions, respectively. To maintain the steady operation of SAARB, targeted acclimation of the microbial community in SAARB should be carried out to cope with potentially harsh operating conditions. Besides, timely mitigation of loads should be implemented when instability characteristics emerge, and carbon sources and electron donors should be provided to restore treatment performance effectively.

Trends in using intraoperative parathyroid hormone monitoring during parathyroidectomy: Protocol and rationale for a cross-sectional survey study of North American surgeons.

Hyperparathyroidism is a common endocrine disorder that occurs secondary to abnormal parathyroid gland functioning. Depending on the type of hyperparathyroidism, surgical extirpation of hyperfunctioning parathyroid glands can be considered for disease cure. Intraoperative parathyroid hormone (IOPTH) monitoring improves outcomes in patients undergoing surgery for primary hyperparathyroidism, but studies are needed to characterize its institutional adoption and its role in surgery for secondary and tertiary hyperparathyroidism, as these entities can be difficult to cure. Hence, we will perform a cross-sectional survey study of surgeon rationale, operational details, and barriers associated with IOPTH monitoring adoption across North America. We will utilize a convenience sampling technique to distribute an online survey to head and neck surgeons and endocrine surgeons across North America. This survey will be distributed via email to three North American professional societies (i.e., Canadian Society for Otolaryngologists-Head and Neck Surgeons, American Head and Neck Society, and American Association of Endocrine Surgeons). The survey will consist of 30 multiple choice questions that are divided into three concepts: (1) participant demographics and training details, (2) details of surgical adjuncts during parathyroidectomy, and (3) barriers to adoption of IOPTH. Descriptive analyses and multiple logistic regression will be used to evaluate the impact of demographic, institutional, and training variables on the use of IOPTH monitoring in surgery for all types of hyperparathyroidism and barriers to IOPTH monitoring adoption. Ethics approval was obtained by the Hamilton Integrated Research Ethics Board (2024-17173-GRA). These findings will characterize surgeon and institutional practices with regards to IOPTH monitoring during parathyroid surgery and will inform future trials aimed to optimize the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism.

miR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease.

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

A clinical study based on bidirectional Mendelian randomization: Correlation between generalized anxiety disorder and weight-bearing joints osteoarthritis.

Objectives: Bidirectional Mendelian randomization (MR) combined with clinical case analysis was used to elucidate the relationship between generalized anxiety disorder (GAD) caused by mental overload and the risk of weight-bearing joint (hip/knee) osteoarthritis (OA). Methods: We performed MR analyses using publicly released genome-wide association study summary statistics to measure the causal effects between mental overload and weight-bearing joint OA risk. The primary MR analysis utilized the inverse-variance weighted (IVW) method, complemented by additional methods, including simple mode, weighted mode, MR-Egger regression, and weighted median. The leave-one-out method was used for sensitivity analysis. Concurrently, data from patients with OA (Kellgren-Lawrence grades III-IV) who needed total knee/hip arthroplasty were collected. Patient assessments were conducted utilizing the Western Ontario and McMaster Universities arthritis index, Penn State worry questionnaire, and visual analogue scale. Results: Genetically predisposed GAD did not correlate with the risk of weight-bearing joint OA (IVW odds ratio [OR] = 0.840, 95 % confidence interval = 0.128, 5.50, P = 0.855). In reverse MR analyses, we detected no causal effect of weight-bearing OA on GAD (IVW OR = 1.00, 95 % CI = 0.985, 1.03, P = 0.687). In the clinical case evaluation, weight overload joint OA and GAD were highly correlated. Conclusion: MR analysis indicated no bidirectional causal effect of GAD caused by mental overload on weight-bearing joint (hip or knee) OA. Clinical studies support the finding that GAD is highly correlated with weight-bearing joint OA. However, whether there is a causal relationship between GAD caused by mental overload and weight-overloading joint OA requires further investigation.

Programmed system for fatigue life prediction of excavator turntables based on multi-body dynamics and finite element analysis.

This study focuses on predicting mechanical fatigue in excavator turntables, critical components susceptible to failure due to variable operational loads. While conventional methods like finite element analysis(FEA) and multiaxial fatigue criteria have been used, they are limited by the complexity and cost of obtaining real operational load spectra. To address this challenge, our research presents a comprehensive approach that integrates multi-body dynamics modeling, finite element analysis, and MATLAB-based fatigue life prediction systems. Our methodology involves creating a finite element model for stress analysis, synthesizing load spectra from operational data, and utilizing Weibull distribution to analyze load magnitude probabilities. Subsequently, MATLAB imported the load spectrum and built the fatigue prediction framework to finalize the analysis. Furthermore, we have fully open-sourced our code on an open platform, incorporating default load profiles and predictive models within the code. Key findings pinpoint areas prone to stress concentration and fatigue. Key findings identify stress concentration areas and fatigue-prone regions, providing valuable insights for design optimization and durability improvement.

What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.

BACKGROUND: Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures. AIM: To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research. METHODS: We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide. RESULTS: Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence. CONCLUSION: Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Effects of dissolved organic matter on distribution characteristics of heavy metals and their interactions with microorganisms in soil under long-term exogenous effects.

Long-term waste accumulation (LTWA) in soil not only alters its physical and chemical properties but also affects heavy metals and microorganisms in polluted soil through the dissolved organic matter (DOM) it produces. However, research on the impact of DOM from LTWA on heavy metals and microorganisms in polluted soil is limited, which has resulted in an incomplete understanding of the mechanisms involved in LTWA soils remediation. This study focuses on the DOM generated by waste accumulation and analyses the physicochemical properties, microbial community structure, and vertical distribution of heavy metals in four types of LTWA soils at different depths (0-100 cm). A causal analysis is conducted using structural equation modelling. The results indicate that due to the retention effect of the soil and microorganisms, heavy metal pollution is concentrated on the soil surface layer (>30 cm). With increasing depth, there is a decrease in heavy metal concentration and an increase in microbial diversity and abundance. DOM plays a significant role in regulating the concentration of soil heavy metals and the diversity and abundance of microorganisms. The DOM from different soils gradually transforms into substances dominated by tyrosine, tryptophan, and fulvic acid, which sustain the normal life activities and gene expression of microorganisms. Bacteria such as Pseudarthrobacter, Desulfurivibrio, Thiobacillus, and Sulfurimonas, which are involved in energy transformation, along with genes such as water channel protein and YDIF, which enhance heavy metal metabolism, ensure that microbial communities can maintain basic life processes in polluted environments and gradually select for dominant species that are adapted to heavy metal pollution. These novel discoveries illuminate the potential for modulating the composition of DOM to amplify microbial activity, while concurrently offering insights into the migration patterns of various long-term exogenous pollutants. This foundational knowledge provides a foundation for the development of efficacious remediation strategies.

A dual-modality complex-valued fusion method for predicting side effects of drug-drug interactions based on graph neural network.

Predicting potential side effects of drug-drug interactions (DDIs), which is a major concern in clinical treatment, can increase therapeutic efficacy. In recent studies, how to use the multi-modal drug features is important for DDI prediction. Thus, it remains a challenge to explore an efficient computational method to achieve the feature fusion cross- and intra-modality. In this paper, we propose a dual-modality complex-valued fusion method (DMCF-DDI) for predicting the side effects of DDIs, using the form and properties of complex-vector to enhance the representations of DDIs. Firstly, DMCF-DDI applies two Graph Convolutional Network (GCN) encoders to learn molecular structure and topological features from fingerprint and knowledge graphs, respectively. Secondly, an asymmetric skip connection (ASC) uses distinct semantic-level features to construct the complex-valued drug pair representations (DPRs). Then, the complex-vector multiplication is used as a fusion operator to obtain the fine-grained DPRs. Finally, we calculate the prediction probability of DDIs by Hermitian inner product in the complex space. Compared with other methods, DMCF-DDI achieves superior performance in all situations using a fusion operator with the lowest parameter numbers. For the case study, we select six diseases and common side effects in clinical treatment to verify identification ability of our model. We also prove the advantage of ASC and complex-valued fusion can achieve to align the cross-modal fused positive DPRs through a comprehensive analysis on the phase-modulus distribution histogram of DPRs. In the end, we explain the reason for alignment based on the similarity of features and node neighbors.

Ligand Binding Affinity Prediction for Membrane Proteins with Alchemical Free Energy Calculation Methods.

Alchemical relative binding free energy (ΔΔG) calculations have shown high accuracy in predicting ligand binding affinity and have been used as important tools in computer-aided drug discovery and design. However, there has been limited research on the application of ΔΔG methods to membrane proteins despite the fact that these proteins represent a significant proportion of drug targets, play crucial roles in biological processes, and are implicated in numerous diseases. In this study, to predict the binding affinity of ligands to G protein-coupled receptors (GPCRs), we employed two ΔΔG calculation methods: thermodynamic integration (TI) with AMBER and the alchemical transfer method (AToM) with OpenMM. We calculated ΔΔG values for 53 transformations involving four class A GPCRs and evaluated the performance of AMBER-TI and AToM-OpenMM. In addition, we conducted tests using different numbers of windows and varying simulation times to achieve reliable ΔΔG results and to optimize resource utilization. Overall, both AMBER-TI and AToM-OpenMM show good agreement with the experimental data. Our results validate the applicability of AMBER-TI and AToM-OpenMM for optimization of lead compounds targeting membrane proteins.

Red-Light Triggered H-Abstraction Photoinitiators for the Efficient Oxygen-Independent Therapy of Hypoxic Tumors.

The clinical application of photodynamic therapy (PDT) is limited by oxygen-dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H-abstraction reaction can address these challenges because they can generate alkyl radical-killing cells independently of oxygen and undergo rapid bleaching following H-abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl-ketone substituted cyanine (ACy-R), the first red-light triggered H-abstraction photoinitiators for hypoxic cancer therapy. These ACy-R molecules inherited the near-infrared absorption of cyanine dye, and aryl-ketone modification imparted H-abstraction capability. Experimental and quantum calculations revealed that modifying the electron-withdrawing groups of the aryl (e.g., ACy-5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H-abstraction ability. Particularly, ACy-5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy-5F initiated red-light induced H-abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy-5F was degraded after H-abstraction, thus avoiding the side effects of long-term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators.

In situ investigation of ice fractions and water states during partial freezing of pork loins and shrimps.

Ice fractions and water states in partially frozen muscle foods greatly affect their quality. In the study, a variable temperature nuclear magnetic resonance (VT-NMR) with a liquid nitrogen temperature control system was employed to in situ investigate the relationship between ice fractions and temperatures and changes in water states during partial freezing and thawing of pork and shrimp. Results indicated that changes in ice fractions ranging from -2 âˆ¼ -20 °C could be divided into 3 stages including slow increase, random leap and remarkable leap. More serious damages to the structures related to immobile water occurred in shrimp than in pork, and partial freezing also caused deterioration in muscle fibres related to free water. Additionally, -2 âˆ¼ -3 °C and - 3.5 °C were the appropriate partial freezing temperatures for pork and shrimp, respectively. Therefore, the VT-NMR method possessed great potential for fundamental studies and applications of partial freezing of muscle foods.

PVA-assisted spray deposited porous Li4Ti5O12 thin film as high-rate and long-cycle anode for lithium-ion thin-film batteries.

Spinel Li4Ti5O12 (LTO), a zero-strain material, is a promising anode material for solid-state thin-film lithium-ion batteries (TFB). However, the preparation of high-performance Li4Ti5O12 thin-film electrodes through facile methods remains a significant challenge. Herein, we present a novel approach to prepare a binder- and conductor-free porous Li4Ti5O12 (P-LTO) thin-film. This approach polyvinyl alcohol (PVA)-assisted spray deposition and does not require the use of complex or expensive methods. Adding PVA to the precursor solution effectively prevents thin-film cracking during high-temperature annealing, enhances adhesion, and forms a highly interconnected porous structure. This unique structure shortens the lithium-ion diffusion pathways and facilitates electron transport. Therefore, P-LTO thin film electrodes demonstrate exceptional rate capacity of 104.1 mAh/g at a current density of 100C. In addition, the electrodes exhibit ultra-long cycle stability, retaining 80.9 % capacity after 10,000 cycles at 10C. This work offers a novel approach for the preparation of high-performance thin-film electrodes for TFBs.

Multi-scenario analysis and optimization strategy of ecological security pattern in the Weihe river basin.

For many years, the Weihe River Basin (WRB) has struggled to achieve a balance between ecological protection and economic growth. Constructing an Ecological Security Pattern (ESP) is extremely important for ensuring ecological security (ES). This study employed a coupling of multi-objective programming (MOP) and the patch-generating land use simulation (PLUS) model to project land use change (LUCC) in 2040 across three scenarios. Leveraging circuit theory, we generated ecological corridors and identified key ecological nodes, enabling a comparative analysis of ESPs within the WRB. The main results showed that: (1) The Ecological Protection (EP) scenario showed the highest proportions of forestland, grassland, and water, indicating an optimal ecological environment. Conversely, the Economic Development (ED) scenario features the greatest proportion of construction land, particularly evident in the rapid urban expansion. The Natural Development (ND) scenario exhibits a more balanced change, aligning closely with historical trends. (2) The ecological source areas in the EP scenario is 13,856.70 km2, with the largest and most intact patch area. The ecological source patches that have been identified in the ED scenario exhibit fragmentation and dispersion, encompassing a total area of 8018.82 km2. The ecological source areas in the ND scenario is most similar to the actual situation in 2020, encompassing 8474.99 km2. (3) The EP scenario demonstrates minimal landscape fragmentation. The ED scenario presents a more intricate corridor pattern, hindering species and energy flow efficiency. The ND scenario is more similar to the actual distribution in 2020. Protecting and restoring key ecological nodes, and ensuring the integrity and connectivity of ecological sources are crucial for ESP optimization in various scenarios. Combining all results, we categorize the WRB's spatial pattern into "three zones, three belts, and one center" and offer strategic suggestions for ecological preservation, promoting sustainable local ecological and socioeconomic development.

Liposome-embedded PtCu nanozymes for improved immunoassay of accurate myocardial infarction.

Herein, we developed a platinum-copper nano-enzyme-linked immunosorbent assay (NLISA) based split diagnostic platform for the ultrasensitive detection of cardiac troponin I (cTnI). The PtCu nanozyme synthesized by one-pot synthesis exhibited ultra-high peroxidase-like activity (35.17 U mg-1), which was about 4.5 times higher than that of the unmodified Pt nanozyme (8.83 U mg-1). Due to the efficient peroxidase-like activity of the copper-platinum complexed nanozyme, transduction and sequential amplification of cTnI biological signals were achieved in combination with a liposome-embedded amplification strategy. The encapsulation efficiency was calculated by introducing a liposomal bilayer model, which showed that the introduction of a single liposomal molecule could amplify the signal up to 870-fold, thus promising a high sensitivity test. Notably, the dynamic response of cTnI was in the range of 0.1-5000 pg mL-1 with an ultra-low detection limit (0.048 pg mL-1). The developed NLISA analysis system provides a new way to discover efficient and sensitive alternatives to ELISA kits, which can meet the practical needs of community healthcare testing conditions and rapid testing in hospitals.

Antithrombotic therapy at discharge and prognosis in patients with chronic coronary syndrome and atrial fibrillation who underwent PCI: a real-world study.

BACKGROUND: This study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI). METHODS: This was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: Between 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22-45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011-3.038) and TAT (HR, 2.708; 95%CI, 1.653-4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136-17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974-0.997) was associated with a lower incidence of bleeding events. CONCLUSIONS: Antithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.

Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.

BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options. METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables. RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression. CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.