NR1I2 as a core biological target in chronic venous ulcer tissues treated with ultrasound therapy.

Ultrasound therapy is a method of applying ultrasonic energy to the stimulation produced by human body to change the function and tissue state of the body in order to achieve the purpose of treating diseases. Chronic venous ulcer is a common chronic skin ulcer. GSE222503 for ultrasound therapy of chronic venous ulcers was downloaded from gene expression omnibus database, which were used to identify differentially expressed genes. Weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis and construction and analysis of protein-protein interaction network were performed. Draw gene expression heatmaps. Comparative toxicogenomics database analysis was performed. Two hundred thirty-five differentially expressed genes were obtained. According to gene ontology analysis, in biological process analysis, they were mainly enriched in positive regulation of cellular biosynthetic process, reproductive cell development, vasculogenesis, vascular morphogenesis, and inflammatory response. In cellular component analysis, they were mainly enriched in leading edge of growing cell, extracellular matrix binding organelle, F-actin capping protein complex. In molecular function analysis, they were mainly concentrated in receptor ligand activity, cytokine receptor binding. In Kyoto encyclopedia of genes and genomes analysis, they were mainly enriched in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, HIF-1 signaling pathway, heme biosynthesis. In weighted gene co-expression network analysis, the soft threshold power was set to 9. Thirty modules were generated. PF4, NR1I2, TTC16, H3C12, KLRB1, CYP21A2 identified by 4 algorithms (MCC, EPC, closeness, stress). Heatmap of core gene expression showed that H3C12, KLRB1, PF4, NR1I2 were all underexpressed in samples of ultrasound-treated chronic venous ulcers and overexpressed in samples of untreated chronic venous ulcers. Comparative toxicogenomics database analysis showed that H3C12, KLRB1, PF4, NR1I2 are associated with thrombophlebitis, phlebitis, vascular malformations, metabolic syndrome, ulcers, and inflammation. In samples of chronic venous ulcer tissue treated with ultrasound, NR1I2 shows low expression, while in samples of chronic venous ulcer tissue without ultrasound treatment, it shows high expression. This finding suggests a potential role of NR1I2 in the process of ultrasound therapy for chronic venous ulcers, which may be related to the therapeutic effect of ultrasound therapy on chronic venous ulcers.

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

Enhancing Protein Solubility via Glycosylation: From Chemical Synthesis to Machine Learning Predictions.

Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.

Engineering a solar formic acid/pentose (SFAP) pathway in Escherichia coli for lactic acid production.

Microbial CO2 fixation into lactic acid (LA) is an important approach for low-carbon biomanufacturing. Engineering microbes to utilize CO2 and sugar as co-substrates can create efficient pathways through input of moderate reducing power to drive CO2 fixation into product. However, to achieve complete conservation of organic carbon, how to engineer the CO2-fixing modules compatible with native central metabolism and merge the processes for improving bioproduction of LA is a big challenge. In this study, we designed and constructed a solar formic acid/pentose (SFAP) pathway in Escherichia coli, which enabled CO2 fixation merging into sugar catabolism to produce LA. In the SFAP pathway, adequate reducing equivalents from formate oxidation drive glucose metabolism shifting from glycolysis to the pentose phosphate pathway. The Rubisco-based CO2 fixation and sequential reduction of C3 intermediates are conducted to produce LA stoichiometrically. CO2 fixation theoretically can bring a 20% increase of LA production compared with sole glucose feedstock. This SFAP pathway in the integration of photoelectrochemical cell and an engineered Escherichia coli opens an efficient way for fixing CO2 into value-added bioproducts.

Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice.

OBJECTIVES: In diabetes, chronic hyperglycemia increases the overactivation of oxidative phosphorylation of mitochondria in the liver, resulting in oxidative stress (OS) damage. The Nrf2 signaling pathway plays a key role in preventing hepatic oxidative injury and inflammation. This study aims to investigate the therapeutic effect and mechanism of Modified Buyang Huanwu Decoction (mBYHWD) on diabetic liver injury (DLI) by regulating oxidative stress mediated by Nrf2 signaling pathway. METHODS: The experiment was divided into three groups: a control group (db/m mice, Con), a diabetes model group (db/db mice, Mod), and a traditional Chinese medicine group (db/m mice, mBYHWD). Post-treatment, serum from each group was analyzed to assess changes of blood glucose, blood lipid, and liver function. These results were combined with data mining to explore the possible pathogenesis of DLI. Liver tissues were collected to observe the pathological morphology and detect related proteins. RESULTS: The results demonstrated that mBYHWD significantly reduced blood lipids and improved liver function following diabetic liver injury. The histopathological results demonstrated that mBYHWD could significantly ameliorate damage of diabetic hepatocytes. Protein analysis revealed that mBYHWD treatment significantly increased the expression of antioxidant proteins in diabetic liver tissue and inhibited inflammation. CONCLUSIONS: The therapeutic mechanism of mBYHWD on DLI may involve activating the Nrf2 signaling pathway to improve oxidative stress, inhibit inflammation, and reduce liver tissue fibrosis.

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma.

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy.

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.

Controlled Self-Assembly of Natural Polyphenols Driven by Multiple Molecular Interactions.

Nature has exhibited a high degree of control over the structures and functions. Supramolecules have been utilized to mimic the subtle assembly in nature. However, sophisticated synthesis of molecular skeletons or programmable design of the driving forces raises great challenges in fabricating high-level superstructures in a controlled manner. Natural polyphenols show great promises as building blocks for a diverse of assemblies with controlled structures and functionalities. The intrinsically embedded phenolic groups (i. e., catechol and galloyl groups) are readily forming multiple molecular interactions, including coordination, hydrogen bonding, and π-π interactions with various materials of inorganic particles, organic compounds, synthetic polymers, and biomacromolecules, providing the self-assembled structures or nanocoating on surfaces. Subsequent assembly occurred by further bonding of polyphenols to construct supraparticles. To gain control over the self-assembly, the key lies in the interplay among the molecular interactions with one or two being dominant. In this Perspective, we introduce the representative polyphenol-based assemblies and their derived supraparticles to exhibit the effective harness of the controlled self-assembly by polyphenols.

The determination of the optimal threshold on measurement of thyroid volume using quantitative SPECT/CT for Graves' hyperthyroidism.

PURPOSE: To investigate the optimal threshold for measuring thyroid volume in patients with Grave's hyperthyroidism (GH) by SPECT/CT. MATERIALS AND METHODS: A 53 mL butterfly-shaped hollow container made of two 45-degree transparent elbows was put into a NEMA IEC phantom tank. The butterfly-shaped container and the tank were then filled with Na99mTcO4 of different radioactive concentrations, respectively, which could simulate thyroid gland with GH by different target-to-background ratios (T/B) (200:1, 600:1, 1000:1). The different T/B of planar imaging and SPECT/CT were acquired by a Discovery NM/CT 670 Pro SPECT/CT. With Thyroid software (Version 4.0) of GE-Xeleris workstation, the region of the thyroid gland in planar imaging was delineated. The thyroid area and average long diameter of both lobes were substituted into the Allen formula to calculate the thyroid volume. The calculation error was compared with the actual volume. Q-Metrix software was used to perform CT-based attenuation correction, scatter correction, resolution recovery. Ordered-subsets expectation maximization was used to reconstruct SPECT data. 20%, 25%, 30%, 40%, 50%, 60% thresholds were selected to automatically delineate the volume of interest and compared with the real volume, which determinated the optimal threshold. We measured the thyroid volume of 40 GH patients using the threshold and compared the volumes obtained by planar imaging and ultrasound three-dimensional. The differences of the volumes with different T/B and thresholds were compared by the ANOVA and least significant difference t test. The volumes delineated by SPECT/CT were evaluated using ANOVA, least significant difference t test, correlation analysis and, linear regression and Bland-Altman concordance test plot. The differences and consistency of thyroid volume were compared among the above three methods. RESULTS: There was no significant difference in the results between different T/B models (P > 0.05). The thyroid volume calculated by the planar imaging formula method was higher than the real volume, with an average overestimation of 22.81%. The volumes delineated by SPECT/CT threshold automatically decreased while the threshold increased. There were significant differences between groups with different thresholds (P < 0.001). With an average error of 3.73%, the thyroid volume analyzed by the threshold of 25% was close to the results of ultrasound measurement (P > 0.05). Thyroid volume measured by planar imaging method was significantly higher than ultrasound and SPECT/CT threshold automatic delineation method (P < 0.05). The agreement between the SPECT/CT 25% threshold and ultrasound (r = 0.956, b = 0.961) was better than that between the planar imaging and ultrasound (r = 0.590, b = 0.574). The Bland-Altman plot also showed that the thyroid volume measured by the 25% threshold automatic delineation method was in good agreement with the ultrasound measurement. CONCLUSIONS: The T/B has no effect on the measurement of thyroid volume in GH patients; planar imaging method can significantly overestimate thyroid volume in GH patients, and 25% threshold automatic delineation method can obtain more accurate thyroid volume in GH patients.

Function and mechanism of GBP1 in the development and progression of cervical cancer.

Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.

The use of cardiac magnetic resonance in hypertrophic cardiomyopathy over the past 10 years [2013-2023]: a CiteSpace-based bibliometric analysis.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder characterized by the hypertrophy of a segment of the myocardium. Cardiac magnetic resonance (CMR) has been widely used in the assessment of HCM. However, no bibliometric assessment has been conducted on the progress of research in this field. This study thus aimed to examine the current state of research into the application of CMR in HCM and the hotspots and trends that have emerged in this field over the past decade. Methods: A systematic search was conducted on the Web of Science regarding CMR in the assessment of HCM. The databases were searched from 2013 to June 2023. CiteSpace is an application that can be used to characterize the underlying knowledge of the scientific literature in a given field. We used it to analyze the relationship between publication year and country, institution, journal, author, bibliography, and keywords in the field of CMR for the assessment of HCM. Results: A total of 1,427 articles were included in the analysis. In the assessment of HCM, the findings from the past decade have consistently demonstrated a progressive rise in the quantity of articles pertaining to CMR. The country with the largest number of publications was the United States [310], and the institution with the greatest number of publications was the University College London [45]. The analysis of keywords revealed the diagnosis and management of HCM with CMR to be the current research focus and emerging trend within this academic field. Conclusions: This study used a novel approach to visually analyze the use of CMR in HCM assessment. The current research trajectory in CMR consists of the diagnosis and management of patients with HCM. Although most studies confirmed the indispensability of CMR in the assessment of HCM, larger-scale cohorts are still needed to more comprehensively evaluate the role of CMR in the differential diagnosis, pre- and post-treatment assessment, and long-term management of patients with HCM.

Manganese Dioxide Nanoplatform with a Hollow Rhombic Dodecahedron Morphology for Drug Delivery.

Manganese dioxide (MnO2) is considered as a promising drug carrier material suitable for the tumor microenvironment while lacking conducive structures for drug loading. Herein, we construct a MnO2 nanoplatform with a hollow rhombic dodecahedral morphology for drug delivery. In this work, we obtained zeolitic imidazolate framework nanoparticles (ZIF-90 NPs) via a coordination reaction. Furthermore, the drug-loading nanoparticles (ZIF-90/DOX NPs) were obtained by Schiff's base reaction and then selected as a sacrificial template to obtain the hollow nanoplatforms (ZIF-90@MnO2 NPs). Moreover, the photothermal effect and multiresponsive drug release behaviors were revealed by loading the photothermal agent IR-820 and the anticancer drug doxorubicin hydrochloride (DOX). Our study demonstrates that the ZIF-90@MnO2 NPs loaded with photosensitizers exhibited excellent photothermal conversion performance. Benefiting from the hollow structure and redox activity, remarkable drug loading and release performances of ZIF-90@MnO2 NPs were achieved. It is shown that ZIF-90@MnO2 NPs achieved a satisfactory drug-loading efficiency (up to ca. 69.7%) for DOX. More promisingly, the ZIF-90@MnO2 NPs exhibited significant glutathione (GSH)/pH-responsive drug release and degradation performances. Overall, this work highlights the potential of controlled drug release of nanocarriers and offers unique insights into the design of nanocarriers with hollow structures.

Early Application of Sacubitril Valsartan Sodium After Acute Myocardial Infarction and its Influence on Ventricular Remodeling and TGF-ß1/Smad3 Signaling Pathway.

Objective: The objective of this study was to investigate the early application of sacubitril valsartan sodium (LCZ696) following acute myocardial infarction (AMI) and its impact on ventricular remodeling and the TGF-ß1/Smad3 signaling pathway in patients. Methods: The clinical data of 73 patients with AMI admitted to the hospital from June 2021 to September 2022 were retrospectively analyzed, and the patients were grouped according to the treatment methods, including 36 cases in the control group (conventional drug treatment) and 37 cases in the observation group (conventional drug + LCZ696 treatment). The clinical efficacy, cardiac function parameters [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), stroke volume (SV)], cardiac function biochemical indicators [N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin 3 (Gal-3), amino-terminal peptide of type III procollagen (PIIINP)], ventricular remodeling indicators [left ventricular posterior wall end-diastolic thickness (PWD), posterior wall end-systolic thickness (PWS), ventricular septal end-systolic thickness (IVSS)], ventricular hydrodynamic parameters [left ventricular flow rate in peak ejection (FRPE), flow reversal rate (FRR), flow reversal interval (FRI)], TGF-ß 1/Smad3 signaling pathway-related indicators (TGF-ß1, Smad3), quality of life score (SF-36 Quality of Life Scale) and occurrence of adverse reactions were compared between the two groups. Results: The main findings of the study are as follows: The observation group was significantly better than the control group in many aspects such as overall clinical effectiveness, cardiac function parameters, biochemical indicators, ventricular structure and function, TGF-ß1/Smad3 signaling pathway, and quality of life. Specifically, the observation group showed more significant positive effects in terms of improvement of cardiac function, adjustment of biochemical status, and adjustment of ventricular structure and fluid dynamics parameters. These results provide strong support for the application of new therapeutic approaches in the management of cardiovascular disease. After treatment, the total clinical effective rate in the observation group (89.19%) was significantly higher than that in the control group (69.44%) (P < .05). LVEF and SV in the two groups were significantly increased (P < .05), while LVEDD was significantly decreased (P < .05), and there were statistically significant differences in parameters between the two groups (P < .05). The levels of NT-proBNP, Gal-3 and PIIINP in both groups were significantly reduced (P < .05), and the levels in the observation group were significantly lower than those in the control group (P < .05). The PWD, PWS and IVSS in both groups significantly declined (P < .05), and the indicators in the observation group were significantly lower than those in the control group (P < .05). The FRPE and FRR in the two groups were significantly enhanced (P < .05), while the FRI was significantly reduced (P < .05), and the differences in the above parameters between the two groups were statistically significant (P < .05). The levels of TGF-ß1 and Smad3 in the two groups were significantly declined (P < .05), and the levels in the observation group were significantly lower than those in the control group (P < .05). During the period from before treatment to 6 months of treatment, the quality of life score in the two groups showed a significant downward trend (P < .05), and the score in the observation group after 3 months to 6 months of treatment was significantly lower than that in the control group (P < .05). During treatment, there was no statistical significance in the total incidence rate of adverse reactions between the two groups (P > .05). Conclusion: Early application of LCZ696 after AMI has a significant efficacy, and it can effectively improve the ventricular remodeling, regulate the expression levels of TGF-ß1 and Smad3, inhibit the TGF-ß1/Smad3 signaling pathway, promote the improvements of cardiac function and quality of life, and it has good safety and is worthy of clinical promotion and application. The study's key findings have important clinical implications for understanding and managing acute myocardial infarction (AMI). The observation group showed significant improvements in overall clinical efficacy, cardiac function, biochemical status, ventricular structure and function, etc., providing strong evidence for comprehensive treatment of AMI patients. This treatment method is expected to become an important part of the care and treatment strategy for AMI patients, help reduce cardiovascular risk, improve quality of life, and provide new research directions for future AMI treatment.

Immobilization of ferrocene and its derivatives within metal-organic frameworks with high loadings toward efficient oxygen evolution reaction.

The use of an appropriate preparation route is the key to immobilize active molecules into a host matrix with high loadings and stability. Herein, we demonstrate a simple and general strategy to immobilize ferrocene and its derivatives into ZIF-8 with high loadings of up to 4.3% Fe content. The unique host pore structure allows for the stabilization of guest molecules and effectively prevents their leaching. As a result, the obtained electrocatalysts exhibit competitive oxygen evolution reaction (OER) catalytic performance. Optimized Fc-CHO/ZIF-8 requires only a low overpotential of 238 mV to achieve 10 mA cm-2, along with a relatively small Tafel slope of 44.4 mV dec-1. This performance is superior to that of commercial IrO2, suggesting its potential application in electrochemical energy conversion.

Green synthesis of epigallocatechin gallate-ferric complex nanoparticles for photothermal enhanced antibacterial and wound healing.

Bacterial infections are a significant global health concern, particularly in the context of skin infections and chronic wounds, which was further exacerbated by the emerging of antibiotic resistance. Therefore, there are urgent needs to develop alternative antibacterial strategies without inducing significant resistance. Photothermal therapy (PTT) is a promising alternative approach but usually faces limitations such as the need for stable and environmental-friendly PTT agents and ensuring biocompatibility with living tissues, necessitating ongoing research for its clinical advancement. Herein, in this study, with the aim to develop a green synthesized PTT agent for photothermal enhanced antibacterial and wound healing, we proposed a facile one-pot method to prepare epigallocatechin gallate-ferric (EGCG-Fe) complex nanoparticles. The obtained nanoparticles showed improved good size distribution and stability with high reproducibility. More importantly, EGCG-Fe complex nanoparticles have additional photothermal conversion ability which can give photothermal enhanced antibacterial effect on various pathogens, including Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) strains. EGCG-Fe complex nanoparticles also showed powerful biofilm prevention and destruction effects with promoted antibacterial and wound healing on mice model. In conclusion, EGCG-Fe complex nanoparticles can be a robust green material with effective and novel light controllable antibacterial properties for photothermal enhanced antibacterial and wound healing applications.

Real-world effectiveness and safety of evolocumab in very high-risk atherosclerotic cardiovascular disease patients with acute ischemic stroke.

BACKGROUND: We investigated evolocumab's real-world effectiveness and safety on a background of statin therapy in the acute phase of ischemic stroke (IS) patients with a very high-risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: A real-world, single-center, retrospective study was conducted in the neurology department at Tianjin Huanhu Hospital in China. Patients were divided into two groups: evolocumab treatment (140 mg every two weeks) or the standard of care (SOC) group. The primary efficacy outcome of the study was the achievement of a targeted lipid control rate and the incidence of major adverse cardiovascular events (MACE) by the end of the follow-up. MACE was defined as a composite of various cardiovascular events, cerebrovascular events such as stroke or TIA, and event-related deaths. Propensity score matching (PSM) analysis was utilized to account for confounding factors between groups. Survival analyses were performed using the Kaplan-Meier method and COX regression modeling. RESULTS: 1080 AIS patients with very high-risk ASCVD were recruited. After PSM, there were 528 individuals, with 206 in the evolocumab group and 322 in the SOC group. At 12 months of follow-up, the proportion of LDL-C < 1.4mmol/L and ≥ 50% reduction was 44.91% in the evolocumab group, compared with only 3.12% of SOC-treated patients (p < 0.01). The median follow-up time for clinical events was 15 months. The evolocumab group was associated with a lower risk of cerebrovascular events compared to the SOC group (HR, 0.45; 95% CI, 0.23-0.89; p = 0.02). CONCLUSIONS: This real-world study suggested that evolocumab on a background of statin reduced the LDL-C levels significantly and lowered the incidence of recurrent cerebrovascular events in the very high-risk ASCVD patients with AIS in China.

Parameter Optimization of Ultrasonic-Microwave Synergistic Extraction of Taxanes from Taxus cuspidata Needles.

Taxanes are the best-known compounds in Taxus cuspidata owing to their strong anticancer effects. However, the traditional taxanes extraction method is the solid-liquid extraction method, which is limited by a large energy consumption and low yield. Therefore, it is urgent to find an efficient method for taxanes extraction. The ultrasonic microwave synergistic extraction (UME) method integrates the cavitation effect of ultrasound and the intensifying heat transfer (ionic conduction and dipole rotation of molecules) effect of microwave to accelerate the release of intracellular compounds and is used in active ingredient extractions. This study aimed to evaluate the performance of UME in extracting taxanes from T. cuspidata needles (dichloromethane-ethanol as extractant). A single-factor experiment, Plackett-Burman design, and the response surface method showed that the optimal UME parameters for taxanes extraction were an ultrasonic power of 300 W, a microwave power of 215 W, and 130 sieve meshes. Under these conditions, the taxanes yield was 570.32 µg/g, which increased by 13.41% and 41.63% compared with the ultrasound (US) and microwave (MW) treatments, respectively. The reasons for the differences in the taxanes yield were revealed by comparing the physicochemical properties of T. cuspidata residues after the UME, US, and MW treatments. The cell structures were significantly damaged after the UME treatment, and numerous tiny holes were observed on the surface. The absorption peaks of cellulose, hemicellulose, and lignin increased significantly in intensity, and the lowest peak temperature (307.40 °C), with a melting enthalpy of -5.19 J/g, was found after the UME treatment compared with the US and MW treatments. These results demonstrate that UME is an effective method (570.32 µg/g) to extract taxanes from T. cuspidata needles by destroying cellular structures.

Cell-Targeted Metal-Phenolic Nanoalgaecide in Hydroponic Cultivation to Enhance Food Sustainability.

The growing global population necessitates substantial increases in food production. Hydroponic cultivation systems afford a critical alternative for food sustainability and enable stable annual production regardless of the climatic and geographical variations. However, the overgrowth of harmful algal blooms significantly threatens the crop yield by competing with nutrition in the solution and producing contaminants. The conventional practice of algaecides fails to control algal proliferation due to the limited efficiency and food safety concerns. Nanopesticides can deliver active ingredients responsively to suppress crop diseases and offer solutions to current practical challenges and difficulties. Inspired by prospects of nanotechnology for agricultural applications, we have utilized natural polyphenols and copper ions (Cu2+ ions) to develop self-assembled nanoalgaecides referred to as CuBes. The nanoalgaecide attached to algal cells via phenolic surface interactions, enabling localized Cu2+ ion release. This cell-targeted delivery suppressed Chlorella vulgaris for over 30 days (99% inhibition). Transcriptomics revealed that the nanoalgaecide disrupted algal metabolism by downregulating photosynthesis and chlorophyll pathways. In a solar-illuminated plant factory, the nanoalgaecide showed higher algal inhibition and lettuce biosafety versus the commercial Kocide 3000. Notably, the use of nanoalgaecide can enhance the nutrient value of lettuces, which meets the daily supply of Cu for adults. By integrating smart nanotechnology design with selective delivery mechanisms, this metal-phenolic nanoalgaecide provides a nanoenabled solution for controlling harmful algal blooms in hydroponics to advance food production.

Deliberately making miskates: Behavioural consistency under win maximization and loss maximization conditions.

We argue that the feedback traditionally used to indicate negative outcomes causes future detrimental performance because of the default goal of win maximization. In gaming paradigms where participants intentionally performed as well (win maximization) and as poorly (loss maximization) as possible, we showed a double dissociation where actions following wins were more consistent during win maximization, but actions following losses were more consistent during loss maximization. This broader distinction between goal-congruent and goal-incongruent feedback suggests that individuals are able to flexibly redefine their definition of 'success', and provide a reconsideration of the way we think about 'losing'.

Simultaneous Detection and Decontamination of Dichromate Ions: The Fluorescence Response and Photocatalysis of Thiadiazole-Modified Zr-Metal-Organic Frameworks.

The simultaneous analysis and removal of highly toxic hexavalent chromium (Cr (VI)) in contaminated water via an easy method remain a serious task. Based on the guidance of bibliometric analysis, a thiadiazole ligand-modified zirconium metal-organic framework (Zr-MOF) heralds a new and simple approach to Cr (VI) treatment. The concentration can be determined by fluorescence quenching with a low detection limit of 1.4 µM and a high quenching constant of 6.88 × 103 M-1. For the sensing mechanism, the fluorescence intensity of the Zr-MOF decreased rapidly due to the competition of Cr (VI) with the Zr-MOF for absorption excitation energy and the induction of Zr-MOF aggregation. The analysis system also displayed satisfactory stability and applicability. Apart from sensing application, Zr-MOF can convert Cr (VI) to Cr (III), and the reduction rate constant was 0.004 min-1 under irradiation. Therefore, the bifunctional Zr-MOF provided a potential application method for controlling the pollution caused by Cr (VI) in wastewater.