Simultaneous immobilization of multiple heavy metal(loid)s in contaminated water and alkaline soil inoculated Fe/Mn oxidizing bacterium.

Two strains of Fe/Mn oxidizing bacteria tolerant to high concentrations of multiple heavy metal(loid)s and efficient decontamination for them were screened. The surface of the bio-Fe/Mn oxides produced by the oxidation of Fe(II) and Mn(II) by Pseudomonas taiwanensis (marked as P4) and Pseudomonas plecoglossicida (marked as G1) contains rich reactive oxygen functional groups, which play critical roles in the removal efficiency and immobilization of heavy metal(loid)s in co-contamination system. The isolated strains P4 and G1 can grow well in the following environments: pH 5-9, NaCl 0-4%, and temperature 20-30°C. The removal efficiencies of Fe, Pb, As, Zn, Cd, Cu, and Mn are effective after inoculation of the strains P4 and G1 in the simulated water system (the initial concentrations of heavy metal(loid) were 1 mg/L), approximately reaching 96%, 92%, 85%, 67%, 70%, 54% and 15%, respectively. The exchangeable and carbonate bound As, Cd, Pb and Cu are more inclined to convert to the Fe-Mn oxide bound fractions in P4 and G1 treated soil, thereby reducing the phytoavailability and bioaccessible of heavy metal(loid)s. This research provides alternatives method to treat water and soil containing high concentrations of multi-heavy metal(loid)s.

The sweet taste receptors in Lemuriformes respond to aspartame, a non-nutritive sweetener and critical residues mediating their taste.

Aspartame is a high potency artificial sweetener which is popularly used in foods and beverages. The species-dependent sweet taste toward aspartame has not been completely understood. In a recent publication, we reported that the prosimians Lemuriformes species, which are proposed as aspartame nontasters, could taste aspartame based on the sequence and structure analysis. In this study, by mutagenesis, cell-based functional analysis and molecular simulations, we reveal that Lemuriformes species can respond to aspartame at the cell-based receptor activity level. Furthermore, it is proved that the conserved critical residues D142 and S40 mediate the species-dependent sweet taste toward aspartame. This research provides a deeper insight on the species taste, structure-activity relationship and evolution for eliciting the sweetness of this important synthetic sweetener.

Hypersensitive MR Angiography for Diagnosis of Ischemic Stroke and Reperfusion Subarachnoid Hemorrhage.

Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.

Modification Strategies of Hexagonal Boron Nitride Nanomaterials for Photocatalysis.

Although hexagonal boron nitride (h-BN) was initially considered a less promising photocatalyst due to its large band gap and apparent chemical inertness, its unique two-dimensional lamellar structure coupled with high stability and environmental friendliness, as the second largest van der Waals material after graphene, provides a unique platform for photocatalytic innovation. This review not only highlights the intrinsic qualities of h-BN with photocatalytic potentials, such as high stability, environmental compatibility, and tunable bandgap through various modification strategies but also provides a comprehensive overview of the recent advances in h-BN-based nanomaterials for environmental and energy applications, as well as an in-depth description of the modification methods and fundamental properties for these applications. In addition, we discuss the challenges and prospects of h-BN-based nanomaterials for future photocatalysis.

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.

Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1ß, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1ß was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

LncRNA H19 knockdown promotes neuropathologic and functional recovery via the Nrf2/HO-1 axis after traumatic brain injury.

AIMS: Traumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non-coding RNA H19 (lncRNA H19) exerts a potential regulator role in the pathology of brain injury. This study investigates the effects of lncRNA H19 knockdown (H19-KD) on the pathophysiology of TBI and its potential neuroprotective mechanisms. METHODS: Controlled cortical impact was employed to establish a stable TBI mouse model. The expression levels of various genes in perilesional cortex and striatum tissue after TBI was detected by RT-qPCR. AAV9-shRNA-H19 was injected into the lateral ventricle of mice to knockdown the expression of lncRNA H19. Various behavioral tests were performed to evaluate sensorimotor and cognitive functions after TBI. Immunofluorescence and Nissl staining were performed to assess brain tissue damage and neuroinflammation. The Nrf2 and HO-1 expression was performed by Western blot. RESULTS: After TBI, the expression of lncRNA H19 was elevated in perilesional tissue and gradually reverted to baseline. Behavioral tests demonstrated that H19-KD significantly promoted the recovery of sensorimotor and cognitive functions after TBI. Besides, H19-KD reduced brain tissue loss, preserved neuronal integrity, and ameliorated white matter damage at the histological level. In addition, H19-KD restrained the pro-inflammatory and facilitated anti-inflammatory phenotypes of microglia/macrophages, attenuating the neuroinflammatory response after TBI. Furthermore, H19-KD promoted activation of the Nrf2/HO-1 axis after TBI, while suppression of Nrf2 partially abolished the neuroprotective effect. CONCLUSION: H19-KD exerts neuroprotective effects after TBI in mice, partially mediated by the activation of the Nrf2/HO-1 axis.

Cinobufacini enhances the therapeutic response of 5-Fluorouracil against gastric cancer by targeting cancer stem cells via AKT/GSK-3ß/ß-catenin signaling axis.

BACKGROUND: Gastric cancer stem cells (GCSCs) play crucial role in the development, recurrence, and resistance of gastric cancer (GC). Cinobufacini, a traditional Chinese medicine, offers significant advantages in improving tumor therapy. However, pre-clinical investigation into the antitumor effect and mechanism of Cinobufacini on GC is still lacking. Additionally, it has not been reported whether Cinobufacini is related to cancer stem cells (CSCs). METHODS: The CCK-8, clone formation, EdU staining, transwell and wound healing experiments were performed to assess the cell toxicity of Cinobufacini and demonstrate the preventive effects of Cinobufacini on proliferation, invasion, and migration of GC cells. Elucidating the underlying mechanism of Cinobufacini in GC based on the transcriptome sequencing. Flow cytometry assays, sphere formation assays, subcutaneous xenograft model in nude mice, and immunofluorescent staining have been used to investigate whether the anti-GC effect of Cinobufacini is associated with GCSCs and enhancing therapeutic response to 5-Fluorouracil (5-FU). RESULTS: Cinobufacini exerts minimal impact on normal human gastric epithelium cell GES-1, while significantly suppressing the proliferation, invasion, and migration of GC cell lines. Additionally, Cinobufacini attenuates the stemness of GCSCs by disrupting the AKT/GSK-3ß/ß-catenin signaling cascade. Moreover, Cinobufacin enhances the anti-tumor effects of 5-FU against GCSCs by reducing in vitro sphere formation and inhibiting subcutaneous graft tumor growth in vivo. CONCLUSIONS: Cinobufacini enhances the therapeutic response of 5-FU against GC by targeting CSCs via AKT/GSK-3ß/ß-catenin signaling axis. Our findings offer a crucial insight into the molecular mechanism of Cinobufacini's anticancer activity in GC.

Improving postsurgical fall detection for older Americans using LLM-driven analysis of clinical narratives.

Postsurgical falls have significant patient and societal implications but remain challenging to identify and track. Detecting postsurgical falls is crucial to improve patient care for older adults and reduce healthcare costs. Large language models (LLMs) offer a promising solution for reliable and automated fall detection using unstructured data in clinical notes. We tested several LLM prompting approaches to postsurgical fall detection in two different healthcare systems with three open-source LLMs. The Mixtral-8×7B zero-shot had the best performance at Stanford Health Care (PPV = 0.81, recall = 0.67) and the Veterans Health Administration (PPV = 0.93, recall = 0.94). These results demonstrate that LLMs can detect falls with little to no guidance and lay groundwork for applications of LLMs in fall prediction and prevention across many different settings.

Sanggenol L induces ferroptosis in non-small cell lung cancer cells via regulating the miR-26a-1-3p/MDM2/p53 signaling pathway.

Ferroptosis is a regulated cell death marked by iron-dependent lipid peroxidation. Tumor cells that survive by evading chemotherapy-induced apoptosis are vulnerable to ferroptosis. Therefore, it is particularly urgent to explore active ingredients that can selectively induce ferroptosis in cancer cells. Here, we revealed that sanggenol L, the active agent of Morus Bark, predisposed non-small cell lung cancer (NSCLC) cells to ferroptosis, evidenced by reactive oxygen species (ROS) accumulation, glutathione depletion, mitochondrial shrinkage, and lipid peroxidation. Furthermore, the ferroptosis-related miRNA array showed that sanggenol L treatment upregulated the level of miR-26a-1-3p, which directly targeted the E3 ubiquitin ligase MDM2. In addition, silencing MDM2 by miR-26a-1-3p resulted in a notable increase in p53 protein levels and decrease of its downstream target SLC7A11, ultimately triggered ferroptosis. The subcutaneous xenograft model and patient-derived tumor xenograft (PDX) model of NSCLC further confirmed the anti-tumor efficacy and safety of sanggenol L in vivo. Collectively, our data suggest that miR-26a-1-3p/MDM2/p53/SLC7A11 signaling axis plays a key role in sanggenol L-induced ferroptosis, which implies that sanggenol L can serves as an anticancer therapeutic arsenal for NSCLC.

Mechanically robust and electrically conductive nanofiber composites with enhanced interfacial interaction for strain sensing.

Electrically conductive fiberfibre/fabric composites (ECFCs) are competitive candidates for use in wearable electronics. Therefore, it is essential to develop mechanically robust ECFC strain sensors with sensing performance. In this study, MXene assembly and hot-pressing were combined to prepare strong yet breathable ECFCs for strain and temperature sensing. Hydrogen bonding between MXene and polyurethane (PU) and ultrasonication-induced interfacial sintering were responsible for MXene nanosheets assembly on the PU nanofibers. MXene decoration made PU nanofibers electrically conductive, resulting in a conductive network. Hot-pressing improved interface adhesion among the conductive nanofibers. Thus, the mechanical properties of the nanofiber composites, including tensile strength, toughness and fracture energy, were enhanced. The nanofiber composites exhibited surface stability and durability. When the nanofiber composites were used as strain sensors, they showed breathability with a linear resistance response ranging from 1 % to 100 % and cycling stability. In addition, they produced stable sensing signals over 1000 cycles when a notch was present. They could also monitor temperature variations with a negative temperature coefficient (-0.146 %/°C). This study provides an interfacial regulation method for the preparation of multi-functional nanofiber composites with potential applications in flexible and wearable electronics.

Integrated Serum Pharmacochemistry, Network Pharmacology, and Molecular Docking to Study the Mechanism of Rhubarb against Atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipids, the formation of lesion plaques, and the narrowing of arterial lumens. Rhubarb has significant effects against AS, but there is a lack of analysis and exploration of the mechanism of action of the transitional components in serum containing rhubarb. OBJECTIVE: This work aims to combine serum pharmacochemistry, network pharmacology, and molecular docking to explore active ingredients and mechanism of rhubarb against AS. METHOD: Firstly, the components of rhubarb in blood samples were identified using HPLC-QTOF/MS. The ingredients-targets-disease interaction network of rhubarb was constructed through network pharmacology. Then, molecular docking between the ingredients and the core targets was carried out using the Autodock Vina software. RESULTS: Eleven active ingredients and five metabolites were preliminarily identified. The network pharmacology results showed that chrysophanol, resveratrol, and emodin might have potential pharmacological effects on AS. The PPI network showed that the key proteins were PTGS2, ESR1, PTGS1, and ELANE. GO analysis revealed that genes were mainly enriched in the inflammatory response and response to exogenous stimuli. Moreover, these genes were related to IL-17 signaling pathways, lipid and atherosclerosis, and other pathways. Molecular docking analyses showed that chrysophanol and emodin have strong binding affinities with the target proteins PTGS2 and PTGS1. CONCLUSION: A comprehensive strategy combining serum pharmacochemistry with network pharmacology and molecular docking was employed to investigate the active ingredients and the mechanism of rhubarb in treating AS, which provided a basis for studying the pharmacological effects and action mechanisms of rhubarb.

Multifunctional lipid droplet probes for observing the polarity change of ferroptosis, inflammation, fatty liver and evaluating the efficacy of drugs.

BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.

A national survey of iodine nutrition in children aged 3-6 years in China and its relationship with children's physical growth.

Iodine, an essential trace element for the human body, plays a pivotal role in sustaining health. Malnutrition has emerged as a pressing public health concern, posing a significant threat to human well-being. Iodine deficiency poses a substantial threat to the development of children, potentially leading to neurological developmental disorders and mental retardation. Conversely, excessive iodine intake can result in structural and functional abnormalities in the thyroid gland. In this study, we selected children aged 3-6 years through a stratified cluster sampling approach in six regions across China to explore the correlation between iodine nutrition and their physical growth. A total of 5920 preschool children participated in this study, with a median urinary iodine concentration (UIC) of 177.33 [107.06, 269.92] µg/L. Among these children, 250 (4.2%) exhibited stunting, 180 (3.0%) were underweight, 198 (3.3%) experienced wasting, 787 (3.3%) were overweight and 414 (7.0%) were classified as obese. The multivariate linear regression revealed that UIC exhibited a positive correlation with body mass index z-Score (BMIZ) in overweight children (ß = 0.038; 95% CI: 0.001, 0.075). In normally growing children, the associations between UIC and height-for-age z-score, weight-for-age z-score and BMIZ displayed nonlinear patterns. Our findings suggest that iodine nutrition is adequate for Chinese children aged 3-6 years. Furthermore, iodine nutrition is intricately linked to the growth and development of these children. Consequently, it is imperative to implement decisive measures to prevent both iodine deficiency and excess.

Construction of a Colorimetric and Near-Infrared Ratiometric Fluorescent Sensor and Portable Sensing System for On-Site Quantitative Measurement of Sulfite in Food.

Sulfites play imperative roles in food crops and food products, serving as sulfur nutrients for food crops and as food additives in various foods. It is necessary to develop an effective method for the on-site quantification of sulfites in food samples. Here, 7-(diethylamino) quinoline is used as a fluorescent group and electron donor, alongside the pyridinium salt group as an electron acceptor and the C=C bond as the sulfite-specific recognition group. We present a novel fluorescent sensor based on a mechanism that modulates the efficiency of intramolecular charge transfer (ICT), CY, for on-site quantitative measurement of sulfite in food. The fluorescent sensor itself exhibited fluorescence in the near-infrared light (NIR) region, effectively minimizing the interference of background fluorescence in food samples. Upon exposure to sulfite, the sensor CY displayed a ratiometric fluorescence response (I447/I692) with a high sensitivity (LOD = 0.061 µM), enabling accurate quantitative measurements in complex food environments. Moreover, sensor CY also displayed a colorimetric response to sulfite, making sensor CY measure sulfite in both fluorescence and colorimetric dual-signal modes. Sensor CY has been utilized for quantitatively measuring sulfite in red wine and sugar with recoveries between 99.65% and 101.90%, and the RSD was below 4.0%. The sulfite concentrations in live cells and zebrafish were also monitored via fluorescence imaging. Moreover, the sulfite assimilated by lettuce leaves was monitored, and the results demonstrated that excessive sulfite in leaf tissue could lead to leaf tissue damage. In addition, the sulfate-transformed sulfite in lettuce stem tissue was tracked, providing valuable insights for evaluating sulfur nutrients in food crops. More importantly, to accomplish the on-site quantitative measurement of sulfite in food samples, a portable sensing system was prepared. Sensor CY and the portable sensing system were successfully used for the on-site quantitative measurement of sulfite in food.

Evaluation of transport mechanisms of methotrexate in human choriocarcinoma cell lines by LC-MS/MS.

Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.

Encapsulation of three different types of polyphenols in casein using a customized pH-driven method: Preparation and characterization.

Phenolic compounds represent natural compounds endowed with diverse biological functionalities. However, their inherent limitations, characterized by poor water solubility and low oral bioavailability, limit their broader applications. Encapsulation delivery systems are emerging as a remedy, able to ameliorate these limitations by enhancing the stability and solubility of phenolic compounds. In this study, a novel, customized pH-driven approach was developed by determining the optimal deprotonation and protonation points of three different types of polyphenols: ferulic acid, resveratrol, and rhein. The polyphenols were successfully encapsulated in a casein carrier. The solubility, stability, LogD, and LogS curves of the three polyphenols at different pH values were analyzed to identify the optimal deprotonation points for ferulic acid (pH 9), resveratrol (pH 11), and rhein (pH 10). Based on these findings, three different nanoparticles were prepared. The encapsulation efficiencies of the three phenolic compounds were 95.86%, 94.62%, and 94.18%, respectively, and the casein nanoparticles remained stable at room temperature for seven days. FTIR spectroscopy, fluorescence spectroscopy, and molecular docking study substantiated the encapsulation of phenolic compounds within the hydrophobic core of casein-based complexes, facilitated by hydrogen bonding interactions and hydrophobic interactions. Furthermore, the analysis of antioxidant activity elucidated that casein nanoparticles heightened both the water solubility and antioxidant efficacy of the phenolic compounds. This customized encapsulation technique, by establishing a transitional pH value, resolves the challenges of chemical instability and facile degradation of polyphenols under alkaline conditions in the application process of pH-driven methods. It presents novel insights for the application of polyphenols in the domains of food and biomedical fields.

Hypoxia makes EZH2 inhibitor not easy-advances of crosstalk between HIF and EZH2.

Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.

In Situ Tracking of Water Oxidation Generated Nanoscale Dynamics in Layered Double Hydroxides Nanosheets.

Layered double hydroxides (LDHs) are potential catalysts for water oxidation, and it is recognized that they undergo dynamic evolution during the operation. However, little is known about the interfacial behaviors at the nanoscale under working conditions nor the underlying effects on electrocatalytic performance. Herein, using electrochemical atomic force microscopy, we in situ visualize the heterogeneous evolution of LDH nanosheets during oxygen evolution reaction (OER). By further combining density functional theory calculations, we elucidate the origin of the heterogeneous dynamics and their impact on the OER efficiency. Our findings demonstrate that NiCo LDHs transform to the catalytically active NiCoOx(OH)2-x phase during OER, and the redox transition between is accompanied by compressive and tensile strain, leading to in-plane contraction and reversible expansion of the nanosheets. Nonisotropic strain and out-of-plane strain relaxation due to defects and interparticle interactions result in cracking and wrinkling in the nanostructure, which is responsible for the partial activation and long-term deterioration of LDH electrocatalysts toward the OER. With this knowledge, we suggest and validate that engineering defects can precisely tune these dynamic behaviors, improving the OER activity and stability among LDH-based electrocatalysts.