Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation.

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time ( > 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

Biomimetic Iron-Based Nanoparticles Remodel Immunosuppressive Tumor Microenvironment for Metabolic Immunotherapy.

Introduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses. Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME). Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response. Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy.

Clinical Efficiency and Safety of Radiofrequency Ablation for Treating Incompetent Great Saphenous Veins in Aged Patients.

INTRODUCTION: Few studies have focused on the safety and efficacy of radiofrequency ablation (RFA) in treating incompetent great saphenous vein (GSV) in aged population. This study was designed to investigate the clinical efficacy of RFA in treating incompetent GSV in the aged patients. METHODS: In this retrospective study, we included 138 consecutive patients (involving 194 limbs) with a mean age of 63.0 years who underwent RFA and microphlebectomy or sclerotherapy due to symptomatic incompetent GSV with saphenofemoral junction reflux. Based on their ages, patients were classified into young group and aged group. Then we compared the preoperative and postoperative Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification, venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire 14 (CIVIQ-14) score between the 2 groups. RESULTS: In both the young and aged groups, patients underwent RFA showed significant decrease in the CEAP and VCSS at month 1, 3 and 6 compared with immediately after RFA (month 0) (all P < .001). In addition, in both groups, significant increase was seen in the CIVIQ-14 score at month 1, 3 and 6 compared with month 0 (all P < .001). Compared with the young group, the post-RFA CEAP, VCSS and CIVIQ-14 scores showed no statistical differences in the aged group at the designated time points, respectively (all P > .05). CONCLUSIONS: RFA of GSV was effective for treating GSV in the aged population, which improved the CEAP, VCSS and CIVIQ-14.

The pleiotropic functions of GOLDEN2-LIKE transcription factors in plants.

The regulation of gene expression is crucial for biological plant growth and development, with transcription factors (TFs) serving as key switches in this regulatory mechanism. GOLDEN2-LIKE (GLK) TFs are a class of functionally partially redundant nuclear TFs belonging to the GARP superfamily of MYB TFs that play a key role in regulating genes related to photosynthesis and chloroplast biogenesis. Here, we summarized the current knowledge of the pleiotropic roles of GLKs in plants. In addition to their primary functions of controlling chloroplast biogenesis and function maintenance, GLKs have been proven to regulate the photomorphogenesis of seedlings, metabolite synthesis, flowering time, leaf senescence, and response to biotic and abiotic stress, ultimately contributing to crop yield. This review will provide a comprehensive understanding of the biological functions of GLKs and serve as a reference for future theoretical and applied studies of GLKs.

Internal Space Modulation of Yolk-Shell FeSe2@Carbon Anode with Peanut-Shaped Morphology Enabling Ultra-Stable and Fast Potassium-Ion Storage.

The poor cycling stability and rate performance of transition metal selenides (TMSs) are caused by their intrinsic low conductivity and poor structural stability, which hinders their application in potassium-ion batteries (PIBs). To address this issue, encapsulating TMSs within carbon nanoshells is considered a viable strategy. However, due to the lack and uncontrollability of internal void space, this structure cannot effectively mitigate the volume expansion induced by large K+, resulting in unsatisfactory electrochemical performance. Herein, peanut-shaped FeSe2@carbon yolk-shell capsules are prepared by modulation of the internal space. The active FeSe2 is encapsulated within a robust carbon shell and an optimal void space is retained between them. The outer carbon shell promotes electronic conductivity and avoids FeSe2 aggregation, while the internal void mitigates volume expansion and effectively ensures the structural integrity of the electrode. Consequently, the FeSe2@carbon anode demonstrates exceptional rate performance (242 mAh g-1 at 10 A g-1) and long cycling stability (350 mAh g-1 after 500 cycles at 1 A g-1). Furthermore, the effect of internal space modulation on electrochemical properties is elucidated. Meanwhile, ex situ characterizations elucidate the K+ storage mechanism. This work provides effective guidance for the design and the internal space modulation of advanced TMSs yolk-shell structures.

Effects of Inonotus obliquus on ameliorating podocyte injury in ORG mice through TNF pathway and prediction of active compounds.

Background: Podocyte injury is a common pathologic mechanism in diabetic kidney disease (DKD) and obesity-related glomerulopathy (ORG). Our previous study confirmed that Inonotus obliquus (IO) improved podocyte injury on DKD rats. The current study explored the pharmacological effects, related mechanisms and possible active components of IO on ORG mice. Methods: Firstly, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis (UPLC-Q-TOF-MS) with network pharmacology to construct the human protein-protein interaction mechanism and enrich the pathway, which led to discover the crucial mechanism of IO against ORG. Then, ORG mice were established by high-fat diet and biochemical assays, histopathology, and Western blot were used to explore the effects of IO on obesity and podocyte injury. Finally, network pharmacology-based findings were confirmed by immunohistochemistry. The compositions of IO absorbed in mice plasma were analyzed by UPLC-Q-TOF-MS and molecular docking was used to predict the possible active compounds. Results: The network pharmacology result suggested that IO alleviated the inflammatory response of ORG by modulating TNF signal. The 20-week in vivo experiment confirmed that IO improved glomerular hypertrophy, podocyte injury under electron microscopy, renal nephrin, synaptopodin, TNF-α and IL-6 expressions with Western blotting and immunohistochemical staining. Other indicators of ORG such as body weight, kidney weight, serum total cholesterol, liver triglyceride also improved by IO intervention. The components analysis showed that triterpenoids, including inoterpene F and trametenolic acid, might be the pharmacodynamic basis. Conclusion: The research based on UPLC-Q-TOF-MS analysis, network pharmacology and in vivo experiment suggested that the amelioration of IO on podocyte injury in ORG mice via its modulation on TNF signal. Triterpenoids were predicated as acting components.

Semantic Interaction Meta-Learning Based on Patch Matching Metric.

Metric-based meta-learning methods have demonstrated remarkable success in the domain of few-shot image classification. However, their performance is significantly contingent upon the choice of metric and the feature representation for the support classes. Current approaches, which predominantly rely on holistic image features, may inadvertently disregard critical details necessary for novel tasks, a phenomenon known as "supervision collapse". Moreover, relying solely on visual features to characterize support classes can prove to be insufficient, particularly in scenarios involving limited sample sizes. In this paper, we introduce an innovative framework named Patch Matching Metric-based Semantic Interaction Meta-Learning (PatSiML), designed to overcome these challenges. To counteract supervision collapse, we have developed a patch matching metric strategy based on the Transformer architecture to transform input images into a set of distinct patch embeddings. This approach dynamically creates task-specific embeddings, facilitated by a graph convolutional network, to formulate precise matching metrics between the support classes and the query image patches. To enhance the integration of semantic knowledge, we have also integrated a label-assisted channel semantic interaction strategy. This strategy merges word embeddings with patch-level visual features across the channel dimension, utilizing a sophisticated language model to combine semantic understanding with visual information. Our empirical findings across four diverse datasets reveal that the PatSiML method achieves a classification accuracy improvement of 0.65% to 21.15% over existing methodologies, underscoring its robustness and efficacy.

Fresnel Diffraction Model for Laser Dazzling Spots of Complementary Metal Oxide Semiconductor Cameras.

Laser dazzling on complementary metal oxide semiconductor (CMOS) image sensors is an effective method in optoelectronic countermeasures. However, previous research mainly focused on the laser dazzling under far fields, with limited studies on situations that the far-field conditions were not satisfied. In this paper, we established a Fresnel diffraction model of laser dazzling on a CMOS by combining experiments and simulations. We calculated that the laser power density and the area of saturated pixels on the detector exhibit a linear relationship with a slope of 0.64 in a log-log plot. In the experiment, we found that the back side illumination (BSI-CMOS) matched the simulations, with an error margin of 3%, while the front side illumination (FSI-CMOS) slightly mismatched the simulations, with an error margin of 14%. We also found that the full-screen saturation threshold for the BSI-CMOS was 25% higher than the FSI-CMOS. Our work demonstrates the applicability of the Fresnel diffraction model for BSI-CMOS, which provides a valuable reference for studying laser dazzling.

Tetrahedral Framework Nucleic Acids Delivery of Pirfenidone for Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo, Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-ß1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.

Topology-driven collective dynamics of nematic colloidal entanglement.

Entanglement in a soft condensed matter system is enabled in the form of entangled disclination lines by using colloidal particles in nematic liquid crystals. These topological excitations are manifested as colloidal entanglement at equilibrium. How to further utilize nonequilibrium disclination lines to manipulate colloidal entanglement remains a nontrivial and challenging task. In this work, we use experiments and simulations to demonstrate the reconfigurations of nematic colloidal entanglement in light-driven spatiotemporal evolutions of disclination lines. Colloidal entanglement can sense subtle changes in the topological structures of disclination lines and realize chirality conversion. This conversion is manifested as the "domino effect" of the collective rotation of colloids in the disclination lines. By programming the topological patterns and the geometry of the disclination lines, colloidal entanglement can be assembled and split. More remarkably, a double-helix entangled structure can be formed by controlling the changes in the morphology of the disclination lines. Thus, this work will provide opportunities to program colloidal composites for smart materials and micromachines.

A flexible electrochemical sensor based on Fe-doped polydopamine derived carbon for simultaneous detection of dopamine and uric acid.

A free-standing electrode based on carbon cloth-supported Fe-doped polydopamine-derived carbon (Fe/PDA-C/CC) was developed for the simultaneous detection of dopamine (DA) and uric acid (UA). First, dopamine was self-polymerized on the surface of the carbon cloth to obtain polydopamine coatings. Subsequently, Fe3+ was introduced through the formation of a coordinate bond with the hydroxyl functional group in the polydopamine layer. After calcination, a flexible and free-standing electrode was obtained. The sensing performance and mechanism of the Fe/PDA-C/CC sensor was investigated and is discussed in detail herein. Experimental results demonstrated that Fe/PDA-C/CC could simultaneously detect DA and UA with a wide detection range of 0.5-300 µM and 0.5-400 µM with low detection limits of 0.041 µM and 0.012 µM, respectively. Meanwhile, Fe/PDA-C/CC possessed excellent anti-interference performance, repeatability, stability, and accuracy in real samples. Overall, this study provides a facile and effective approach for simultaneous detection of UA and DA.

The Bidirectional Relation Between Bullying/Victimization and Negative Automatic Thoughts among Children.

As a common form of negative interpersonal interaction in childhood, school bullying is closely related to individual negative cognition. Few studies have assessed whether there is an interaction between different kinds of school bullying roles and negative cognition. The present study administered four questionnaire follow-up tests among Chinese children over two years to explore the bidirectional relation and underlying mechanisms between bullying/victimization and negative automatic thoughts (about self/others). A total of 993 children with MT1age = 9.66 ± 0.72 participated in the study, including 647(65.16%) boys and 346(34.84%) girls. Results indicated a bidirectional relation between victimization and negative automatic thoughts (about self/others); negative automatic thoughts (about self/others) predicting bullying; negative automatic thoughts (about self/others) form two vicious cycles with victimization separately, in which victimization plays a mediating role. The findings suggest that considering improving children's negative cognition of self and others is an important pathway to reduce the occurrence of bullying and victimization in children and to stop children from falling into the cycle of victimization, which is crucial for children to have healthy relationships later in adolescence.

Biodegradable Piezoelectric-Conductive Integrated Hydrogel Scaffold for Repair of Osteochondral Defects.

Osteochondral injury is a prevalent condition for which no specific treatment is currently available. This study presents a piezoelectric-conductive scaffold composed of a piezoelectric cartilage-decellularized extracellular matrix (dECM) and piezoelectric-conductive modified gelatin (Gel-PC). The piezoelectricity of the scaffold is achieved through the modification of diphenylalanine (FF) assembly on the pore surface, while the conductive properties of scaffold are achieved by the incorporating poly(3,4-ethylenedioxythiophene). In vitro experiments demonstrate that bone marrow mesenchymal stem cells (BMSCs) undergo biphasic division during differentiation. In vivo studies using a Parma pig model of osteochondral defects demonstrate that the piezoelectric-conductive scaffold exhibits superior reparative efficacy. Notably, the generation of electrical stimulation is linked to joint movement. During joint activity, mechanical forces compress the scaffold, leading to deformation and the subsequent generation of an electric potential difference. The positive charges accumulated on the upper layer of the scaffold attract BMSCs, promoting their migration to the upper layer and chondrogenic differentiation. Meanwhile, the negative charges in the lower layer induce the osteogenic differentiation of BMSCs. Overall, this piezoelectric-conducive scaffold provides a promising platform for the effective repair of osteochondral defects.

Blueberry extract attenuates DSS-induced inflammatory bowel disease in mice through inhibiting ER stress-mediated colonic apoptosis in mice.

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.

Luteipulveratus flavus sp. nov. isolated from two lichen species.

Two novel strains, YIM 133132T and YIM 133296, were isolated from lichen samples collected from Yunnan Province, Southwest PR China. YIM 133132T and YIM 133296 are aerobic, Gram-staining-positive, non-motile actinomycetes. They are also catalase-positive and oxidase-negative, and YIM 133132T formed flat yellowish colonies that were relatively dry on YIM38 agar medium. Flat yellowish colonies of YIM 133296 were also observed on YIM38 agar medium. YIM 133132T grew at 25-35 °C (optimum 25-30 °C), pH 6.0-9.0 (optimum pH 7.0) and in the presence of 0-8% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains YIM 133132T and YIM 133296 represented members of the genus Luteipulveratus and exhibited high sequence similarity (96.93%) with Luteipulveratus halotolerans C296001T. The genomic DNA G+C content of both strains was 71.8%. The DNA-DNA hybridisation (dDDH) values between YIM 133132T and YIM 133296 were 85.1%, and the DNA-DNA hybridisation value between YIM 133132T and YIM 133296 and L. halotolerans C296001T was 23.4%. On the basis of the draft genome sequences, the average nucleotide identity (ANI) between strains YIM 133132T and YIM 133296 and L. halotolerans C296001T was 80.8%. The major menaquinones that were identified were MK-8(H4), MK-9 and MK-8(H2). The polar lipids were diphosphatidylglycerol and phosphatidylinositol. On the basis of the morphological, physiological, biochemical, genomic, phylogenetic and chemotaxonomic characteristics, strains YIM 133132T and YIM 133296 can be clearly distinguished from L. halotolerans C296001T, and the two strains represent a novel species for which the name L. flavus sp. nov. is proposed. The type strain is YIM 133132T (CGMCC= 1.61357T and KCTC= 49824T).

The novel HSP90 monoclonal antibody 9B8 ameliorates articular cartilage degeneration by inhibiting glycolysis via the HIF-1 signaling pathway.

Osteoarthritis (OA) is a prevalent chronic degenerative disease that affects the bones and joints, particularly in middle-aged and elderly individuals. It is characterized by progressive joint pain, swelling, stiffness, and deformity. Notably, treatment with a heat shock protein 90 (HSP90) inhibitor has significantly curtailed cartilage destruction in a rat model of OA. Although the monoclonal antibody 9B8 against HSP90 is recognized for its anti-tumor properties, its potential therapeutic impact on OA remains uncertain. This study investigated the effects of 9B8 on OA and its associated signaling pathways in interleukin-1ß (IL-1ß)-stimulated human chondrocytes and a rat anterior cruciate ligament transection (ACLT) model. A specific concentration of 9B8 preserved cell viability against IL-1ß-induced reduction. In vitro, 9B8 significantly reduced the expression of extracellular matrix-degrading enzyme such as disintegrin and metallopeptidase-4 (ADAMTS4) of thrombospondin motifs, matrix metalloproteinase-13 (MMP-13), as well as cellular inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which were upregulated by IL-1ß. In vivo, 9B8 effectively protected the articular cartilage and subchondral bone of the rat tibial plateau from ACLT-induced damage. Additionally, gene microarray analysis revealed that IL-1ß substantially increased the expression of SLC2A1, PFKP, and ENO2 within the HIF-1 signaling pathway, whereas 9B8 suppressed the expression of these genes. Thus, 9B8 effectively mitigates ACLT-induced osteoarthritis in rats by modulating the HIF-1 signaling pathway, thereby inhibiting overexpression involved in glycolysis. These results collectively indicate that 9B8 is a promising novel drug for the prevention and treatment of OA.

In vitro digestion and functional properties of bovine ß-casein: A comparison between adults and infants.

Gastrointestinal digestibility behavior, structural and functional characteristics of bovine ß-casein (ß-CN) were studied in vitro under infant and adult conditions. This direct comparison helps reveal the effects of different physiological stages on the digestive behavior of ß-CN. Not only was the degree of hydrolysis (DH) of ß-CN analyzed, but also the changes in its digestive morphology, microstructure, and secondary structure during digestion were explored in depth. Meanwhile, we focused on the physicochemical properties of ß-CN digesta, including solubility, emulsifying and foaming properties, as well as their functional properties, such as antimicrobial and antioxidant activities. Key results showed that ß-CN underwent more extensive hydrolysis in the adult digestion model, with approximately twice the DH compared to the infant model. The adult model exhibited faster digestion kinetics, less protein flocculation, and a more loosened secondary structure, indicating a more efficient digestion process. Notably, the digesta from the adult model displayed significantly improved solubility and emulsifying properties, and also enhanced antioxidant capacities, with significantly better inhibition of two common pathogenic bacteria than the infant model, and an average increase in the diameter of the inhibition zone of approximately 2 mm. These findings underscore the differential digestive behavior and functional potential of ß-CN across physiological stages. This comprehensive assessment approach contributes to a more comprehensive insight into the digestive behavior of ß-CN. Therefore, we conclude that producing products from unmodified ß-CN may be more suitable for the adult population, and that the digesta in the adult model exhibit higher functional properties.

Enhanced Effects of Intermittent Fasting by Magnetic Fields in Severe Diabetes.

Intermittent fasting (IF) is a convenient dietary intervention for multiple diseases, including type 2 diabetes. However, whether it can be used as a long-term antidiabetic approach is still unknown. Here, we confirm that IF alone is beneficial for both moderate and severe diabetic mice, but its antidiabetic effects clearly diminish at later stages, especially for severe diabetic db/db mice, which have obviously impaired autophagy. We found that static magnetic fields can directly promote actin assembly and boost IF-induced autophagy. Consequently, the pancreatic islet and liver were improved, and the antidiabetic effects of IF were boosted. In fact, at later stages, combined static magnetic field and IF could reduce the blood glucose level of moderate type 2 diabetic mice by 40.5% (P < 0.001) and severe type 2 diabetes by 34.4% (P < 0.05), when IF alone no longer has significant blood glucose reduction effects. Therefore, although IF is generally beneficial for diabetes, our data reveal its insufficiency for late-stage diabetes, which can be compensated by a simple, noninvasive, long-lasting, and nonpharmacological strategy for effective long-term diabetic control.