Natural polysaccharides as promising reno-protective agents for the treatment of various kidney injury.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

Efficacy of auxetic lattice structured shoe sole in advancing footwear comfort-From the perspective of plantar pressure and contact area.

Introduction: Designing footwear for comfort is vital for preventing foot injuries and promoting foot health. This study explores the impact of auxetic structured shoe soles on plantar biomechanics and comfort, motivated by the integration of 3D printing in footwear production and the superior mechanical properties of auxetic designs. The shoe sole designs proposed in this study are based on a three-dimensional re-entrant auxetic lattice structure, orthogonally composed of re-entrant hexagonal honeycombs with internal angles less than 90 degrees. Materials fabricated using this lattice structure exhibit the characteristic of a negative Poisson's ratio, displaying lateral expansion under tension and densification under compression. Methods: The study conducted a comparative experiment among three different lattice structured (auxetic 60°, auxetic 75° and non-auxetic 90°) thermoplastic polyurethane (TPU) shoe soles and conventional polyurethane (PU) shoe sole through pedobarographic measurements and comfort rating under walking and running conditions. The study obtained peak plantar pressures (PPPs) and contact area across seven plantar regions of each shoe sole and analyzed the correlation between these biomechanical parameters and subjective comfort. Results: Compared to non-auxetic shoe soles, auxetic structured shoe soles reduced PPPs across various foot regions and increased contact area. The Auxetic 60°, which had the highest comfort ratings, significantly lowered peak pressures and increased contact area compared to PU shoe sole. Correlation analysis showed that peak pressures in specific foot regions (hallux, second metatarsal head, and hindfoot when walking; second metatarsal head, third to fifth metatarsal head, midfoot, and hindfoot when running) were related to comfort. Furthermore, the contact area in all foot regions was significantly associated with comfort, regardless of the motion states. Conclusion: The pressure-relief performance and conformability of the auxetic lattice structure in the shoe sole contribute to enhancing footwear comfort. The insights provided guide designers in developing footwear focused on foot health and comfort using auxetic structures.

In Situ Growth of Amorphous MnO2 on Graphite Felt via Mild Etching Engineering as a Powerful Catalyst for Advanced Vanadium Redox Flow Batteries.

Owing to the advantages of low cost, high safety, and a desirable cycling lifetime, vanadium redox flow batteries (VRFBs) have attracted great attention in the large-scale energy storage field. However, graphite felts (GFs), widely used as electrode materials, usually possess an inferior catalytic activity for the redox reaction of vanadium ions, largely limiting the energy efficiency and rate performance of VRFBs. Here, an in situ growth of amorphous MnO2 on graphite felt (AMO@GF) was designed for application in VRFBs via mild and rapid etching engineering (5 min). After the etching process, the graphite felt fibers showed a porous and defective surface, contributing to abundant active sites toward the redox reaction. In addition, formed amorphous MnO2 can also serve as a powerful catalyst to facilitate the redox couples of VO2+/VO2+ based on density functional theoretical (DFT) calculations. As a result, the VRFB using AMO@GF displayed an elevated energy efficiency and superior stability after 2400 cycles at 200 mA cm-2, and the maximum current density can reach 300 mA cm-2. Such a high-efficiency and convenient design strategy for the electrode material will drive the further development and industrial application of VRFBs and other flow battery systems.

STCS-Net: a medical image segmentation network that fully utilizes multi-scale information.

In recent years, significant progress has been made in the field of medical image segmentation through the application of deep learning and neural networks. Numerous studies have focused on optimizing encoders to extract more comprehensive key information. However, the importance of decoders in directly influencing the final output of images cannot be overstated. The ability of decoders to effectively leverage diverse information and further refine crucial details is of paramount importance. This paper proposes a medical image segmentation architecture named STCS-Net. The designed decoder in STCS-Net facilitates multi-scale filtering and correction of information from the encoder, thereby enhancing the accuracy of extracting vital features. Additionally, an information enhancement module is introduced in skip connections to highlight essential features and improve the inter-layer information interaction capabilities. Comprehensive evaluations on the ISIC2016, ISIC2018, and Lung datasets validate the superiority of STCS-Net across different scenarios. Experimental results demonstrate the outstanding performance of STCS-Net on all three datasets. Comparative experiments highlight the advantages of our proposed network in terms of accuracy and parameter efficiency. Ablation studies confirm the effectiveness of the introduced decoder and skip connection module. This research introduces a novel approach to the field of medical image segmentation, providing new perspectives and solutions for future developments in medical image processing and analysis.

Impacts of futile reperfusion and reperfusion injury in acute ischemic stroke.

Acute ischemic stroke (AIS) remains to be a challenging cerebrovascular disease. The mainstay of AIS management is endovascular reperfusion therapy, including thrombectomy and thrombolysis. However, ineffective (futile) reperfusion (FR) or reperfusion injury (RI) can be seen in a significant number of patients undergoing reperfusion strategy. In this article, we discuss two clinically relevant concepts known as "time window" and "tissue window" that can impact the clinical outcome of reperfusion therapy. We also explore patient risk factors, leading to FR and RI as well as an emerging concept of "no-reflow phenomenon" seen in ineffective reperfusion. These fundamental concepts provide insight into the clinical management of AIS patients and provide references for future research.

NYUS.2: an automated machine learning prediction model for the large-scale real-time simulation of grapevine freezing tolerance in North America.

Accurate and real-time monitoring of grapevine freezing tolerance is crucial for the sustainability of the grape industry in cool climate viticultural regions. However, on-site data are limited due to the complexity of measurement. Current prediction models underperform under diverse climate conditions, which limits the large-scale deployment of these methods. We combined grapevine freezing tolerance data from multiple regions in North America and generated a predictive model based on hourly temperature-derived features and cultivar features using AutoGluon, an automated machine learning engine. Feature importance was quantified by AutoGluon and SHAP (SHapley Additive exPlanations) value. The final model was evaluated and compared with previous models for its performance under different climate conditions. The final model achieved an overall 1.36°C root-mean-square error during model testing and outperformed two previous models using three test cultivars at all testing regions. Two feature importance quantification methods identified five shared essential features. Detailed analysis of the features indicates that the model has adequately extracted some biological mechanisms during training. The final model, named NYUS.2, was deployed along with two previous models as an R shiny-based application in the 2022-23 dormancy season, enabling large-scale and real-time simulation of grapevine freezing tolerance in North America for the first time.

Deep Learning Detection of Aneurysm Clips for Magnetic Resonance Imaging Safety.

Flagging the presence of metal devices before a head MRI scan is essential to allow appropriate safety checks. There is an unmet need for an automated system which can flag aneurysm clips prior to MRI appointments. We assess the accuracy with which a machine learning model can classify the presence or absence of an aneurysm clip on CT images. A total of 280 CT head scans were collected, 140 with aneurysm clips visible and 140 without. The data were used to retrain a pre-trained image classification neural network to classify CT localizer images. Models were developed using fivefold cross-validation and then tested on a holdout test set. A mean sensitivity of 100% and a mean accuracy of 82% were achieved. Predictions were explained using SHapley Additive exPlanations (SHAP), which highlighted that appropriate regions of interest were informing the models. Models were also trained from scratch to classify three-dimensional CT head scans. These did not exceed the sensitivity of the localizer models. This work illustrates an application of computer vision image classification to enhance current processes and improve patient safety.

Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/ß-catenin.

Icariin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanism by which Icariin regulates osteogenic differentiation needs to be further revealed. The viability of BMSCs was assessed by cell counting kit 8 assay. BMSC osteogenic differentiation ability was evaluated by detecting alkaline phosphatase activity and performing alizarin red S staining. The protein levels of osteogenic differentiation-related markers, sirtuin 1 (SIRT1), ubiquitin-specific protease 47 (USP47), and Wnt/ß-catenin-related markers were determined using western blot. SIRT1 mRNA level was measured using quantitative real-time PCR. The regulation of USP47 on SIRT1 was confirmed by ubiquitination detection and co-immunoprecipitation analysis. Icariin could promote BMSC osteogenic differentiation. SIRT1 expression was enhanced by Icariin, and its knockdown suppressed Icariin-induced BMSC osteogenic differentiation. Moreover, deubiquitinating enzyme USP47 could stabilize SIRT1 protein expression. Besides, SIRT1 overexpression reversed the inhibiting effect of USP47 knockdown on BMSC osteogenic differentiation, and USP47 knockdown also restrained Icariin-induced BMSC osteogenic differentiation. Additionally, Icariin enhanced the activity of the Wnt/ß-catenin pathway by upregulating SIRT1. Icariin facilitated BMSC osteogenic differentiation via the USP47/SIRT1/Wnt/ß-catenin pathway.

Electrical stimulation promoting the angiogenesis in diabetic rat perforator flap through attenuating oxidative stress-mediated inflammation and apoptosis.

Background: Skin flap transplantation is one of the effective methods to treat the diabetes-related foot ulceration, but the intrinsic damage to vessels in diabetes mellitus (DM) leads to the necrosis of skin flaps. Therefore, the discovery of a non-invasive and effective approach for promoting the survival of flaps is of the utmost importance. Electrical stimulation (ES) promotes angiogenesis and increases the proliferation, migration, and elongation of endothelial cells, thus being a potential effective method to improve flap survival. Objective: The purpose of this study was to elucidate the mechanism used by ES to effectively restore the impaired function of endothelial cells caused by diabetes. Methods: A total of 79 adult male Sprague-Dawley rats were used in this study. Gene and protein expression was assessed by PCR and western blotting, respectively. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the morphology and density of the microvessels in the flap. Results: The optimal duration for preconditioning the flap with ES was 7 days. The flap survival area percentage and microvessels density in the DMES group were markedly increased compared to the DM group. VEGF, MMP2, and MMP9 protein expression was significantly upregulated. ROS intensity was significantly decreased and GSH concentration was increased. The expression of IL-1ß, MCP­1, cleaved caspase-3, and Bax were downregulated in the DMES group, while TGF-ß expression was upregulated. Conclusions: ES improves the angiogenesis in diabetic ischemic skin flaps by attenuating oxidative stress-mediated inflammation and apoptosis, eventually increasing their viability.

Gooderoside A from Anoectochilus elatus attenuates acute and chronic pains by inhibiting NO/cGMP and IRAK4/IRAK1/TAK1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. AIM OF THE STUDY: To investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. MATERIALS AND METHODS: Acetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A. elatus (EEA) and GA. Formalin test was used to ascertain the antinociceptive pattern of GA. Entobarbital sodium induced sleep test was adopted to exclude its hypnotic effect, while open-field test was performed to rule out its motor impairment effect. Chronic constriction injury (CCI)-induced neuropathic pain in rats was developed to evaluate its efficacy on neuropathic pain, and BV-2 cells were used to explore the underlying mechanism. RESULTS: EEA and GA, significantly inhibited chemical and thermal nociception. GA suppressed nociception in formalin test in both phase I and II, whereas methylene blue and L-NAME partially reversed its efficacy. GA located inner and slightly blocked sodium channel current, and did not show any hypnotic effect or motor impairment effect. Crucially, GA markedly attenuated chronic neuropathic pain in rats, inhibited the phosphorylation of IRAK4, IRAK1 and TAK1, and suppressed MAPKs pathway in BV-2 cells. CONCLUSION: GA relieved acute and chronic pains in vivo. The mechanism of action involves the blocking of NO/cGMP and IRAK4/IRAK1/TAK1 pathways. These results suggested GA may be a promising candidate for antinociceptive drug development.

Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration.

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake.

Rhizosphere interface microbiome reassembly by arbuscular mycorrhizal fungi weakens cadmium migration dynamics.

The prevalence of cadmium (Cd)-polluted agricultural soils is increasing globally, and arbuscular mycorrhizal fungi (AMF) can reduce the absorption of heavy metals by plants and improve mineral nutrition. However, the immobilization of the rhizosphere on cadmium is often overlooked. In this study, Glomus mosseae and Medicago sativa were established as symbiotes, and Cd migration and environmental properties in the rhizosphere were analyzed. AMF reduced Cd migration, and Cd2+ changed to an organic-bound state. AMF symbiosis treatment and Cd exposure resulted in microbial community variation, exhibiting a distinct deterministic process (|ßNTI| > 2), which ultimately resulted in a core microbiome function of heavy metal resistance and nutrient cycling. AMF increased available N and P, extracellular enzyme activity (LaC, LiP, and CAT), organic matter content (TOC, EOC, and GRSP), and Eh of the rhizosphere soil, significantly correlating with decreased Cd migration (p < 0.05). Furthermore, AMF significantly affected root metabolism by upregulating 739 metabolites, with flavonoids being the main factor causing microbiome variation. The structural equation model and variance partial analysis revealed that the superposition of the root metabolites, microbial, and soil exhibited the maximum explanation rate for Cd migration reduction (42.4%), and the microbial model had the highest single explanation rate (15.5%). Thus, the AMF in the rhizosphere microenvironment can regulate metabolite-soil-microbial interactions, reducing Cd migration. In summary, the study provides a new scientific explanation for how AMF improves plant Cd tolerance and offers a sustainable solution that could benefit both the environment and human health.