Therapeutic Effect of Smilax glabra Roxb. on Weaning Rats Against Pb-Induced Nephrotoxicity Based on Network Pharmacology.

Lead (Pb) is a major environmental pollutant that can cause nephrotoxicity, hepatotoxicity, encephalopathy, and even death. Smilax glabra Roxb. has been used to treat heavy metal poisoning in China for over 500 years. We hypothesized that the Smilax glabra flavonoid extract (SGF) can ameliorate lead poisoning and investigated the possible mechanisms using network pharmacology. In total, 13 active compounds of Smilax glabra Roxb. and 71 overlapping potential targets were identified. The drug-compound-target-disease network analysis revealed that oxidative stress, inflammation, and apoptosis were mainly involved in the treatment of lead poisoning. Gene Ontology (GO) enrichment analysis showed that the biological processes involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning included biological processes, cellular components, and molecular functions. Additionally, 112 Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were obtained with the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways showing strong associations with lead poisoning by KEGG enrichment. The results of target pathway analysis showed that NF-κB was the most relevant gene involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning and was closely related to the MAPK signaling pathway. In vivo experiments confirmed that SGF treatment alleviated the pathological damage caused by lead-induced nephrotoxicity in weaning rats. Furthermore, SGF treatment markedly inhibited the expression of key proteins involved in the NF-κB/MAPK signaling pathway, highlighting the strong therapeutic effect of SGF against lead-induced nephrotoxicity. Results from network pharmacology and experimental verification indicated that SGF mitigated Pb-induced nephrotoxicity by downregulating the NF-κB/MAPK signaling pathway.

Anthocyanins in Vascular Health and Disease: Mechanisms of Action and Therapeutic Potential.

ABSTRACT: Unhealthy lifestyles have placed a significant burden on individuals' cardiovascular health. Anthocyanins are water-soluble flavonoid pigments found in a wide array of common foods and fruits. Anthocyanins have the potential to contribute to the prevention and treatment of cardiovascular disease by improving lipid profiles and vascular function, reducing blood glucose levels and blood pressure, and inhibiting inflammation. These actions have been demonstrated in numerous clinical and preclinical studies. At the cellular and molecular level, anthocyanins and their metabolites could protect endothelial cells from senescence, apoptosis, and inflammation by activating the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthases, silent information regulator 1 (SIRT1), or nuclear factor erythroid2-related factor 2 pathways and inhibiting the nuclear factor kappa B, Bax, or P38 mitogen-activated protein kinase pathways. Furthermore, anthocyanins prevent vascular smooth muscle cell from platelet-derived growth factor -induced or tumor necrosis factor-α-induced proliferation and migration by inhibiting the focal adhesion kinase and extracellular regulated protein kinases signaling pathways. Anthocyanins could also attenuate vascular inflammation by reducing the formation of oxidized lipids, preventing leukocyte adhesion and infiltration of the vessel wall, and macrophage phagocytosis of deposited lipids through reducing the expression of cluster of differentiation 36 and increasing the expression of ATP-binding cassette subfamily A member 1 and ATP-binding cassette subfamily G member 1. At the same time, anthocyanins could lower the risk of thrombosis by inhibiting platelet activation and aggregation through down-regulating P-selectin, transforming growth factor-1, and CD40L. Thus, the development of anthocyanin-based supplements or derivative drugs could provide new therapeutic approaches to the prevention and treatment of vascular diseases.

Optimization of Phenolic-Enriched Extracts from Olive Leaves via Ball Milling-Assisted Extraction Using Response Surface Methodology.

This study aims to extract phenolic-enriched compounds, specifically oleuropein, luteoloside, and hydroxytyrosol, from olive leaves using ball milling-assisted extraction (BMAE). Response surface methodology (RSM) and the Box-Behnken design (BBD) were used to evaluate the effects of the temperature, solvent-to-solid ratio, and milling speed on extraction recovery. The contents of the extract were determined by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and converted to recoveries to evaluate the extraction efficiency. The optimal extraction conditions for oleuropein, luteoloside, and hydroxytyrosol were identified. Oleuropein had a recovery of 79.0% ± 0.9% at a temperature of 56.4 °C, a solvent-to-solid ratio of 39.1 mL/g, and a milling speed of 429 rpm. Luteoloside's recovery was 74.6% ± 1.2% at 58.4 °C, 31.3 mL/g, and 328 rpm. Hydroxytyrosol achieved 43.1% ± 1.3% recovery at 51.5 °C, 32.7 mL/g, and 317 rpm. The reason for the high recoveries might be that high energy ball milling could reduce the sample size further, breaking down the cell walls of olive leaves, to enhance the mass transfer of these components from the cell to solvent. BMAE is displayed to be an efficient approach to extracting oleuropein, luteoloside, and hydroxytyrosol from olive leaves, which is easy to extend to industrial production.

[Changes in Soil Organic Carbon Density and Its Response to Climate Change and Human Activities Before and After the Grain for Green Project on the Loess Plateau].

Accurately assessing the changes in soil organic carbon storage （SOCS） before and after the Grain for Green Project （GFG） in the Loess Plateau （LP） and exploring the relationship between its spatial and temporal distribution and the influencing factors were important references for the development of regional recycling as well as the formulation of ecological protection policies. Based on the data of climate, human activities, and SOCD in the surface （0-20 cm） and deep （0-100 cm） soil before and after GFG in the LP from 2001 to 2020, we investigated the changes in SOCD at different spatial and temporal scales by using the methods of trend analysis, the kriging method, and variance partitioning analysis. The results showed that： ① Before and after the GFG, the surface SOCS of the whole region increased by 8 338.7×104 t； the deep SOCS increased by 1 160.02×104 t. ② In each bioclimatic subregion, the whole-region average SOCD of Ⅰ （Semi-Humid Forest Region）, Ⅱ （Semi-Humid Semi-Arid Forest and Grassland Region）, and Ⅲ （Semi-Arid Typical Grassland Region） showed a significant increasing trend, with a decreasing trend in Ⅳ （arid semi-arid desert grassland area） and Ⅴ （arid desert area）. ③ The average surface SOCS increase in different ecosystems was ranked as follows： cropland > grassland > woodland > shrubs > bare land and sparse vegetation. The deep soil increase was ranked as follows： grassland > cropland > woodland > shrubs > bare land and sparse vegetation. ④ Climate factors were the most important driving factors for changes in SOCD； the annual average temperature and precipitation were significantly positively correlated with changes in SOCD. The results of the study could provide data support for regional ecological management and land use policy formulation to promote high quality development of the ecological environment in the LP.

SEF-UNet: advancing abdominal multi-organ segmentation with SEFormer and depthwise cascaded upsampling.

The abdomen houses multiple vital organs, which are associated with various diseases posing significant risks to human health. Early detection of abdominal organ conditions allows for timely intervention and treatment, preventing deterioration of patients' health. Segmenting abdominal organs aids physicians in more accurately diagnosing organ lesions. However, the anatomical structures of abdominal organs are relatively complex, with organs overlapping each other, sharing similar features, thereby presenting challenges for segmentation tasks. In real medical scenarios, models must demonstrate real-time and low-latency features, necessitating an improvement in segmentation accuracy while minimizing the number of parameters. Researchers have developed various methods for abdominal organ segmentation, ranging from convolutional neural networks (CNNs) to Transformers. However, these methods often encounter difficulties in accurately identifying organ segmentation boundaries. MetaFormer abstracts the framework of Transformers, excluding the multi-head Self-Attention, offering a new perspective for solving computer vision problems and overcoming the limitations of Vision Transformers and CNN backbone networks. To further enhance segmentation effectiveness, we propose a U-shaped network, integrating SEFormer and depthwise cascaded upsampling (dCUP) as the encoder and decoder, respectively, into the UNet structure, named SEF-UNet. SEFormer combines Squeeze-and-Excitation modules with depthwise separable convolutions, instantiating the MetaFormer framework, enhancing the capture of local details and texture information, thereby improving edge segmentation accuracy. dCUP further integrates shallow and deep information layers during the upsampling process. Our model significantly improves segmentation accuracy while reducing the parameter count and exhibits superior performance in segmenting organ edges that overlap each other, thereby offering potential deployment in real medical scenarios.

Semi-Supervised Semantic Segmentation for Light Field Images Using Disparity Information.

Light field (LF) images enable numerous applications due to their ability to capture information for multiple views. Semantic segmentation is an essential task for LF scene understanding. However, existing supervised methods heavily rely on a large number of pixel-wise annotations. To relieve this problem, we propose a semi-supervised LF semantic segmentation method that requires only a small subset of labeled data and harnesses the LF disparity information. First, we design an unsupervised disparity estimation network, which can determine the disparity map for every view. With the estimated disparity maps, we generate pseudo-labels along with their weight maps for the peripheral views when only the labels of central views are available. We then merge the predictions from multiple views to obtain more reliable pseudo-labels for unlabeled data, and introduce a disparity-semantics consistency loss to enforce structure similarity. Moreover, we develop a comprehensive contrastive learning scheme that includes a pixel-level strategy to enhance feature representations and an object-level strategy to improve segmentation for individual objects. Our method demonstrates state-of-the-art performance on the benchmark LF semantic segmentation dataset under a variety of training settings and achieves comparable performance to supervised methods when trained under 1/2 protocol.

Whole genome sequencing and genomic characteristics analysis of carbapenem-resistant Acinetobacter baumannii clinical isolates in two hospitals in China.

Nosocomial outbreaks caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains are rapidly emerging worldwide and are cause for concern. Herein, we aimed to describe the genomic characteristics of CRAB strains isolated from two hospitals in China in 2023. The A. baumannii isolates were mainly collected from the ICU and isolated from the sputum (71.43%, 15/21), followed by urine (14.29%, 3/21). Twenty-one A. baumannii strains possessed a multidrug-resistant (MDR) profile, and whole-genome sequencing showed that they all carried blaOXA-23. Based on the Pasteur multilocus sequence typing (MLST) scheme, all strains were typed into a sequence type 2 (ST2). Based on the Oxford MLST scheme, six strains belonged to ST540, three of which were ST208, and four strains were assigned to ST784. Kaptive showed most of the strains (38.10%, 8/21) contained KL93. As for the lipoolygosaccharide (OC locus) type, OCL1c and OCL1d were identified, accounting for 33.33% (7/21) and 66.67% (14/21), respectively. Based on the BacWGSTdb server, we found that the strains belonging to ST540 and ST784 were all collected from China. However, the ST938 strains were isolated from Malaysia and Thailand. Comparative genomics analysis showed that the AB10 strain had a closed relationship with SXAB10-SXAB13 strains, suggesting the transmission happened in these two hospitals and other hospital in China. In addition, the 4300STDY7045869 strain, which was collected from Thailand, possessed near genetic relationship with our isolates in this study, suggesting the possible spread among various countries. Additionally, 3-237 single nucleotide polymorphisms were observed among these strains. In conclusion, this study conducted a genome-based study for A. baumannii strains collected from two hospitals in China and revealed their epidemiological and molecular features. Clone spreading occurred in these two hospitals. Hence, there is an urgent need for increased surveillance in hospitals and other clinical settings to prevent and control CRAB spreading.

Fabric structure and polymer composition as key contributors to micro(nano)plastic contamination in face masks.

The surge in face mask use due to COVID-19 has raised concerns about micro(nano)plastics (MNPs) from masks. Herein, focusing on fabric structure and polymer composition, we investigated MNP generation characteristics, mechanisms, and potential risks of surgical polypropylene (PP) and fashionable polyurethane (PU) masks during their wearing and photoaging based on stereomicroscope, µ-Fourier transform infrared spectroscopy (µ-FTIR), and scanning electron microscope (SEM) techniques. Compared with new PP and PU masks (66 ± 16 MPs/PP-mask, 163 ± 83 MPs/PU-mask), single- and multiple-used masks exhibited remarkably increased MP type and abundance (600-1867 MPs/PP-mask, 607-2167 MPs/PU-mask). Disinfection exacerbated endogenous MP generation in masks, with washing (416 MPs/PP-mask, 30,708 MPs/PU-mask) being the most prominent compared to autoclaving (219 MPs/PP-mask, 553 MPs/PU-mask) and alcohol spray (162 MPs/PP-mask, 18,333 MPs/PU-mask). Photoaging led to massive generation of MPs (8.8 × 104-3.7 × 105 MPs/PP-layer, 1.0 × 105 MPs/PU-layer) and NPs (5.2 × 109-3.6 × 1013 NPs/PP-layer, 3.5 × 1012 NPs/PU-layer) from masks, presenting highly fabric structure-dependent aging modes as "fragmentation" for fine fiber-structure PP mask and "erosion" for 3D mesh-structure PU mask. The MNPs derived from PP/PU mask caused significant deformities of Zebrafish (Danio rerio) larvae. These findings underscore the potential adverse effects of masks on humans and aquatic organisms, advocating to enhance proper use and rational disposal for masks.

Carrier effects of face mask-derived microplastics on metal ions: Enhanced adsorption by photoaging combined with biofilms, exemplified with Pb(â ¡).

Face masks have emerged as a significant source of microplastics (MPs) under the influence of biotic and abiotic interactions. However, the combined effects of abiotic photoaging and biofilm-loading on mask-derived MPs as carriers of metal ions are not clear. We investigated the Pb(Ⅱ) adsorption onto polypropylene (PP) and polyurethane (PU) mask-derived MPs treated by photoaging, biofilm-loading, and both combinations, evaluating the composite risks. PU mask-derived MPs (1.157.47 mg/g) exhibited greater Pb(Ⅱ) adsorption capacity than PP mask-derived MPs (0.842.08 mg/g) because of the presence of intrinsic carbonyl functional groups. Photoaging (30.5%, 88.4%), biofilm-loading (110.7%, 87.1%), and both combinations (146.7%, 547.0%) of PP and PU masks enhanced Pb(Ⅱ) adsorption compared to virgin mask-derived MPs due to the increase of oxygen-containing functional groups. High-throughput sequencing indicated that the structural morphology and chemical composition of masks significantly affected the microbial community. Adsorption mechanisms involved electrostatic force and surface complexation. A combination of photoaging and biofilms increased the ecological risk index of mask-derived MPs in freshwater, showing the risk level to be high (PP mask) and very high (PU mask). This research highlights the crucial role of photoaging combined with biofilms in controlling metal ion adsorption onto mask-derived MPs, thereby increasing the composite risks.

Microbial creation of ß-Nicotinamide mononucleotide and its regulation of lipid metabolism in the liver of high-fat diet mice.

ß-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide adenine dinucleotide (NAD+). To determine the safety and biological activity of NMN resources, we constructed a recombinant strain of P. pastoris that heterologously expresses nicotinamide-phosphate ribosyltransferase (NAMPT), and subsequently catalyzed and purified the expressed product to obtain NMN. Consequently, this study established a high-fat diet (HFD) obese model to investigate the lipid-lowering activity of NMN. The findings showed that NMN supplementation directly increased the NAD+ levels, and reduced HFD-induced liver injury and lipid deposition. NMN treatment significantly decreased total cholesterol (TC) and triglyceride (TG) in serum and liver, as well as alanine aminotransferase (ALT) and insulin levels in serum (p < .05 or p < .01). In conclusion, this study combined synthetic biology with nutritional evaluation to confirm that P. pastoris-generated NMN modulated lipid metabolism in HFD mice, offering a theoretical framework and evidence for the application of microbially created NMN.

CmPIF8-CmERF27-CmACS10-mediated ethylene biosynthesis modulates red light-induced powdery mildew resistance in oriental melon.

Powdery mildew is a serious fungal disease in protected melon cultivation that affects the growth, development and production of melon plants. Previous studies have shown that red light can improve oriental melon seedlings resistance to powdery mildew. Here, after inoculation with Podosphaera xanthii, an obligate fungal pathogen eliciting powdery mildew, we found that red light pretreatment increased ethylene production and this improved the resistance of melon seedlings to powdery mildew, and the ethylene biosynthesis gene CmACS10 played an important role in this process. By analysing the CmACS10 promoter, screening yeast one-hybrid library, it was found that CmERF27 positively regulated the expression of CmACS10, increased powdery mildew resistance and interacted with PHYTOCHROME INTERACTING FACTOR8 (CmPIF8) at the protein level to participate in the regulation of ethylene biosynthesis to respond to the red light-induced resistance to P. xanthii, Furthermore, CmPIF8 also directly targeted the promoter of CmACS10, negatively participated in this process. In summary, this study revealed the specific mechanism by which the CmPIF8-CmERF27-CmACS10 module regulates red light-induced ethylene biosynthesis to resist P. xanthii infection, elucidate the interaction between light and plant hormones under biological stress, provide a reference and genetic resources for breeding of disease-resistant melon plants.

Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.

Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.

The natural polyphenol fisetin in atherosclerosis prevention: a mechanistic review.

The incidence and mortality rate of atherosclerotic cardiovascular disease (ASCVD) is increasing yearly worldwide. Recently, a growing body of evidence has unveiled the anti-atherosclerotic properties of fisetin, a natural polyphenol compound. In this article, we reviewed the pharmacologic actions of fisetin on experimental atherosclerosis and its protective effects on disease-relevant cell types such as endothelial cells, macrophages, vascular smooth muscle cells, and platelets. Based on its profound cardiovascular actions, fisetin holds potential for clinical translation and could be developed as a potential therapeutic option for atherosclerosis and its related complications. Large-scale randomized clinical trials are warranted to ascertain the safety and efficacy of fisetin in patients with or high risk for ASCVD.

Surface Treatment with Tailored π-Conjugated Fluorene Derivatives Significantly Enhances the Performance of Perovskite Light-Emitting Diodes.

Surface defect passivation and carrier injection regulation have emerged as effective strategies for enhancing the performance of perovskite light-emitting diodes (Pero-LEDs). It usually requires two functional molecules to realize defect passivation and carrier injection regulation separately. In other words, developing one single molecule possessing these capabilities remains challenging. Herein, we utilized π-conjugated fluorene derivatives as surface treatment materials, 9,9-Spirobi[fluorene] (SBF), 9,9-Spirobifluoren-2-yl-diphenylphosphine oxide (SPPO1), and 2,7-bis(diphenylphosphoryl)-9,9'-spirobifluorene (SPPO13), to investigate the influence of their chemical structure on device optoelectronic performance, especially for defect passivation and carrier injection regulation. Consequently, the passivation capability of double-bonded SPPO13 surpassed single-bonded SPPO1 and nonbonded SBF, which all showed excellent electron transport properties, enhancing electron injection. The maximum external quantum efficiencies (EQE) for Pero-LEDs treated with SBF, SPPO1, and SPPO13 were 8.13, 17.48, and 22.10%, respectively, exceeding that of the derivative-free device (6.55%). Notably, SPPO13-treated devices exhibited exceptional reproducibility, yielding an average EQE of 20.00 ± 1.10% based on 30 devices. This result emphasizes the potential of tailored fluorene derivatives for enhancing the device performance of Pero-LEDs.

Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases.

Under normal physiological conditions, reactive oxygen species (ROS) are produced through redox reactions as byproducts of respiratory and metabolic activities. However, due to various endogenous and exogenous factors, the body may produce excessive ROS, which leads to oxidative stress (OS). Numerous studies have shown that OS causes a variety of pathological changes in cells, including mitochondrial dysfunction, DNA damage, telomere shortening, lipid peroxidation, and protein oxidative modification, all of which can trigger apoptosis and senescence. OS also induces a variety of aging-related diseases, such as retinal disease, neurodegenerative disease, osteoarthritis, cardiovascular diseases, cancer, ovarian disease, and prostate disease. In this review, we aim to introduce the multiple internal and external triggers that mediate ROS levels in rodents and humans as well as the relationship between OS, aging, and aging-related diseases. Finally, we present a statistical analysis of effective antioxidant measures currently being developed and applied in the field of aging research.

The validity of the Physical Literacy in Children Questionnaire in children aged 4 to 12.

BACKGROUND: Given the growing evidence on the health benefits associated with physical literacy (PL), it is necessary to develop sound measures to assess the levels of PL in children. The Physical Literacy in Children Questionnaire (PL-C Quest) is the first self-report pictorial-based scale to assess children's perceived PL. It has good validity and reliability in Australian children aged 7 to 12 years, but little is known in younger children and in other cultural contexts. The aim of this study was to examine the validity and reliability in an expanded age range. METHODS: A total of 1,870 Chinese children (girls, n = 871; 46.6%), aged 4 to 12 years (M = 8.07 ± 2.42) participated in validity testing. Structural equation modeling with the Weighted Least Squares with Mean and Variance approach was used to assess construct validity. The hypothesized theoretical model used the 30 items and four hypothesized factors: physical, psychological, social and cognitive capabilities. Multigroup confirmatory factor analysis was used to assess sex and age group (4-6 years, 7-9 years and 10-12 years) measurement invariance. Internal consistency analyses were conducted using polychoric alpha. A random subsample (n = 262) was selected to determine test-retest reliability using Intra-Class Correlations (ICC). RESULTS: All items except one (moving with equipment-skateboarding) loaded on sub-domains with λ > 0.45. The hypothesized model had a good fit (CFI = 0.954, TLI = 0.950, RMSEA = 0.042), with measurement equivalence across sex and age groups separately. Internal consistency values were good to excellent (overall: α = 0.94; physical: α = 0.86; psychological: α = 0.83; social: α = 0.81; cognitive: α = 0.86). Test-retest reliability was adequate to excellent (overall: ICC = 0.90, physical: ICC = 0.86, psychological: ICC = 0.75, social: ICC = 0.71, cognitive: ICC = 0.72). CONCLUSION: The Chinese version of the PL-C Quest is valid and reliable for testing the self-reported PL of Chinese children aged 4 to 12. This study provides the first evidence of validity for this tool in children aged 4-6 years and also evidence that the PL-C Quest would be a meaningful instrument to assess PL in Chinese children.

Selenium protects against Pb-induced renal oxidative injury in weaning rats and human renal tubular epithelial cells through activating NRF2.

BACKGROUND: Lead (Pb) poisoning posing a crucial health risk, especially among children, causing devastating damage not only to brain development, but also to kidney function. Thus, an urgent need persists to identify highly effective, safe, and low-toxicity drugs for the treatment of Pb poisoning. The present study focused on exploring the protective effects of Se on Pb-induced nephrotoxicity in weaning rats and human renal tubular epithelial cells, and investigated the possible mechanisms. METHODS: Forty weaning rats were randomly divided into four groups in vivo: control, Pb-exposed, Pb+Se and Se. Serum creatinine (Cr), urea nitrogen (BUN) and hematoxylin and eosin (H&E) staining were performed to evaluate renal function. The activities of antioxidant enzymes in the kidney tissue were determined. In vitro experiments were performed using human renal tubular epithelial cells (HK-2 cells). The cytotoxicity of Pb and Se was detected by 3-(4,5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Inverted fluorescence microscope was used to investigate cell morphological changes and the fluorescence intensity of reactive oxygen species (ROS). The oxidative stress parameters were measured by a multi-detection reader. Nuclear factor-erythroid-2-related factor (NRF2) signaling pathways were measured by Western blot and reverse transcription polymerase chain reaction (RT-PCR) in HK-2 cells. RESULTS: We found that Se alleviated Pb-induced kidney injury by relieving oxidative stress and reducing the inflammatory index. Se significantly increased the activity of the antioxidant enzymes glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), whereas it decreased the excessive release of malondialdehyde (MDA) in the kidneys of weaning rats and HK-2 cells. Additionally, Se enhanced the antioxidant defense systems via activating the NRF2 transcription factor, thereby promoting the to downstream expression of heme oxygenase 1. Furthermore, genes encoding glutamate-cysteine ligase synthetase catalytic (GCLC), glutamate-cysteine ligase synthetase modifier (GCLM) and NADPH quinone oxidoreductase 1 (NQO1), downstream targets of NRF2, formed a positive feedback loop with NRF2 during oxidative stress responses. The MTT assay results revealed a significant decrease in cell viability with Se treatment, and the cytoprotective role of Se was blocked upon knockdown of NRF2 by small interfering RNA (siRNA). MDA activity results also showed that NRF2 knockdown inhibited the NRF2-dependent transcriptional activity of Se. CONCLUSIONS: Our findings demonstrate that Se ameliorated Pb-induced nephrotoxicity by reducing oxidative stress both in vivo and in vitro. The molecular mechanism underlying Se's action in Pb-induced kidney injury is related to the activation of the NRF2 transcription factor and the activity of antioxidant enzymes, ultimately suppressing ROS accumulation.

High-Throughput and Scalable Exfoliation of Large-Sized Ultrathin 2D Materials by Ball-Milling in Supercritical Carbon Dioxide.

The 2D materials exhibit numerous technological applications, but their scalable production is a core challenge. Herein, ball milling exfoliation in supercritical carbon dioxide (scCO2) and polystyrene (PS) is demonstrated to completely exfoliate hexagonal boron nitride nanosheets (BNNSs), graphene, molybdenum disulfide (MoS2), and tungsten disulfide (WS2). The exfoliation yield of 91%, 93%, 92%, and 92% and average aspect ratios of 743, 565, 564, and 502 for BNNSs, graphene, MoS2, and WS2, respectively, are achieved. Integrating exfoliated BNNSS in the polystyrene matrix, 3768 % thermal conductivity in the axial direction and 316% in the cross-plane direction at 12 wt.% loading is increased. Also, the in-plane and cross-plane electrical conductivity of 6.3 × 10-4 S m-1 and 6.6 × 10-3 S m-1, respectively, and the electromagnetic interference (EMI) of 63.3 dB is achieved by exfoliated graphene nanosheets based composite. High thermal and electrical conductivities and EMI shielding are attributed to the high aspect ratio and ultrathin morphology of the exfoliated nanosheets, which exert high charge mobility and form better the percolation network in the composite films due to their high surface area. The process demonstrate herein can produce substantial quantities of diverse 2D nanosheets for widespread commercial utilization.

Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/ß-catenin signalling pathway.

INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.

Inhibitory effects of Acanthopanax sessiliflorus Harms extract on the etiology of rheumatoid arthritis in a collagen-induced arthritis mouse model.

BACKGROUND: The biological function of Acanthopanax sessiliflorus Harm (ASH) has been investigated on various diseases; however, the effects of ASH on arthritis have not been investigated so far. This study investigates the effects of ASH on rheumatoid arthritis (RA). METHODS: Supercritical carbon dioxide (CO2) was used for ASH extract preparation, and its primary components, pimaric and kaurenoic acids, were identified using gas chromatography-mass spectrometer (GC-MS). Collagenase-induced arthritis (CIA) was used as the RA model, and primary cultures of articular chondrocytes were used to examine the inhibitory effects of ASH extract on arthritis in three synovial joints: ankle, sole, and knee. RESULTS: Pimaric and kaurenoic acids attenuated pro-inflammatory cytokine-mediated increase in the catabolic factors and retrieved pro-inflammatory cytokine-mediated decrease in related anabolic factors in vitro; however, they did not affect pro-inflammatory cytokine (IL-1ß, TNF-α, and IL-6)-mediated cytotoxicity. ASH effectively inhibited cartilage degradation in the knee, ankle, and toe in the CIA model and decreased pannus development in the knee. Immunohistochemistry demonstrated that ASH mostly inhibited the IL-6-mediated matrix metalloproteinase. Gene Ontology and pathway studies bridge major gaps in the literature and provide insights into the pathophysiology and in-depth mechanisms of RA-like joint degeneration. CONCLUSIONS: To the best of our knowledge, this is the first study to conduct extensive research on the efficacy of ASH extract in inhibiting the pathogenesis of RA. However, additional animal models and clinical studies are required to validate this hypothesis.