Acovenosigenin A ß-glucoside mediates JAK2-STAT3 signaling pathway by targeting GP130 in A549 and H460 cells based on integrative analysis of transcriptome and proteome and biological verification.

Acovenosigenin A ß-glucoside (AAG) is a cardiac glycoside derived from Streptocaulon juventas (Lour.) Merr, which exhibited the potential in treating lung cancer in our previous research. However, the action mechanism remains unclear. In this research, JAK2-STAT3 signaling pathway was predicted to be the critical regulation pathway based on the integrative analysis of transcriptome and proteome. Western blotting and qPCR assays were performed to identify that AAG can regulate JAK2-STAT3 signaling pathway and its downstream genes, such as c-Myc, Survivin, Cyclin B1, CDK1, Bcl-2. And this action of AAG depended on the suppression of STAT3 phosphorylation and its nuclear translocation through the experiments of Immunofluorescence, transient transfection and cryptotanshinone treatment. Additionally, AAG was discovered to mediate the JAK2-STAT3 pathway in IL-6-driven A549 and H460 cells, which in turn inhibited cell proliferation, promoted mitochondria-related apoptosis, and arrested the cell cycle progression. By molecular docking analysis, CETSA and SIP experiments, the protein of GP130 was identified as the specific target of AAG in A549 and H460 cells. Further studies suggested that AAG inhibited JAK2-STAT3 pathway and its downstream genes by targeting GP130 in nude mice xenograft model in vivo. This research presented that AAG exhibits the promising potential in the treatment of NSCLC.

Plant-derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold.

Plant-derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti-inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)-loaded plant-derived exosomes (ISL@PE) from L. barbarum L. within a 3D-printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS-IACUC-2020121602.

Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-l-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a new nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

RD-OpenMax: Rethinking OpenMax for Robust Realistic Open-Set Recognition.

Open-set recognition (OSR) toward a practical open-world setting has attracted increasing research attention in recent years. However, existing OSR settings are either too idealized or focus on specific scenes such as long-tailed distribution and few-shot samples, which fail to capture the complexity of real-world scenarios. In this article, we propose a realistic OSR (ROSR) setting that covers a diverse range of challenging and real-world scenarios, including fine-grained cases with strong semantic correlation and a large number of species, few-shot samples, long-tailed sample distribution, dynamic inputs (e.g., images, spatio-temporal, and multimodal signals) and cross-domain adaptation. In particular, we rethink the simple and basic OpenMax for the ROSR setting and introduce a novel method, regularized discriminative OpenMax (RD-OpenMax), to handle the challenges in the ROSR setting. RD-OpenMax improves upon the basic OpenMax approach by introducing a covariance attention-based covariance pooling (CACP) module as a global aggregation step before the deep architecture's classifier. This module explores rich statistical information on features and provides discriminative distance scores for OpenMax. To address the instability of extreme value theory (EVT) estimation due to insufficient training samples under few-shot and long-tailed scenarios, we propose a regularized EVT (REVT) method based on Monte Carlo sampling to recalibrate the distribution of distance scores. As such, our RD-OpenMax performs a REVT model of distance scores generated by discriminative CACP representations to distinguish known classes and recognize unknown ones effectively and robustly. Extensive experiments are conducted on more than ten visual benchmarks across several scenarios, and the empirical comparisons show that the ROSR setting challenges existing state-of-the-art OSR approaches. Moreover, our RD-OpenMax clearly outperforms its counterparts under the ROSR setting while performing favorably against state-of-the-arts under the traditional OSR setting.

Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury.

This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut-liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1ß, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.

A fungal polysaccharide from Fomitopsis officinalis as a multi-target molecule to combat cancer.

Some macrofungi have a long history of being used as traditional or folk medicines, making significant contributions to human health. To discover bioactive molecules with potential anticancer properties, a homogeneous heteropolysaccharide (FOBP90-1) was purified from the medicinal macrofungus Fomitopsis officinalis. FOBP90-1 was found to have a molecular weight of 2.87 × 104 g/mol and mainly consist of →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, →6)-ß-d-Glcp-(1→, α-d-Manp-(1→, and 3-O-Me-α-l-Fucp-(1→ according to UV, FT-IR, methylation analysis, and NMR data. In addition to its structural properties, FOBP90-1 displayed anticancer activity in zebrafish models. The following mechanistic analysis discovered that the in vivo antitumor effect was linked to immune activation and angiogenesis inhibition. These effects were mediated by the interactions of FOBP90-1 with TLR-2, TLR-4, PD-L1, and VEGFR-2, as determined through a series of experiments involving cells, transgenic zebrafish, molecular docking simulations, and surface plasmon resonance (SPR). All the experimental findings have demonstrated that FOBP90-1, a purified fungal polysaccharide, is expected to be utilized as a cancer treatment agent.

Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

CCP-GNN: Competitive Covariance Pooling for Improving Graph Neural Networks.

Graph neural networks (GNNs) have advanced graph classification tasks, where a global pooling to generate graph representations by summarizing node features plays a critical role in the final performance. Most of the existing GNNs are built with a global average pooling (GAP) or its variants, which however, take no full consideration of node specificity while neglecting rich statistics inherent in node features, limiting classification performance of GNNs. Therefore, this article proposes a novel competitive covariance pooling (CCP) based on observation of graph structures, i.e., graphs generally can be identified by a (small) key part of nodes. To this end, our CCP generates node-level second-order representations to explore rich statistics inherent in node features, which are fed to a competitive-based attention module for effectively discovering key nodes through learning node weights. Subsequently, our CCP aggregates node-level second-order representations in conjunction with node weights by summation to produce a covariance representation for each graph, while an iterative matrix normalization is introduced to consider geometry of covariances. Note that our CCP can be flexibly integrated with various GNNs (namely CCP-GNN) to improve the performance of graph classification with little computational cost. The experimental results on seven graph-level benchmarks show that our CCP-GNN is superior or competitive to state-of-the-arts. Our code is available at https://github.com/Jillian555/CCP-GNN.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. AIM OF THE STUDY: This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. MATERIALS AND METHODS: The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE-/- mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE-/- mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. CONCLUSION: This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

PARP inhibitors suppress tumours via centrosome error-induced senescence independent of DNA damage response.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients' survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. METHODS: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. FINDINGS: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. INTERPRETATION: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. FUNDING: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Modulating the d-Band Center of RuO2 via Ni Incorporation for Efficient and Durable Li-O2 batteries.

Rechargeable Li-O2 batteries (LOBs) are considered as one of the most promising candidates for new-generation energy storage devices. One of major impediments is the poor cycle stability derived from the sluggish reaction kinetics of unreliable cathode catalysts, hindering the commercial application of LOBs. Therefore, the rational design of efficient and durable catalysts is critical for LOBs. Optimizing surface electron structure via the negative shift of the d-band center offers a reasonable descriptor for enhancing the electrocatalytic activity. In this study, the construction of Ni-incorporating RuO2 porous nanospheres is proposed as the cathode catalyst to demonstrate the hypothesis. Density functional theory calculations reveal that the introduction of Ni atoms can effectively modulate the surface electron structure of RuO2 and the adsorption capacities of oxygen-containing intermediates, accelerating charge transfer between them and optimizing the growth pathway of discharge products. Resultantly, the LOBs exhibit a large discharge specific capacity of 19658 mA h g-1 at 200 mA g-1 and extraordinary cycle life of 791 cycles. This study confers the concept of d-band center modulation for efficient and durable cathode catalysts of LOBs.

Layer-Specific Knowledge Distillation for Class Incremental Semantic Segmentation.

Recently, class incremental semantic segmentation (CISS) towards the practical open-world setting has attracted increasing research interest, which is mainly challenged by the well-known issue of catastrophic forgetting. Particularly, knowledge distillation (KD) techniques have been widely studied to alleviate catastrophic forgetting. Despite the promising performance, existing KD-based methods generally use the same distillation schemes for different intermediate layers to transfer old knowledge, while employing manually tuned and fixed trade-off weights to control the effect of KD. These KD-based methods take no consideration of feature characteristics from different intermediate layers, limiting the effectiveness of KD for CISS. In this paper, we propose a layer-specific knowledge distillation (LSKD) method to assign appropriate knowledge schemes and weights for various intermediate layers by considering feature characteristics, aiming to further explore the potential of KD in improving the performance of CISS. Specifically, we present a mask-guided distillation (MD) to alleviate the background shift on semantic features, which performs distillation by masking the features affected by the background. Furthermore, a mask-guided context distillation (MCD) is presented to explore global context information lying in high-level semantic features. Based on them, our LSKD assigns different distillation schemes according to feature characteristics. To adjust the effect of layer-specific distillation adaptively, LSKD introduces a regularized gradient equilibrium method to learn dynamic trade-off weights. Additionally, our LSKD makes an attempt to simultaneously learn distillation schemes and trade-off weights of different layers by developing a bi-level optimization method. Extensive experiments on widely used Pascal VOC 12 and ADE20K show our LSKD clearly outperforms its counterparts while achieving state-of-the-art results.

Effects of the catastrophic 2020 Yangtze River seasonal floods on microcystins and environmental conditions in Three Gorges Reservoir Area, China.

Introduction: During July and August 2020, Three Gorges Reservoir Area (TGRA) suffered from catastrophic seasonal floods. Floods changed environmental conditions and caused increase in concentration of microcystins (MCs) which is a common and potent cyanotoxin. However, the effects and seasonal variations of MCs, cyanobacteria, and environmental conditions in TGRA after the 2020 Yangtze River extreme seasonal floods remain largely unclear, and relevant studies are lacking in the literature. Methods: A total of 12 representative sampling sites were selected to perform concentration measurement of relevant water quality objectives and MCs in the representative area of the TGRA. The sampling period was from July 2020 to October 2021, which included the flood period. Organic membrane filters were used to perform the DNA extraction and analyses of the 16S rRNA microbiome sequencing data. Results: Results showed the seasonal floods result in significant increases in the mean values of microcystin-RR (MCRR), microcystin-YR (MCYR), and microcystin-LR (MCLR) concentration and some water quality objectives (i.e., turbidity) in the hinterland of TGRA compared with that in non-flood periods (p < 0.05). The mean values of some water quality objectives (i.e., total nitrogen (TN), total phosphorus (TP), total dissolved phosphorus (TDP), and turbidity), MC concentration (i.e., MCRR, MCYR, and MCLR), and cyanobacteria abundance (i.e., Cyanobium_PCC-6307 and Planktothrix_NIVA-CYA_15) displayed clear tendency of increasing in summer and autumn and decreasing in winter and spring in the hinterland of TGRA. Discussions: The results suggest that seasonal floods lead to changes in MC concentration and environmental conditions in the hinterland of TGRA. Moreover, the increase in temperature leads to changes in water quality objectives, which may cause water eutrophication. In turn, water eutrophication results in the increase in cyanobacteria abundance and MC concentration. In particular, the increased MC concentration may further contribute to adverse effects on human health.

Structural characterization and anti-oxidant activity of polysaccharide HVP-1 from Volvariella volvacea.

In this study, a novel homogeneous polysaccharide (HVP-1) was purified from the Volvariella volvacea. Its structural characteristics and anti-oxidant activity in vitro were further evaluated. The results revealed that HVP-1 was composed of mannose, glucose, galactose and arabinose in a molar ratio (mol %) of 55.37: 15.74: 25.20: 3.69. Its main chain consisted of →4)-ß-D-Galp-(1→, →6)-α-D-Glcp-(1→, →3)-α-D-Glcp-(1→, →4)-ß-D-Manp-(1→ and →3,6)-ß-D-Manp-(1→. The branched structure α-L-Araf-(1→, →2)-ß-D-Glcp-(1→ and →6)-ß-D-Manp-(1→ were connected to →3,6)-ß-D-Manp-(1→ through the O-3 position. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that HVP-1 had porous sheet-like structure with a triple helix conformation. Anti-oxidant activity experiments showed that HVP-1 alleviated H2O2-induced oxidative damage by reducing the accumulation of reactive oxygen species, increasing the activity of related enzymes in cells, and activating the Nrf2/HO-1 signaling pathway. These results suggested that HVP-1 had the potential to be used as a natural anti-oxidant in functional foods and pharmaceuticals.

Multifunctional Graphene Metasurface for Highly Flexible Control of Microwave Absorption.

Reconfigurable multifunctional electromagnetic absorbers have shown broad application prospects in effectively dealing with a series of problems caused by complex electromagnetic environments due to their dynamic reflection wave control characteristics. In this work, we experimentally propose a multifunctional absorber based on a graphene metasurface. Its absorption mode can be flexibly switched among three modes of dual band, broadband, and single band. The reflection amplitude in each absorption mode can be controlled simultaneously. The measurement results of the prepared graphene metasurface indicate that the absorption modes and amplitudes can be dynamically controlled by changing two independent sets of bias voltages applied to the patterned graphene sandwich structures. The proposed graphene metasurface achieves peak absorption rates above 99.9% in both dual-band and single-band absorption modes. Specifically, in the broadband absorption mode, the bandwidth with an absorption rate greater than 90% reaches 17.8 GHz. In addition, it also integrates many advantages, such as optical transparency, polarization-insensitivity, stability of oblique incidence angles, and conformability to the application targets. Therefore, the proposed graphene metasurface is expected to be applied in platforms with optical windows that require resistance to electromagnetic interference and avoidance of electromagnetic radiation.

The multilevel extensive diversity across the cynomolgus macaque captured by ultra-deep adaptive immune receptor repertoire sequencing.

The extent to which AIRRs differ among and within individuals remains elusive. Via ultra-deep repertoire sequencing of 22 and 25 tissues in three cynomolgus macaques, respectively, we identified 84 and 114 novel IGHV and TRBV alleles, confirming 72 (85.71%) and 100 (87.72%) of them. The heterogeneous V gene usage patterns were influenced, in turn, by genetics, isotype (for BCRs only), tissue group, and tissue. A higher proportion of intragroup shared clones in the intestinal tissues than those in other tissues suggests a close intra-intestinal adaptive immunity network. Significantly higher mutation burdens in the public clones and the inter-tissue shared IgM and IgD clones indicate that they might target the shared antigens. This study reveals the extensive heterogeneity of the AIRRs at various levels and has broad fundamental and clinical implications. The data generated here will serve as an invaluable resource for future studies on adaptive immunity in health and diseases.

Multi-level chemical characterization and anti-inflammatory activity evaluation of the polysaccharides from Prunella vulgaris.

Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76-24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2-14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides. Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 µg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.