Functional trait-based phytoplankton biomass and assemblage analyses in the pre-growing season for comprehensive algal bloom risk assessment.

Algal bloom (AB) risk assessment is critical for maintaining ecosystem health and human sustainability. Previous AB risk assessments have focused on the potential occurrence of ABs and related factors in the growing season, whereas their hazards, especially in the pre-growing season, have attracted less attention. Here, we performed a comprehensive AB risk assessment, including water trophic levels, phytoplankton biomass, functional trait-based assemblages, and related environmental factors, in the pre-growing season in Dongting Lake, China. Although mesotrophic water and low phytoplankton biomass suggested low AB potential, toxic taxa, which constituted 13.28% of the phytoplankton biomass, indicated non-negligible AB hazards. NH4+ and water temperature were key factors affecting phytoplankton motility and toxicity. Our study establishes a new paradigm for quantitative AB risk assessment, including both potential AB occurrence and hazards. We emphasize the importance of phytoplankton functional traits for early AB warning and NH4+ reduction for AB control in the pre-growing season.

Multifunctional nanoparticles for enhanced sonodynamic-chemodynamic immunotherapy with glutathione depletion.

Aim: This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.

The effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis.

BACKGROUND: Anemia associated with heart failure is frequent and can exacerbate the symptoms of heart failure. Dapagliflozin is the first SGLT-2 inhibitor with significant cardiovascular protection. However, the effect of dapagliflozin on anemia in elderly patients with heart failure is unknown. OBJECTIVE: We aimed to study the effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis. METHODS: The target genes were determined, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network and modules were constructed. The dapagliflozin-targets network in anemia and heart failure was constructed. Molecular docking experiments between dapagliflozin and its key target AKT1 were performed. RESULTS: We found 1 dapagliflozin related target gene and 2 disease related genes. Totally, 134 target genes of dapagliflozin on anemia in elderly patients with heart failure were determined. The pathways may involve lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, insulin signaling pathway, fluid shear stress and atherosclerosis, neurotrophin signaling pathway, insulin resistance, toxoplasmosis, colorectal cancer, and EGFR tyrosine kinase inhibitor resistance. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. CONCLUSIONS: The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited.

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats.

THE ETHNOPHARMACOLOGICAL SIGNIFICANCE: Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. AIM OF THE STUDY: In this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. MATERIALS AND METHODS: The effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. RESULTS: GD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. CONCLUSION: The findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.

Accelerating Wound Closure With Metrnl in Normal and Diabetic Mouse Skin.

Impaired wound healing and ulcer complications are major causes of morbidity in patients with diabetes. Impaired wound healing is associated with increased inflammation and poor angiogenesis in diabetes patients. Here, we demonstrate that topical administration of a secreted recombinant protein (Meteorin-like [Metrnl]) accelerates wound epithelialization and angiogenesis in mice. We observed a significant increase in Metrnl expression during physiological wound healing; however, its expression remained low during diabetic wound healing. Functionally, the recombinant protein Metrnl significantly accelerated wound closure in normal and diabetic mice models including db/db, high-fat diet/streptozotocin (HFD/STZ), and STZ mice. Mechanistically, keratinocytes secrete quantities of Metrnl to promote angiogenesis; increase endothelial cell proliferation, migration, and tube formation; and enhance macrophage polarization to the M2 type. Meanwhile, M2 macrophages secrete Metrnl to further stimulate angiogenesis. Moreover, the keratinocyte- and macrophage-produced cytokine Metrnl drives postinjury angiogenesis and reepithelialization through activation of AKT phosphorylation (S473) in a KIT receptor tyrosine kinase (c-Kit)-dependent manner. In conclusion, our study suggests that Metrnl has a biological effect in accelerating wound closure through c-Kit-dependent angiogenesis and epithelialization.

Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage.

Sanguisorba officinalis L., a traditional Chinese medicine, is frequently used to treat burns and scalds. But even so, it is unknown whether S. officinalis L. can accelerate diabetic wounds (DW) healing. Here, to bridge the gap, we employed in vivo and in vitro evaluations to assess the positive effect of S. officinalis L. ethanol extract (ESO) on DW. Results demonstrated that ESO dramatically improved the DW healing rate. With ESO treatment, the inappropriately elevated levels of IL6, IL1ß and TNFα in DW were reduced, while the expression of IL10 was increased, indicating that the abnormal inflammation in DW was also under control. Moreover, the abnormally elevated expression of CD86 was significantly inhibited and the expression of CD206 was significantly up-regulated following treatment with ESO. The global level of NF-κB protein was not affected by ESO treatment, but it suppressed the expression of phosphorylated NF-κB and prevented its nuclear entry. In addition, in RAW264.7 cells activated with lipopolysaccharide (LPS), the expression of NLRP3, Caspase1 and IL1ß were significantly diminished following ESO treatment. In conclusion, ESO was proved to be a promising treatment for DW healing due to its potential to accelerate the healing process by suppressing the inflammatory response. This was achieved by increasing the ratio of M2 to M1 polarization through blocking the NF-κB/NLRP3 signaling pathway.

Quantitative proteomics combined with network pharmacology analysis unveils the biological basis of Schisandrin B in treating diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN. OBJECTIVE: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats. METHODS: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis. RESULTS: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1ß, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified. CONCLUSION: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

COVID-19 vaccine booster dose hesitancy among key groups: A cross-sectional study.

Vaccination is an important tool for controlling the spread of coronavirus disease. Notably, it is important to achieve higher vaccine booster coverage across key groups - including front-line workers who could be exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and those who live and work in crowded places - to prevent or reduce the risk of severe infection and poor disease outcomes. The purpose of the study was to understand the COVID-19 vaccine booster hesitancy among key groups in Luzhou, China, to analyze its influencing factors, and to provide scientific basis and theoretical guidance for the implementation of targeted intervention. Guided by the "3Cs" model, a self-designed questionnaire was prepared through a literature search using the Delphi method. All questionnaires were completed online through a QR code. Among the 548 participants, 173 had vaccine hesitation, accounting for 31.6%. Indeed, the scores for perceived safety, expected vaccine effectiveness, and trust in the vaccine delivery system were all lower in the hesitance group than in the non-hesitance group. However, the scores for low necessity were higher in the hesitance group. The factors influencing booster hesitancy were examined, and the probability of hesitancy decreased by 72.2% and 62.5% for every 1-point increase in the confidence and safety scores, respectively. Meanwhile, the probability of hesitancy increased by 25.8% for every 1-point increase in the low necessity score. Although the COVID-19 vaccine booster hesitancy reported in the study was relatively low, a large gap remains in the willingness to receive COVID-19 vaccination in China. Therefore, the state and relevant departments should take targeted measures to help reduce vaccine hesitancy among the public and enable smooth progress in the large-scale COVID-19 vaccine booster campaign in the future.

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress.

Difficult or even non-healing diabetic foot ulcers (DFU) are a global medical challenge. Although current treatments such as debridement, offloading, and infection control have resulted in partial improvement in DFU, the incidence, amputation, and mortality rates of DFU remain high. Therefore, there is an urgent need to find new or more effective drugs. Numerous studies have shown that oxidative stress plays an important role in the pathophysiology of DFU. The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the advanced glycated end products (AGEs)-receptor for advanced glycation endproducts (RAGE), protein kinase C (PKC), polyol and hexosamine biochemical pathways play critical roles in the regulation of oxidative stress in the body. Targeting these pathways to restore redox balance can control and alleviate the occurrence and development of DFU. Natural biologics are a major source of potential drugs for these relevant targets, and their antioxidant potential has been extensively demonstrated. Here, we discussed the pathophysiological mechanism of oxidative stress in DFU, and identifiled natural biologics targeting these pathways to accelerate DFU healing, in order to provide a new or potential direction for clinical treatment, nursing and related basic research of DFU.

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.

Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.

Comparison between different infiltration models to describe the infiltration of permeable brick pavement system via a laboratory-scale experiment.

The permeable brick pavement system (PBPs) is one of a widely used low impact development (LID) measures to alleviate runoff volume and pollution caused by urbanization. The performance of PBPs on decreasing runoff volume is decided by its permeability, and it was general described by hydraulic conductivity based on Darcy's law. But there is large error when using hydraulic conductivity to describe the infiltration of PBPs, and which infiltration process is not following Darcy's law, so it is important to find more accurate infiltration models to describe the infiltration of PBPs. The Horton, Philip, Green-Ampt, and Kostiakov infiltration models were selected to find an optimal model to investigate infiltration performance of PBPs via a laboratory-scale experiment, and the maximum absolute error (MAE), Bias, and coefficient of determination (R2) were selected to evaluate the models' errors via fitting with experiment data. The results showed that the fitting accuracy of Kostiakov, Philip, and Green-Ampt models was significantly affected by the monitoring area and hydraulic gradients. Meanwhile, Horton model fitted well (MAE = 0.25-0.32 cm/h, Bias = 0.07-0.11 cm/h, and R2 = 0.98-0.99) with the experiment data, and the parameters of the Horton model often can be achieved by monitoring, such as the maximum infiltration rate and the stable infiltration rate. Therefore, the Horton model is an optimal model to describe the infiltration performance of PBPs, which can also be adopted to evaluate hydrological characterization of PBPs.