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Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo . In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.

The constantly mutating SARS-CoV-2 has been infected an increasing number of people, hence the safe and efficacious treatment are urgently needed to combat the COVID-19 pandemic. Currently, neutralizing antibodies (Nabs), targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are potentially effective therapeutics against COVID-19. As a new form of antibody, bispecific single chain antibodies (BscAbs) can be easily expressed in and exhibits broad-spectrum antiviral activity. In this study, we constructed two BscAbs 16-29, 16-3022 and three single chain variable fragments (scFv) S1-16, S2-29 and S3022 as a comparison to explore their antiviral activity against SARS-CoV-2. The affinity of the five antibodies was characterized by ELISA and SPR and the neutralizing activity of them was analyzed using pseudovirus or authentic virus neutralization assay. Bioinformatics and competitive ELISA methods were used to identify different epitopes on RBD. Our results revealed the potent neutralizing activity of two BscAbs 16-29 and 16-3022 against SARS-CoV-2 original strain and Omicron variant infection. In addition, we also found that SARS-CoV RBD-targeted scFv S3022 could play a synergistic role with other SARS-CoV-2 RBD-targeted antibodies to enhance neutralizing activity in the form of a BscAb or in cocktail therapies. This innovative approach offers a promising avenue for the development of subsequent antibody therapies against SARSCoV-2. Combining the advantages of cocktails and single-molecule strategies, BscAb therapy has the potential to be developed as an effective immunotherapeutic for clinical use to mitigate the ongoing pandemic.

Increasing studies have concentrated on investigating circular RNAs (circRNAs) as pivotal regulators in the progression of numerous diseases and biological processes and abundant evidence shows that circRNAs are participated in the regulation of innate immune responses. Several studies showed that Ricin Toxin (RT) could induce inflammatory injury. There was no research on the particular functions and underlying mechanisms of circRNAs in RT-induced inflammation. In this study, RNA sequencing performed on RT-treated and normal RAW264.7 macrophage cells was used to investigated the differentially expressed circRNAs. Based on the dataset, the expression of circEpc1 (mmu_circ_0,000,842) was identified higher in RT-treated cells. Moreover, gain-and-loss function assays showed that circEpc1 function as a promoter in RT-induced inflammation in vivo and in vitro . Mechanistically, circEpc1 acted as a miR-5114 sponge to relieve the suppressive effect of miR-5114 on its target NOD2 and thereby activating NF-κB and MAPK signaling pathways. Our results illuminated a link between RT-induced inflammation and the circEpc1 regulatory loop and provided novel insight into the functions of circRNA in innate immune, which may emerge as a potential target in immunotherapy to control the RT-induced inflammatory injury.

[This corrects the article DOI: 10.3389/fcimb.2023.1155293.].[This corrects the article DOI: 10.3389/fcimb.2023.1155293.].

Ricin toxin binding subunit B (RTB) is a galactose-binding lectin protein derived from the beans of the castor oil plant ( Ricinus communis ). Our previous studies have reported a direct immunomodulatory effect of recombinant RTB, which stimulates RAW264.7 cells to produce cytokines including TNF-α. However, the role of RTB in innate immune response and its specific mechanism have not been reported in detail. In this work, the results showed that RTB treatment of macrophages significantly increased TLR4 protein levels. RTB also activated TLR4 downstream events, including MyD88, IRAK, and TRAF6, resulting in macrophage activation and TNF-α production. This process is reflected in the increase of IκB phosphorylation. TLR4 knockdown macrophages treated with RTB exhibited greatly reduced IκB phosphorylation and TNF-α secretion. Moreover, treatment with MyD88 inhibitor also suppressed TNF-α production. The docking of RT and TLR4 was simulated by computer, and the contact residues were concentrated on RTB. Our results suggest that recombinant RTB can activate mouse macrophages to secrete TNF-α through activation of NF-κB via the TLR4 signaling pathways.

Type 2 diabetes constitutes a serious threat to the health of patients, but there is currently no ideal treatment in the clinic. Glucagon-like peptide-1 and human umbilical cord mesenchymal stem cells have been confirmed to have antidiabetic effects, but both of them have certain defects in the process of antidiabetes, which cannot meet the need of clinical treatment. We hypothesized that human umbilical cord mesenchymal stem cells can be used as a vector to construct a novel cell line that expresses GLP-1 in vivo for a long time. And this cell strain results in lowering blood glucose in type 2 diabetic mice. The results showed that after 3 weeks of intramuscular injection of the new cell line, the fasting blood glucose of type 2 diabetic mice returned to the normal range, and the hypoglycemic effect was maintained within 3 weeks after putting an end to the drug. At the same time, during the administration, the mice lost weight, the food intake decreased, the half-life of GLP-1 in the body prolonged, the IR reduced, and the pancreatic function recovered. The results of this study indicate that the novel cell line can prolong the half-life of GLP-1 in vivo and effectively lower blood sugar, which is a feasible method to improve type 2 diabetes.

Main Problem Glioblastoma (GB) is one of the most prevalent and devastating types of brain cancer for which efficient treatments are currently lacking because of limitations such as antitumor efficacy, brain delivery, tumor selectivity, and drug resistance. A promising strategy to overcome these obstacles is developing anticancer agents that can be delivered to GB tissues to inhibit tumors with low toxicity to normal brain tissue. Methods We developed liposomes encapsulating resveratrol (RES), a polyphenolic compound, and α‐melittin (α‐MEL), which is composed of melittin conjugated with an amphiphilic α‐helical peptide at its N‐terminus. RES‐, α‐MEL‐, and α‐MEL‐RES‐loaded liposomes (Lips) were modified with Angiopep‐2 (ANG). The effects of the above liposomes on GB cells were assessed, and the possible mechanisms were analyzed. Results ANG‐modified α‐MEL‐RES‐Lips treatment facilitated the passage of these agents through the blood–brain barrier (BBB), increased tumor targeting, and significantly reduced α‐MEL‐associated hemolysis. The combined management of α‐MEL with RES impeded GB cell growth and prolonged the lifespan of GB tumor‐bearing model mice. α‐MEL‐RES‐Lips treatment triggered GB cell apoptosis and induced pyroptosis‐associated protein expressions of gasdermin‐D (GSDMD), gasdermin E (GSDME), cleaved caspase 3, and NLR family pyrin domain containing 3 (NLRP3), and inhibited epithelial–mesenchymal transition (EMT) by modulating the Wnt/β‐catenin signaling pathway. Conclusion ANG‐modified α‐MEL‐RES‐Lips might be a potential nanosystem for GB therapy, and polyphenolic compounds combined with antimicrobial peptides may promote the induction of apoptosis, pyroptosis, and the apoptosis–pyroptosis switch in GB. ANG‐modified liposomes encapsulating α‐melittin and resveratrol increase their blood–brain barrier penetration and GB cell selectivity. The combined treatment of α‐melittin with resveratrol markedly facilitates apoptosis and pyroptosis, and promotes the apoptosis–pyroptosis switch in the GB cells via downregulating the Wnt/β‐catenin signaling.

With the rapid advancement of electronic devices toward higher frequencies, faster speeds, increased integration, and miniaturization, the resulting elevated operating temperatures pose significant challenges to the performance and longevity of electronic components. These developments have intensified the demand for high-performance thermal interface materials (TIMs). Conventional silicone rubber-based TIMs often suffer from silicone oil-bleeding and the volatilization of low-molecular-weight siloxanes under elevated temperatures and mechanical stress. The release of these volatile organic compounds can lead to their deposition on circuit boards and electronic components, causing signal interference or distortion in optical and electronic systems, ultimately compromising device functionality. Additionally, the intrinsic thermal conductivity of traditional TIMs is insufficient to meet the escalating demands for efficient heat dissipation. To overcome these limitations, this study introduces a novel, non-silicone TIM based on a calcium ion-crosslinked sodium alginate matrix, prepared via ion-exchange curing. This bio-derived polymer matrix serves as an environmentally benign alternative to silicone rubber. Furthermore, a brush-coating technique is employed to induce the oriented alignment of boron nitride (BN) fillers within the alginate matrix. Experimental characterization reveals that this aligned microstructure markedly enhances the thermal conductivity of the composite, achieving a value of 7.87 W·m−1·K−1. The resulting material also exhibits outstanding thermal and mechanical stability, with no observable leakage or condensate formation under high-temperature and high-pressure conditions. This work offers a new design paradigm for environmentally friendly, high-performance TIMs with considerable potential for advanced electronic and optoelectronic applications.

Purpose This study aims to investigate the mediating role of nutritional status and the inflammatory marker C-reactive protein (CRP) in the relationship between oral frailty and cognitive function in elderly patients with chronic diseases. Methods A cross-sectional design was employed, and From June to December 2024, patients aged ≥ 60 years with chronic diseases from three tertiary hospitals in Henan Province were selected using convenience sampling. Data were collected using questionnaires, including the general information questionnaire, the Oral Frailty Screening Index-8 (OFI-8), the Mini Nutritional Assessment Short Form, the Montreal Cognitive Assessment, and laboratory tests for CRP. Descriptive demographic analysis and Pearson correlation analysis were conducted using SPSS 26.0, and the model 6 in macro program Process 4.1 was employed to test the chain mediation effect. Results (1) Regression analysis showed that oral frailty had a significant direct impact on cognitive function ( β = -0.154, P  < 0.01), and nutritional status ( β  = 0.228, P  < 0.001) and CRP ( β = -0.200, P  < 0.001) also had significant effects on cognitive function. (2) The results of the mediating effect analysis showed that the simple mediating effects of nutritional status and CRP between oral frailty and cognitive function were -0.088 (95% CI : -0.138 to -0.048) and -0.056(95% CI : -0.097 to -0.029), respectively, and the chain mediating effect was - 0.022 (95% CI : -0.040 to -0.010). Conclusion This study found direct and chain-mediated effects of nutritional status and CRP between oral frailty and cognitive function. It suggests that cognitive function can be improved by early identification of oral frailty, improving nutritional status and reducing chronic inflammation levels to delay or even reverse the onset and progression of cognitive dysfunction in elderly patients with chronic diseases.

In the realm of thermal interface materials (TIMs), high thermal conductivity and low density are key for effective thermal management and are particularly vital due to the growing compactness and lightweight nature of electronic devices. Efficient directional arrangement is a key control strategy to significantly improve thermal conductivity and comprehensive properties of thermal interface materials. In the present work, drawing inspiration from natural leaf and branch structures, a simple-to-implement approach for fabricating oriented thermal conductivity composites is introduced. Utilizing carbon fibers (CFs), known for their ultra-high thermal conductivity, as branches, this design ensures robust thermal conduction channels. Concurrently, boron nitride (BN) platelets, characterized by their substantial in-plane thermal conductivity, act as leaves. These components not only support the branches but also serve as junctions in the thermal conduction network. Remarkably, the composite achieves a thermal conductivity of 11.08 W/(m·K) with just an 11.1 wt% CF content and a 1.86 g/cm3 density. This study expands the methodologies for achieving highly oriented configurations of fibrous and flake materials, which provides a new design idea for preparing high-thermal conductivity and low-density thermal interface materials.