Observation of the Therapeutic Effect of Hydrogel Combined with Alginate Dressings for a Patient with Grade 4 Acute Radiation Dermatitis: A Case Report.

ABSTRACT: In this case report, the authors summarize their experience of using hydrogel combined with alginate dressings in the wound care of a patient with grade 4 acute radiation dermatitis. With the combination of hydrogel and alginate dressings, the authors achieved autolytic debridement of the wound and created a moist healing environment to facilitate wound closure. Hydrogel helps the dressing adhere better to the wound bed, ensuring that it does not easily detach during the wound healing process. It also eliminates the need for traditional adhesive tapes for fixation, thus avoiding damage to the fragile skin in the radiation field.The wound gradually decreased in size from an area of 10 × 12 cm, and exudate decreased continuously. The wound completely healed in 20 days with a total of 17 dressing changes. As the wound gradually healed, the patient's psychological burden decreased and comfort level increased. The patient expressed satisfaction and hope for the gradual healing of the wound.Thus, the treatment of severe acute radiation dermatitis with hydrogel combined with alginate dressings yields remarkable results, aligning the noninvasive, low-adhesive, absorbent, conformable, and comfortable attributes of optimized wound care. This experience provides a practical foundation for wound management in acute radiation dermatitis and supports clinical application and promotion of the approach.

A mosquito proboscis-inspired cambered microneedle patch for ophthalmic regional anaesthesia.

INTRODUCTION: One of the methods for pain management involves the use of local anesthesia, which numbs sensations in specific body regions while maintaining consciousness. OBJECTIVES: Considering the certain limitations (e.g., pain, the requirement of skilled professionals, or slow passive diffusion) of conventional delivery methods of local anesthetics, developing alternative strategies that offer minimally invasive yet therapeutically effective delivery systems is of great concern for ophthalmic regional anesthesia. METHODS AND RESULTS: In this study, a rapidly dissolving cambered microneedle (MNs) patch, composed of poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) and served as a delivery system for lidocaine (Lido) in local anesthesia, was developed taking inspiration from the mosquito proboscis's ability to extract blood unnoticed. The lidocaine-containing MNs patch (MNs@Lido) consisted of 25 microneedles with a four-pronged cone structure (height: 500 µm, base width: 275 µm), arranged in a concentric circle pattern on the patch, and displays excellent dissolubility for effective drug delivery of Lido. After confirming good cytocompatibility, MNs@Lido was found to possess adequate rigidity to penetrate the cornea without causing any subsequent injury, and the created corneal pinhole channels completely self-healed within 24 h. Interestingly, MNs@Lido exhibited effective analgesic effects for local anesthesia on both heel skin and eyeball, with the sustained anesthetic effect lasting for at least 30 min. CONCLUSIONS: These findings indicate that the mosquito proboscis-inspired cambered MNs patch provides rapid and painless local anesthesia, overcoming the limitations of conventional delivery methods of local anesthetics, thus opening up new possibilities in the treatment of ophthalmic diseases.

High Hydrophilic and Antibacterial Efficient UV-Curable Silicone-Containing Choline Chloride Quaternary Ammonium Salts Functionalized Materials.

Antibacterial materials with high hydrophobicity have drawbacks such as protein adsorption, bacterial contamination, and biofilm formation, which are responsible for some serious adverse health events. Therefore, antibacterial materials with high hydrophilicity are highly desired. In this paper, UV-curable antibacterial materials are prepared from silicone-containing Choline chloride (ChCl) functionalized hyperbranched quaternary ammonium salts (QAS) and tri-hydroxylethyl acrylate phosphate (TAEP). The materials show high hydrophilic performance because their water contact angle is as low as 19.3°. The materials also exhibit quite high antibacterial efficiency against S. aureus over 95.6%, fairly high transmittance over 90%, and good mechanical performance with tensile strength as high as 6.5 MPa. It reveals that it is a feasible strategy to develop antibacterial materials with low hydrophobicity from silicone-modified ChCl-functionalized hyperbranched QAS.

[Construction of ATMT system of Fusarium oxysporum and evaluation of its promoting effect on Glycyrrhiza uralensis].

This study aims to evaluate the in vivo function of Fusarium oxysporum in Glycyrrhiza uralensis by salt tolerance,indoleacetic acid(IAA) production capacity, phosphate-dissolving capacity, and iron carrier production capacity. The stable genetic transformation system of the F. oxysporum was established by Agrobacterium tumefaciens-mediated genetic transformation( ATMT)technology, and the stability and staining efficiency of transformants were detected by the cloning of the marker gene green fluorescent protein(GFP) and the efficiency of ß-glucuronidase staining(GUS). Efficient and stable transformants were selected for restaining G. uralensis and evaluating its influence on the growth of the G. uralensis seedlings. The results show that F. oxysporum has good salt tolerance and could still grow on potato glucose agar(PDA) medium containing 7% sodium chloride, but the growth rate slows down with the increase in sodium chloride content in PDA medium. F. oxysporum has the function of producing indoleacetic acid, and the concentration of IAA in its fermentation broth is about 3. 32 mg · m L~(-1). In this study, the genetic transformation system of F. oxysporum is successfully constructed, and the ATMT system is efficient and stable. One transformant with both high staining efficiency and genetic stability is selected, and the restaining rate of the transformant in G. uralensis is 76. 92%, which could significantly improve the main root length of one-month-old G. uralensis seedlings and promote the growth and development of G. uralensis seedlings. The results of this study can lay the foundation for the development of biological bacterial fertilizer and the growth regulation of high-quality G. uralensis.

Robust Bi-anchoring carbon dot/BiOCl sheet heterojunction photocatalysts toward superior photocatalytic activity.

BiOCl has attracted much attention due to its robust layered structure, excellent photocatalytic activity and nontoxicity. However, its practical application is hindered by its narrowband UV photoresponse and rapid recombination of photocarriers. Herein, zero-dimensional Bi-anchoring carbon quantum dot (Bi-CD)/two-dimensional BiOCl heterojunction (Bi-CD/BiOCl) photocatalysts are designed and synthesized by a facile hydrothermal method. Under 190-1100 nm broadband light irradiation, the optimized Bi-CD/BiOCl sample exhibits a superb rhodamine B (RhB) degradation rate of nearly 100%, which is 2.3 (1.7) times that of pristine BiOCl (CD/BiOCl). Additionally, the optimized sample exhibits an RhB degradation rate of up to 88.1% even under direct outdoor light and robust durability in water solution. Experimental results combined with DFT calculations reveal that the superior photocatalytic activity arises from the synergetic effects of broader light absorption due to the incorporation of CD, extra hot electron excitation by the localized surface plasmon resonance (LSPR) effect of metallic Bi, and enhanced electron transfer across the heterojunction interface as well as the existence of more oxygen vacancy traps in BiOCl. This work gives insights into the structure and photocatalytic properties of Bi-CD/BiOCl and provides a new strategy for the design and fabrication of robust high-performance photocatalysts under wide spectrum light irradiation.

The causal role of immune cells on lung cancer: a bi-directional Mendelian randomization (MR) study.

Immune cells play a vital role in the development and progression of lung cancer (LC). We aimed to explore the causal role of immune cells in LC with Mendelian randomization (MR) study. Summary statistic data used in the study were obtained from genome-wide association studies (GWAS). A comprehensive two-sample MR was carried out to explore the causal role of 731 immune cell traits (ICTs) in LC, Non-small cell lung cancer (NSCLC), and Small cell lung cancer (SCLC). An inverse-variance weighted (IVW) approach was applied to present the MR estimates. The heterogeneity test was performed using Cochran's Q statistic. MR-Egger intercept test and MR-PRESSO were utilized for the pleiotropy test. MR showed that 15, 31, and 11 ICTs had protective effects on LC, NSCLC, and SCLC, respectively, and 12, 31, and 11 ICTs had adverse effects on LC, NSCLC, and SCLC, respectively. Of note, CD3 on CD28+ CD4+ in the Treg panel could significantly increase the risk of LC, as well as NSCLC and SCLC. Moreover, the MR results revealed that LC was vital in IgD on IgD+ in the B cell panel and NSCLC on CCR2 on CD14- CD16- in the Monocyte panel. Our study revealed multiple close connections between immune cells and LC.

Mother-reliant or self-reliant: the germination strategy of seeds in a species-rich alpine meadow is associated with the existence of pericarps.

BACKGROUND AND AIMS: Some plants germinate their seeds enclosed by a pericarp, whereas others lack the outer packaging. As a maternal tissue, the pericarp might impart seeds with different germination strategies. Plants in a community with different flowering times might separately disperse and germinate their seeds; therefore, flowering time can be considered as one manifestation of maternal effects on the offspring. The mass of the seed is another important factor influencing germination and represents the intrinsic resource of the seed that supports germination. Using seeds from a species-rich alpine meadow located in the Hengduan Mountains of China, a global biodiversity hotspot, we aimed to illustrate whether and how the type of seed (with or without a pericarp) modulates the interaction of flowering time and seed mass with germination. METHODS: Seeds were germinated in generally favourable conditions, and the speed of germination [estimated by mean germination time (MGT)] was calculated. We quantified the maternal conditions by separation of flowering time for 67 species in the meadow, of which 31 produced seeds with pericarps and 36 yielded seeds without pericarps. We also weighed 100 seeds of each species to assess their mass. KEY RESULTS: The MGT varied between the two types of seeds. For seeds with pericarps, MGT was associated with flowering time but not with seed mass. Plants with earlier flowering times in the meadow exhibited more rapid seed germination. For seeds without a pericarp, the MGT depended on seed mass, with smaller seeds germinating more rapidly than larger seeds. CONCLUSIONS: The distinct responses of germination to flowering time and seed mass observed in seeds with and without a pericarp suggest that germination strategies might be mother-reliant for seeds protected by pericarps but self-reliant for those without such protection. This new finding improves our understanding of seed germination by integrating ecologically mediated maternal conditions and inherent genetic properties.

The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

Pore-blocking steric mass-action model for adsorption of bioparticles.

The steric mass-action (SMA) model has been widely reported to describe the adsorption of proteins in different types of chromatographic adsorbents. Here in the present work, a pore-blocking steric mass-action model (PB-SMA) was developed for the adsorption of large-size bioparticles, which usually exhibit the unique pore-blocking characteristic on the adsorbent and thus lead to a fraction of ligands in the deep channels physically inaccessible to bioparticles adsorption, instead of being shielded due to steric hindrance by adsorbed bioparticles. This unique phenomenon was taken into account by introducing an additional parameter, Lin, which is defined as the inaccessible ligand densities in the physically blocked pore area, into the PB-SMA model. This fraction of ligand densities (Lin) will be deducted from the total ligand (Lt) for model development, thus the steric factor (σ) in the proposed PB-SMA will reflect the steric shielding effect on binding sites by adsorbed bioparticles more accurately than the conventional SMA model, which assumes that all ligands on the adsorbent have the same accessibility to the bioparticles. Based on a series of model assumptions, a PB-SMA model was firstly developed for inactivated foot-and-mouth disease virus (iFMDV) adsorption on immobilized metal affinity chromatography (IMAC) adsorbents. Model parameters for static adsorption including equilibrium constant (K), characteristic number of binding sites (n), and steric factor (σ) were determined. Compared with those derived from the conventional SMA model, the σ values derived from the PB-SMA model were dozens of times smaller and much closer to the theoretical maximum number of ligands shielded by a single adsorbed iFMDV, indicating the modified model was more accurate for bioparticles adsorption. The applicability of the PB-SMA model was further validated by the adsorption of hepatitis B surface antigen virus-like particles (HBsAg VLPs) on an ion exchange adsorbent with reasonably improved accuracy. Thus, it is considered that the PB-SMA model would be more accurate in describing the adsorption of bioparticles on different types of chromatographic adsorbents.

Three-Dimensional Cross-Linking Network Coating for the Flame Retardant of Bio-Based Polyamide 56 Fabric by Weak Bonds.

Weak bonds usually make macromolecules stronger; therefore, they are often used to enhance the mechanical strength of polymers. Not enough studies have been reported on the use of weak bonds in flame retardants. A water-soluble polyelectrolyte complex composed of polyethyleneimine (PEI), sodium tripolyphosphate (STPP) and melamine (MEL) was designed and utilized to treat bio-based polyamide 56 (PA56) by a simple three-step process. It was found that weak bonds cross-linked the three compounds to a 3D network structure with MEL on the surface of the coating under mild conditions. The thermal stability and flame retardancy of PA56 fabrics were improved by the controlled coating without losing their mechanical properties. After washing 50 times, PA56 still kept good flame retardancy. The cross-linking network structure of the flame retardant enhanced both the thermal stability and durability of the fabric. STPP acted as a catalyst for the breakage of the PA56 molecular chain, PEI facilitated the char formation and MEL released non-combustible gases. The synergistic effect of all compounds was exploited by using weak bonds. This simple method of developing structures with 3D cross-linking using weak bonds provides a new strategy for the preparation of low-cost and environmentally friendly flame retardants.

Discovery of novel positive allosteric modulators targeting GluN1/2A NMDARs as anti-stroke therapeutic agents.

Excitotoxicity due to excessive activation of NMDARs is one of the main mechanisms of neuronal death during ischemic stroke. Previous studies have suggested that activation of either synaptic or extrasynaptic GluN2B-containing NMDARs results in neuronal damage, whereas activation of GluN2A-containing NMDARs promotes neuronal survival against ischemic insults. This study applied a systematic in silico, in vitro, and in vivo approach to the discovery of novel and potential GluN1/2A NMDAR positive allosteric modulators (PAMs). Ten compounds were obtained and identified as potential GluN1/2A PAMs by structure-based virtual screening and calcium imaging. The neuroprotective activity of the candidate compounds was demonstrated in vitro. Subsequently, compound 15 (aegeline) was tested further in the model of transient middle cerebral artery occlusion (tMCAO) in vivo, which significantly decreased cerebral infarction. The mechanism by which aegeline exerts its effect on allosteric modulation was revealed using molecular dynamics simulations. Finally, we found that the neuroprotective effect of aegeline was significantly correlated with the enhanced phosphorylation of cAMP response element-binding protein (CREB). Our study discovered the neuroprotective effect of aegeline as a novel PAM targeting GluN1/2A NMDAR, which provides a potential opportunity for the development of therapeutic agents for ischemic stroke.

Effect of thoracic paravertebral nerve block on delirium in patients after video-assisted thoracoscopic surgery: a systematic review and meta-analysis of randomized controlled trials.

Background: Nerve blocks are widely used in various surgeries to alleviate postoperative pain and promote recovery. However, the impact of nerve block on delirium remains contentious. This study aims to systematically evaluate the influence of Thoracic Paravertebral Nerve Block (TPVB) on the incidence of delirium in patients post Video-Assisted Thoracoscopic Surgery (VATS). Methods: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases in June 2023. The search strategy combined free-text and Medical Subject Headings (MeSH) terms, including perioperative cognitive dysfunction, delirium, postoperative cognitive dysfunction, paravertebral nerve block, thoracic surgery, lung surgery, pulmonary surgery, and esophageal/esophagus surgery. We utilized a random effects model for the analysis and synthesis of effect sizes. Results: We included a total of 9 RCTs involving 1,123 participants in our study. In VATS, TPVB significantly reduced the incidence of delirium on postoperative day three (log(OR): -0.62, 95% CI [-1.05, -0.18], p = 0.01, I2 = 0.00%) and postoperative day seven (log(OR): -0.94, 95% CI [-1.39, -0.49], p < 0.001, I2 = 0.00%). Additionally, our study indicates the effectiveness of TPVB in postoperative pain relief (g: -0.82, 95% CI [-1.15, -0.49], p < 0.001, I2 = 72.60%). Conclusion: The comprehensive results suggest that in patients undergoing VATS, TPVB significantly reduces the incidence of delirium and notably diminishes pain scores. Systematic review registration: CRD42023435528. https://www.crd.york.ac.uk/PROSPERO.

Effect of quality nursing intervention on wound healing in patients with burns: A meta-analysis.

This meta-analysis aimed to explore the effects of quality nursing intervention on wound healing in patients with burns. A computerised search was conducted for randomised controlled trials (RCTs) on the effect of quality nursing intervention on wound healing in patients with burns in the PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from the date of database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on the inclusion and exclusion criteria. Stata 17.0 software was used for the data analysis. Twenty-nine RCTs involving 2637 patients with burns were included. The meta-analysis revealed that compared with conventional nursing, the implementation of quality nursing intervention in patients with burns significantly shortened the wound healing time (standardised mean difference [SMD] = -2.93, 95% confidence interval [CI]: -3.44 to -2.42, p < 0.001). The incidence of wound infections (odds ratio [OR] = 0.14, 95% CI: 0.07-0.27, p < 0.001) and complications (OR = 0.16, 95% CI: 0.11-0.23, p < 0.001) was also reduced significantly. This meta-analysis shows that applying quality nursing interventions in patients with burns can significantly shorten the wound healing time and reduce the incidence of wound infection and complications, thus promoting early patient recovery.

Anesthesia, Anesthetics, and Postoperative Cognitive Dysfunction in Elderly Patients.

Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients.

CT Image-Based Radiomic Analysis for Detecting PD-L1 Expression Status in Bladder Cancer Patients.

RATIONALE AND OBJECTIVES: The role of Programmed death-ligand 1 (PD-L1) expression is crucial in guiding immunotherapy selection. This study aims to develop and evaluate a radiomic model, leveraging Computed Tomography (CT) imaging, with the objective of predicting PD-L1 expression status in patients afflicted with bladder cancer. MATERIALS AND METHODS: The study encompassed 183 subjects diagnosed with histologically confirmed bladder cancer, among which the PD-L1(+) cohort constituted 60.1% of the total population. Stratified random sampling was utilized at a 7:3 ratio. We employed five diverse machine learning algorithms-Decision Tree, Random Forest, Linear Support Vector Classification, Support Vector Machine, and Logistic Regression-to establish radiomic models on the training dataset. These models endeavored to predict PD-L1 expression status premised on radiomic features derived from region-of-interest segmentation. Subsequent to this, the predictive performance of these models was examined on a validation set employing the receiver operating characteristic (ROC) curve. The DeLong test was utilized to contrast ROC curves, thereby pinpointing the model with superior predictive accuracy. RESULTS: 16 features were chosen for the model construction. All five models revealed strong performance in the training set (AUC, 0.920-1) and commendable predictive ability in the validation set (AUC, 0.753-0.766). As per the DeLong test, no statistically significant disparities were observed among any of the models (P > 0.05) in the validation set. Additional verification through the calibration curve and decision curve analysis indicated that the Logistic Regression model exhibited extraordinary precision and practicality. CONCLUSION: Our machine learning model, grounded on radiomic features, demonstrated its proficiency in accurately distinguishing bladder cancer patients with high PD-L1 expression. Future research, incorporating more exhaustive datasets, could potentially augment the predictive efficiency of radiomic algorithms, thereby advancing their clinical utility.

Functional outcome following spontaneous intracerebral hemorrhage between ultrasound guidance endoscopic surgery and conventional craniotomy: A retrospective population-based study.

OBJECTIVES: Ultrasound guidance endoscopic surgery (ES) has been widely used in the treatment of cerebral hemorrhage in recent years, but relevant research articles are still scarce. Our study aims to investigate the effect of ES compared with conventional craniotomy (CC) on the postoperative complications, and prognosis of patients with intracerebral hemorrhage. MATERIALS AND METHODS: The clinical data of 1201 patients with ICH treated in our hospital from January 2017 to January 2020 were collected. The t-test, Chi-squared test and Fisher's exact test were used to analyze the clinical baseline data. Among 1021 spontaneous ICH patients, 193 patients who underwent hematoma evacuation were included in the present analysis. RESULTS: The Glasgow Outcome Scale (GOS) score at 6 months had a favorable prognosis in ES group (p = 0.003). ES group had fewer postoperative complications compared with CC group. Operating time and intraoperative blood loss were significantly lower in ES group than CC group (p = 0.001 and p = 0.002). CONCLUSIONS: Our study revealed that receiving ES improved the prognosis of ICH patients. Additionally, endoscopic surgery diminishes operative time, and intraoperative blood loss and reduces the incidence of postoperative complications.

Engineering the Sulfide Semiconductor/Photoinactive-MOF Heterostructure with a Hollow Cuboctahedral Structure to Enhance Photocatalytic CO2-Epoxide-Cycloaddition Efficiency.

Providing efficient electronic transport channels has always been a promising strategy to mitigate the recombination of photogenerated charge carriers. In this study, a heterostructure composed of a semiconductor/photoinactive-metal-organic framework (MOF) was constructed to provide innovative channels for electronic transport. Prepared using a previously reported method ( Angew. Chem., Int. Ed. 2016, 55, 15301-15305) with slight modifications to temperature and reaction time, the CuS@HKUST-1 hollow cuboctahedron was synthesized. The CuS@HKUST-1 heterostructure possessed a well-defined cuboctahedral morphology with a uniform size of about 500 nm and a hollow structure with a thickness of around 50 nm. The CuS nanoparticles were uniformly distributed on the HKUST-1 shell. Structural characterization in cooperation with density functional theory (DFT) calculations revealed that CuS can effectively transfer photogenerated electrons to HKUST-1. CuS@HKUST-1 hollow cuboctahedrons were first introduced to the photocatalytic cycloaddition reaction of CO2 with epoxides, demonstrating excellent photocatalytic activity and stability at mild conditions (room temperature, solvent-free, and 1 atm CO2 pressure). The high photocatalytic performance of the CuS@HKUST-1 hollow cuboctahedron could be attributed to (1) the unique hollow cuboctahedron morphology, which provided a large specific surface area (693.1 m2/g) and facilitated the diffusion and transfer of reactants and products; and (2) CuS@HKUST-1 providing electronic transport channels from CuS to HKUST-1, which could enhance the adsorption and activation of CO2. Cu2+ carrying surplus electrons can activate CO2 to CO2-. The charge separation and transfer in the photocatalytic process can also be effectively promoted. This work provides a cost-effective and environmentally friendly approach for CO2 utilization reactions under ambient conditions, addressing the critical issue of rising atmospheric CO2 levels.

Achieving highly efficient 2D SnC monolayer-based photocatalyst for water splitting via a synergistic strategy of S-scheme heterostructure construction and silicon doping.

Owing to its stable graphene-like honeycomb structure, suitable band gap, and nontoxicity, SnC monolayer (ML) has attracted increasing attention in photocatalytic applications. One pertinent obstacle inherent to SnC ML-based photocatalysts has been the high energy barrier in hydrogen evolution reaction (HER) that always requires external energy input and/or strongly acidic conditions. Herein, we propose a two-dimensional (2D) SnC/ZrS2 van der Waals heterostructure (vdWHS) for highly efficient photocatalytic water splitting using first-principles calculations. The results show that the pristine vdWHS is an S-scheme heterostructure that works in acidic conditions for water splitting owing to the high energy barrier in HER. Notably, detailed further investigations show that doping Si in the SnC ML of the vdWHS can solve this high barrier problem, leading to a high-performance low-cost photocatalyst. Our work offers a convenient strategy to solve the notorious high barrier problem in HER that often troubles the SnC ML and other 2D materials such as transition metal dichalcogenide MLs for the design and fabrication of highly efficient photocatalysts.

In situ bio-mineralized Mn nanoadjuvant enhances anti-influenza immunity of recombinant virus-like particle vaccines.

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist Mn3O4 inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating. Such inside Mn3O4 immunostimulator-outside rHA antigen design, together with the chimeric M2e antigen on the HBc skeleton, enabled the synthesized hybrid nanovaccines THM-HA@Mn to well imitate the spatial distribution of M2e/HA antigens and immunostimulant in natural influenza virus. In vitro cellular experiments indicated that compared with the THM-HA antigen without Mn3O4 and a mixture vaccine consisting of THM-HA + MnOx, the THM-HA@Mn hybrid nanovaccines showed the highest efficacies in dendritic cells uptake and in promoting BMDC maturation, as well as inducing expression of TNF-α and type I interferon IFN-ß. The THM-HA@Mn also displayed the most sustained antigen release at the injection site, the highest efficacies in promoting the DC maturation in lymph nodes and germinal center B cells activation in the spleen of the immunized mice. The co-delivery of immunostimulant and antigens enabled the THM-HA@Mn nanovaccines to induce the highest systemic antigen-specific antibody responses and cellular immunogenicity in mice. Together with the excellent colloid dispersion stability, low cytotoxicity, as well as good biosafety, the synthetic hybrid nanovaccines presented in this study offers a promising strategy to design VLP-based vaccine with robust natural and adaptive immunogenicity against emerging viral pathogens.

The µ-opioid receptor-mediated Gi/o protein and ß-arrestin2 signaling pathways both contribute to morphine-induced side effects.

The µ-opioid receptor-biased agonist theory holds that Gio protein signaling mediates the analgesic effect of opioids and the related side effects via the ß-arrestin2 signaling pathway. A series of µ-opioid-biased agonists have been developed in accordance with this theory, and the FDA has approved TRV130 (as a representative of biased agonists) for marketing. However, several reports have raised the issue of opioid side effects associated with the use of agonists. In this study, five permeable peptides were designed to emulate 11 S/T phosphorylation sites at the µ-opioid receptor (MOR) carboxyl-terminal. In vitro experiments were performed to detect the activation level of G proteins from the cAMP inhibition assay and the ß-arrestin2 recruitment by the BRET assay. Designed peptides might effectively interfere with the activation of the Gio and ß-arrestin2 pathways when combined with morphine. The resulting morphine-induced tolerance, respiratory inhibition, and constipation in mice showed that the ß-arrestin2 pathway was responsible for morphine tolerance while the Gio signaling pathway was involved with respiratory depression and constipation and that these side effects were significantly related to phosphorylation sites S363 and T370. This study may provide new directions for the development of safer and more effective opioid analgesics, and the designed peptides may be an effective tool for exploring the mechanism by which µ-opioid receptors function, with the potential of reducing the side effects that are associated with clinical opioid treatment.