Antiviral activity of Vigna radiata extract against feline coronavirus in vitro.

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Preparation and Characterization of a Hypoglycemic Complex of Gallic Acid-Antarctic Krill Polypeptide Based on Polylactic Acid-Hydroxyacetic Acid (PLGA) and High-Pressure Microjet Microencapsulation.

Gallic acid-Antarctic krill peptides (GA-AKP) nanocapsules (GA-AKP-Ns) were prepared using a dual delivery system with complex emulsion as the technical method, a high-pressure microjet as the technical means, polylactic acid-hydroxyacetic acid (PLGA) as the drug delivery vehicle, and GA-AKP as the raw material for delivery. This study aimed to investigate the effects of microjet treatment and the concentration of PLGA on the physicochemical properties and stability of the emulsion. Under optimal conditions, the physicochemical properties and hypoglycemic function of nano-microcapsules prepared after lyophilization by the solvent evaporation method were analyzed. Through the microjet treatment, the particle size of the emulsion was reduced, the stability of the emulsion was improved, and the encapsulation rate of GA-AKP was increased. The PLGA at low concentrations decreased the particle size of the emulsion, while PLGA at high concentrations enhanced the encapsulation efficiency of the emulsion. Additionally, favorable results were obtained for emulsion preparation through high-pressure microjet treatment. After three treatment cycles with a PLGA concentration of 20 mg/mL and a microjet pressure of 150 MPa (manometric pressure), the emulsion displayed the smallest particle size (285.1 ± 3.0 nm), the highest encapsulation rates of GA (71.5%) and AKP (85.2%), and optimal physical stability. GA-AKP was uniformly embedded in capsules, which can be slowly released in in vitro environments, and effectively inhibited α-amylase, α-glucosidase, and DPP-IV at different storage temperatures. This study demonstrated that PLGA as a carrier combined with microjet technology can produce excellent microcapsules, especially nano-microcapsules, and these microcapsules effectively improve the bioavailability and effectiveness of bioactive ingredients.

Syringe-assisted test-aspiration with mechanical aspiration thrombectomy results in good safety and short-term outcomes in the treatment of patients with deep venous thrombosis.

OBJECTIVE: To evaluate the short-term outcomes and safety of syringe-assisted test-aspiration with mechanical aspiration thrombectomy in the treatment of deep venous thrombosis. METHODS: This was a single-center, retrospective study of hospitalized patients with iliofemoral and/or inferior vena caval deep venous thrombosis, excluding those with pulmonary embolism. We collected the following patient data from the electronic medical records: age, sex, provoked/unprovoked deep venous thrombosis, symptom duration, thrombosed segments, and the presence of a tumor, thrombophilia, diabetes, and/or iliac vein compression syndrome. Venography and computed tomographic venography were performed in all patients before the procedure. All patients underwent syringe-assisted test-aspiration with mechanical aspiration thrombectomy under local anesthesia and sedation, and all received low-molecular-weight heparin peri-operatively. All patients underwent implantation of an inferior vena caval filter. Rivaroxaban was administered post-procedure, instead of heparin, for 3-6 months, with lower extremity compression. RESULTS: Overall, 29 patients with deep venous thrombosis underwent syringe-assisted test-aspiration with mechanical aspiration thrombectomy from January 2022 to October 2022 in our institution. Technical success (>70% thrombus resolution) was achieved in all patients, and using a single procedure in 25/29 patients (86%). Concomitant stenting was performed in 18/29 (62%) of the patients, and 21/29 (69%) underwent angioplasty. The median (interquartile range) procedure time was 110 min (100-122), the median intra-operative bleeding volume was 150 mL (120-180), and the median decrease in the hemoglobin concentration from pre- to post-operative was 7 g/L (4-14). The median follow-up duration was 7 months (5-9). All patients obtained symptomatic relief, and 27/29 achieved near-remission or full remission (combined total). No patients experienced peri-operative bleeding complications, or symptom recurrence or post-thrombectomy syndrome during follow-up. CONCLUSION: The short-term outcomes following syringe-assisted test-aspiration with mechanical aspiration thrombectomy in the treatment of deep venous thrombosis were excellent, and the procedure was safe.

Engineering stable and non-immunogenic immunoenzymes for cancer therapy via in situ generated prodrugs.

Engineering human enzymes for therapeutic applications is attractive but introducing new amino acids may adversely affect enzyme stability and immunogenicity. Here we used a mammalian membrane-tethered screening system (ECSTASY) to evolve human lysosomal beta-glucuronidase (hBG) to hydrolyze a glucuronide metabolite (SN-38G) of the anticancer drug irinotecan (CPT-11). Three human beta-glucuronidase variants (hBG3, hBG10 and hBG19) with 3, 10 and 19 amino acid substitutions were identified that display up to 40-fold enhanced enzymatic activity, higher stability than E. coli beta-glucuronidase in human serum, and similar pharmacokinetics in mice as wild-type hBG. The hBG variants were two to three orders of magnitude less immunogenic than E. coli beta-glucuronidase in hBG transgenic mice. Intravenous administration of an immunoenzyme (hcc49-hBG10) targeting a sialyl-Tn tumor-associated antigen to mice bearing human colon xenografts significantly enhanced the anticancer activity of CPT-11 as measured by tumor suppression and mouse survival. Our results suggest that genetically-modified human enzymes represent a good alternative to microbially-derived enzymes for therapeutic applications.

Pulmonary Hypertension Induces Serotonin Hyperreactivity and Metabolic Reprogramming in Coronary Arteries via NOX1/4-TRPM2 Signaling Pathway.

BACKGROUND: Clinical evidence revealed abnormal prevalence of coronary artery (CA) disease in patients with pulmonary hypertension (PH). The mechanistic connection between PH and CA disease is unclear. Serotonin (5-hydroxytryptamine), reactive oxygen species, and Ca2+ signaling have been implicated in both PH and CA disease. Our recent study indicates that NOXs (NADPH [nicotinamide adenine dinucleotide phosphate] oxidases) and TRPM2 (transient receptor potential cation channel subfamily M member 2) are key components of their interplay. We hypothesize that activation of the NOX-TRPM2 pathway facilitates the remodeling of CA in PH. METHODS: Left and right CAs from chronic hypoxia and monocrotaline-induced PH rats were collected to study vascular reactivity, gene expression, metabolism, and mitochondrial function. Inhibitors or specific siRNA were used to examine the pathological functions of NOX1/4-TRPM2 in CA smooth muscle cells. RESULTS: Significant CA remodeling and 5-hydroxytryptamine hyperreactivity in the right CA were observed in PH rats. NOX1/4-mediated reactive oxygen species production coupled with TRPM2-mediated Ca2+ influx contributed to 5-hydroxytryptamine hyperresponsiveness. CA smooth muscle cells from chronic hypoxia-PH rats exhibited increased proliferation, migration, apoptosis, and metabolic reprogramming in an NOX1/4-TRPM2-dependent manner. Furthermore, the NOX1/4-TRPM2 pathway participated in mitochondrial dysfunction, involving mitochondrial DNA damage, reactive oxygen species production, elevated mitochondrial membrane potential, mitochondrial Ca2+ accumulation, and mitochondrial fission. In vivo knockdown of NOX1/4 alleviated PH and suppressed CA remodeling in chronic hypoxia rats. CONCLUSIONS: PH triggers an increase in 5-hydroxytryptamine reactivity in the right CA and provokes metabolic reprogramming and mitochondrial disruption in CA smooth muscle cells via NOX1/4-TRPM2 activation. This signaling pathway may play an important role in CA remodeling and CA disease in PH.

Genetic exploration of roles of acid-sensing ion channel subtypes in neurosensory mechanotransduction including proprioception.

Although acid-sensing ion channels (ASICs) are proton-gated ion channels responsible for sensing tissue acidosis, accumulating evidence has shown that ASICs are also involved in neurosensory mechanotransduction. However, in contrast to Piezo ion channels, evidence of ASICs as mechanically gated ion channels has not been found using conventional mechanoclamp approaches. Instead, ASICs are involved in the tether model of mechanotransduction, with the channels gated via tethering elements of extracellular matrix and intracellular cytoskeletons. Methods using substrate deformation-driven neurite stretch and micropipette-guided ultrasound were developed to reveal the roles of ASIC3 and ASIC1a, respectively. Here we summarize the evidence supporting the roles of ASICs in neurosensory mechanotransduction in knockout mouse models of ASIC subtypes and provide insight to further probe their roles in proprioception.

Storage reliability prediction of electromechanical components based on virtual manufacturing and testing.

Electromechanical components (EMCs) such as relays and contactors have been used extensively in industrial and military areas. The storage reliability of these EMCs has a direct impact on the reliability of the system that contains them. However, during the design phase, it is difficult to predict the storage reliability of EMCs because of few failure rate data of parts, as well as limited testing time and budgets. To address these problems, a virtual Manufacturing and testing method is proposed in this paper, so as to simulate the storage degradation process of batch EMCs. By considering the influence of the quality screening process in the manufacturing process, as well as the unit-to-unit variability of EMCs on the storage degradation paths and the overall life distribution of batch products, the storage failure distribution function is obtained, based on Wiener process. At the same time, the distribution of the diffusion coefficient in the degradation model and the failure distribution model is quantified by introducing testing data of related products as priori information, so as to reflect the uncertainty of the storage degradation process of EMCs. A case study of an electromagnetic relay is carried out to illustrate the effectiveness of the proposed approach.

Prediction of extranodal extension in head and neck squamous cell carcinoma by CT images using an evolutionary learning model.

BACKGROUND: Extranodal extension (ENE) in head and neck squamous cell carcinoma (HNSCC) correlates to poor prognoses and influences treatment strategies. Deep learning may yield promising performance of predicting ENE in HNSCC but lack of transparency and interpretability. This work proposes an evolutionary learning method, called EL-ENE, to establish a more interpretable ENE prediction model for aiding clinical diagnosis. METHODS: There were 364 HNSCC patients who underwent neck lymph node (LN) dissection with pre-operative contrast-enhanced computerized tomography images. All the 778 LNs were divided into training and test sets with the ratio 8:2. EL-ENE uses an inheritable bi-objective combinatorial genetic algorithm for optimal feature selection and parameter setting of support vector machine. The diagnostic performances of the ENE prediction model and radiologists were compared using independent test datasets. RESULTS: The EL-ENE model achieved the test accuracy of 80.00%, sensitivity of 81.13%, and specificity of 79.44% for ENE detection. The three radiologists achieved the mean diagnostic accuracy of 70.4%, sensitivity of 75.6%, and specificity of 67.9%. The features of gray-level texture and 3D morphology of LNs played essential roles in predicting ENE. CONCLUSIONS: The EL-ENE method provided an accurate, comprehensible, and robust model to predict ENE in HNSCC with interpretable radiomic features for expanding clinical knowledge. The proposed transparent prediction models are more trustworthy and may increase their acceptance in daily clinical practice.

Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway.

Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased pAMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD.

Assessing traffic-related air pollution-induced fiber-specific white matter degradation associated with motor performance declines in aged rats.

Fine particulate matter (PM2.5) is thought to exacerbate Parkinson's disease (PD) in the elderly, and early detection of PD progression may prevent further irreversible damage. Therefore, we used diffusion tensor imaging (DTI) for probing microstructural changes after late-life chronic traffic-related PM2.5 exposure. Herein, 1.5-year-old Fischer 344 rats were exposed to clean air (control), high-efficiency particulate air (HEPA)-filtered ambient air (HEPA group), and ambient traffic-related PM2.5 (PM2.5 group, 9.933 ± 1.021 µg/m3) for 3 months. Rotarod test, DTI tractographic analysis, and immunohistochemistry were performed in the end of study period. Aged rats exposed to PM2.5 exhibited motor impairment with decreased fractional anisotropy and tyrosine hydroxylase expression in olfactory and nigrostriatal circuits, indicating disrupted white matter integrity and dopaminergic (DA) neuronal loss. Additionally, increased radial diffusivity and lower expression of myelin basic protein in PM2.5 group suggested ageing progression of demyelination exacerbated by PM2.5 exposure. Significant production of tumor necrosis factor-α was also observed after PM2.5 exposure, revealing potential inflammation of injury to multiple fiber tracts of DA pathways. Microstructural changes demonstrated potential links between PM2.5-induced inflammatory white matter demyelination and behavioral performance, with indication of pre-manifestation of DTI-based biomarkers for early detection of PD progression in the elderly.

The balanced unsaturated fatty acid supplement constituted by woody edible oils improved lipid metabolism and gut microbiota in high-fat diet mice.

The dietary intervention has demonstrated effectiveness in improving hyperlipidemia and obesity. Woody edible oils are rich in unsaturated fatty acids (UFAs) that could positively affect lipid metabolism. In this study, the blended oil (BLO), a balanced UFA supplement, constituted by Zanthoxylum bungeanum (Chinese Red Pepper) seed oil, walnut (Juglans regia) oil, camellia (Camema oleifera) seed oil and perilla (Perilla frutescens) seed oil was established referring to the Chinese dietary reference intakes, in which the ratios of monounsaturated/polyunsaturated fatty acids and ω-6/ω-3 polyunsaturated fatty acids were 1:1 and 4:1, respectively. The BLO was administrated to KM mice fed a high-fat diet (HFD) by gavage every day at a dose of 3.0 mL/kg·bw for 10 weeks to assess its effects on serum lipid levels, liver antioxidant activities and gut microbial composition. The results showed that the BLO improved hepatic steatosis, liver oxidative stress, and serum lipid levels. Additionally, there was an increased abundance of Lactobacillus, Allobaculum, and Blautia, along with a decreased abundance of Staphylococcus in cecal contents. These changes were found to be positively correlated with the metabolic improvements, as indicated by Spearman's correlation analysis. These findings implied the practicality of the balanced unsaturated fatty acid consumption in preventing hyperlipidemia and obesity.

A nomogram for predicting the risk of new vertebral compression fracture after percutaneous kyphoplasty.

BACKGROUND: New vertebral compression fractures (NVCFs) are common adverse events in percutaneous kyphoplasty (PKP). The present study aimed to investigate the risk factors for NVCFs in patients after PKP and to construct a nomogram for the prediction of the risk of re-fracture. METHODS: We retrospectively analyzed the medical records of patients after PKP surgery between January 2017 and December 2020. Patients were divided into an NVCF group (n = 225) and a control group (n = 94) based on the presence or absence of NVCFs, respectively, at follow-up within 2 years after surgery. Lasso regression was used to screen for risk factors for re-fracture. Based on the results, a Lasso-logistic regression model was developed, and its prediction performance was evaluated using receiver operating characteristic curves, calibration, and decision curve analysis. The model was visualized, and a nomogram was constructed. RESULTS: A total of eight potential predictors were obtained from Lasso screening. Advanced age, low body mass index, low bone mineral density, lack of anti-osteoporosis treatment, low preoperative vertebral body height, vertebral body height recovery ≥ 2, cement leakage, and shape D (lack of simultaneous contact of bone cement with the upper and lower plates) were included in the logistic regression model. CONCLUSIONS: A nomogram for predicting postoperative NVCF in PKP was developed and validated. This model can be used for rational assessment of the magnitude of the risk of developing NVCFs after PKP, and can help orthopedic surgeons make clinical decisions aimed at reducing the occurrence of NVCFs.

STOP-Bang Questionnaire Is Associated With Aortic Remodeling in Patients With Acute Type B Aortic Dissection Undergoing Standard Thoracic Endovascular Aortic Repair.

PURPOSE: To determine whether the STOP-Bang questionnaire, which is a tool for evaluating obstructive sleep apnea, is associated with aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD). METHODS: Patients with TBAD who underwent standard TEVAR at our center from January 2015 to December 2020 were enrolled. For the included patients, we recorded baseline characteristics, comorbidities, preoperative computed tomographic angiography findings, procedure details, and complications. The STOP-Bang questionnaire was administered to each patient. Total scores comprised points for 4 yes/no questions and 4 clinical measurements. STOP-Bang ≥5 and STOP-Bang <5 groups were then created using the STOP-Bang total scores. We evaluated aortic remodeling 1 year after discharge and the reintervention rate, as well as false lumen complete thrombosis (FLCT) and non-FLCT length. RESULTS: Fifty-five patients were enrolled in the study; STOP-Bang <5, n=36, and STOP-Bang ≥5, n=19. Compared with the STOP-Bang ≥5 group, the STOP-Bang <5 group achieved statistically significantly higher descending aorta positive aortic remodeling (PAR) rates in zones 3 to 5 (zone 3: p=0.002; zone 4: p=0.039; zone 5: p=0.023), higher total descending aorta-PAR rate (66.7% vs 36.8%, respectively; p=0.004), and lower reintervention rate (8.1% vs 38.9%, respectively; p=0.005). In the logistic regression analysis, STOP-Bang ≥5 had an odds ratio of 0.12 (95% confidence interval: 0.03-0.58; p=0.008). There was no significant difference in overall survival between the groups. CONCLUSION: STOP-Bang questionnaire scores were associated with aortic remodeling after TEVAR in patients with TBAD. Increasing the frequency of surveillance after TEVAR might be beneficial in these patients. CLINICAL IMPACT: We analysed aortic remodelling 1 year after thoracic endovascular aortic repair (TEVAR) in acute type B aortic dissection (TBAD) patients with STOP-Bang < 5 and STOP-Bang ≥ 5. Aortic remodelling was better, and the reintervention rate was higher in patients with STOP-Bang < 5 compared with patients with STOP-Bang ≥ 5. In patients with STOP-Bang ≥ 5, aortic remodelling was worse in zones 3-5 compared with zones 6-9. This study suggests that the STOP-Bang questionnaire results is associated with aortic remodelling after TEVAR in patients with TBAD.

Pediatric Cardiac Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

Cardiac lymphoma is rare in children. Treatment typically includes chemotherapy, combination of radiotherapy, or surgery. We report a case of stage IV precursor B lymphoblastic lymphoma with secondary involvement of the heart in an 11-year-old girl who was treated with acute lymphoblastic leukemia-based chemotherapy. Also, we review the literature on this uncommon malignancy.

Study of vacuole glycerate transporter NPF8.4 reveals a new role of photorespiration in C/N balance.

The photorespiratory intermediate glycerate is known to be shuttled between the peroxisome and chloroplast. Here, localization of NPF8.4 in the tonoplast, together with the reduced vacuolar glycerate content displayed by an npf8.4 mutant and the glycerate efflux activity detected in an oocyte expression system, identifies NPF8.4 as a tonoplast glycerate influx transporter. Our study shows that expression of NPF8.4 and most photorespiration-associated genes, as well as the photorespiration rate, is upregulated in response to short-term nitrogen (N) depletion. We report growth retardation and early senescence phenotypes for npf8.4 mutants specifically upon N depletion, suggesting that the NPF8.4-mediated regulatory pathway for sequestering the photorespiratory carbon intermediate glycerate in vacuoles is important to alleviate the impact of an increased C/N ratio under N deficiency. Thus, our study of NPF8.4 reveals a novel role for photorespiration in N flux to cope with short-term N depletion.

Mouse Abdominal Aortic Aneurysm Model Induced by Periarterial Incubation of Papain.

For decades, numerous experimental animal models have been developed to examine the pathophysiologic mechanisms and potential treatments for abdominal aortic aneurysms (AAAs) in diverse species with varying chemical or surgical approaches. This study aimed to create an AAA mouse model by the periarterial incubation with papain, which can mimic human AAA with advantages such as simplicity, convenience, and high efficiency. Eighty C57BL/6J male mice were randomly assigned to 1 of the 4 groups: papain (1.0 or 2.0 mg), porcine pancreatic elastase, and phosphate-buffered solution. The aortic segment was wrapped for 20 minutes, and the diameter was measured using ultrasound preoperatively and postoperative days 7 and 14. Then, the mice were killed for histomorphometric and immunohistochemical analyses. According to ultrasound measurements and histomorphometric analyses, on postoperative day 7, 65% of mice in the 1.0-mg papain group and 60% of mice in the 2.0-mg papain group developed AAA. In both papain groups, 100% of mice developed AAA, and 65% of mice in the porcine pancreatic elastase group developed AAA on postoperative day 14. Furthermore, hematoxylin/eosin, elastin van Gieson, and Masson staining of tissues from the papain group revealed thickened media and intimal hyperplasia, collagen sediments, and elastin destruction, indicating that AAA histochemical alteration was similar to that of humans. In addition, the immunohistochemical analysis was conducted to detect infiltrated inflammatory cells, such as macrophages and leukocytes, in the aortic wall and hyperplasic adventitia. The expression of matrix metalloproteinase 2 and 9 was significantly upregulated in papain and human AAA tissues. Periarterial incubation with 1.0 mg of papain for 20 minutes can successfully create an experimental AAA model in mice for 14 days, which can be used to explore the mechanism and treatment of human AAA.

Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.

Nanomedicines and macromolecular drugs can induce hypersensitivity reactions (HSRs) with symptoms ranging from flushing and breathing difficulties to hypothermia, hypotension, and death in the most severe cases. Because many normal individuals have pre-existing antibodies that bind to poly(ethylene glycol) (PEG), which is often present on the surface of nanomedicines and macromolecular drugs, we examined if and how anti-PEG antibodies induce HSRs to PEGylated liposomal doxorubicin (PLD). Anti-PEG IgG but not anti-PEG IgM induced symptoms of HSRs including hypothermia, altered lung function, and hypotension after PLD administration in C57BL/6 and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Hypothermia was significantly reduced by blocking FcγRII/III, by depleting basophils, monocytes, neutrophils, or mast cells, and by inhibiting secretion of histamine and platelet-activating factor. Anti-PEG IgG also induced hypothermia in mice after administration of other PEGylated liposomes, nanoparticles, or proteins. Humanized anti-PEG IgG promoted binding of PEGylated nanoparticles to human immune cells and induced secretion of histamine from human basophils in the presence of PLD. Anti-PEG IgE could also induce hypersensitivity reactions in mice after administration of PLD. Our results demonstrate an important role for IgG antibodies in induction of HSRs to PEGylated nanomedicines through interaction with Fcγ receptors on innate immune cells and provide a deeper understanding of HSRs to PEGylated nanoparticles and macromolecular drugs that may facilitate development of safer nanomedicines.

Recent Progress in Microencapsulation of Active Peptides-Wall Material, Preparation, and Application: A Review.

Being a natural active substance with a wide variety of sources, easy access, significant curative effect, and high safety, active peptides have gradually become one of the new research directions in food, medicine, agriculture, and other fields in recent years. The technology associated with active peptides is constantly evolving. There are obvious difficulties in the preservation, delivery, and slow release of exposed peptides. Microencapsulation technology can effectively solve these difficulties and improve the utilization rate of active peptides. In this paper, the commonly used materials for embedding active peptides (natural polymer materials, modified polymer materials, and synthetic polymer materials) and embedding technologies are reviewed, with emphasis on four new technologies (microfluidics, microjets, layer-by-layer self-assembly, and yeast cells). Compared with natural materials, modified materials and synthetic polymer materials show higher embedding rates and mechanical strength. The new technology improves the preparation efficiency and embedding rate of microencapsulated peptides and makes the microencapsulated particle size tend to be controllable. In addition, the current application of peptide microcapsules in different fields was also introduced. Selecting active peptides with different functions, using appropriate materials and efficient preparation technology to achieve targeted delivery and slow release of active peptides in the application system, will become the focus of future research.

Motivating Individuals to Take Responsible Ocean Action: The Mediatory Effects of Attitude toward the Ocean.

When considering how to improve public literacy and behavior related to specific themes, top priority is usually given to strategies that enhance relevant knowledge. Fostering attitude comes later. Understanding the mechanisms of behavior may help us develop better policy and educational strategies. However, how knowledge and attitude impact behavior is still under investigation. The aim of this study is to explore the relationships among ocean knowledge, attitude toward the ocean, and the intention to behave responsibly in the marine setting. Specifically, we investigated a potential mediation mechanism by recruiting a total of 266 participants, whose ocean knowledge, attitudes toward the ocean, and intention to behave responsibly were evaluated using questionnaires. The results indicate that a person's attitude toward the ocean may indeed be a mediating factor between ocean knowledge and their intention to show positive marine behavior. In order to engage people in responsible ocean behavior, other forms of assistance from marine policy and education are recommended. Additionally, it would be of interest for future studies to investigate the effects of attitude and attitude-related knowledge in the development of ocean actions.