Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation.

Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy.

A Biomimic Nanobullet with Ameliorative Inflammatory Microenvironment for Alzheimer's Disease Treatments.

Aß oligomers, formed prior to diagnostic marker-amyloid ß (Aß) plaques, can damage neurons and trigger neuroinflammation, which accelerate the neuronal injury in Alzheimer's disease (AD). Herein, the combination of eliminating the Aß oligomers and alleviating the inflammation is a promising therapeutic strategy for AD. However, the presence of the blood-brain barrier (BBB) and the intrinsic deficiencies of the drugs severely restrict their therapeutic effects. Inspired by the properties of rabies virus, a biomimic nanobullet (PBACR@NRs/SA) targeting neurons has been developed. The biomimic nanobullets possess the BBB penetrating character based on iron oxide nanorods; it can sequentially release rosmarinic acid and small interfering RNA targeting NF-κB triggered by microenvironment, which improve the microenvironment inflammation and realize the cure for AD. Compared with non-biomimic systems, the biomimic nanobullets exhibit a less caveolin-dependent internalization pathway, which reduces ROS production and mitochondrial fission in neurons. Therefore, the biomimic nanobullet is hopeful for the treatment of ADs and provides a promising platform for other brain diseases' treatments.

Effects of the Fibrous Root of Polygonatum cyrtonema Hua on Growth Performance, Meat Quality, Immunity, Antioxidant Capacity, and Intestinal Morphology of White-Feathered Broilers.

This study was designed to evaluate the effects of different doses of the fibrous roots of Polygonatum cyrtonema Hua on the growth performance, slaughter parameters, meat quality, immune function, cytokines, antioxidant capacity, and intestinal morphology of white-feathered broilers. Also, the mechanism to improve immune functions of broilers was explored through network pharmacology and molecular docking technology. A total of 360 AA-white-feathered broilers were randomly divided into six groups (not separated by sex), with six repetitions per group (n = 10). The groups were as follows: basal diet (CON group), basal diet supplemented with 300 mg/kg aureomycin (ANT group), basal diet supplemented with 2%, 3%, and 4% fibrous root raw powder (LD, MD, and HD group), or basal diet supplemented with 3% fibrous root processed powder (PR group), in a 42-day experiment. The dietary inclusion of P. cyrtonema fibrous roots increased slaughter performance (p < 0.05), reduced the fat rate (p < 0.05), improved intestinal morphology (p < 0.05), and improved the immune organ index to varying degrees. It also significantly improved pH reduction, drip loss, and pressure loss of breast muscle and leg muscle (p < 0.05). Furthermore, it significantly improved immune and antioxidant functions including decreased MDA content of serum (p < 0.01), increased GSH-Px content (p < 0.01), IgG, IgA, and C4 contents (p < 0.05), and increased expression of IL-2 and IFN-γ (p < 0.01). Additionally, the mechanism by which fibrous roots improve immune function in broilers was explored using network pharmacology and molecular docking technology. Network pharmacology and molecular docking revealed that flavonoids such as baicalein, 4',5-Dihydroxyflavone, 5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, and 5,7-dihydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-6,8-dimethyl-chroman-4-one were key components that enhanced immune function through the MAPK1 and other key targets involved in regulating the MAPK signaling pathway. From the findings, it can be concluded that incorporating P. cyrtonema Hua fibrous root as a natural feed supplement and growth promoter in broiler diets had a positive impact on bird health and performance.

Engineered Extracellular Vesicles for Delivery of an IL-1 Receptor Antagonist Promote Targeted Repair of Retinal Degeneration.

Retinal degeneration (RD) is an irreversible blinding disease that seriously affects patients' daily activities and mental health. Targeting hyperactivated microglia and regulating polarization are promising strategies for treating the disease. Mesenchymal stem cell (MSC) transplantation is proven to be an effective treatment due to its immunomodulatory and regenerative properties. However, the low efficiency of cell migration and integration of MSCs remains a major obstacle to clinical use. The goal of this study is to develop a nanodelivery system that targets hyperactivated microglia and inhibits their release of proinflammatory factors, to achieve durable neuroprotection. This approach is to engineer extracellular vesicles (EVs) isolated from MSC, modify them with a cyclic RGD (cRGD) peptide on their surface, and load them with an antagonist of the IL-1 receptor, anakinra. Comparing with non-engineered EVs, it is observed that engineered cRGD-EVs exhibit an increased targeting efficiency against hyperactivated microglia and strongly protected photoreceptors in experimental RD cells and animal models. This study provides a strategy to improve drug delivery to degenerated retinas and offers a promising approach to improve the treatment of RD through targeted modulation of the immune microenvironment via engineered cRGD-EVs.

Identifying TNF and IL6 as potential hub genes and targeted drugs associated with scleritis: A bio-informative report.

Background: Scleritis is a serious inflammatory eye disease that can lead to blindness. The etiology and pathogenesis of scleritis remain unclear, and increasing evidence indicates that some specific genes and proteins are involved. This study aimed to identify pivotal genes and drug targets for scleritis, thus providing new directions for the treatment of this disease. Methods: We screened candidate genes and proteins associated with scleritis by text-mining the PubMed database using Python, and assessed their functions by using the DAVID database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the functional enrichment of these genes and proteins. Then, the hub genes were identified with CytoHubba and assessed by protein-protein interaction (PPI) network analysis. And the serum from patients with active scleritis and healthy subjects were used for the validation of hub genes. Finally, the DGIdb database was used to predict targeted drugs for the hub genes for treating scleritis. Results: A total of 56 genes and proteins were found to be linked to scleritis, and 65 significantly altered pathways were identified in the KEGG analysis (FDR < 0.05). Most of the top five pathways involved the categories "Rheumatoid arthritis," "Inflammatory bowel disease", "Type I diabetes mellitus," and "Graft-versus-host disease". TNF and IL6 were considered to be the top 2 hub genes through CytoHubba. Based on our serum samples, hub genes are expressed at high levels in active scleritis. Five scleritis-targeting drugs were found among 88 identified drugs. Conclusions: This study provides key genes and drug targets related to scleritis through bioinformatics analysis. TNF and IL6 are considered key mediators and possible drug targets of scleritis. Five drug candidates may play an important role in the diagnosis and treatment of scleritis in the future, which is worthy of the further experimental and clinical study.

Nucleic acid drug vectors for diagnosis and treatment of brain diseases.

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.

Does similarity trigger cooperation? Dyadic effect of similarity in social value orientation and cognitive resources on cooperation.

Although a considerable amount of research has demonstrated a robust relationship between social value orientation and cooperation, these studies may be limited by focusing solely on the individual. Building on the growing literature documenting the effect of group formation on cooperation and personality similarity on negotiation, the present study explored whether similarity in social value orientation (both being pro-social or pro-self) leads to more cooperation in social dilemmas among dyad members. Drawing from expectancy theory and the concept of cognitive resources, we further predicted that the relationship between similarity in social value orientation and cooperation uniquely depends on whether the individual is cognitively busy. To test our hypothesis, we grouped our participants according to their social value orientation into three different dyads (similar-pro-self, similar-pro-social, and pro-self-pro-social) to complete a repeated prisoner's dilemma task, and controlled their cognitive resources using a simultaneous digit memory task. The results suggested that (1) heterogeneous dyads' (pro-self-pro-social) cooperation possibility experience a steeper decay as the number of rounds increases compared with the two homogeneous dyads (similar-pro-self, similar-pro-social). In addition, (2) similarity in social value orientation, interacting with participants' cognitive resources, significantly influenced individual-level cooperation. Specifically, both pro-selfs and pro-socials, paired with unlike-minded counterparts, were more cooperative when they had abundant cognitive resources. However, cognitive resources had no significant influence on dyads with similar social value orientation. Overall, these findings demonstrate the importance of considering personality configuration when attempting to understand cooperation in social dilemmas among dyads. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03276-8.

Numb deficiency impairs retinal structure and visual function in mice.

PURPOSE: Numb is expressed in the progenitor and mature neurons throughout the development progress of the retina. We attempted to investigate the role of Numb in the retina and visual system, and the effects of Numb deficiency on retinal structure and visual function. METHODS: Conditional Numb/Nbl double-knockout mice were generated to observe the retinal damage in Numb deficiency mice. HE staining and immunofluorescence stain were used to observe the structural and molecular changes. The visual function was assessed by electroretinogram (ERG) and optomotor response (OMR). RNA-Seq and RT-PCR were used to detect the differential expression of genes and the related signaling pathways. RESULTS: Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment observed by HE staining and immunofluorescence stain. The impaired retinal structure and visual function were assessed by ERG and OMR. RNA-seq analysis indicated loss of photoreceptors, synapses and phototransduction related molecules. Immunofluorescence stain of molecular markers recoverin, arrestin, rhodopsin showed disrupted structural integrity of photoreceptors. Additional bipolar cells and synapses related molecular markers indicate synaptic connections were damaged in Numb deficiency mice. CONCLUSIONS: Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment. Ablation of Numb in retina significantly impaired visual function. The impaired visual function in Numb deficiency mice is related to the damage of photoreceptors, ion/cation channel activity, synapse formation and phototransduction.

The Effect of Work Connectivity Behavior After-Hours on Employee Psychological Distress: The Role of Leader Workaholism and Work-to-Family Conflict.

Background: The work connectivity behavior after-hours (WCBA) has become increasingly intense among Chinese employees in recent years, especially in the rapidly developed internet industry. This has made the after-hours work connectivity behavior, a popular topic in the organizational psychology field. Based on boundary theory, we explored the mechanism of after-hour work connectivity behavior on employees' psychological distress and identified the work-to-family conflict (WFC) as mediator. Besides, leader characteristics are essential environmental variables and always play as moderators, among which leader workaholism is prevalent in the internet industry. However, the impact of leader workaholism on employees' behavior is still inconsistent and even contradictory. Thus, this study further examines the moderating effect of leader workaholism between the after-hour work connectivity behavior and employees' psychological distress. Methods: We conducted a multitime, multisource questionnaire survey in Internet companies in China. Before collecting the data, all participants were assured that their responses would be confidential and used only for academic research. At time 1, the team leader rated his or her workaholism, and team members rated WCBA. At time 2 (3 weeks later), team members were asked to complete the questionnaire containing scales of WFC, psychological distress. The two rounds of data collection resulted in 211 matched team leader-team member responses. We performed a path analysis using Mplus 7.4. Results: Both the duration and frequency of WCBA can positively predict employees' psychological distress through WFC (the mediating effect = 0.628, 95% CI = [0.593, 0.663]). Specifically, WCBA can increase the level of WFC, which leads to the employees' psychological distress further. Leader workaholism can negatively moderate the relationship between WCBA and WFC, further moderating the mediating effect of WFC. Conclusions: Work-to-family conflict played as a mediator in the relationship between WCBA and employees' psychological distress. These results may be helpful to recognize the negative effect of WCBA and the role of leader workaholism in the relationship.

Effects of Kadsura coccinea L. Fruit Extract on Growth Performance, Meat Quality, Immunity, Antioxidant, Intestinal Morphology and Flora of White-Feathered Broilers.

This study aimed to determine whether adding Kadsura coccinea fruit extract to the diet of broilers could replace antibiotics. For this study, 300 one-day-old AA white feathered broilers were divided into five groups (no sex separated), with six repetitions per group (n = 10), as follows: blank control group (basal feed, CK group), positive drug (basal feed + 300 mg/kg aureomycin, PD group), and Kadsura coccinea low-dose, medium-dose, and high-dose groups (basal feed + 100 mg/kg, 200 mg/kg, and 300 mg/kg of Kadsura coccinea fruit extract, LD group, MD group and HD group). The experiment period was divided into early (1−21 days) and late (22−42 days) stage. We found that supplementation with Kadsura coccinea fruit extract in the diet significantly improved the growth performance of broilers (p < 0.05), reduced the feed to meat ratio (p < 0.05), reduced the fat percentage (p < 0.05), while had no significant effect on meat quality (p > 0.05) and Kadsura coccinea fruit extract could promote the development of immune organs to different extents, enhance antioxidant capacity, the contents of SOD and GSH-Px in serum were significantly increased (p < 0.05), improve the ratio of villus height to crypt depth. Finally, Kadsura coccinea fruit extract increased the relative abundance of probiotics and beneficial bacteria (Bacteroidales, NK4A214, Subdoligranulum and Eubacterium hallii) (p < 0.05) and reduced the relative abundance of harmful bacteria (Erysipelatoclostridium) (p < 0.05) in the gut of broilers. Compared with positive drug group, most of the indexes in the medium-dose group were better or had similar effects. We believe that Kadsura coccinea fruit extract can be used as a potential natural antibiotic substitute in livestock and poultry breeding programs.

Charge-switchable zwitterionic polycarboxybetaine particle as an intestinal permeation enhancer for efficient oral insulin delivery.

Insulin, a peptide hormone, is one of the most common and effective antidiabetic drugs. Although oral administration is considered to be the most convenient and safe choice for patients, the oral bioavailability of insulin is very low due to the poor oral absorption into blood circulation. Intestinal epithelium is a major barrier for the oral absorption of insulin. Therefore, it is vital to develop intestinal permeation enhancer to increase the antidiabetic efficacy of insulin after oral administration. Methods: Charge-switchable zwitterionic polycarboxybetaine (PCB) was used to load insulin to form PCB/insulin (PCB/INS) particles through the electrostatic interaction between positively charged PCB in pH 5.0 and negatively charged insulin in 0.01 M NaOH. The opening effect of PCB/INS particles on intestinal epithelium was evaluated by detecting the changes of claudin-4 (CLDN4) protein and transepithelial electrical resistance (TEER) after incubation or removal. The mechanism was further elucidated based on the results of Western blot and fluorescence images. The PCB/INS particles were then used for type 1 diabetes mellitus therapy after oral administration. Results: PCB could load insulin with the loading efficiency above 86% at weight ratio of 8:1. PCB/INS particles achieved sustained release of insulin at pH 7.4 due to their charge-switchable ability. Surprisingly, PCB/INS particles induced the open of the tight junctions of intestinal epithelium in endocytosis-mediated lysosomal degradation pathway, which resulted in increased intestinal permeability of insulin. Additionally, the opening effect of PCB/INS particles was reversible, and the decreased expression of CLDN4 protein and TEER values were gradually recovered after particles removal. In streptozotocin-induced type 1 diabetic rats, oral administration of PCB/INS particles with diameter sub-200 nm, especially in capsules, significantly enhanced the bioavailability of insulin and achieved longer duration of hypoglycemic effect than the subcutaneously injected insulin. Importantly, there was no endotoxin and pathological change during treatment, indicating that PCB/INS particles were safe enough for in vivo application. Conclusion: These findings indicate that this system can provide a platform for oral insulin and other protein drugs delivery.

Advances of Nanoparticles for Leukemia Treatment.

Leukemia is a liquid tumor caused by a hematopoietic stem cell malignant clone, which seriously affects the normal function of the hematopoietic system. Conventional drugs have poor therapeutic effects due to their poor specificity and stability. With the development of nanotechnology, nonviral nanoparticles bring hope for the efficient treatment of leukemia. Nanoparticles are easily modified. They can be designed to target lesion sites and control drug release. Thereby, nanoparticles can improve the effects of drugs and reduce side effects. This review mainly focuses on and summarizes the current research progress of nanoparticles to deliver different leukemia therapeutic drugs, as to demonstrate the potential of nanoparticles in leukemia treatment.

Effect of mesoporous silica nanoparticles-based nano-fragrance on the central nervous system.

Fragrances are widely used in our daily lives and can make us feel happy. However, traditional aromatic products release fragrance quickly and have a strong aroma. This not only worsens our scenting experience, but also severely shortens the useful life of fragrance products. In this study, nano-fragrances based on mesoporous silica nanoparticles with great encapsulation efficiency and slow-release function were designed and prepared. In addition, this nano-fragrances are applied to wallpapers. Open field tests showed that this nano-fragrance had significant stress relief and anti-depressant effects.

Chitosan-based nanofragrance with antibacterial function applied to wallpaper.

Adding fragrances to the wallpaper can optimize our living environment and office environment. However, the poor adhesion and rapid release of fragrances on wallpapers have limited their application. In this study, vanillin was encapsulated in particles based on chitosan and poly(lactic-co-glycolic acid), thereby achieving a slow release of the fragrance. In addition, due to the addition of chitosan, the adhesion of the fragrance on the wallpaper was enhanced, and the wallpaper was given antibacterial properties.

Hollow Mesoporous Silica Nanoparticles Loaded with Eugenol for Regulating the Central Nervous System.

Fragrances are extensively applied in food, daily chemicals, tobacco and medicine industries. However, too strong volatility of fragrances results in a fast release rate, thereby reducing the usage time of aromatherapy products. Although loading fragrances into nanomaterials is capable of slowing their rates of release, the encapsulation efficiency of traditional nanomaterials is very low, and the nanomaterials themselves are not stable. Herein, hollow mesoporous silica nanoparticles (hMSNs) were designed for encapsulation of eugenol and the nano-fragrance was named EG@hMSNs. The structure of hMSNs was stable and the encapsulation rate of eugenol reached 46.5%. Besides, EG@hMSNs could significantly slow the release rate of eugenol. Subsequently, the EG@hMSNs were testified that they had positive roles in stress relief by open field tests. The molecular mechanisms of these positive effects on the central nervous system were then explored. Furthermore, the preparation method of hMSCs was simple, and the preparation cost was low. Therefore, EG@hMSNs are expected to be industrially produced and have a great application prospect.

Reactive mesoporous silica nanoparticles loaded with limonene for improving physical and mental health of mice at simulated microgravity condition.

Astronauts are under high stress for a long time because of the microgravity condition, which leads to anxiety, affects their learning and memory abilities, and seriously impairs the health of astronauts. Aromatherapy can improve the physical and mental health of astronauts in a way that moisturizes them softly and silently. However, the strong volatility of fragrances and inconvenience of aroma treatment greatly limit their application in the field of spaceflight. In this study, reactive mesoporous silica nanoparticles were prepared to encapsulate and slowly release limonene. The limonene loaded nanoparticles were named limonene@mesoporous silica nanoparticles-cyanuric chloride (LE@MSNs-CYC). LE@MSNs-CYC were then applied to wallpaper to improve the convenience of aromatherapy. LE@MSNs-CYC could chemically react with the wallpaper, thus firmly adsorbed on the wallpaper. In the following, the mice were treated with hindlimb unloading (HU) to simulate a microgravity environment. The results showed that 28-day HU led to an increase in the level of anxiety and declines in learning, memory, and physical health in mice. LE@MSNs-CYC showed significant relief effects on anxiety, learning, memory, and physical health of HU treated mice. Subsequently, the molecular mechanisms were explored by hypothalamic-pituitary-adrenal axis related hormones, immune-related cytokines, learning, and memory-related neurotransmitters and proteins.

Association between microRNA 25 expression in serum and lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aims to identify the association between microRNA 25 (mRNA 25) expression in serum and lung cancer (LC). METHODS: This planned study will cover all eligible case-controlled studies that report association between mRNA 25 expression in serum and LC. It will include published studies from inception to the present in Cochrane Library, PUBMED, EMBASE, Web of Science, Allied and Complementary Medicine Database, VIP database, and China National Knowledge Infrastructure regardless language and geographical location. We will also search other sources, such as conference abstracts and reference lists of related known studies and experts in the domain consulted to avoid missing potential studies. Two contributors will independently examine and select studies, collect all necessary data, and judge study quality for all included studies. We will perform statistical analysis using RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will summarize current evidence to present first systematic review of research on the association between mRNA 25 expression in serum and LC. CONCLUSION: This study will present comprehensive evidence to determine whether mRNA 25 expression in serum is associated with LC, and will provide helpful evidence for the future studies. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040056.

Zwitterionic Polymer-Based Nanoparticles Encapsulated with Linalool for Regulating Central Nervous System.

Aromatherapy is widely used in the treatment of diseases of the central nervous system, such as depression and anxiety. However, the rapid and uncontrolled release of aroma weakens the effects of aromatherapy. In this study, zwitterionic polymer-based nanoparticles encapsulated with linalool were prepared to improve the regulation of the central nervous system. First, the nanoparticles were modified with positive charges to adhere to the surface of silk via electrostatic interactions between the cationic nanoparticles and anionic silk. Besides, the fragrance was sustainably and controllably released from the nanoparticles. The effects of polymerization degree, polymer structure, and zeta potential on encapsulation efficiency, adhesion efficiency, and release profiles of linalool were then explored. The results showed that the linalool-encapsulated nanoparticles had the best performances of encapsulation, adhesion and release of fragrance when the polymerization degrees of hydrophilic block and hydrophobic block were 20 and 5, respectively. In addition, open field tests evaluated the regulation of nanoparticles on the central nervous system at the behavioral level. Measurements of dopamine, acetylcholine, and γ-aminobutyric acid expressions explored the mechanism of moderating effects on the central nervous system at the molecular level.

Lorf9 deletion significantly eliminated lymphoid organ atrophy induced by meq-deleted very virulent Marek's disease virus.

Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset of T cell lymphomas in chickens. MDV continues to break through vaccinal immunity due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV results in attenuated vaccines that protect against disease when chickens are infected with highly virulent strains. However, meq-deleted viruses still retain the ability to induce lymphoid organ atrophy, which raises safety concerns. In an earlier study, we found that deletion of lorf9 counteracts this lymphoid organ atrophy. Here, we describe the generation of a double deletion mutant virus lacking virus-encoded meq and lorf9. In vitro studies revealed that during replication, the mutant virus had kinetic characteristics similar to the parental virus; however, in vivo the replication capability was significantly reduced. Results of animal studies revealed no obvious MDV-specific symptoms and lesions. Importantly, the double deletion mutant virus lost the capacity to induce lymphoid organ atrophy, which has been the main obstacle during development of a good vaccine candidate.