HBeAg induces neutrophils activation impairing NK cells function in patients with chronic hepatitis B.

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.

Cellular structural and functional imaging of donor and pathological corneas with label-free dual-mode full-field optical coherence tomography.

In this study, a dual-mode full-field optical coherence tomography (FFOCT) was customized for label-free static and dynamic imaging of corneal tissues, including donor grafts and pathological specimens. Static images effectively depict relatively stable structures such as stroma, scar, and nerve fibers, while dynamic images highlight cells with active intracellular metabolism, specifically for corneal epithelial cells. The dual-mode images complementarily demonstrate the 3D microstructural features of the cornea and limbus. Dual-modal imaging reveals morphological and functional changes in corneal epithelial cells without labeling, indicating cellular apoptosis, swelling, deformation, dynamic signal alterations, and distinctive features of inflammatory cells in keratoconus and corneal leukoplakia. These findings propose dual-mode FFOCT as a promising technique for cellular-level cornea and limbus imaging.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

Salidroside Ameliorates Lung Injury Induced by PM 2.5by Regulating SIRT1-PGC-1α in Mice.

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.

Effect of Acceptance and Commitment Therapy on Emotion Regulation in Adolescent Patients with Nonsuicidal Self-Injury.

Objective: This study aimed to explore the effect of acceptance and commitment therapy (ACT) on emotion regulation in adolescent patients with nonsuicidal self-injury (NSSI). Methods: A total of 72 adolescent patients with NSSI were selected as research subjects from June 2022 to May 2023 for retrospective analysis. They were divided into control group (CG) and experimental group (EG) in accordance with different management methods. CG received routine psychological support treatment, whereas EG was given ACT management on the basis of routine psychological support. The clinical management effects of the 2 groups were compared. Results: At the end of week 6 (T1) and the end of week 12 (T2), the EG had significantly higher scores of positive emotion regulation and cognitive fusion questionnaire-fusion (CFQ-F) (P < .05). However, they had significantly lower scores on the negative emotion regulation, behavior questionnaire, function questionnaire, and adolescent self-rating life events checklist (ASLEC) than the CG (P < .05). Conclusion: Acceptance and commitment therapy can effectively regulate the emotional state of adolescent patients with NSSI, improve psychological flexibility, reduce the effectiveness of self-injury behavior, and help such adolescents acquire the correct values in life.

Different correlation between depressive symptoms and sleep duration on weekdays/weekends among adolescents in Taiyuan, North China.

OBJECTIVE: In Chinese adolescents, the co-occurrence of depressive symptoms and short sleep duration constitute a serious public health issue. This study investigates the association between depressive symptoms and sleep duration of Chinese adolescents on weekdays as well as weekends. METHODS: A multistage random cluster selection was utilized to select 2660 adolescents in Taiyuan, China. The survey contents included demographic characteristics, sleep duration, and depressive symptoms. RESULTS: About 41.95 % of students reported depressive symptoms with an average sleep duration of 7.71 ± 0.90 h. After adjusting for covariates, depressive symptoms were found to be positively correlated with sleep duration <6 h (OR = 1.88, 95 % CI: 1.20, 2.95) and 6 ~ h (OR = 1.61, 95 % CI: 1.18, 2.20) on weekdays, and sleep duration <6 h (OR = 2.10, 95 % CI: 1.17, 3.79) and 6 ~ hours (OR = 1.74, 95 % CI: 1.16, 2.62) on weekends compared with a sleep duration of 8 ~ hours. Only on weekdays, sleep duration of 7 ~ hours was positively correlated with depressive symptoms (OR = 1.39, 95%CI: 1.05, 1.84). On weekends, it was not associated with depressive symptoms (OR = 1.06, 95%CI: 0.82, 1.39). In subgroup analyses, female students (OR = 2.88, 1.97, 1.50) and middle school students (OR = 3.50, 2.07, 1.50) were more likely to experience depressive symptoms on weekdays with a sleep duration of <6 h, 6 ~ hours and 7 ~ hours. LIMITATIONS: Sleep duration and depressive symptoms were self-reported measures. CONCLUSION: The study highlights that short sleep duration (< 7 h) increases the risk of depressive symptoms among adolescents regardless of weekdays or weekends. Just on weekdays, the sleep duration of 7 ~ hours was a risk factor for depressive symptoms. Further, gender, grade, and the only-child played significant modification effects between depressive symptoms and sleep duration. To conclude, this study will assist in the effective promotion of the education of adolescents' sleep health.

AATCT-IDS: A benchmark Abdominal Adipose Tissue CT Image Dataset for image denoising, semantic segmentation, and radiomics evaluation.

BACKGROUND AND OBJECTIVE: The metabolic syndrome induced by obesity is closely associated with cardiovascular disease, and the prevalence is increasing globally, year by year. Obesity is a risk marker for detecting this disease. However, current research on computer-aided detection of adipose distribution is hampered by the lack of open-source large abdominal adipose datasets. METHODS: In this study, a benchmark Abdominal Adipose Tissue CT Image Dataset (AATCT-IDS) containing 300 subjects is prepared and published. AATCT-IDS publics 13,732 raw CT slices, and the researchers individually annotate the subcutaneous and visceral adipose tissue regions of 3213 of those slices that have the same slice distance to validate denoising methods, train semantic segmentation models, and study radiomics. For different tasks, this paper compares and analyzes the performance of various methods on AATCT-IDS by combining the visualization results and evaluation data. Thus, verify the research potential of this data set in the above three types of tasks. RESULTS: In the comparative study of image denoising, algorithms using a smoothing strategy suppress mixed noise at the expense of image details and obtain better evaluation data. Methods such as BM3D preserve the original image structure better, although the evaluation data are slightly lower. The results show significant differences among them. In the comparative study of semantic segmentation of abdominal adipose tissue, the segmentation results of adipose tissue by each model show different structural characteristics. Among them, BiSeNet obtains segmentation results only slightly inferior to U-Net with the shortest training time and effectively separates small and isolated adipose tissue. In addition, the radiomics study based on AATCT-IDS reveals three adipose distributions in the subject population. CONCLUSION: AATCT-IDS contains the ground truth of adipose tissue regions in abdominal CT slices. This open-source dataset can attract researchers to explore the multi-dimensional characteristics of abdominal adipose tissue and thus help physicians and patients in clinical practice. AATCT-IDS is freely published for non-commercial purpose at: https://figshare.com/articles/dataset/AATTCT-IDS/23807256.

[Ecological Environment Dynamical Evaluation of Hutuo River Basin Using Remote Sensing].

Hutuo River Basin straddles Shanxi and Hebei provinces, and Hutuo River was once cut off due to economic development and urban expansion after 2000; however, with the national emphasis on ecological civilization and the implementation of the South-North Water Diversion Project, the ecological protection of Hutuo River Basin has been significantly improved. MODIS data, Landsat data, and night light remote sensing data were selected based on the google earth engine (GEE) platform, and a new evaluation index system was generated by combining the biological richness index, vegetation cover index, land stress index, and pollution load index in the ecological environment index (EI) and the humidity index in the remote sensing ecological index (RSEI), using the variation coefficient method and entropy weighting method to assign weights to these indices. An ecological environment evaluation model was constructed to evaluate and classify the ecological environment quality of Hutuo River Basin from 2000 to 2020, and the driving factors were interpreted by using geographic probes. The results showed that:① on a time scale, the ecological environment of Hutuo River Basin was in a decline period from 2000 to 2015 and a recovery period from 2015 to 2020. From a grid scale, the ecological environment quality in the central part of the basin showed a state of improvement year by year, and in the western and eastern parts of the basin, the ecological environment quality in the decline period decreased year by year, whereas the ecological environment quality in the recovery period improved. ② Hot spot analysis showed that the spatial distribution of the ecological environment quality in Hutuo River Basin was high in the middle and low on both sides. Cold spot regions were mainly located in major cities and towns in the eastern and southern parts and scattered in the river valley area on the west side. ③ Geodetection analysis showed that the single factor detection drivers were mainly population density, vegetation net primary productivity (NPP), fractional vegetation cover (FVC), and geomorphological type. The dominant factor of cross-detection was "geomorphological type + FVC." With the deepening of ecological civilization construction and the implementation of Hutuo River Protection Regulations, in combination with different factors such as the natural environment and social characteristics in this basin, the research on ecological environment evaluation in Hutuo River Basin can provide data support for proposing localized policies to improve the ecological environment.

100-Phones: A Large VI-SLAM Dataset for Augmented Reality Towards Mass Deployment on Mobile Phones.

Visual-inertial SLAM (VI-SLAM) is a key technology for Augmented Reality (AR), which allows the AR device to recover its 6-DoF motion in real-time in order to render the virtual content with the corresponding pose. Nowadays, smartphones are still the mainstream devices for ordinary users to experience AR. However the current VI-SLAM methods, although performing well on high-end phones, still face robustness challenges when deployed on a larger stock of mid- and low-end phones. Existing VI-SLAM datasets use either very ideal sensors or only a limited number of devices for data collection, which cannot reflect the capability gaps that VI-SLAM methods need to solve when deployed on a large variety of phone models. This work proposes 100-Phones. the first VI-SLAM dataset covering a wide range of mainstream phones in the market. The dataset consists of 350 sequences collected by 100 different models of phones. Through analysis and experiments on the collected data, we conclude that the quality of visual-inertial data vary greatly among the mainstream phones, and the current open source VI-SLAM methods still have serious robustness issues when it comes to mass deployment on mobile phones. We release the dataset to facilitate the robustness improvement of VI-SLAM and to promote the mass popularization of AR. Project page: https://github.com/zju3dv/100-Phones.

Oral administration of egg ovalbumin allergen induces dysregulation of tryptophan metabolism in sensitized BALB/c mice.

Food allergy (FA), triggered by specific dietary allergens, has emerged as a substantial global concern for food safety and public health. While studies have elucidated changes in immune cells and cytokines associated with allergen exposure, a comprehensive analysis of the host's metabolic features and the interaction between metabolites and the gut microbiota has not been conducted. In this study, egg allergen ovalbumin (OVA) was administered by the oral route to sensitized BALB/c mice to faithfully replicate key aspects of human FA, including severe allergic diarrhea, mast cell infiltration, and elevated levels of serum IgE, mMCPT-1, and Th2 cell hallmark cytokines (such as IL-4, IL-5, and IL-13). Furthermore, the untargeted and targeted metabolomic analyses indicated that FA in mice precipitated a substantial decrease in the tryptophan metabolites indole-3-acrylic acid (IA) and indole-3-lactic acid (ILA). The integration of shotgun metagenome and metabolome data further unveiled that the dysregulation of indole metabolism is related to a decline in the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium. Additionally, disruption of the tryptophan indole derivative pathway compromises the maintenance of intestinal mucosal function through the AHR signaling pathway, manifested by decreased expression of Reg3g and IL22. Taken together, this study demonstrated that the anaphylaxis triggered by oral ingestion of food allergens can lead to disruptions in tryptophan metabolism, consequently impairing intestinal immune homeostasis.

Phyllanthus emblica Linn: A comprehensive review of botany, traditional uses, phytonutrients, health benefits, quality markers, and applications.

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.

Imaging assessment of conjunctival goblet cells in dry eye disease.

Dry eye disease (DED) is a widespread, multifactorial, and chronic disorder of the ocular surface with disruption of tear film homeostasis as its core trait. Conjunctival goblet cells (CGCs) are specialised secretory cells found in the conjunctival epithelium that participate in tear film formation by secreting mucin. Changes in both the structure and function of CGCs are hallmarks of DED, and imaging assessment of CGCs is important for the diagnosis, classification, and severity evaluation of DED. Existing imaging methods include conjunctival biopsy, conjunctival impression cytology and in vivo confocal microscopy, which can be used to assess the morphology, distribution, and density of the CGCs. Recently, moxifloxacin-based fluorescence microscopy has emerged as a novel technique that enables efficient, non-invasive and in vivo imaging of CGCs. This article presents a comprehensive overview of both the structure and function of CGCs and their alterations in the context of DED, as well as current methods of CGCs imaging assessment. Additionally, potential directions for the visual evaluation of CGCs are discussed.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study.

BACKGROUND: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk. METHODS: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors. RESULTS: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 µmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77). CONCLUSIONS: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.

The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention.

BACKGROUND: The prognostic value of coronary collateral circulation (CC) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is underdetermined. The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI. METHODS: We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December 2013. All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC (grade 2 vs. grade 0-1) or Rentrop (grade 3 vs. grade 0-2) grading system. The primary endpoint was 5-year cardiac death. RESULTS: Of 2452 enrolled patients, the overall technical success rate was 74.1%. Well-developed collaterals were present in 686 patients (28.0%) defined by Werner's CC grade 2, and in 1145 patients (46.7%) by Rentrop grade 3. According to Werner's CC grading system, patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poor-developed collaterals (1.6% vs. 3.3%, P = 0.02), those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization (4.7% vs. 0.8%, P = 0.01) and failure patients (4.7% vs. 1.6%, P = 0.12). However, the similar effect was not shown in Rentrop grading system. CONCLUSIONS: In patients with the single-vessel CTO underwent PCI, well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death. Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

N-Terminal α-Helices in Domain I of Bacillus thuringiensis Vip3Aa Play Crucial Roles in Disruption of Liposomal Membrane.

Bacillus thuringiensis Vip3 toxins form a tetrameric structure crucial for their insecticidal activity. Each Vip3Aa monomer comprises five domains. Interaction of the first four α-helices in domain I with the target cellular membrane was proposed to be a key step before pore formation. In this study, four N-terminal α-helix-deleted truncations of Vip3Aa were produced and, it was found that they lost both liposome permeability and insecticidal activity against Spodoptera litura. To further probe the role of domain I in membrane permeation, the full-length domain I and the fragments of N-terminal α-helix-truncated domain I were fused to green fluorescent protein (GFP), respectively. Only the fusion carrying the full-length domain I exhibited permeability against artificial liposomes. In addition, seven Vip3Aa-Cry1Ac fusions were also constructed by combination of α-helices from Vip3Aa domains I and II with the domains II and III of Cry1Ac. Five of the seven combinations were determined to show membrane permeability in artificial liposomes. However, none of the Vip3Aa-Cry1Ac combinations exhibited insecticidal activity due to the significant reduction in proteolytic stability. These results indicated that the N-terminal helix α1 in the Vip3Aa domain I is essential for both insecticidal activity and liposome permeability and that domain I of Vip3Aa preserved a high liposome permeability independently from domains II-V.

Blockade of exosome release alleviates the hypersensitive reaction by influencing the T helper cell population in cow's milk allergic mice.

The aim of this work was to evaluate the ameliorative effects of exosome biogenesis in cow's milk allergy (CMA) response. In this context, BALB/c mice were systemically sensitized with cow's milk proteins plus an aluminum adjuvant to induce CMA. The inhibitor GW4869 of exosome biogenesis was added before sensitization and then the anaphylactic reactions were evaluated both in vivo (clinical score and body temperature) and in vitro (serum histamine, allergen-specific antibodies, cytokines by ELISA and cell analysis by flow cytometry) to explore the role of exosomes in the development of CMA. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) showed that the size distribution and morphology of CMA-derived exosomes were not changed after GW4869 preconditioning, and the concentration of exosomes was much lower than that of the CMA group. In the GW4869 group, inhibition of release of exosomes modulated the induction of T helper 2 cell (Th2)-related substances, with a decrease in histamine and allergen-specific immunoglobulin (Ig) E, and the expression of Th1, Th2, and Th17 cells all decreased as well. Moreover, the experimental data were integrated by means of principal component analysis (PCA) to give an overview that the percentage of Th cells and concentrations of cytokines were more influenced by GW4869 treatment. These data for the first time demonstrated that exosomes are involved in the development of CMA and the blockade of exosome release with GW4869 suppressed the IgE-mediated immune response in CMA.

A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Spray performance of flexible shield canopy opener and rotor wind integrated boom-sprayer application in soybean: effects on droplet deposition distribution.

BACKGROUND: Canopy density is high during mid-to-late soybean growth as a result of dense planting to improve yield, which seriously affects the control of pests and diseases. The dilemmas of difficult droplet penetration, nonuniform deposition, and droplet drift in field spraying remain challenges to the precise control of droplet distribution. This paper proposed a novel spraying application mode combined flexible shield canopy opener (FSCO) with rotor wind. The design of the key components of the new boom-spraying machine are described. The effects of the comparative spraying modes on spray deposition and droplet drift were studied in a field validation test to explore the feasibility of the novel spraying application. RESULTS: The study found that droplet coverage inside the soybean canopy was significantly affected by spraying mode, rotor wind speed and opener depth. The spraying operation that used the FSCO and rotor wind integrated mode was optimal for droplet uniformity on the adaxial and abaxial surfaces of the canopy leaves, with droplet uniformity indices of 0.966 and 0.934, respectively. At a rotor wind speed of 6 m s-1 and opener depth of 15 cm, the soybean canopy droplet coverage uniformity effect achieved the highest composite score of 0.937. The spraying mode used in this study improved droplet coverage uniformity by 82.30% and droplet anti-drift performance improved by 99.73% compared to the conventional boom-spraying mode. CONCLUSION: The study shows validity of the spraying mode combined FSCO with rotor wind to open dense canopy and improved droplet deposition uniformity in canopy and anti-drift performance. © 2024 Society of Chemical Industry.