Transmission of droplet aerosols in an elevator cabin: Effect of the ventilation mode.

The recent outbreak of COVID-19 has threatened public health. Owing to the relatively sealed environment and poor ventilation in elevator cabins, passengers are at risk of respiratory tract infection. However, the distribution and dispersion of droplet aerosols in elevator cabins remain unclear. This study investigated the transmission of droplet aerosols exhaled by a source patient under three ventilation modes. Droplet aerosols produced by nose breathing and mouth coughing were resolved using computational fluid dynamics (CFD) simulations. We adopted the verified renormalization group (RNG) k-ε turbulence model to simulate the flow field and the Lagrangian method to track the droplet aerosols. In addition, the influence of the ventilation mode on droplet transmission was evaluated. The results showed that droplet aerosols gathered in the elevator cabin and were difficult to discharge under the mixed and displacement ventilation modes with specific initial conditions. The inhalation proportion of droplet aerosols for air curtain was 0.016%, which was significantly lower than that for mixed ventilation (0.049%) and displacement ventilation (0.071%). The air curtain confined the transmission of droplet aerosols with the minimum ratios of inhalation, deposition, and suspension and is thus recommended to reduce the exposure risk.

Cellulose accumulation mediated by PbrCSLD5, a cellulose synthase-like protein, results in cessation of pollen tube growth in Pyrus bretschneideri.

Cellulose, a key component of the cell wall, plays an important role in maintaining the growth of pollen tubes. However, the molecular mechanism of cellulose participating in the cessation of pear pollen tube growth remains unclear. Here, we reported that at 15 h post-cultured (HPC), the slow-growth pear pollen tubes showed thickened cell walls and cellulose accumulation in the inner wall. Transcriptome data and quantitative real-time PCR analysis showed that PbrCSLD5, a cellulose synthesis-like gene, was highly expressed in the 15 HPC pear pollen tubes. Knockdown of PbrCSLD5 caused a decrease in cellulose content in pear pollen tubes. Moreover, PbrCSLD5 overexpression in Arabidopsis resulted in the accumulation of cellulose and disruption of normal pollen tube growth. Transcription factor PbrMADS52 was found to bind to the promoter of PbrCSLD5 and enhanced its expression. Our results suggested that the PbrMADS52-PbrCSLD5 signaling pathway led to increased cellulose content in the pear pollen tube cell wall, thereby inhibiting pollen tube growth. These results provided new insights into the regulation of pollen tube growth.

Lignin as a MALDI matrix for small molecules: a proof of concept.

Driven by the interest in metabolomic studies and the progress of imaging techniques, small molecule analysis is booming, while it remains challenging to be realized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Herein, lignin, the second most abundant biomass in nature, was applied as a dual-ion-mode MALDI matrix for the first time to analyze small molecules. The low ionization efficiency and strong optical absorption properties make lignin a potential MALDI matrix in small molecule analysis. A total of 30 different small molecules were identified qualitatively and six kinds of representative molecules were detected quantitatively with a good linear response (R2 > 0.995). To verify the accuracy of our quantitative method in MALDI, myricitrin, a major bioactive component in Chinese bayberry, was analyzed in different cultivars and tissues. The myricitrin content in real samples detected by MALDI was highly consistent (R2 > 0.999) with that detected by high-performance liquid chromatography, thus indicating the applicability of the lignin matrix. Further characterization by ultraviolet and nuclear magnetic resonance spectroscopy was carried out to explain the possible mechanism of lignin as a matrix and provide more theories for a rational matrix design.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

[Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial].

OBJECTIVE: To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). METHODS: A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. RESULTS: A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P<0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P>0.05). CONCLUSIONS: The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.

Matrix stiffness modulates the differentiation of neural crest stem cells in vivo.

Stem cells are often transplanted with scaffolds for tissue regeneration; however, how the mechanical property of a scaffold modulates stem cell fate in vivo is not well understood. Here we investigated how matrix stiffness modulates stem cell differentiation in a model of vascular graft transplantation. Multipotent neural crest stem cells (NCSCs) were differentiated from induced pluripotent stem cells, embedded in the hydrogel on the outer surface of nanofibrous polymer grafts, and implanted into rat carotid arteries by anastomosis. After 3 months, NCSCs differentiated into smooth muscle cells (SMCs) near the outer surface of the polymer grafts; in contrast, NCSCs differentiated into glial cells in the most part of the hydrogel. Atomic force microscopy demonstrated a stiffer matrix near the polymer surface but much lower stiffness away from the polymer graft. Consistently, in vitro studies confirmed that stiff surface induced SMC genes whereas soft surface induced glial genes. These results suggest that the scaffold's mechanical properties play an important role in directing stem cell differentiation in vivo, which has important implications in biomaterials design for stem cell delivery and tissue engineering.

Complement Activation by PEGylated Gold Nanoparticles.

Gold nanoparticles (AuNPs) are widely used in biomedical applications, but much less is known about their immunological properties, particularly their interaction with the complement system, a key component of innate immunity serving as an indicator of their biocompatibility. Using a library of different-sized AuNPs (10, 20, 40, and 80 nm) passivated with polyethylene glycol (PEG) of different molecular weight ( Mw = 1, 2, 5, and 10 kDa), we demonstrated that citrate-capped AuNPs activated the whole complement system in a size-dependent manner, characterized by the formation of the end-point activation product, SC5b-9, in human serum. Although PEGylation of AuNPs mitigated, but did not abolish, the activation level, complement activation by PEGylated AuNPs was independent of both the core size of AuNPs and the molecular weight of PEG. The cellular uptake of both citrate-capped and PEGylated AuNPs by human U937 promonocytic cells which expresses complement receptors were highly correlated to the level of complement activation. Taken together, our results provided new insights on the innate complement activation by PEGylated AuNPs that are widely considered to be inert biocompatible nanomaterials.

EjNAC3 transcriptionally regulates chilling-induced lignification of loquat fruit via physical interaction with an atypical CAD-like gene.

Lignin is an important component of many plant secondary cell walls. In the fruit of loquat (Eriobotrya japonica), lignification of cell walls in the fleshy tissue occurs when fruit are subjected to low-temperature storage, which is commonly used to avoid the rapid senescence that occurs at room temperature. In this study, two NAC domain genes, EjNAC3 and EjNAC4, were isolated and shown to be significantly induced at 0 °C, which was concomitant with an increase in the fruit lignification index. Lignification and expression of both EjNAC3 and EjNAC4 were inhibited by low-temperature conditioning and by heat treatment. In addition, EjNAC3 trans-activated the lignin biosynthesis-related EjCAD-like promoter, which was measured using a dual-luciferase assay. Further analysis with yeast one-hybrid and electrophoretic mobility shift assays indicated that EjNAC3 could physically bind to the promoter of the EjCAD-like gene. Thus, EjNAC3 is a direct regulator of loquat chilling-induced lignification, via regulations of EjCAD-like.

Regulation of loquat fruit low temperature response and lignification involves interaction of heat shock factors and genes associated with lignin biosynthesis.

Transcriptional regulatory mechanisms underlying lignin metabolism have been widely studied in model plants and woody trees, as well as fruit, such as loquat (Eriobotrya japonica). Unlike the well-known NAC, MYB and AP2/ERF transcription factors, the roles of heat shock factors (HSFs) in lignin regulation have been rarely reported. Two treatments (heat treatment, HT; low temperature conditioning, LTC) were applied to alleviate low temperature-induced lignification in loquat fruit. Gene expression analysis indicated that EjHSF1 transcript abundance, in parallel with heat shock protein genes (EjHsp), was induced by HT, while expression of EjHSF3 was repressed by LTC. Using dual-luciferase assays, EjHSF1 and EjHSF3 trans-activated the promoters of EjHsp genes and lignin biosynthesis-related genes, respectively. Thus, two distinct regulatory mechanisms of EjHSF transcription factors in chilling injury-induced fruit lignification are proposed: EjHSF1 transcriptionally regulated EjHsp genes are involved in chilling tolerance, while EjHSF3 transcriptionally regulated lignin biosynthesis. Furthermore, the relations between EjHSF3 and previously characterized fruit lignification regulators, including EjAP2-1, EjMYB1 and EjMYB2, were also investigated. Yeast-two hybrid (Y2H) and biomolecular fluorescence complementation (BiFC) assays demonstrated protein-protein interaction between EjHSF3 and EjAP2-1. Thus, the involvement of EjHSF3 in fruit lignification is via both lignin biosynthetic genes and the regulator, EjAP2-1.

Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis.

OBJECTIVE: To review the efficacy and safety of aripiprazole (ARI) for Tourette's syndrome (TS). METHODS: This review included randomized controlled trials (RCTs) of children and adolescents (6-18 years) with TS comparing ARI monotherapy with another monotherapies in relation to clinical improvement and adverse events. RESULTS: Six RCTs with a total of 528 subjects (ARI treatment group: n = 253; control group: n = 275) met the inclusion criteria. These included two RCTs (n = 255) that compared ARI monotherapy with tiapride (TIA). Tic symptoms control assessed by Yale Global Tic Severity Scale (Standard Mean Difference (SMD) = -0.38 (Confidence Interval (CI) = -1.32 to 0.56); I(2) = 90%, P = 0.42) revealed no significant differences between the two groups. Extrapyramidal symptoms were significantly different when ARI (1.5%) was compared with haloperidol (HAL) (43.5%). No significant group differences were found in the rates of nausea/vomiting, dizziness, and dry mouth between ARI and TIA (RR = 0.57 to 1.00 (95%CI = 0.14-4.20); I(2) = 0% to 69%, P = 0.35 to 1.00). CONCLUSION: This review found that ARI has similar efficacy to TIA and HAL for TS, while extrapyramidal symptoms were significantly less with ARI than with HAL. ARI can be considered as an alternative treatment option for TS.

Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.

To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.

EjAP2-1, an AP2/ERF gene, is a novel regulator of fruit lignification induced by chilling injury, via interaction with EjMYB transcription factors.

Lignin biosynthesis is regulated by many transcription factors, such as those of the MYB and NAC families. However, the roles of AP2/ERF transcription factors in lignin biosynthesis have been rarely investigated. Eighteen EjAP2/ERF genes were isolated from loquat fruit (Eriobotrya japonica), which undergoes postharvest lignification during low temperature storage. Among these, expression of EjAP2-1, a transcriptional repressor, was negatively correlated with fruit lignification. The dual-luciferase assay indicated that EjAP2-1 could trans-repress activities of promoters of lignin biosynthesis genes from both Arabidopsis and loquat. However, EjAP2-1 did not interact with the target promoters (Ej4CL1). Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated protein-protein interactions between EjAP2-1 and lignin biosynthesis-related EjMYB1 and EjMYB2. Furthermore, repression effects on the Ej4CL1 promoter were observed with the combination of EjAP2-1 and EjMYB1 or EjMYB2, while EjAP2-1 with the EAR motif mutated (mEjAP2-1) lost such repression, although mEjAP2-1 still interacted with EjMYB protein. Based on these results, it is proposed that EjAP2-1 is an indirect transcriptional repressor on lignin biosynthesis, and the repression effects were manifested by EAR motifs and were conducted via protein-protein interaction with EjMYBs.

Facile synthesis of porous bimetallic alloyed PdAg nanoflowers supported on reduced graphene oxide for simultaneous detection of ascorbic acid, dopamine, and uric acid.

Porous bimetallic alloyed palladium silver (PdAg) nanoflowers supported on reduced graphene oxide (PdAg NFs/rGO) were prepared via a facile and simple in situ reduction process, with the assistance of cetyltrimethylammonium bromide as a structure directing agent. The as-prepared nanocomposite modified glassy carbon electrode (PdAg NFs/rGO/GCE) showed enhanced catalytic currents and enlarged peak potential separations for the oxidation of ascorbic acid (AA), dopamine (DA), and uric acid (UA) as compared to those of PdAg/GCE, rGO/GCE, commercial Pd/C/GCE, and bare GCE. The as-developed sensor can selectively detect AA, DA, and UA with a good anti-interference ability, wide concentration ranges of 1.0 µM-2.1 mM, 0.4-96.0 µM, and 1.0-150.0 µM, respectively, together with low detection limits of 0.057, 0.048, and 0.081 µM (S/N = 3), respectively. For simultaneous detection of AA, DA, and UA, the linear current-concentration responses were observed from 1.0 µM-4.1 mM, 0.05-112.0 µM, and 3.0-186.0 µM, with the detection limits of 0.185, 0.017, and 0.654 µM (S/N = 3), respectively.

Activator- and repressor-type MYB transcription factors are involved in chilling injury induced flesh lignification in loquat via their interactions with the phenylpropanoid pathway.

Lignin biosynthesis and its transcriptional regulatory networks have been studied in model plants and woody trees. However, lignification also occurs in some fleshy fruit and has rarely been considered in this way. Loquat ( Eriobotrya japonica ) is one such convenient tissue for exploring the transcription factors involved in regulating fruit flesh lignification. Firmness and lignin content of 'Luoyangqing' loquat were fund to increase during low-temperature storage as a typical symptom of chilling injury, while heat treatment (HT) and low-temperature conditioning (LTC) effectively alleviated them. Two novel EjMYB genes, EjMYB1 and EjMYB2, were isolated and were found to be localized in the nucleus. These genes responded differently to low temperature, with EjMYB1 induced and EjMYB2 inhibited at 0 °C. They also showed different temperature responses under HT and LTC conditions, and may be responsible for different regulation of flesh lignification at the transcriptional level. Transactivation assays indicated that EjMYB1 and EjMYB2 are a transcriptional activator and repressor, respectively. EjMYB1 activated promoters of both Arabidopsis and loquat lignin biosynthesis genes, while EjMYB2 countered the inductive effects of EjMYB1. This finding was also supported by transient overexpression in tobacco. Regulation of lignification by EjMYB1 and EjMYB2 is likely to be achieved via their competitive interaction with AC elements in the promoter region of lignin biosynthesis genes such as Ej4CL1.

Poly(ε-caprolactone) scaffolds of highly controlled porosity and interconnectivity derived from co-continuous polymer blends: model bead and cell infiltration behavior.

Porous structures destined for tissue engineering applications should ideally show controlled and narrow pore size distributions with fully interconnected pores. This study focuses on the development of novel poly(ε-caprolactone) (PCL) structures with fully connected pores of 84, 116, 141, and 162 µm average diameter, from melt blending of PCL with poly(ethylene oxide) (PEO) at the co-continuous composition, followed by static annealing and selective extraction of PEO. Our results demonstrate a low onset concentration for PEO continuity and a broad region of phase inversion. A novel in vitro assay was used to compare scaffold infiltration by 10-µm diameter polystyrene beads intended to mimic trypsinized human bone marrow stromal cells (hBMSCs). Beads showed a linear increase in the extent of scaffold infiltration with increasing pore size, whereas BMSCs infiltrated 162 and 141 µm pores, below which the cells aggregated and adhered near the seeding area with low infiltration into the porous device. While providing a baseline for non-aggregated systems, the beads closely mimic trypsinized cells at pore sizes equal to or larger than 141 µm, where optimal retention and distribution of hBMSCs are detected. A cytotoxicity assay using L929 cells showed that these scaffolds were cytocompatible and no cell necrosis was detected. This study shows that a melt blending approach produces porous PCL scaffolds of highly controlled pore size, narrow size distribution and complete interconnectivity, while the bead model system reveals the baseline potential for a homogeneous, non-aggregated distribution of hBMSCs at all penetration depths.

Enhanced denitrification of biodegradable polymers using Bacillus pumilus in aerobic denitrification bioreactors: Performance and mechanism.

Nitrate accumulation is an important issue that affects animal health and causes eutrophication. This study combined biodegradable polymers with degrading bacteria to lead to high denitrification efficiency. The results showed polycaprolactone had the highest degradation and carbon release rate (0.214 mg/g∙d) and nitrogen removal was greatest when the Bacillus pumilus and Halomonas venusta ratio was 1:2. When the hydraulic retention time was extended to 12 h, the nitrate removal rate for H. venusta with B. pumilus and polycaprolactone increased by 48 %. Furthermore, the group with B. pumilus contained more Proteobacteria (77.34 %) and denitrifying functional enzymes than the group without B. pumilus. These findings indicated B.pumilus can enhance the degradation of biodegradable polymers especially polycaprolactone to improve the denitrification of the aerobic denitrification bacteria H.venusta when treating maricultural wastewater.

An optimized caries model of Streptococcus mutans in rats and its application for evaluating prophylactic vaccines.

Dental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.

Non-negligible impact of microplastics on wetland ecosystems.

There has been much concern about microplastic (MP) pollution in marine and soil environments, but attention is gradually shifting towards wetland ecosystems, which are a transitional zone between aquatic and terrestrial ecosystems. This paper comprehensively reviews the sources of MPs in wetland ecosystems, as well as their occurrence characteristics, factors influencing their migration, and their effects on animals, plants, microorganisms, and greenhouse gas (GHG) emissions. It was found that MPs in wetland ecosystems originate mainly from anthropogenic sources (sewage discharge, and agricultural and industrial production) and natural sources (rainfall-runoff, atmospheric deposition, and tidal effects). The most common types and forms of MPs identified in the literature were polyethylene and polypropylene, fibers, and fragments. The migration of MPs in wetlands is influenced by both non-biological factors (the physicochemical properties of MPs, sediment characteristics, and hydrodynamic conditions) and biological factors (the adsorption and growth interception by plant roots, ingestion, and animal excretion). Furthermore, once MPs enter wetland ecosystems, they can impact the resident microorganisms, animals, and plants. They also have a role in global warming because MPs act as unique exogenous carbon sources, and can also influence GHG emissions in wetland ecosystems by affecting the microbial community structure in wetland sediments and abundance of genes associated with GHG emissions. However, further investigation is needed into the influence of MP type, size, and concentration on the GHG emissions in wetlands and the underlying mechanisms. Overall, the accumulation of MPs in wetland ecosystems can have far-reaching consequences for the local ecosystem, human health, and global climate regulation. Understanding the effects of MPs on wetland ecosystems is essential for developing effective management and mitigation strategies to safeguard these valuable and vulnerable environments.

Pulmonary administration of tetrandrine loaded Zinc-Alginate nanogels attenuates pulmonary fibrosis in rats.

Pulmonary fibrosis is a chronic and progressive disease, current systemic administration is not fully effective with many side effects, such as gastrointestinal and liver injury. The pulmonary delivery system for pulmonary fibrosis may contribute to maximize therapeutic benefit. Natural compounds might have prominence as potential drug candidates, but the low bioavailabilities affect their clinical use. Tetrandrine is a natural alkaloid with good anti-inflammatory, antifibrogenetic and antioxidant effects, and it is used as a clinical therapeutic drug for the treatment of silicosis in China. In the present study, we explore a new strategy of pulmonary delivery system to improve low solubility and pesticide effect of tetrandrine. Tetrandrine was loaded into alginate nanogels by reverse microemulsion method. The release behavior of tetrandrine reached zero-order kinetics release and the maximum free radical clearance rates reached up to 90%. The pulmonary fibrosis rats were treated with tetrandrine nanogels by using ultrasonic atomizing inhalation. Tetrandrine nanogels decreased the development and progression of fibrosis by reducing inflammation response and bating the deposition of extra cellular matrix. In conclusion, ultrasonic atomizing inhalation of tetrandrine nanogels provided a new therapeutic strategy for pulmonary fibrosis.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.