Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate

The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the; in vitro; release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch. The results showed that there was no significant difference in permeation rates between the developed reservoir-type patch and the commercially available ISDN patch (;p;>; 0.05). Moreover, the cumulative release ratio of the commercially available ISDN patch in 48 h was up to 89.8%, whereas the developed patch was only 34.9%, which meant the sustained release time of the developed patch was much longer than the commercially available ISDN patch, and would promote the satisfaction of the patient.;O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação; in vitro; da formulação transdérmica de dinitrato de isossorbida desenvolvida foi estudada em comparação com a formulação de dinitrato de isossorbida disponível comercialmente. Os resultados mostraram que não existem diferenças significativa nas taxas de permeação entre o tipo de reservatório desenvolvido e o de dinitrato de isossorbida desenvolvido comercialmente (;p;>;0,05). Ademais, a taxa de liberação cumulativa da formulação de dinitrato de isossorbida disponível comercialmente em 48 horas foi de até 89,8% e a da formulação desenvolvida, de apenas de 34,9%, o que provou que a liberação sustentada da formulação desenvolvida foi muito maior do que a de dinitrato de isossorbida desenvolvida comercialmente, o que promoveria a satisfação do paciente.

Bis[4-(1-imino­eth­yl)-3-methyl-1-phenyl-1H-pyrazol-5-olato-κ2 O,N 4]copper(II)

In the title complex, [Cu(C12H12N3O)2], the CuII ion is tetra­coordinated by two N atoms and two O atoms from two bis-chelating 4-(1-imino­eth­yl)-3-methyl-1-phenyl-1H-pyrazol-5-olate ligands in a square-planar geometry. The two N atoms and two O atoms around the CuII atom are trans to each other, as the CuII atom lies on an inversion centre. The six-membered ring composed of the Cu, an O, an N and three C atoms of the ligand and the pyrazole ring is nearly planar, the largest deviation being 0.037 (4) Å for an N atom. In the crystal, weak inter­molecular C—H⋯N hydrogen-bonding inter­actions link the mol­ecules into chains along the c axis

Antifungal activity of metabolites of the endophytic fungus Trichoderma brevicompactum from garlic

The endophytic fungus strain 0248, isolated from garlic, was identified as Trichoderma brevicompactum based on morphological characteristics and the nucleotide sequences of ITS1-5.8SITS2 and tef1. The bioactive compound T2 was isolated from the culture extracts of this fungus by bioactivity-guided fractionation and identified as 4β-acetoxy-12,13-epoxy-Δ9-trichothecene (trichodermin) by spectral analysis and mass spectrometry. Trichodermin has a marked inhibitory activity on Rhizoctonia solani, with an EC50 of 0.25 µgmL-1. Strong inhibition by trichodermin was also found for Botrytis cinerea, with an EC50 of 2.02 µgmL-1. However, a relatively poor inhibitory effect was observed for trichodermin against Colletotrichum lindemuthianum (EC50 = 25.60 µgmL-1). Compared with the positive control Carbendazim, trichodermin showed a strong antifungal activity on the above phytopathogens. There is little known about endophytes from garlic. This paper studied in detail the identification of endophytic T. brevicompactum from garlic and the characterization of its active metabolite trichodermin

IP102: A large-scale benchmark dataset for insect pest recognition

Insect pests are one of the main factors affecting agricultural product yield. Accurate recognition of insect pests facilitates timely preventive measures to avoid economic losses. However, the existing datasets for the visual classification task mainly focus on common objects, e.g., flowers and dogs. This limits the application of powerful deep learning technology on specific domains like the agricultural field. In this paper, we collect a large-scale dataset named IP102 for insect pest recognition. Specifically, it contains more than 75,000 images belonging to 102 categories, which exhibit a natural long-tailed distribution. In addition, we annotate about 19, 000 images with bounding boxes for object detection. The IP102 has a hierarchical taxonomy and the insect pests which mainly affect one specific agricultural product are grouped into the same upper level category. Furthermore, we perform several baseline experiments on the IP102 dataset, including handcrafted and deep feature based classification methods. Experimental results show that this dataset has the challenges of interand intra- class variance and data imbalance. We believe our IP102 will facilitate future research on practical insect pest control, fine-grained visual classification, and imbalanced learning fields. We make the dataset and pre-trained models publicly available at https://github.com/ xpwu95/IP10

Characterization of fibroblast growth factor 1 in obese children and adolescents

Background: Fibroblast growth factor 1 (FGF1) can regulate glucose and lipid metabolism in obese mice. Serum FGF1 has increased in type 2 diabetes mellitus adults and correlated with BMI. This study aimed to indicate conventional weight loss effects on FGF1 in obese children and adolescents. Materials and methods: Clinical and metabolic parameters of 88 lean and obese individuals (ages 5–15 years) and 39 obese individuals followed with 6 months of lifestyle intervention were collected. Serum FGF1 levels were detected through enzyme-linked immunosorbent assays. Results: FGF1 levels were increased in obese individuals. Serum FGF1 levels were significantly correlated with BMI and waist circumferences (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise linear regression analyses showed that FGF1 levels were significantly correlated with HbA1c and HOMA-IR (β = 0.371, P = 0.008; β = 0.323, P = 0.021, respectively). Weight loss (2.3 ± 0.1 kg) was accompanied by a significant reduction of circulating FGF1 levels (7.2 ± 0.4 pg/mL). Changes in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR and low-density lipoprotein cholesterol (β = 0.277, P = 0.020; β = 0.474, P < 0.001; β = 0.320, P = 0.008, respectively). Conclusion: FGF1 was related to increased risk of insulin resistance in obese children and adolescents. Serum FGF1 reduced after weight loss in obese individuals and was associated with the improvement of insulin resistance. Changes in serum FGF1 were more correlated with insulin resistance than changes in obesity per se

Construction and Synergistic Effect of Recombinant Yeast Co-expressing Pig IL-2/4/6 on Immunity of Piglets to PRRS Vaccination

AbstractIn order to develop cost-effective immunomodulator, the recombinant Pichia pastoris were firstly constructed to co-express porcine IL-2/4/6 genes, and then fermented to feed 45-days Tibetan piglets at different doses to evaluate its effects on immunity of piglets to PRRS vaccination, which simultaneously received intramuscular injection of inactivated PRRS vaccine. The results were found that the leukocytes, IgG and specific antibody to PRRSV, Th and Tc cells increased significantly in the blood of treated piglets in comparison with those of the control (P<0.05); the mRNA expression of TLRs (TLR-2, 3, 4, 7, 9), IFN-γ, IL-2, IL-4, IL-6, IL-7, IL-12 and IL-15 genes were elevated significantly in the immune cells from the blood of treated piglets (P<0.05). Moreover, the growth of the treated piglets also markedly improved whose average net weight gain was significantly higher than the control on 58 days post inoculation (P<0.05). These results suggest that the recombinant yeast can effectively enhance the systematic innate and adaptive immunity of piglets as well as promote the growth of piglet, which could be further developed as cost-effective promising immunomodulator to improve the control of pig PRRS disease

FGL2 deficiency alleviates maternal inflammation-induced blood-brain barrier damage by blocking PI3K/NF-κB mediated endothelial oxidative stress

IntroductionThe impairment of blood-brain barrier (BBB) is one of the key contributors to maternal inflammation induced brain damage in offspring. Our previous studies showed Fibrinogen-like protein 2 (FGL2) deficiency alleviated maternal inflammation induced perinatal brain damage. However, its role in BBB remains undefined.MethodsLipopolysaccharide (LPS) was intraperitoneally injected to dams at Embryonic day 17 to establish maternal inflammation model. FGL2 knockout mice and primary brain microvascular endothelial cells (BMECs) were used for the in-vivo and in-vitro experiments. BBB integrity was assessed by sodium fluorescein extravasation and tight junction (TJ) protein expression. Oxidative stress and the activation of PI3K/NF-κB pathway were evaluated to explore the mechanisms underlying.ResultsUpon maternal inflammation, BBB integrity was remarkedly reduced in neonatal mice. Meanwhile, FGL2 expression was consistently increased in BBB-impaired brain as well as in LPS-treated BMECs. Moreover, FGL2 deficiency attenuated the hyperpermeability of BBB, prevented the decline of TJ proteins, and reduced the cytokine expressions in LPS-exposed pups. Mechanistically, the indicators of oxidative stress, as well as the activation of PI3K/NF-κB pathway, were upregulated after LPS exposure in vivo and in vitro. FGL2 deletion decreased the generation of ROS and NO, reduced the endothelial iNOS and NOX2 expressions, and suppressed the PI3K/NF-κB pathway activation. Besides, inhibition of PI3K by LY294002 decreased the oxidative stress in LPS-treated wild-type BMECs. While, overexpression of PI3K by lentivirus reemerged the induction of NOX2 and iNOS as well as NF-κB activation in FGL2-deleted BMECs.ConclusionOur findings indicate that FGL2 deficiency alleviates the maternal inflammation-induced BBB disruption by inhibiting PI3K/NF-κB mediated oxidative stress in BMECs. Targeting FGL2 may provide a new therapy for prenatal brain damage of offspring

Disrupted Asymmetry of Inter- and Intra-Hemispheric Functional Connectivity at Rest in Medication-Free Obsessive-Compulsive Disorder

Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale–Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs