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•Dissolving microneedles are promising devices used for painless transdermal drug delivery.•Ginsenoside Rg3 engineered liposomes are easily manufactured, stable, and provide a novel ...potential platform for psoriasis.•Liposome-in-microneedles strategy can provide site-specific drug delivery, increase drug accumulation in the epidermis.
Psoriasis is a chronic scaly skin disease, which is associated with abnormal immune system function, inflammatory cell infiltration. The disadvantages of traditional treatment of psoriasis are poor efficacy, recurrence of the condition, long treatment time, and systemic side effects due to a lack of an appropriate drug delivery system. A liposome-in-Microneedles (MNs) based transdermal drug delivery system had been developed to provide efficient site-specific drug delivery, stable drug release and enhanced permeability. Firstly, liposomes were loaded with Ginsenoside Rg3 (a small molecular compound with anti-inflammatory and immune regulation functions), then Rg3-liposomes (Rg3-Lipo) were successfully loaded into MNs. Rg3-Liposome-MNs (Rg3-MNs) with the mechanical property of 0.59 N/needle, could easily penetrate the epidermis and release Rg3-lipo to regulate the immune response. The efficacy of Rg3-MNs was evaluated by IMQ-induced psoriasis-like dermatitis in mice. Rg3-MNs significantly (p < 0.01) decreased the epidermal thickness, dermal papillary edema, and the possible mechanism was to markedly reduce (p < 0.01) the levels of IL-17, IL-23, and TNF-α. In addition, we found that Rg3-MNs might improve psoriasis by inhibiting the activation of the STAT3/p-STAT3 signaling pathway. In brief, this study provides an ideal loaded anti-inflammatory and immunoregulatory drug delivery system to treat psoriasis.
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•Electrospray as a novel method to prepare micro/nanoparticles are described.•Illustrated a variety of polymer used in electrosprayed microspheres.•Presented the application of ...electrosprayed micro/nanoparticles in drug delivery.•Future perspectives of electrospray in combination with medical field are discussed.
Micro/nanoparticles-based drug delivery system has emerged significantly and has influenced the pharma industry up to considerable extent. At the same time, the development of production methods that are cost effective, scalable and reproducible becomes crucial to ensure the clinical translation of any development. The application of electrospray (ES) technology in micro-nano drug delivery system not only has the above advantages, but also can quickly obtain uniform and stable micro/nanoparticles as drug carriers through its own characteristics. Natural or synthetic polymers are often used as raw materials for these micro/nanoparticles. The micro/nanoparticles carriers prepared by these polymers can change the solubility and bioavailability of drugs and reduce the toxicity caused by mass accumulation after sudden drug release. And after reaching the target site, they’re easy to degrade and will not accumulate in the body. In this review, taken together, we briefly describe the principle and advantages of ES, as well as the common polymers for the preparation of micro/nanoparticles by this method. The types of electrosprayed micro/nanoparticles and their advantages as micro-nano drug delivery systems in different drug delivery routes and different diseases were also discussed. And prospects are made for the future development of electrospray in the field of medicine.
The characteristics of changes in wetlands in different coastal areas vary, so it is necessary to select representative experimental areas to research wetland degradation, ecosystem service values ...(ESVs) and differences in changes among various wetland types in different ecological service function fields. The goal of this study is to better realize the spatiotemporal characteristics of wetland degradation and ESV in order to balance economic advancement and wetland ecological protection. The evolution of the wetland ESVs was analyzed by using the ESV equivalent correction technique and ecological contribution degree. The random forest (RF) classification model was utilized to extract wetland information in the Yellow River Delta (YRD) in four years (1990, 2000, 2010, and 2020). Thoroughly exploring the mechanism of impact and proposing reasonable suggestions based on a close combination of wetland changes and ecological services are conducive to the healthy development of global wetlands. The results demonstrated that the total area of wetlands expanded from 1459.5 km2 in 1990–1975.5 km2 in 2020, an increase of 28.5 %, with artificial wetlands increasing from 151.4 km2 to 1059.1 km2 and natural wetlands decreasing from 1308.1 km2 to 916.5 km2. The wetland ESV increased from 18.4 billion USD in 1990–28.6 billion USD in 2020. The transformation between types of natural wetlands tended to increase the ESV, while the transformation from natural wetlands to constructed wetlands reduced the ESV. The tidal flats and herbaceous wetlands have great value in terms of not only hydrological regulation but also gene diversity and climate regulation. The significant changes in various wetlands cause changes in different ecological service functions and promote changes in the ESV. Wetland protection, restoration, reconstruction, and rational utilization must be incorporated into urban land planning, and wetland parks and wetland protection zones should be established according to local conditions. This above research can provide typical examples and references for global wetland protection and sustainable development.
Space charge accumulation in the insulating layers of high voltage direct current cables is the key factor that leads to their degradation and limits the operation safety. Hence, it is necessary to ...effectively inhibit space charge injection to these layers. In this study, a new method is proposed to suppress the charge injection to cable insulation layer: a certain amount of Li
4
Ti
5
O
12
nanopowder is doped into the semiconductive screen to enhance the internal conductive network and homogenize the electric field. The influences of Li
4
Ti
5
O
12
particles in the semiconductive composite screen on the positive temperature coefficient effect and space charge injection process are explored. The obtained results reveal that the charge quantity in the insulation layer corresponding to the minimum peak resistivity is reduced by 49.7%, 58.9%, and 46.9% after polarization at a Li
4
Ti
5
O
12
content of 4 wt% and electric field strengths of 10, 20, and 30 kV/mm, respectively.
Fowl adenovirus serotype 4 (FAdV-4) and FAdV-8b are causative agents of hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH), respectively. HHS and IBH co-infections were ...often reported in clinical, yet there are no commercially available bivalent vaccines for prevention and control of both FAdV-4 and -8b. In the present study, a chimeric FAdV-4 was firstly generated by substituting fiber-1 of FAdV-4 with fiber of FAdV-8b. The chimeric virus, rFAdV-4-fiber/8b, exhibited similar replication ability in vitro and pathogenicity in vivo to the parental wild type FAdV-4. A single dosage of vaccination with the inactivated rFAdV-4-fiber/8b induced high antibody titers against fiber-2 of FAdV-4 and fiber of FAdV-8b and provided full protection against FAdV-4 and -8b challenge. These results demonstrated that fiber of FAdV-8b could replace the role of fiber-1 of FAdV-4 in the process of viral infection, and rFAdV-4-fiber/8b could be used to make a potential bivalent vaccine for the control and prevention of HHS and IBH.
Coastal tidal flats are important ecological resources. As the dividing line between marine and terrestrial ecosystems, tidal flats provide a large number of ecosystem services. However, with the ...excessive development of coastal areas, tidal flat resources have been drastically reduced, leading to the deterioration of coastal ecosystems. There is an urgent need to acquire accurate information on the changes in tidal flat resources. This research proposes a tidal flat extraction model (RF-W model) that combines the random forest (RF) method and waterline method, which aims to improve the accuracy of tidal flat extraction. This method can effectively eliminate the shortcomings of the RF method in determining the lower boundary of tidal flats and those of the waterline method in distinguishing river channels and tidal flats. The tidal flat extraction of Qingdao Jiaozhou Bay in 2020 is performed as an example of the model. The results show that the user’s and producer’s accuracies of the RF-W model were both the highest, indicating that the improved model can accurately extract tidal flat information. Then, we used the RF-W model to extract tidal flat information for Jiaozhou Bay in seven periods (1990, 1995, 2000, 2005, 2010, 2015, and 2020) and to study the spatiotemporal changes in the tidal flats and influencing factors from 1990 to 2020. The tidal flat area of Jiaozhou Bay showed an overall downward trend before 2015, and the area decreased by 21.9 km2, with a reduction in the rate of approximately 1.1%/year. After 2015, the tidal flat area rebounded slightly. The overall change in Jiaozhou Bay showed reclamation and expansion toward the sea. The reduction in the sand content of the rivers entering the sea, reclamation and cultivation, and land development were the main factors contributing to the reduction in the tidal flat area in Jiaozhou Bay. In addition, sea level rise due to climate warming is a long-term potential factor.
Tea (
(L.) Kuntze) is one of the most important economic plants in China, and has many benefits for human health. Anthracnose is one of the most serious diseases of tea in China, and control of the ...fungus is important since most Chinese cultivars are susceptible to it. The agent of tea anthracnose was initially described as
I. Miyake in Japan, which was later transferred to
, but this taxonomic position remains problematic. To shed light on these taxonomic and phylogenetic issues, the tea anthracnose pathogens were re-studied. Combining the morphological characteristics and a multigene phylogenetic analysis of nrITS, nrLSU,
, and
sequence data, a new genus
was proposed to accommodate the causal fungi of tea anthracnose, including a new species
and a new combination
. Furthermore, the pathogenicity of the pathogens was determined according to Koch's postulates. This study thoroughly resolves the long-standing taxonomic and phylogenetic problems of the tea anthracnose pathogens.
The ventral tegmental area (VTA) reportedly regulates sleep and wakefulness through communication with the lateral hypothalamus (LH). It has also been suggested that adequate anesthesia produced by ...administration of chloral hydrate, ketamine, or halothane significantly reduces the GABAergic neuronal firing rate within the VTA. However, the exact effects on GABAergic neurons in the VTA and the mechanisms through which these neurons modulate anesthesia through associated neural circuits is still unclear. Here, we used optogenetic and chemogenetic methods to specifically activate or inhibit GABAergic neuronal perikarya in the VTA or their projections to the LH in Vgat-Cre mice. Electroencephalogram (EEG) spectral analyses and burst suppression ratio (BSR) calculations were conducted following administration of 0.8 or 1.0% isoflurane, respectively; and loss of righting reflex (LORR), recovery of righting reflex (RORR), and anesthesia sensitivity were assessed under 1.4% isoflurane anesthesia. The results showed that activation of GABAergic neurons in the VTA increased delta wave power from 40.0 to 46.4% (
= 0.006) and decreased gamma wave power from 15.2 to 11.5% (
= 0.017) during anesthesia maintenance. BSR was increased from 51.8 to 68.3% (
= 0.017). Induction time (LORR) was reduced from 333 to 290 s (
= 0.019), whereas arousal time (RORR) was prolonged from 498 to 661 s (
= 0.007). Conversely, inhibition of VTA GABAergic neurons led to opposite effects. In contrast, optical activation of VTA-LH GABAergic projection neurons increased power of slow delta waves from 44.2 to 48.8% (
= 0.014) and decreased that of gamma oscillations from 10.2 to 8.0%. BSR was increased from 39.9 to 60.2% (
= 0.0002). LORR was reduced from 330 to 232 s (
= 0.002), and RORR increased from 396 to 565 s (
= 0.007). Optical inhibition of the projection neurons caused opposite effects in terms of both the EEG spectrum and the BSR, except that inhibition of this projection did not accelerate arousal time. These results indicate that VTA GABAergic neurons could facilitate the anesthetic effects of isoflurane during induction and maintenance while postponing anesthetic recovery, at least partially, through modulation of their projections to the LH.
Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype 4 (FAdV-4) has caused huge economic losses to poultry industries. The key genes responsible for different virulence of ...FAdV-4 strains are not fully elucidated. Previous studies indicated that hexon of pathogenic FAdV-4 has a conserved arginine (R) at position 188, and a conserved isoleucine (I) is present at this position in reported nonpathogenic FAdV-4. Recently, it was reported that R188 of hexon is the determinant site for pathogenicity of the emerging Chinese FAdV-4 strain. However, the role of hexon amino acid 188 (aa188) has not been examined in the nonpathogenic FAdV-4 strain. In this study, three recombinant FAdV-4 viruses, H/H/R188I, O/O/I188R, and H/O/I188R, were constructed by mutating hexon aa188 of FAdV-4 pathogenic strain CH/HNJZ/2015 (H) and nonpathogenic strain ON1 (O), and pathogenicity was assessed in specific-pathogen-free (SPF) chickens. Consistent with previous findings, H/O/I188R exhibited pathogenicity similar to that of CH/HNJZ/2015, yet H/H/R188I induced no mortality. Unexpectedly, all chickens infected with O/O/I188R survived. Postmortem examination of O/O/I188R-infected chickens showed typical lesions of inclusion body hepatitis rather than HHS. Expression of proinflammatory cytokines in CH/HNJZ/2015- and H/O/I188R-infected chickens was significantly higher than that in H/H/R188I-, ON1-, and O/O/I188R-infected chickens. Analysis of predicted hexon protein structures indicated that aa188 mutation leads to conformational changes in the L1 loop of HNJZ-hexon but not in ON1-hexon. In summary, the present study demonstrated that the role of hexon aa188 in the virulence of FAdV-4 varies between different strains. Induction of HHS requires factors aside from hexon aa188 in the emerging Chinese FAdV-4 strain.
HHS induced by FAdV-4 has caused huge economic losses to the poultry industry. The key determinants for the different virulence of FAdV-4 have not been fully elucidated. Here, we investigated the role of hexon aa188 in FAdV-4 strains with different virulence and showed that the role of hexon aa188 varies in FAdV-4 strains with different genetic contents. The hexon R188 may be the key amino acid for causing inclusion body hepatitis by the pathogenic FAdV-4 strain, and induction of HHS by FAdV-4 may need other viral cofactors. Moreover, the hexon R188I mutation greatly affected the expression of proinflammatory cytokines induced by the pathogenic strain CH/HNJZ/2015, but no significant difference was observed between the nonpathogenic strain ON1 and ON1 with hexon I188R mutation. We found that hexon aa188 mutation induced conformational changes to hexon protein in CH/HNJZ/2015 but not in ON1, which might be the underlying reason for the changing virulence.
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