•The ecosystem services and ecological sensitivity are evaluated to identify hubs.•Identified links primely rely on study area’s river system and farmland.•This network is of the dual significance of ...ecology and sustainable development.•This study suggests designating this network into forbidden construction areas.
With the continuous reduction and destruction of ecological land during rapid urbanization, eco-environment problems have become more severe. This study proposes an idea that identifies and constructs a green infrastructure (GI) network from the perspectives of ecosystem services and ecological sensitivity. The aim of this GI network is to improve and protect the ecosystem's stability and better guide the cities and villages towards green and sustainable development. This study uses quantitative evaluation methods and a least-cost path model to obtain the GI network's hubs and links. The results indicate that Harbin's hubs mainly consist of areas covered by woodland and water bodies, and links rely primarily on the urban river system and farmland. These are critical areas for ecological protection and the urban-rural sustainable development of Harbin. It can be concluded that identifying hubs by evaluation of ecosystem services and ecological sensitivity is feasible. This study suggests that the width of links should be at least 100 m to maintain biodiversity, and proposes some practical measures, such as space control, should be taken to protect the created GI network.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Due to their good absorption, satisfactory biocompatibility, and high safety, hydrogels have been widely used in the field of biomedicine, including for drug delivery and tissue regeneration. In this ...review, we introduce the characteristics and crosslinking methods of natural and synthetic hydrogels. Then, we highlight the design and principle of intelligent hydrogels (i.e., responsive hydrogels) used for drug release. Moreover, we introduce the application of the application of hydrogels in drug release and tissue engineering, and the limitations and research directions of hydrogel in drug release and tissue engineering are also considered. We hope that this review can provide a reference for follow-up studies in related fields.
Introduction
Gelsemine is a natural alkaloid extracted from
Gelsemium elegans
Benth.
,
a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce ...neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases.
Results
In this study, we have found, for the first time, that gelsemine at low concentrations (5–10 μg/kg) significantly alleviated cognitive impairments induced by β-amyloid (Aβ) oligomer, a main neurotoxin of Alzheimer’s disease (AD). In addition, gelsemine substantially prevented Aβ oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3β (GSK3β), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aβ oligomer-induced reduction of PSD-95, a representative post-synaptic protein.
Conclusion
All these results directly demonstrated the anti-Aβ oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aβ-associated neurodegeneration disorders, including AD in particular.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Related to ABI3/VP1 (RAV) transcription factors have important roles in plant stress responses; however, it is unclear whether RAVs regulates oxidative stress response in cassava (Manihot esculenta). ...In this study, we report that MeRAV1/2 positively regulate oxidative stress resistance and catalase (CAT) activity in cassava. Consistently, RNA sequencing (RNA-seq) identifies three MeCATs that are differentially expressed in MeRAV1/2-silenced cassava leaves. Interestingly, MeCAT6 and MeCAT7 are identified as direct transcriptional targets of MeRAV1/2 via binding to their promoters. In addition, protein kinase MeKIN10 directly interacts with MeRAV1/2 to phosphorylate them at Ser45 and Ser44 residues, respectively, to promote their direct transcriptional activation on MeCAT6 and MeCAT7. Site mutation of MeRAV1S45A or MeRAV2S44A has no significant effect on the activities of MeCAT6 and MeCAT7 promoters or on oxidative stress resistance. In summary, this study demonstrates that the phosphorylation of MeRAV1/2 by MeKIN10 is essential for its direct transcriptional activation of MeCAT6/7 in response to oxidative stress.
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•MeRAV1/2 positively regulate oxidative stress resistance in cassava•MeRAV1/2 target MeCAT6 and MeCAT7 promoters to activate their transcripts•MeKIN10 physically interacts with and phosphorylates MeRAV1/2•MeRAV1S45 and MeRAV2S44 are essential for their phosphorylation
Wang et al. show that the phosphorylation of MeRAV1 and MeRAV2 at MeRAV1S45 and MeRAV2S44 by MeKIN10 is essential for the direct transcriptional activation of MeRAV1/2 on MeCAT6/7 via CACCTG or CAACA elements in MeCAT6/7 promoters, which further underlie CAT activity and oxidative stress resistance in cassava.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Passive radar detection emerges as a pivotal method for environmental perception and target detection within radar applications. Through leveraging its advantages, including minimal electromagnetic ...pollution and efficient spectrum utilization, passive radar methodologies have garnered increasing interest. In recent years, there has been an increasing selection of passive radar signal sources, and the emerging 5G has the characteristics of a high-frequency band, high bandwidth, and a large number of base stations, which give it significant advantages for use in passive radar. Therefore, in this paper, we introduce a passive radar target detection method based on 5G signals and design a rotating target speed measurement experiment. In the experiment, this paper validated the method of detecting rotating targets using 5G signals and evaluated the measurement accuracy, providing a research foundation for passive radar target detection using 5G signals and detecting rotating targets such as drone rotors.
To examine the expression of pro-interleukin-1β (pro-IL-1β) and interleukin-1β (IL-1β) in the vitreous body of patients with neovascular age-related macular degeneration(nAMD), polypoidal choroidal ...vasculopathy (PCV), proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or Eales' disease to further elucidate the role of IL-1β and inflammation in the pathogenesis of neovascular retinal disease.
Prospective clinical laboratory investigation study.
All patients enrolled had vitreous hemorrhage due to nAMD, PCV, PDR, RVO or Eales' disease that required vitrectomy. Patients were excluded for any history of active intraocular inflammation, or other ophthalmic surgery besides vitrectomy. Control samples were obtained from patients with idiopathic macular epiretinal membrane. A total of fifty vitreous samples were collected from patient during vitrectomy. Pro-IL-1β and IL-1β expression were measured by enzyme-linked immunosorbent assay (ELISA). Results were analyzed statistically using nonparametric tests.
Expression of pro-IL-1β protein was increased by 2.83-fold and 9.19-fold in PCV and nAMD vitreous samples relative to control, respectively. Expression of IL-β protein was increased by 10-fold and 4.83-fold in PCV and nAMD vitreous samples relative to control, respectively.
Our results demonstrate that expression of pro-IL-1β and IL-1β proteins is higher in PCV and nAMD. The roles of pro-IL-1β and IL-1β as inflammatory mediators in the development of PCV and nAMD may be associated with photoreceptor degeneration and neovascularization which necessitates further study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Retinal ischemia/reperfusion (IR) is common in eye disorders. Pattern-recognition receptors (PRRs) are reported to initiate sterile inflammatory response. The role of PRRs in retinal IR injury is ...currently unknown. Thus, we investigated the expression and function of membrane and cytoplasmic PRRs during retinal IR.
Retinal IR was induced in adult Brown Norway rats by clipping the retinal vessels for 30 minutes. RNA and proteins were extracted during the course of reperfusion, and the expression levels of the following proteins were determined: Toll-like receptor 2 (TLR2), TLR4, myeloid differentiation factor 88 (MyD88), TNF receptor-associated factor 6 (TRAF6), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP1), NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18. TLR4 expression in the retina was studied using immunohistochemistry. In addition, a TLR4 inhibitor was injected into the vitreous body as a therapeutic agent. After the treatment of TLR4 inhibitors, the levels of the above factors were evaluated, the apoptosis of cells in the retina, expression of cleaved-caspase-3 (c-casp-3), death of retinal ganglion cells, and the retina electroretinography was assessed.
After releasing the artery clamp, the retinal vessels were reperfused in 5 minutes. During the reperfusion, TLR4, MyD88, TRAF6, NF-κB, NLRP1, NLRP3, mature IL-1β, and IL-18 were upregulated, but not TLR2. In the IR model, TLR4 was highly expressed in ganglion cell and glia cell. Additionally, the inhibition of TLR4 significantly downregulated the activation of NLRP3, but not NLRP1, and the secretion of mature IL-1β and IL-18 also were inhibited. Moreover, the TLR4 inhibitor partially attenuated the injury of the retina, including alleviated retina apoptosis, downregulated c-casp-3 expression, rescued retinal ganglion cells death, and restored retina function.
These findings suggest that TLR4-signaling activation, triggered by damage-associated molecular patterns, regulates the activation of the NLRP3 inflammasomes and is responsible for the function of the retina in retinal IR injury.
Diabetic retinopathy (DR) diagnosis methods in the literature are usually criticized as being limit in diagnosing DR-related features or being lack of interpretability. To deal with these issues, ...this paper investigates the feasibility of diagnosing both DR severity levels and the presence of DR-related features in a two-step procedure. Specifically, this paper first analyzes the quality of annotations in DR grading by measuring inter-grader variability. Cosine similarity is considered to evaluate the inter-grader variability of the presence of DR-related features, and quadratic weighted Cohen's kappa is employed to assess the inter-grader variability of DR severity levels. Next, different annotation methods as follows are compared to DR severity prediction performance using logistic regression: 1) single annotations by single grader (SASG); 2) single annotations from multiple graders (SAMG); 3) multiple annotations by voting (MAV); and 4) double annotations with adjudication of disagreement (DAAD). Based on the comparison results, the feasibility of diagnosing both DR severity and features is investigated. In the experiments, 1589 fundus images graded by three retinal specialists and four general ophthalmologists are considered. The results demonstrate that retinal specialists are more consistent than general ophthalmologists in grading both the presence of DR-related features and DR severity. The SASG and MAV should be avoided if possible while the DAAD is the good option when prediction performance is the highest priority and the SAMG is especially beneficial when both prediction performance and grading costs are considered. The upper limit performance of DR severity prediction gets accuracy 95.6% and kappa 0.962. When DR-related feature prediction achieves average cosine similarity 0.823, it is potential to get accuracy 91.2% and kappa 0.905 for DR severity prediction in real applications. These results together suggest the potential of diagnosis of both DR severity and the presence of DR-related features in a two-step procedure.
To investigate the progression of epiretinal membranes after intravitreal bevacizumab (IVB) injection therapy in patients with proliferative membranes and evaluate the changes in fibrosis-related ...cytokines in retinal pigment epithelial cells and glial cells after treatment with bevacizumab.
Retrospective study of the proliferative membranes in patients with and without IVB therapy. In vitro, the human adult retinal pigment epithelial (ARPE-19) cells and BV2 microglial cell lines were incubated in different bevacizumab concentrations under hypoxic conditions. Cell culture supernatants and cell lysates were harvested after incubation for 24, 48 or 72 hours for ELISA and western blot.
Bevacizumab accelerated fibrosis in patients with proliferative membranes. Immunofluorescence analysis revealed more intense transforming growth factor β2 (TGFβ2) and connective tissue growth factor (CTGF) staining in IVB-treated proliferative diabetic retinopathy (PDR) membranes compared with membranes of patients not receiving IVB therapy. This result was consistent with real-time PCR results. Bevacizumab incubation significantly upregulated TGFβ2 and CTGF in ARPE-19 cells and BV2 microglial cells, but ciliary neurotrophic factor (CNTF) expression was upregulated only in BV2 microglial cells.
Anti-vascular endothelial growth factor treatment likely accelerates fibrosis in PDR patients via upregulation of TGFβ2, CTGF and CNTF, suggesting the importance of adjunctive therapy for retinal fibrosis.
Anti-vascular endothelial growth factor (VEGF) therapy as an effective therapeutic method has been a standard treatment strategy in retinal neovascular disease, contributing to restore vision and ...reduce the prevalence of blindness. With the research on the pathogenesis of retinal neovascular disease and implementation of clinical trials, anti-VEGF therapy is continuously optimized. Meanwhile, the complications after the use of anti-angiogenetic drugs are exposed. The present article summarizes the update and challenge of anti-VEGF therapy in retinal neovascular disease.
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