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Introduction: Cannabidiol (CBD) has a variety of pharmacological effects including antiepileptic, antispasmodic, anxiolytic and anti-inflammatory among other pharmacological effects. However, since CBD is a terpene-phenolic compound, its clinical application is limited by its poor water solubility, low stability, and low bioavailability. Methods: In this study, we used several strategies to address the above problems. Hydrochloric acid was used to modify zein to improve the molecular flexibility. Flexible zein nanoparticles (FZP-CBD) loaded with CBD was prepared to improve the stability and bioavailability of CBD. The parameters were evaluated in terms of morphology, particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), loading capacity (LC%), and storage stability. Simulated gastrointestinal fluid release experiment and bioavailability assay were applied in the evaluation. Results: The simulated gastrointestinal fluid experiment showed that the release rates of FZP-CBD and natural zein nanoparticles (NZP-CBD) loaded with CBD were 3.57% and 89.88%, respectively, after digestion with gastric fluid for 2 h, 92.12% and 92.56%, respectively, after intestinal fluid digestion for 2 h. Compared with NZP-CBD, the C max of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively. Discussion: The experimental results showed that FZP-CBD could protect most of the CBD from being released in the stomach, and then control its release in the intestines, promote the absorption of CBD in the small intestine, and increase the bioavailability of CBD. Therefore, FZP-CBD could improve the utilization value of CBD and provide a new idea for the application of CBD in medicine and pharmacy.
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The growing interest in cost-effective and high-performing perovskite solar cells (PSCs) has driven extensive research. However, the challenge lies in upscaling PSCs while maintaining high performance. This study focuses on achieving uniform and compact perovskite films without pinholes and interfacial voids during upscaling from small PSCs to large-area modules. Competition in nucleation at concavities with various angles on rough-textured substrates during the gas-pumping drying process, coupled with different drying rates across the expansive film, aggravates these issues. Consequently, substrate roughness notably influences the deposition window of compact large-area perovskite films. We propose a supersaturation regulation approach aimed at achieving compact deposition of high-quality perovskite films over large areas. This involves introducing a rapid drying strategy to induce a high-supersaturation state, thereby equalizing nucleation across diverse concavities. This breakthrough enables the production of perovskite photovoltaics with high efficiencies of 25.58, 21.86, and 20.62% with aperture areas of 0.06, 29, and 1160 square centimeters, respectively.
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Background and Aims: Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors while sparing healthy tissues. This study aimed to investigate the effects of SVA on HCC cells in vitro and in vivo and to elucidate its mechanisms of action. Methods: The cell counting kit-8 assay and colony formation assay were conducted to examine cell proliferation. Flow cytometry and nuclear staining were employed to analyze cell cycle distribution and apoptosis occurrence. A subcutaneous tumor xenograft HCC mouse model was created in vivo using HepG2 cells, and Ki67 expression in the tumor tissues was assessed. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were employed to evaluate HCC apoptosis and the toxicity of SVA on mouse organs. Results: In vitro, SVA effectively suppressed the growth of tumor cells by inducing apoptosis and cell cycle arrest. However, it did not have a notable effect on normal hepatocytes (MIHA cells). In an in vivo setting, SVA effectively suppressed the growth of HCC in a mouse model. SVA treatment resulted in a significant decrease in Ki67 expression and an increase in apoptosis of tumor cells. No notable histopathological alterations were observed in the organs of mice during SVA administration. Conclusions: SVA inhibits the growth of HCC cells by inducing cell cycle arrest and apoptosis. It does not cause any noticeable toxicity to vital organs.
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INTRODUCTION: Early identification of patients with sepsis at high risk of death remains a challenge, and whether brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a prognostic effect on patients with sepsis is controversial. Here, we clarified the prognostic value of BNP and NT-proBNP and sought to establish suitable cutoff values and intervals. METHODS: We searched five databases to identify studies that met the inclusion criteria. The primary outcomes were the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and corresponding 95% credible interval (95% CI) of BNP and NT-proBNP. The secondary outcomes were the sensitivity and specificity of BNP or NT-proBNP in subgroup analyses. RESULTS: Forty-seven studies were included in our meta-analysis. The pooled sensitivity of NT-proBNP (0.77 [0.68, 0.84]) was weaker than that of BNP (0.82 [0.76, 0.87]), the pooled specificity of NT-proBNP (0.70 [0.60, 0.77]) was less than that of BNP (0.77 [0.71, 0.82]), and the AUC of BNP (0.87 [0.83-0.89]) was greater than that of NT-proBNP (0.80 (0.76-0.83]). The results of the subgroup analysis showed that the cutoff range of 400-800 pg/mL for BNP had high sensitivity (0.86 [0.74-0.98]) and specificity (0.87 [0.81-0.93]) and was probably the most appropriate cutoff range. CONCLUSIONS: Elevated levels of BNP and NT-proBNP were significantly related to the mortality of patients with sepsis and had a moderate prognostic value in predicting the mortality of patients with sepsis. In addition, our meta-analysis preliminarily established appropriate cutoff values for BNP and NT-proBNP.
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Biomarcadores , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Sepse , Humanos , Peptídeo Natriurético Encefálico/sangue , Sepse/mortalidade , Sepse/sangue , Sepse/diagnóstico , Biomarcadores/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
P-type hydrogenated nanocrystalline silicon (nc-Si:H) has been used as a hole-selective layer for efficient n-type crystalline silicon heterojunction (SHJ) solar cells. However, the presence of an additional valence band offset at the interface between intrinsic amorphous hydrogenated silicon and p-type nc-Si:H films will limit the hole carrier transportation. In this work, it has been found that when a heavily boron-doped silicon oxide layer deposited with high hydrogen dilution to silane (pB) was inserted into their interface, the fill factor of SHJ solar cells increases 3% absolutely because of the reduced valence band offset and the increased opportunity to provide a hopping tunnel assisted by the doping energy level and valence band tail states. Furthermore, the additional boron incorporation in intrinsic amorphous silicon adjacent to pB helps to enhance the built-in electric field, thus increasing the hole selectivity. By these means, the power conversion efficiency was improved from 23.9% to approximately 25%.
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Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.
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Prolactinoma was the most common functional pituitary neuroendocrine tumor tissue type, which was caused by excessive proliferation of pituitary prolactin (PRL) cells. Drug therapy of dopamine receptor agonists was generally considered as the prior treatment for prolactinoma patients. However, there were still prolactinoma patients who were resistant to dopamine agonists. Studies have been reported that paeoniflorin can inhibit the secretion of PRL in prolactinoma cells lacking dopamine D2 receptor (D2R) expression, and paeoniflorin can be metabolized into albiflorin by intestinal flora in rats. The effect of albiflorin on prolactinoma has not been reported yet. In this study, network pharmacology was used to analyze the mechanism of paeoniflorin and its metabolite albiflorin as multi-target therapy for prolactinoma, and the experimental verification was carried out. In order to clarify the complex relationship among paeoniflorin, albiflorin and prolactinoma, we constructed a component-target-disease network, and further constructed interaction network, MMP9, EGFR, FGF2, FGFR1 and LGALS3 were screened as the core targets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that paeoniflorin and albiflorin may be involved in various pathways in the treatment of prolactinoma, included relaxin signaling pathway and PI3K-Akt signaling pathway. Molecular docking analysis showed that paeoniflorin and albiflorin had good binding activity with MMP9. Western blotting results showed that paeoniflorin and albiflorin could significantly reduce the expression of MMP9, and ELISA results showed that paeoniflorin and albiflorin could significantly reduce the concentration of PRL in GH3 cells, and the reduce degree of albiflorin was stronger than paeoniflorin at 50 µM, which indicated that albiflorin might be a potential drug to treat prolactinoma, which can regulate prolactinoma through MMP9 and reduce the concentration of PRL. Our study provided a new therapeutic strategy for prolactinoma.
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The high concentration of organic waste liquid obtained from the mini flush pipeline discharge technology based on source separation has the potential for fertilizer utilization. However, there are concerns about the risk of secondary pollution. This study proposes the idea of aeration treatment for regenerated liquid fertilizers to induce beneficial changes in their material composition and properties. Initially, this study compares the characteristic changes in nitrogen transformation of liquid fertilizer through aeration treatment. Subsequently, it examines the effects of different types of liquid fertilizers on soil properties, plant physiology, and soil microbial communities. Finally, we elucidate the flow and distribution of nitrogen in soil, plants, and nitrogen-containing gas emissions in agricultural ecosystems through material flow accounting. The study found that aeration treatment can reduce the ammonia nitrogen ratio while increasing the proportions of nitrite nitrogen and nitrate nitrogen. The regenerated liquid fertilizer through aeration treatment not only significantly increased the chlorophyll, protein, and polysaccharide content of vegetable leaves (P < 0.05) but also reduced nitrate accumulation. Moreover, it can reduce the risk of soil nitrate nitrogen leaching and increase the diversity of soil bacterial communities, enhancing the ecological functions of bacteria involved in carbon and nitrogen cycling. Material flow accounting indicated that aeration treatment for liquid fertilizer could reduce gaseous nitrogen loss by 50.0 %, improve the nitrogen utilization efficiency of vegetables by 95.5 %, and enhance soil nitrogen retention by 11.4 %. Overall, the results show that aeration treatment can improve the agricultural utilization of liquid fertilizer and reduce the risk of secondary pollution, providing preliminary decision-making support for optimizing resource treatment strategies for mini-flush toilet fecal waste to realize the agricultural cycle.
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Agricultura , Fertilizantes , Nitrogênio , Agricultura/métodos , Nitrogênio/análise , Microbiologia do Solo , Solo/químicaRESUMO
In the context of escalating urban heat events due to climate change, air conditioning (AC) has become a critical factor in maintaining indoor thermal comfort. Yet the usage of AC can also exacerbate outdoor heat stress and burden the electricity system, and there is little scientific knowledge regarding how to balance these conflicting goals. To address this issue, we established a coupled modeling approach, integrating the Weather Research and Forecasting model with the building energy model (WRF_BEP + BEM), and designed multiple AC usage scenarios. We selected Chongqing, China's fourth-largest megacity, as our study area due to its significant socioeconomic importance, the severity of extreme heat events, and the uniqueness of its energy infrastructure. Our analysis reveals that AC systems can substantially reduce indoor temperatures by up to 18 °C; however, it also identifies substantial nighttime warming (2-2.5 °C) and a decline in thermal comfort. Particularly for high-density neighborhoods, when we increase 2 °C indoors, the outdoor temperature can be alleviated by up to 1 °C. Besides, despite the limited capacity to regulate peak electricity demand, we identified that reducing the spatial cooled fraction, increasing targeted indoor temperature by 2 °C, and implementing temporal AC schedules can effectively lower energy consumption in high-density neighborhoods, especially the reduction of spatial cooled fraction (up to 50%). Considering the substantial demand for cooling energy, it is imperative to carefully assess the adequacy and continuity of backup energy sources. The study underscores the urgency of reassessing energy resilience and advocates for addressing the thermal equity between indoor and outdoor environments, contributing to the development of a sustainable and just urban climate strategy in an era of intensifying heat events.
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Ar Condicionado , Mudança Climática , China , Temperatura , Modelos TeóricosRESUMO
Transformer-based one-stream trackers are widely used to extract features and interact information for visual object tracking. However, the current one-stream tracker has fixed computational dimensions between different stages, which limits the network's ability to learn context clues and global representations, resulting in a decrease in the ability to distinguish between targets and backgrounds. To address this issue, a new scalable one-stream tracking framework, ScalableTrack, is proposed. It unifies feature extraction and information integration by intrastage mutual guidance, leveraging the scalability of target-oriented features to enhance object sensitivity and obtain discriminative global representations. In addition, we bridge interstage contextual cues by introducing an alternating learning strategy and solve the arrangement problem of the two modules. The alternating learning strategy uses alternate stacks of feature extraction and information interaction to focus on tracked objects and prevent catastrophic forgetting of target information between different stages. Experiments on eight challenging benchmarks (TrackingNet, GOT-10k, VOT2020, UAV123, LaSOT, LaSOT [Formula: see text] , OTB100, and TC128) show that ScalableTrack outperforms state-of-the-art (SOTA) methods with better generalization and global representation ability.
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The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.
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Afídeos , Sistema Enzimático do Citocromo P-450 , Resistência a Inseticidas , Inseticidas , MicroRNAs , Neonicotinoides , Nitrocompostos , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Animais , Inseticidas/farmacologia , Resistência a Inseticidas/genética , Afídeos/genética , Afídeos/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Imidazóis/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Volatile oil is widely used in traditional Chinese medicine owing to its unique hydrophobic and lipophilic properties and rapid skin absorption. Artemisia annua L. (A.annua) essential oil (AAEO), a volatile oil extracted from A. annua, exhibits anti-inflammatory properties. However, few studies have investigated its effects on skin inflammation. AIM OF THE STUDY: To investigate and elucidate the mechanisms of action of AAEO in the treatment of atopic dermatitis (AD). MATERIALS AND METHODS: Network pharmacology was used to predict the targets and pathways of AAEO for the treatment of AD. The AD mouse model was established by topical application of 2,4-dintrochlorobenzene (DNCB), AAEO, and the positive control drug hydrocortisone butyrate cream (HBC). We evaluated the symptoms of AD, SCORAD scores, histological analysis, and serum IgE and TNF-α levels in mice. Immunofluorescence, western blotting, and qPCR were used to investigate the signaling pathways. RESULTS: Network pharmacology analysis indicated that AAEO may exert its effects via the MAPK/NF-κB signaling pathway. Animal experiments demonstrated that topical application of AAEO and HBC significantly ameliorated skin lesions, reduced dermatitis score, and decreased spleen weight compared to DNCB treatment. AAEO reduced skin epidermal thickness and mast cell infiltration. DNCB markedly reduced the protein levels of filaggrin (FLG) and loricrin (LOR), whereas AAEO reversed these changes. Notably, the 5% concentration of AAEO demonstrated substantial improvement in skin barrier function. Compared to the DNCB group, the levels of FLG and LOR remained almost unchanged following HBC treatment. DNCB markedly elevated IgE and TNF-α levels, which were reversed by AAEO and HBC treatment. Among the inflammatory cytokines, DNCB increased mRNA expression of TNF-α, IL-1ß, and IL-6, however, it reduced IL-10, with AAEO and HBC reversing these changes to various degrees. Additionally, DNCB-induced ERK, JNK, and P38 phosphorylation, associated with the upregulation of phosphorylation of NF-κB, whereas, AAEO and HBC exhibited potent inhibition of the MAPK/NF-κB signaling pathway. CONCLUSIONS: This study systematically demonstrated the possible therapeutic effects and mechanisms of AAEO in AD via network pharmacological analysis and experimental confirmation. These results revealed that topical application of AAEO can suppress skin inflammation and restore skin barrier function. These findings provide the potential application of AAEO in synthesizing external preparations for both pharmacological and cosmetic industries.
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Artemisia annua , Dermatite Atópica , Dinitroclorobenzeno , Proteínas Filagrinas , Camundongos Endogâmicos BALB C , Óleos Voláteis , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Óleos Voláteis/farmacologia , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Camundongos , Artemisia annua/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , NF-kappa B/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Modelos Animais de Doenças , Masculino , Administração Cutânea , Imunoglobulina E/sangue , Administração Tópica , Transdução de Sinais/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genéticaRESUMO
Underwater images usually exhibit severe color cast, hazy appearance, and/or dark regions because of the complex lighting absorption and scattering in water. How to increase the quality of these degraded underwater images has emerged as a key issue for various underwater application tasks. Recent efforts have been made to deal with single type degradation, however, it is still challenging to deal with multiple degradations that usually coexist in an underwater image with a general network. The degradations in underwater images can be divided into medium-agnostic (hazy or low-light which also encountered in in-air images) and medium-specific (color distortion caused by the specific light attenuation property in water) ones. According to this observation, this article proposes a cascaded multimodule underwater image enhancement (UIE) framework to address the coexisted multiple degradations. In the proposed framework, an in-air image enhancement module and a novel proposed adaptive color channel compensation network (AC 3 Net) are cascaded, in which the former focuses primarily on solving medium-agnostic degradations and the latter is for handling the medium-specific degradation. This framework has good flexibility by cascading different types of in-air image enhancement networks with AC 3 Net to achieve various UIE. The effectiveness of the proposed framework has been extensively validated on various degraded underwater images as well as different underwater visual perception tasks.
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As the power core of an electric vehicle, the performance of lithium-ion batteries (LIBs) is directly related to the vehicle quality and driving range. However, the charge-discharge performance and cycling performance are affected by the temperature. Excessive temperature can cause internal short circuits and even lead to safety issues, such as thermal runaway. The separator plays a crucial role in protecting the battery from regular operation, preventing direct touch between the cathode and the anode while allowing the transport of lithium ions. In this study, we have designed a thermoregulating separator in the shape of calabash, which uses melamine-encapsulated paraffin phase change material (PCM) with a wide enthalpy (0-168.52 J g-1) to dissipate the heat generated inside the battery promptly. Under extra-long-use conditions, the heat emitted by the battery is absorbed by the PCM without causing a significant temperature rise that triggers thermal runaway. The PCM separator can effectively suppress the temperature increase caused by battery penetration. Due to the unique structure of the PCM, the battery is short-circuited; it can significantly delay the internal temperature rise of the battery and quickly dissipate the heat, which is consistent with the characteristics of natural calabash in nutrient absorption and water diffusion, improving the melting and heat storage efficiency of the PCM. The design of the phase change separator provides an effective reference for overheat protection and improved safety in lithium-ion batteries.
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Hepatitis B virus (HBV) infection is a major global health burden with 820 000 deaths per year. In our previous study, we found that the knockdown of autophagy-related protein 5 (ATG5) significantly upregulated the interferon-stimulated genes (ISGs) expression to exert the anti-HCV effect. However, the regulation of ATG5 on HBV replication and its underlying mechanism remains unclear. In this study, we screened the altered expression of type I interferon (IFN-I) pathway genes using RT² Profiler™ PCR array following ATG5 knock-down and we found the bone marrow stromal cell antigen 2 (BST2) expression was significantly increased. We then verified the upregulation of BST2 by ATG5 knockdown using RT-qPCR and found that the knockdown of ATG5 activated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. ATG5 knockdown or BST2 overexpression decreased Hepatitis B core Antigen (HBcAg) protein, HBV DNA levels in cells and supernatants of HepAD38 and HBV-infected NTCP-HepG2. Knockdown of BST2 abrogated the anti-HBV effect of ATG5 knockdown. Furthermore, we found that ATG5 interacted with BST2, and further formed a ternary complex together with HBV-X (HBx). In conclusion, our finding indicates that ATG5 promotes HBV replication through decreasing BST2 expression and interacting with it directly to antagonize its antiviral function.
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Antígenos CD , Proteína 5 Relacionada à Autofagia , Antígeno 2 do Estroma da Médula Óssea , Proteínas Ligadas por GPI , Vírus da Hepatite B , Replicação Viral , Humanos , Antígenos CD/genética , Antígenos CD/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Técnicas de Silenciamento de Genes , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/genética , Células Hep G2 , Hepatite B/virologia , Hepatite B/genética , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/genética , Interações Hospedeiro-Patógeno , Transdução de Sinais , Antígeno 2 do Estroma da Médula Óssea/metabolismoRESUMO
Photobiomodulation (PBM) therapy uses light of different wavelengths to treat various retinal degeneration diseases, but the potential damage to the retina caused by long-term light irradiation is still unclear. This study were designed to detect the difference between long- and short-wavelength light (650-nm red light and 450-nm blue light, 2.55 mW/cm2, reference intensity in PBM)-induced injury. In addition, a comparative study was conducted to investigate the differences in retinal light damage induced by different irradiation protocols (short periods of repeated irradiation and a long period of constant irradiation). Furthermore, the protective role of PARP-1 inhibition on the molecular mechanism of blue light-induced injury was confirmed by a gene knockdown technique or a specific inhibitor through in vitro and in vivo experiments. The results showed that the susceptibility to retinal damage caused by irradiation with long- and short-wavelength light is different. Shorter wavelength lights, such as blue light, induce more severe retinal damage, while the retina exhibits better resistance to longer wavelength lights, such as red light. In addition, repeated irradiation for short periods induces less retinal damage than constant exposure over a long period. PARP-1 plays a critical role in the molecular mechanism of blue light-induced damage in photoreceptors and retina, and inhibiting PARP-1 can significantly protect the retina against blue light damage. This study lays an experimental foundation for assessing the safety of phototherapy products and for developing target drugs to protect the retina from light damage.
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Luz , Poli(ADP-Ribose) Polimerase-1 , Retina , Degeneração Retiniana , Animais , Poli(ADP-Ribose) Polimerase-1/metabolismo , Camundongos , Luz/efeitos adversos , Retina/efeitos da radiação , Retina/patologia , Degeneração Retiniana/etiologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/prevenção & controle , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/metabolismo , Modelos Animais de Doenças , Western Blotting , Masculino , Terapia com Luz de Baixa Intensidade , Luz AzulRESUMO
Chronic cerebral hypoperfusion (CCH) is a primary contributor to cognitive decline in the elderly. Enriched environment (EE) is proved to improve cognitive function. However, mechanisms involved remain unclear. The purpose of the study was exploring the mechanisms of EE in alleviating cognitive deficit in rats with CCH. To create a rat model of CCH, 2-vessel occlusion (2-VO) surgery was performed. All rats lived in standard or enriched environments for 4 weeks. Cognitive function was assessed using the novel object recognition test and Morris water maze test. The protein levels of glutamatergic synapses, neurotoxic reactive astrocytes, reactive microglia, and JAK2-STAT3 signaling pathway were measured using Western blot. The mRNA levels of synaptic regulatory factors, C1q, TNF-α, and IL-1α were identified using quantitative PCR. Immunofluorescence was used to detect glutamatergic synapses, neurotoxic reactive astrocytes, and reactive microglia, as well as the expression of p-STAT3 in astrocytes in the hippocampus. The results demonstrated that the EE mitigated cognitive impairment in rats with CCH and enhanced glutamatergic synaptogenesis. EE also inhibited the activation of neurotoxic reactive astrocytes. Moreover, EE downregulated microglial activation, levels of C1q, TNF-α and IL-1α and phosphorylation of JAK2 and STAT3. Our results suggest that inhibition of neurotoxic reactive astrocytes may be one of the mechanisms by which EE promotes glutamatergic synaptogenesis and improves cognitive function in rats with CCH. The downregulation of reactive microglia and JAK2-STAT3 signaling pathway may be involved in this process.
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Isquemia Encefálica , Disfunção Cognitiva , Humanos , Idoso , Animais , Ratos , Astrócitos , Complemento C1q , Fator de Necrose Tumoral alfa , Cognição , Janus Quinase 2 , Fator de Transcrição STAT3RESUMO
BACKGROUND: The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model. METHODS: A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43). RESULTS: Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury. CONCLUSION: The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.
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Axônios , Interleucina-4 , Regeneração Nervosa , Células Ganglionares da Retina , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Animais , Interleucina-4/farmacologia , Axônios/efeitos dos fármacos , Axônios/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Traumatismos do Nervo Óptico/patologia , Traumatismos do Nervo Óptico/tratamento farmacológico , N-Metilaspartato/farmacologia , Estaurosporina/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas Recombinantes/farmacologiaRESUMO
Large-aperture, lightweight, and high-resolution imaging are hallmarks of major optical systems. To eliminate aberrations, traditional systems are often bulky and complex, whereas the small volume and light weight of diffractive lenses position them as potential substitutes. However, their inherent diffraction mechanism leads to severe dispersion, which limits their application in wide spectral bands. Addressing the dispersion issue in diffractive lenses, we propose a chromatic aberration correction algorithm based on compressed sensing. Utilizing the diffractive lens's focusing ability at the reference wavelength and its degradation performance at other wavelengths, we employ compressed sensing to reconstruct images from incomplete image information. In this work, we design a harmonic diffractive lens with a diffractive order of M=150, an aperture of 40 mm, a focal length f0=320 mm, a reference wavelength λ0=550 nm, a wavelength range of 500-800 nm, and 7 annular zones. Through algorithmic recovery, we achieve clear imaging in the visible spectrum, with a peak signal-to-noise ratio (PSNR) of 22.85 dB, a correlation coefficient of 0.9596, and a root mean square error (RMSE) of 0.02, verifying the algorithm's effectiveness.
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The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two-step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro-([1,1'-biphenyl]-4,4'-diyl)-dimethanaminium (OFPP) iodide which does not form low-dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP-PVK) film. Combined with the effective defect passivation, the OFPP-PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP-based perovskite solar cells exhibit a champion efficiency of 24.76 % with better device stability. Moreover, a superior efficiency of 21.04 % was achieved in a large-area perovskite module (100â cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.