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The subgroup J avian leukosis virus (ALV-J), a retrovirus, uses its gp85 protein to bind to the receptor, the chicken sodium hydrogen exchanger isoform 1 (chNHE1), facilitating viral invasion. ALV-J is the main epidemic subgroup and shows noteworthy mutations within the receptor-binding domain (RBD) region of gp85, especially in ALV-J layer strains in China. However, the implications of these mutations on viral replication and transmission remain elusive. In this study, the ALV-J layer strain JL08CH3-1 exhibited a more robust replication ability than the prototype strain HPRS103, which is related to variations in the gp85 protein. Notably, the gp85 of JL08CH3-1 demonstrated a heightened binding capacity to chNHE1 compared to HPRS103-gp85 binding. Furthermore, we showed that the specific N123I mutation within gp85 contributed to the enhanced binding capacity of the gp85 protein to chNHE1. Structural analysis indicated that the N123I mutation primarily enhanced the stability of gp85, expanded the interaction interface, and increased the number of hydrogen bonds at the interaction interface to increase the binding capacity between gp85 and chNHE1. We found that the N123I mutation not only improved the viral replication ability of ALV-J but also promoted viral shedding in vivo. These comprehensive data underscore the notion that the N123I mutation increases receptor binding and intensifies viral replication.
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Vírus da Leucose Aviária , Leucose Aviária , Doenças das Aves Domésticas , Animais , Vírus da Leucose Aviária/genética , Vírus da Leucose Aviária/química , Mutação , Galinhas , Isoformas de Proteínas/genética , Proteínas do Envelope Viral/genéticaRESUMO
Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation. IMPORTANCE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.
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2',5'-Oligoadenilato Sintetase , Autofagia , Infecções por Birnaviridae , Galinhas , Vírus da Doença Infecciosa da Bursa , Proteínas Estruturais Virais , Replicação Viral , Vírus da Doença Infecciosa da Bursa/fisiologia , Animais , Infecções por Birnaviridae/virologia , Infecções por Birnaviridae/metabolismo , Proteínas Estruturais Virais/metabolismo , Proteínas Estruturais Virais/genética , 2',5'-Oligoadenilato Sintetase/metabolismo , 2',5'-Oligoadenilato Sintetase/genética , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/metabolismo , Interações Hospedeiro-Patógeno , Células HEK293 , Humanos , Linhagem CelularRESUMO
In arid regions, montane lakes are valuable water sources and play important ecological roles. However, recent human-induced inputs of organic pollutants are threatening lake ecology in such regions and becoming a matter of great concern. To investigate pollutant histories and sources, we measured polycyclic aromatic hydrocarbons (PAHs) and n-alkanes in a dated sediment core that spans the last â¼350 years, from montane Lake Issyk-Kul (Kyrgyzstan, Central Asia). Results showed that organic pollutants were delivered to Lake Issyk-Kul in four stages and that their concentrations increased from Stage I (â¼1670-1800 CE) to Stage IV (â¼2000-2010 CE). Furthermore, we tracked the sources of sedimented PAHs using their ratios combined with n-alkanes data. Ratios of PAHs Ant/(Ant + Phe), Flt/(Flt + Pyr) and Bap/BghiP indicated that inputs during Stage II (â¼1800-1970 CE) and Stage III (â¼1970-2000 CE) came mainly from high-temperature combustion of coal and vehicle emissions. PAHs in Stage I and Stage IV, however, were mainly derived from low-temperature combustion and petrogenic sources. Diagnostic PAH ratios, combined with the natural n-alkane ratio (NARï¼0) and unresolved complex mixtures (UCM), showed that the sources of PAHs in Stage I were mainly from erosion of bedrock and partly influenced by forest wildfires, different from the source during Stage IV, which was mainly from refined petroleum caused by accidental spills. Our assessment of the contamination history of the lake indicates that toxicity risk to the waterbody from sediment PAHs is low, but recent discharges arising from traffic deserve attention.
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Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Lagos/química , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Quirguistão , Alcanos/análiseRESUMO
BACKGROUND: Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. METHODS: C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. RESULTS: Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1ß. CONCLUSION: These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
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Autofagia , Catepsina B , Doenças Desmielinizantes , Gotículas Lipídicas , Lisofosfatidilcolinas , Camundongos Endogâmicos C57BL , MicroRNAs , Microglia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Microglia/patologia , Camundongos , Gotículas Lipídicas/metabolismo , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/patologia , Catepsina B/metabolismo , Catepsina B/genética , Lisofosfatidilcolinas/metabolismo , Modelos Animais de Doenças , Masculino , Regulação da Expressão Gênica , Linhagem CelularRESUMO
Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage.
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Glicosídeos Iridoides , Rehmannia , Glicosídeos Iridoides/farmacologia , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Humanos , Células Hep G2 , Estrutura Molecular , Rehmannia/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
Mitigation of nitrous oxide (N2O) emissions in full-scale wastewater treatment plant (WWTP) has become an irreversible trend to adapt the climate change. Monitoring of N2O emissions plays a fundamental role in understanding and mitigating N2O emissions. This paper provides a comprehensive review of direct and indirect N2O monitoring methods. The techniques, strengths, limitations, and applicable scenarios of various methods are discussed. We conclude that the floating chamber technique is suitable for capturing and interpreting the spatiotemporal variability of real-time N2O emissions, due to its long-term in-situ monitoring capability and high data acquisition frequency. The monitoring duration, location, and frequency should be emphasized to guarantee the accuracy and comparability of acquired data. Calculation by default emission factors (EFs) is efficient when there is a need for ambiguous historical N2O emission accounts of national-scale or regional-scale WWTPs. Using process-specific EFs is beneficial in promoting mitigation pathways that are primarily focused on low-emission process upgrades. Machine learning models exhibit exemplary performance in the prediction of N2O emissions. Integrating mechanistic models with machine learning models can improve their explanatory power and sharpen their predictive precision. The implementation of the synergy of nutrient removal and N2O mitigation strategies necessitates the calibration and validation of multi-path mechanistic models, supported by long-term continuous direct monitoring campaigns.
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Monitoramento Ambiental , Óxido Nitroso , Águas Residuárias , Óxido Nitroso/análise , Águas Residuárias/análise , Águas Residuárias/química , Monitoramento Ambiental/métodos , Eliminação de Resíduos Líquidos/métodosRESUMO
Monoculture is widely practiced to increase crop productivity, but long-term adaptation has drawbacks as it increases the depletion of soil nutrients and reduces soil quality, especially in dryland areas. Conversion from traditional maize monoculture to intercropping improves sustainable production. However, maize/peanut intercropping, especially rotation of planting strips impacts of maize/peanut intercropping in dryland on carbon (C) budgets and economic benefits remain unclear. In this study, a 5-year field experiment was conducted to evaluate the influence of maize/peanut intercropping with rotation of planting strips on soil health, indirect CO2-eq greenhouse gas emissions, and ecosystem C inputs. Four intercropping treatments viz. maize monoculture, peanut monoculture, maize/peanut intercropping, and maize/peanut rotation-intercropping were tested from 2018 to 2022. Maize/peanut rotation intercropping significantly improved the land equivalent ratio followed by intercropping and monoculture. Rotation-intercropping also improved economic benefits over intercropping and monoculture which were mainly associated with increased peanut yield where the border rows contributed the maximum, followed by the middle rows. Moreover, rotation-intercropping significantly increased the soil organic C and nitrogen (N) content. Rotation-intercropping decreased indirect CO2-eq greenhouse gas emissions and ecosystem C inputs by 3.11% and 18.04%, whereas increased ecosystem C outputs and net ecosystem C budget by 10.38% and 29.14%, respectively, over the average of monoculture. On average for intercropping and monoculture, rotation-intercropping increased ecosystem C emission efficiency for economic benefits by 51.94% and 227.27% in 2021 and 2022, respectively, showing the highest C utilization efficiency than other treatments. In the long run, maize/peanut rotation-intercropping can be practiced in dryland agriculture to achieve sustainable agriculture goals.
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Ecossistema , Gases de Efeito Estufa , Arachis , Zea mays , Dióxido de Carbono , Agricultura , Solo , ChinaRESUMO
Biomarkers n-alkanes and pertinent indices in lake sediments are frequently used to infer past changes in climate and environmental conditions in and around lakes. Interpretation of n-alkane records can be confounded by a lack of understanding of the multiple factors that control n-alkanes in sediments. Here, we studied n-alkanes in sediment cores from two alpine lakes, Lakes Son-Kul and Issyk-Kul, and from terminal Lake Balkhash, in arid Central Asia to identify natural and human-mediated influences on sediment n-alkane profiles. Altitudinal differences in climate, as well as in lake trophic status, proved to be important drivers of n-alkane compositional differences in the lake sediments. In the alpine lakes, the distribution of n-alkanes was biased toward long-chain components (n-C29, n-C31, and n-C33), and showed higher carbon preference index (CPIH) values, which come from dense terrestrial plant communities, promoted by greater precipitation. In contrast, n-alkanes in the core from the terminal lake displayed higher proportions of short-chain n-alkanes (n-C17, n-C19, and n-C21) because a greater proportion of the organic matter (OM) input to the sediments was derived from algae, a consequence of higher temperatures and trophic status. In recent decades, increasing nutrient inputs from human activities have caused greater accumulation of short-chain n-alkanes in sediments of alpine, oligotrophic Lake Issyk-Kul. In Lake Balkhash, n-C20 and n-C22 alkanes are exceptionally abundant, suggesting large contributions from microbial reworking of terrestrial OM. In all three study lakes, ∑(n-C29-n-C33) was elevated in sediments that correspond to periods of intense agricultural exploitation. Moreover, expansion of agriculture from low to high altitudes resulted in both synchronous and asynchronous peaks in ∑ (n-C29-n-C33) in the studied cores, suggesting the n-alkanes faithfully record the history of agricultural expansion. These findings provide insights into applications of n-alkane proxies and the response of the lake system to climate and anthropogenic impacts.
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Clinical evaluation evidence and model explainability are key gatekeepers to ensure the safe, accountable, and effective use of artificial intelligence (AI) in clinical settings. We conducted a clinical user-centered evaluation with 35 neurosurgeons to assess the utility of AI assistance and its explanation on the glioma grading task. Each participant read 25 brain MRI scans of patients with gliomas, and gave their judgment on the glioma grading without and with the assistance of AI prediction and explanation. The AI model was trained on the BraTS dataset with 88.0% accuracy. The AI explanation was generated using the explainable AI algorithm of SmoothGrad, which was selected from 16 algorithms based on the criterion of being truthful to the AI decision process. Results showed that compared to the average accuracy of 82.5±8.7% when physicians performed the task alone, physicians' task performance increased to 87.7±7.3% with statistical significance (p-value = 0.002) when assisted by AI prediction, and remained at almost the same level of 88.5±7.0% (p-value = 0.35) with the additional assistance of AI explanation. Based on quantitative and qualitative results, the observed improvement in physicians' task performance assisted by AI prediction was mainly because physicians' decision patterns converged to be similar to AI, as physicians only switched their decisions when disagreeing with AI. The insignificant change in physicians' performance with the additional assistance of AI explanation was because the AI explanations did not provide explicit reasons, contexts, or descriptions of clinical features to help doctors discern potentially incorrect AI predictions. The evaluation showed the clinical utility of AI to assist physicians on the glioma grading task, and identified the limitations and clinical usage gaps of existing explainable AI techniques for future improvement.
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Inteligência Artificial , Glioma , Humanos , Algoritmos , Encéfalo , Glioma/diagnóstico por imagem , NeurocirurgiõesRESUMO
Patchouli oil has exhibited remarkable efficacy in the treatment of colitis. However, its volatility and potential irritancy are often drawbacks when extensively used in clinical applications. Oil gel is a semisolid and thermoreversible system that has received extensive interest for its solubility enhancement, inhibition of bioactive component recrystallization, and the facilitation of controlled bioactive release. Therefore, we present a strategy to develop an oil gel formulation that addresses this multifaceted problem. Notably, a patchouli oil gel formulation was designed to solidify and trap patchouli oil into a spatially stable crystal-particle structure and colonic released delivery, which has an advantage of the stable structure and viscosity. The patchouli oil gel treatment of zebrafish with colitis improved goblet cells and decreased macrophages. Additionally, patchouli oil gel showed superior advantages for restoring the tissue barrier. Furthermore, our investigative efforts unveiled patchouli oil's influence on TRP channels, providing evidence for its potential role in mechanisms of anti-inflammatory action. While the journey continues, these preliminary revelations provide a robust foundation for considering the adoption of patchouli oil gel as a pragmatic intervention for managing colitis.
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Colite , Géis , Peixe-Zebra , Animais , Géis/química , Colite/tratamento farmacológico , Colite/patologia , Colite/induzido quimicamente , Sistemas de Liberação de Medicamentos , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Camundongos , Humanos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Óleos/químicaRESUMO
Thoroughly exploring carbon emissions within Urban Rail Transit (URT) systems is crucial for effectively reducing emissions while satisfying increasing energy demands. This study evaluated the spatiotemporal characteristics of carbon emissions in China's URT sector. Tapio decoupling and the Logarithmic Mean Divisia Index, used to scrutinize decoupling states and identify principal contributing factors, respectively, revealed the following: (1) Total emissions increased by 217 %, with significant spatiotemporal heterogeneity from 2015 to 2022. Type I and Type II cities accounted for >85 % of emissions but exhibited lower carbon intensity. (2) Most URT cities showed expansion-negative decoupling between economic growth and carbon emissions. Developed regions show strong decoupling, and the overall decoupling status improved in 2021-2022. (3) Emissions growth was influenced by energy intensity and economic activity, and transportation intensity was the main inhibitor for Type I cities and a driving force for other cities. Finally, recommendations for carbon emission reduction in the URT industry are proposed.
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In the context of global climate change, sudden rainstorms and typhoons induce fluctuations in hydraulic shocks to wastewater treatment plants (WWTPs) in coastal areas, causing two challenges of stable effluent quality and low-carbon operation. We established a quantitative evaluation method for resistance of wastewater treatment processes to hydraulic shocks based on the water-energy-carbon nexus using operational data from a WWTP in southeast coastal China from July 2018 to December 2022. The effects of hydraulic shocks on the operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process were analyzed following five steps. The results showed that the gray water footprint (GWF) of the process was 9.3% lower than that of the A2/O process. The energy footprint (ENF) and carbon footprint (CF) were approximately 2.1 times and 1.7 times higher than those of the A2/O process, respectively. The resistance to hydraulic shocks of the A2/O-MBR process is approximately 5.5 times higher than that of the A2/O process. In conclusion, the A2/O-MBR process exhibits higher process operational stability when subjected to hydraulic shocks, which is more conducive to the efficient and stable operation of WWTPs in rainstorm and typhoon-prone areas. The evaluation methodology provides qualitative technical support for selecting upgrading processes for WWTPs in different regions.
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BACKGROUND: Hypertension is one of the most common chronic diseases with a low control rate globally. The effect of communication skills training contributing to hypertension control remains uncertain. The aim of the present study was to assess the effectiveness of an educational intervention based on the Calgary-Cambridge guide in improving hypertensive management. METHODS: A cluster randomized controlled trial enrolled 27 general practitioners (GPs) and 540 uncontrolled hypertensive patients attending 6 community health centers in Chengdu, China. GPs allocated to the intervention group were trained by an online communication course and two face-to-face workshops based on Calgary-Cambridge guides. The primary outcome was blood pressure (BP) control rates and reductions in systolic and diastolic BP from baseline to 3 months. The secondary outcome was changes in GPs' communication skills after one month, patients' knowledge and satisfaction after 3 months. Bivariate analysis and the regression model assessed whether the health provider training improved outcomes. RESULTS: After the communication training, the BP control rate was significantly higher (57.2% vs. 37.4%, p < 0.001) in the intervention groups. Compared to the control group, there was a significant improvement in GP's communication skills (13.0 vs 17.5, p < 0.001), hypertensive patients' knowledge (18.0 vs 20.0, p < 0.001), and systolic blood pressure (139.1 vs 134.7, p < 0.001) after 3 months of follow-up. Random effects least squares regression models showed significant interactions between the intervention group and time period in the change of GP's communication skills (Parameter Estimated (PE): 0.612, CI:0.310,0.907, p = 0.006), hypertensive patient's knowledge (PE:0.233, CI: 0.098, 0.514, p < 0.001), satisfaction (PE:0.495, CI: 0.116, 0.706, p = 0.004), SBP (PE:-0.803, CI: -1.327, -0.389, p < 0.001) and DBP (PE:-0.918, CI: -1.694, -0.634, p < 0.001), from baseline to follow-up. CONCLUSION: Communication training based on the Calgary-Cambridge guide for GPs has shown to be an efficient way in the short term to improve patient-provider communication skills and hypertension outcomes among patients with uncontrolled BPs. TRIAL REGISTRATION: The trial was registered on Chinese Clinical Trials Registry on 2019-04-03. (ChiCTR1900022278).
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Medicina Geral , Hipertensão , Humanos , Medicina de Família e Comunidade , Pressão Sanguínea , ComunicaçãoRESUMO
AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.
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Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.
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Homeostase , Oxirredução , Espécies Reativas de Oxigênio , Cicatrização , Animais , Camundongos , Homeostase/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pé Diabético/tratamento farmacológico , Pé Diabético/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/químicaRESUMO
This project is to investigate chemical compositions from the roots of Erythrina corallodendron. Through the methods of silica gel,ODS,Sephadex LH-20 column chromatography and preparative HPLC,15 compounds were isolated from the 95% ethanol extract of the roots of E. corallodendron. Based on spectroscopic techniques,the structures of these compounds were identified as 10,11-dioxoerythraline( 1),erythrinine( 2),erythraline( 3),11-methoxyerythraline( 4),cristanines B( 5),erythratine( 6),erysotrine( 7),medioresinol( 8),( ±)-ficusesquilignan A( 9),( +)-pinoresinol( 10),nicotinic acid( 11),dibutyl phthalate( 12),vanillic acid( 13),3-hydroxy-1-( 4-hydroxy-3-methoxyphenyl)-1-propanone( 14),and syringic acid( 15). Compounds 8-10 are isolated from genus Erythrina for the first time and all compounds are isolated from E. corallodendron for the first time. Furthermore,this paper screened the antioxidant and cytotoxic activities of the compounds using models of liver microsomal oxidation inhibition and MTT.
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Antioxidantes , Cromatografia Líquida de Alta Pressão , Erythrina , Química , Microssomos Hepáticos , Compostos Fitoquímicos , Extratos Vegetais , Raízes de Plantas , QuímicaRESUMO
This project is to investigate lignans from the seed of Hydnocarpus anthelminthica. Thirteen lignans were isolated from the 95% ethanol extract of the seed of H. anthelminthica, by polyamide resin, Sephadex LH-20, ODS column chromatography and preparative HPLC. Their structures were elucidated as(+)-syringaresinol(1), lirioresinol A(2),(+)-medioresinol(3),(7R,8R,8'R)-4'-guaiacylglyceryl-evofolin B(4), leptolepisol C(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5,5',5″-hexamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5,5'-pentamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'ses-quineolignan-7″,9″-diol(7), ceplignan(8), hydnocarpusol(9), isohydnocarpin(10),(-)-hydnocarpin(11), hydnocarpin(12), and hydnocarpin-D(13) by spectroscopic data analysis. Compounds 1-8 were obtained from the genus Hydnocarpus for the first time.
Assuntos
Lignanas , Magnoliopsida , Química , Estrutura Molecular , Compostos Fitoquímicos , Extratos Vegetais , Sementes , QuímicaRESUMO
The aim of this paper was to investigate and compare the penetration-enhancing characteristics of menthol and essential oil from Mentha haplocalyx(M.haplocalyx oil) on the transdermal absorption of the complex traditional Chinese medicine(TCM) components. A series of TCM components were selected as model drugs based on their lipophilicity (logP value), namely osthole(OT, logP=3.85), tetramethylpyrazine(TMP, logP=2.34), ferulic acid(FA, logP=1.26), puerarin(PR, logP=-0.35) and geniposide(GP, logP=-1.01), in order to simply and characterize the TCM complex components system. Transdermal experiment in vitro was employed to investigate and compare the penetration-enhancing characteristics of menthol and M.haplocalyx oil on the transdermal absorption of these model drugs. Meanwhile, Fourier transform infrared spectroscopy(FTIR) was used to further compare the effect of menthol and M. haplocalyx oil on the molecular structure of stratum corneum(SC). The results showed that both of menthol and M.haplocalyx oil at proper concentration could promote the transdermal absorption of the selected model drugs. After application of menthol, the drug logP values gradually tended to have negative linear relationship with the logarithm of penetration enhancement ratio(ER); while after application of M.haplocalyx oil, the logP values tended to have parabolic relationship with the logarithm of ER. However, both menthol and M.haplocalyx oil exhibited higher efficiency for the drugs with relative low lgP value(ie hydrophilic drugs), with similar penetration-enhancing characteristics between these two. Infrared spectroscopy results showed that menthol and M.haplocalyx oil could affect the skin barrier functions mainly via stratum corneum lipids, with similar effect intensity, and this was consistent with the results of transdermal experiment in vitro. Thus, Menthol had similar penetration-enhancing characteristics with M.haplocalyx oil, and had same effect on the SC molecular structure. Therefore, as transdermal penetration enhancer, the menthol with single composition could be considered to replace M.haplocalyx oil with complex compositions.
RESUMO
To prepare pellets of supercritical fluid extraction (SFE) of Angelica Sinensis Radix by using the ionic crosslinking method, and the drug loading and encapsulation efficiency were used as the index to investigate the multiple factors which may impact the drug loading and encapsulation efficiency. Box-Behnken design and response surface analysis method were then taken to optimize the prescription of pellets and study the coating technology. Through the study on the release of pellets in vitro, an optimal coating technology and prescription of colon-specific pellets of Angelica Sinensis Radix SFE were selected and their colon targeting was evaluated. The optimal preparation parameters of pellets were determined as follows: 3% pectin; 4∶1 for pectin/lecithin; 4∶5 for pectin/SFE of Angelica Sinensis Radix; 4% zinc acetate solution as crosslinking agent, blending temperature 35 ℃, crosslinking temperature 35 ℃, crosslinking time 30 min; coating technology: coating material Eudragit FS 30D, 1.5% triethyl citrate and polyoxyethylene sorbitan monooleate(tween-80), 1.2% monostearin and 15% coating weight gained. The colon-specific pellets of Angelica Sinensis Radix SFE prepared with optimized conditions were almost not released in simulated gastric fluid in 2 h, released less than 20% in simulated intestine fluid in 4 h, and released more than 90% in simulated colon fluid in 6 h, indicating that the colon-specific pellets of Angelica Sinensis Radix SFE had an excellent colon targeting property.