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Alzheimer's disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer's disease. Currently, the efficacy of drugs in treating Alzheimer's disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer's disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer's disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer's disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer's disease. The application of nanotechnology to the development of Alzheimer's disease drugs brings new ideas and approaches for future treatment of this disease.
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Specific leaf area (SLA) and leaf dry matter content (LDMC) are key leaf functional traits often used to reflect plant resource utilization strategies and predict plant responses to environmental changes. In general, grassland plants at different elevations exhibit varying survival strategies. However, it remains unclear how grassland plants adapt to changes in elevation and their driving factors. To address this issue, we utilized SLA and LDMC data of grassland plants from 223 study sites at different elevations in China, along with climate and soil data, to investigate variations in resource utilization strategies of grassland plants along different elevational gradients and their dominant influencing factors employing linear mixed-effects models, variance partitioning method, piecewise Structural Equation Modeling, etc. The results show that with increasing elevation, SLA significantly decreases, and LDMC significantly increases (P < 0.001). This indicates different resource utilization strategies of grassland plants across elevation gradients, transitioning from a "faster investment-return" at lower elevations to a "slower investment-return" at higher elevations. Across different elevation gradients, climatic factors are the main factors affecting grassland plant resource utilization strategies, with soil nutrient factors also playing a non-negligible coordinating role. Among these, mean annual precipitation and hottest month mean temperature are key climatic factors influencing SLA of grassland plants, explaining 28.94% and 23.88% of SLA variation, respectively. The key factors affecting LDMC of grassland plants are mainly hottest month mean temperature and soil phosphorus content, with relative importance of 24.24% and 20.27%, respectively. Additionally, the direct effect of elevation on grassland plant resource utilization strategies is greater than its indirect effect (through influencing climatic and soil nutrient factors). These findings emphasize the substantive impact of elevation on grassland plant resource utilization strategies and have important ecological value for grassland management and protection under global change.
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The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.
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Nanoestruturas , Doenças Neurodegenerativas , Nanomedicina Teranóstica , Humanos , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendências , Nanoestruturas/uso terapêutico , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/diagnóstico por imagem , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , AnimaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY: This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND METHODS: LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage. RESULTS: Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis. CONCLUSION: Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.
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Atherosclerotic plaque formation is largely attributed to the impaired efferocytosis, which is known to be associated with the pathologic upregulation of cluster of differentiation 47 (CD47), a key antiphagocytic molecule. By gene expression omnibus (GEO) datasets analysis, we identified that four miRNAs are aberrantly downregulated in atherosclerosis, coronary artery disease, and obesity. Of them, hsa-miR-299-3p (miR-299-3p) was predicted to target the 3'UTR of human CD47 mRNA by bioinformatics analysis. Further, we demonstrated that miR-299-3p negatively regulates CD47 expression by binding to the target sequence "CCCACAU" in the 3'UTR of CD47 mRNA through luciferase reporter assay and site-directed mutagenesis. Additionally, we found that miR-299-3p was downregulated by ~32% in foam cells in response to oxidized low-density lipoprotein (ox-LDL) stimulation, thus upregulating CD47 and contributing to the impaired efferocytosis. Whereas, restoration of miR-299-3p reversed the ox-LDL-induced upregulation of CD47, thereby facilitating efferocytosis. In high-fat diet (HFD) fed ApoE-/- mice, we discovered that miR-299-3p was downregulated thus leading to upregulation of CD47 in abdominal aorta. Conversely, miR-299-3p restoration potently suppressed HFD-induced upregulation of CD47 and promoted phagocytosis of foam cells by macrophages in atherosclerotic plaques, thereby reducing necrotic core, increasing plaque stability, and mitigating atherosclerosis. Conclusively, we identify miR-299-3p as a negative regulator of CD47, and reveal a molecular mechanism whereby the ox-LDL-induced downregulation of miR-299-3p leads to the upregulation of CD47 in foam cells thus contributing to the impaired efferocytosis in atherosclerosis, and propose miR-299-3p can potentially serve as an inhibitor of CD47 to promote efferocytosis and ameliorate atherosclerosis.
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Aterosclerose , Antígeno CD47 , Eferocitose , MicroRNAs , Animais , Humanos , Camundongos , Regiões 3' não Traduzidas , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Antígeno CD47/metabolismo , Antígeno CD47/genética , Dieta Hiperlipídica/efeitos adversos , Células Espumosas/metabolismo , Células Espumosas/patologia , Lipoproteínas LDL/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Vision plays a crucial role in the survival of animals, and the visual system has particularly selectively evolved in response to the visual environment, ecological niche, and species habitats in vertebrate species. To date, a horizontal streak of retinal ganglion cell (RGC) distribution pattern is observed across mammal species. Here, we report that the giant panda's vertically oriented visual streak, combined with current evidence of the animal's forward-placed eyes, ocular structure, and retinal neural topographic distribution patterns, presents the emergence of a well-adapted binocular visual system. Our results suggest that the giant panda may use a unique way to processing binocular visual information. Results of mathematical simulation are in favor of this hypothesis. The topographic distribution properties of RGCs reported here could be essential for understanding the visual adaptation and evolution of this living fossil.
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Células Ganglionares da Retina , Ursidae , Animais , Células Ganglionares da Retina/citologia , Ursidae/anatomia & histologia , Ursidae/fisiologia , Retina/citologia , Retina/anatomia & histologiaRESUMO
BACKGROUND: Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis. METHODS AND RESULTS: We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in ß-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera. CONCLUSION: These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.
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Microbioma Gastrointestinal , Síndrome Metabólica , Esquizofrenia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , China , Comorbidade , Citocinas/metabolismo , Disbiose/microbiologia , Disbiose/imunologia , Disbiose/complicações , População do Leste Asiático , Fezes/microbiologia , Imunidade , Síndrome Metabólica/microbiologia , Síndrome Metabólica/imunologia , Síndrome Metabólica/complicações , Esquizofrenia/microbiologia , Esquizofrenia/imunologia , Esquizofrenia/complicaçõesRESUMO
Background and objectives: The advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses. Methods: We classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up. Results: Compared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and ß-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year. Conclusions: The PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.
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This study explored 1-year follow-up of Parmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) in patients with acute ST-segment elevation myocardial infarction (STEMI). The follow-up endpoints were major adverse cardiovascular events (MACEs) occurring within 30 days and 1 year, as well as postoperative bleeding events. The study ultimately included 150 subjects, with 75 in the primary percutaneous coronary intervention (PPCI) group and 75 in the PHDP group. This study found that the PHDP group had a shorter FMC-reperfusion time (42.00 min vs 96.00 min, P < 0.001). During PCI, the PHDP group had a lower percutaneous transluminal coronary angioplasty (PTCA) (P = 0.021), intropin (P = 0.002) and tirofiban (P < 0.001) use. And the incidence of intraoperative arrhythmia, malignant arrhythmia, and slow flow/no-reflow was lower in the PHDP group (P < 0.001). At the 30-day follow-up, there was a significantly higher proportion of patients in the PPCI group who were readmitted due to unstable angina (P = 0.037). After 1 year of follow-up, there was no statistically significant difference in MACEs between the two groups (P = 0.500). The incidence of postoperative major bleeding, intracranial bleeding, and minor bleeding did not differ between the PHDP and PPCI groups (P > 0.05). The PHDP facilitates early treatment of infarct-related vessels, shortens FMC-reperfusion time, and does not increase the risk of MACEs.
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Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Pessoa de Meia-Idade , Seguimentos , Idoso , Prognóstico , Intervenção Coronária Percutânea/métodos , Proteínas Recombinantes/uso terapêuticoRESUMO
Recent years have witnessed the explosive development of highly sensitive smart sensors based on conductive polymer foam materials. However, the design and development of multifunctional polymeric foam composites as smart sensors applied in complex solvent and oil environments remain a critical challenge. Herein, we design and synthesize vinyl-terminated polytrifluoropropylmethylsiloxane through anionic ring-opening polymerization to fabricate fluorosilicone rubber foam (FSiRF) materials with nanoscale wrinkled surfaces and reactive Si-H groups via a green and rapid chemical foaming strategy. Based on the strong adhesion between FSiRF materials and consecutive oxidized ketjen black (OKB) nano-network, multifunctional FSiRF nanocomposites were prepared by a dip-coating strategy followed by fluoroalkylsilane modification. The optimized F-OKB@FSiRF nanocomposites exhibit outstanding mechanical flexibility in wide-temperature range (100 cycle compressions from -20 to 200 °C), structure stability (no detached particles after being immersed into various aqueous solutions for up to 15 days), surface superhydrophobicity (water contact angle of 154° and sliding angle of â¼7°), and tunable electrical conductivity (from 10-5 to 10-2 S m-1). Additionally, benefiting from the combined actions of multiple lines of defense (low surface energy groups, physical barriers, and "shielding effect"), the F-OKB@FSiRF sensor presents excellent anti-swelling property and high sensitivity in monitoring both large-deformation and tiny vibrations generated by knocking the beaker, ultrasonic action, agitating, and sinking objects in weak-polar or nonpolar solvents. This work conceivably provides a chemical strategy for the fabrication of multifunctional polymeric foam nanocomposite materials as smart sensors for broad applications.
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Two novel phenylpropanoids (compounds 1 and 2) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high-resolution electrospray ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit-8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound-healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell-cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer.
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Accurately assessing the changes in soil organic carbon storage ï¼SOCSï¼ before and after the Grain for Green Project ï¼GFGï¼ in the Loess Plateau ï¼LPï¼ and exploring the relationship between its spatial and temporal distribution and the influencing factors were important references for the development of regional recycling as well as the formulation of ecological protection policies. Based on the data of climate, human activities, and SOCD in the surface ï¼0-20 cmï¼ and deep ï¼0-100 cmï¼ soil before and after GFG in the LP from 2001 to 2020, we investigated the changes in SOCD at different spatial and temporal scales by using the methods of trend analysis, the kriging method, and variance partitioning analysis. The results showed thatï¼ â Before and after the GFG, the surface SOCS of the whole region increased by 8 338.7×104 tï¼ the deep SOCS increased by 1 160.02×104 t. â¡ In each bioclimatic subregion, the whole-region average SOCD of â ï¼Semi-Humid Forest Regionï¼, â ¡ ï¼Semi-Humid Semi-Arid Forest and Grassland Regionï¼, and â ¢ ï¼Semi-Arid Typical Grassland Regionï¼ showed a significant increasing trend, with a decreasing trend in â £ ï¼arid semi-arid desert grassland areaï¼ and â ¤ ï¼arid desert areaï¼. ⢠The average surface SOCS increase in different ecosystems was ranked as followsï¼ cropland > grassland > woodland > shrubs > bare land and sparse vegetation. The deep soil increase was ranked as followsï¼ grassland > cropland > woodland > shrubs > bare land and sparse vegetation. ⣠Climate factors were the most important driving factors for changes in SOCDï¼ the annual average temperature and precipitation were significantly positively correlated with changes in SOCD. The results of the study could provide data support for regional ecological management and land use policy formulation to promote high quality development of the ecological environment in the LP.
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Carbono , Mudança Climática , Solo , Solo/química , China , Carbono/análise , Compostos Orgânicos/análise , Conservação dos Recursos Naturais , Atividades Humanas , Florestas , Ecossistema , Monitoramento Ambiental/métodos , Altitude , Pradaria , Sequestro de Carbono , Humanos , Produtos Agrícolas/crescimento & desenvolvimentoRESUMO
Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.
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The early detection of bacterial species plays a crucial role in patient prognosis and the development of effective therapeutic regimens. This study introduces an accessible and promising colorimetric sensor array designed to classify gram-positive (G+) and gram-negative (G-) bacterial species. The classification relies on 6 chemical ligands with dimethylamino/amino groups as sensing elements and silver nanotriangles as colorimetric probes. Using these specific sensor arrays, we successfully differentiated G- and G+ bacterial species and discriminated individual bacterial strains, and the sensors exhibited remarkable reproducibility and high sensitivity. Moreover, the sensor array can identify bacterial mixtures and bacteria at varying concentrations, underscoring its versatility. In summary, this sensor array offers an effective tool for bacterial analysis with promising applications in the field of biomedical diagnostics.
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Colorimetria , Ligantes , Colorimetria/métodos , Prata/química , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Nanopartículas Metálicas/química , Reprodutibilidade dos TestesRESUMO
Coastal marine areas are frequently affected by human activities and face ecological and environmental threats, such as algal blooms and climate change. The community structure of phytoplankton-primary producers in marine ecosystems-is highly sensitive to environmental factors, such as temperature, salinity, and nutrients. However, traditional methods for exploring the relationship between phytoplankton communities and environmental factors in eutrophic marine areas are limited by various factors. Therefore, this study employed interpretable machine learning models, integrating high-dimensional data analysis and complex system modeling, to quantitatively and thoroughly analyze the dynamic relationship between phytoplankton communities and environmental variables in high-frequency samples collected over 53 weeks from eutrophic marine areas. The cell abundance of phytoplankton exhibited a distinct "two-peak pattern" variation. Interpretable machine learning model analysis revealed the dynamic contributions of different environmental factors during changes in the phytoplankton community structure. The results showed that temperature was a key environmental factor that affected phytoplankton growth during peak periods. In addition, the contribution of salinity increased during the second peak in phytoplankton abundance, highlighting its central role in the ecological dynamics of this phase. During green tide outbreaks, particularly in Area 01, the contributions of factors such as temperature and salinity increased, whereas those of phosphates and silicates decreased, indicating that green tide outbreaks substantially altered the nutritional dynamics of the ecosystem. Furthermore, different phytoplankton species, such as Skeletonema costatum, Thalassiosira spp., and Nitzschia spp., exhibit varying responses to environmental factors. Hence, the predictions made using random forest and generalized additive models for phytoplankton cell abundance in two marine areas revealed complex nonlinear relationships between environmental factors, such as temperature, salinity, and phytoplankton abundance.
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BACKGROUND: With the decline of global fertility, drug therapeutic of ectopic pregnancy is of great significance. Lithospermum erythrorhizon is using for embryo killing as herbal medicine. Shikonin is the critical nucleus of Lithospermum erythrorhizon; however, the mechanism is still unclear. The study aimed to explore the mechanism of shikonin against ectopic pregnancy. MATERIAL AND METHODS: In this study, we examined the viability and LDH release of HTR-8/SVneo cells by assays, observed pore formation in cell membranes by microscopy imaging and PI staining, and IL-1ß release by WB and ELISA assay kit. Then, we used network pharmacology to analyse the potential interaction between shikonin, ectopic pregnancy and pyroptosis and used molecular docking techniques to verify interactions between shikonin and core common targets. Finally, western blotting and immunofluorescence assay were used to explore the mechanism of shikonin-inducing pyroptosis of HTR-8/SVneo cells. RESULTS: Shikonin could cause a significant inhibition of HTR-8/SVneo cell viability in a concentration- and time-dependent manner. In HTR-8/SVneo cells, shikonin-induced cell swelling, bubble formation, an increase in the release of lactate dehydrogenase (LDH) and up-regulation of several pyroptosis-associated factors. And network pharmacology showed that The main targets of shikonin-ectopic pregnancy-pyroptosis were IL-1ß and caspase-1, and molecular docking results showed that shikonin can closely bind to IL-1ß, caspase-1 and GSDMD. Additionally, the necroptosis inhibitor GSK'872 could not suppress the expression of mature-IL-1ß and prevent the pyroptosis phenotype from developing. However, the nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inhibitor MCC-950 could downregulate the expression of pyroptosis-associated factors and prevent the pyroptosis phenotype from developing. Shikonin led to an elevation in the expression of cathepsin B (CTSB), and the CTSB inhibitor CA-074 abolished pyroptosis induced by shikonin; however, the NLRP3 inhibitor MCC-950 could not inhibit the expression of CTSB. CONCLUSIONS: Our results suggest that shikonin activates CTSB to induce NLRP3-dependent pyroptosis in HTR-8/SVneo cells. This study has important clinical implications for the treatment of ectopic pregnancy.
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Inflamassomos , Lithospermum , Simulação de Acoplamento Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Naftoquinonas , Piroptose , Trofoblastos , Naftoquinonas/farmacologia , Humanos , Piroptose/efeitos dos fármacos , Lithospermum/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Feminino , Gravidez , Linhagem Celular , Interleucina-1beta/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Farmacologia em RedeRESUMO
For convenience and experimental control, cognitive science has relied largely on images as stimuli rather than the real, tangible objects encountered in the real world. Recent evidence suggests that the cognitive processing of images may differ from real objects, especially in the processing of spatial locations and actions, thought to be mediated by the dorsal visual stream. Perceptual and semantic processing in the ventral visual stream, however, has been assumed to be largely unaffected by the realism of objects. Several studies have found that one key difference accounting for differences between real objects and images is actability; however, less research has investigated another potential difference - the three-dimensional nature of real objects as conveyed by cues like binocular disparity. To investigate the extent to which perception is affected by the realism of a stimulus, we compared viewpoint adaptation when stimuli (a face or a kettle) were 2D (flat images without binocular disparity) vs. 3D (i.e., real, tangible objects or stereoscopic images with binocular disparity). For both faces and kettles, adaptation to 3D stimuli induced stronger viewpoint aftereffects than adaptation to 2D images when the adapting orientation was rightward. A computational model suggested that the difference in aftereffects could be explained by broader viewpoint tuning for 3D compared to 2D stimuli. Overall, our finding narrowed the gap between understanding the neural processing of visual images and real-world objects by suggesting that compared to 2D images, real and simulated 3D objects evoke more broadly tuned neural representations, which may result in stronger viewpoint invariance.
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Disparidade Visual , Humanos , Adulto , Feminino , Adulto Jovem , Masculino , Disparidade Visual/fisiologia , Percepção de Profundidade/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adaptação Fisiológica/fisiologia , Estimulação Luminosa , Percepção Visual/fisiologiaRESUMO
To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT-qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.