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Miniaturization and integration of plasmonic nanodevices are fundamentally limited by quantum tunneling, which leads to quantum plasmonics with reduced local E-field intensity. Despite significant efforts devoted to modeling and deterring the detrimental effect of quantum plasmonics, the modulation and application of electron transport through the subnanometer gaps seems rarely exploited due to the limited tunability of conventional quantum materials. Here, we establish a supramolecular plasmonic system made of pillar[5]arene complexes and plasmonic resonators (nanoparticle-on-mirror, NPoM). The supramolecular assemblies significantly enhance the gap conductance of NPoM, which results in a blue-shift of the coupled plasmons. Plasmonic hot-electron transport with laser excitation further modulates the gap plasmons, which are fully reversible and beneficial for enhanced chiroptic sensing. Such a conductive supramolecular plasmonic system not only suggests an optoelectronic switching strategy for charge transfer plasmons but also provides a superior sensing platform for single molecules.
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Liver fibrosis represents an inevitable stage of various chronic liver diseases. The activated hepatic stellate cells (aHSCs) are the main drivers for promoting the development of liver fibrosis. Meanwhile, liver macrophages can secrete pro-inflammatory cytokines, thus accelerating the deterioration of the liver. Regulating both aHSCs and the inflammatory microenvironment in the liver simultaneously may be an effective strategy for treating liver fibrosis. A multi-pronged nano-bioconjugated system, HNP-B-aEV, was developed according to the above strategy. Based on cell aggregate-derived extracellular vesicles (aEVs) and hydroxychloroquine (HCQ)-loaded nanoparticles (HNP) modified with retinol, HNP-B-aEV is prepared via a reactive oxygen species (ROS)-responsive boronate linker. In the ROS-rich microenvironment of liver fibrosis, aEVs and HNP are released, eliminating ROS, and targeting aHSCs and macrophages respectively to inhibit the activation of HSCs. Both in vitro and in vivo studies demonstrated that HNP-B-aEV can significantly inhibit the release of inflammatory factors from M1 macrophages, remodeling the microenvironment and preventing the activation of HSCs, offering a multi-pronged treatment for liver fibrosis. This strategy can inhibit the progression of liver fibrosis at its source, providing a new perspective for the clinical treatment of liver fibrosis.
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INTRODUCTION: Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation. AREAS COVERED: Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ. EXPERT OPINION: In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.
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Climate change is causing an intensification of soil drying and rewetting events, altering microbial functioning and potentially destabilizing soil organic carbon. After rewetting, changes in microbial community carbon use efficiency (CUE), investment in life history strategies, and fungal to bacterial dominance co-occur. Still, we have yet to generalize what drives these dynamic responses. Here, we collated 123 time series of microbial community growth (G, sum of fungal and bacterial growth, evaluated by leucine and acetate incorporation, respectively) and respiration (R) after rewetting and calculated CUE = G/(G + R). First, we characterized CUE recovery by two metrics: maximum CUE and time to maximum CUE. Second, we translated microbial growth and respiration data into microbial investments in life history strategies (high yield (Y), resource acquisition (A), and stress tolerance (S)). Third, we characterized the temporal change in fungal to bacterial dominance. Finally, the metrics describing the CUE recovery, investment in life history strategies, and fungal to bacterial dominance after rewetting were explained by environmental factors and microbial properties. CUE increased after rewetting as fungal dominance declined, but the maximum CUE was explained by the CUE under moist conditions, rather than specific environmental factors. In contrast, higher soil pH and carbon availability accelerated the decline of microbial investment in stress tolerance and fungal dominance. We conclude that microbial CUE recovery is mostly driven by the shifting microbial community composition and the metabolic capacity of the community, whereas changes in microbial investment in life history strategies and fungal versus bacterial dominance depend on soil pH and carbon availability.
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Carbono , Mudança Climática , Fungos , Microbiologia do Solo , Solo , Solo/química , Carbono/metabolismo , Fungos/fisiologia , Fungos/metabolismo , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Microbiota , Concentração de Íons de HidrogênioRESUMO
Few studies have investigated affective flexibility in individuals with high autistic traits. In the present study, we employed affective task-switching paradigm combined with event related potential (ERP) technology to explore affective flexibility in individuals with high autistic traits. Participants were instructed to switch between identifying the gender (gender task) and emotion (emotion task) of presented faces. Two groups of participants were recruited based on the Autism Spectrum Quotient (AQ) scores: a High Autistic Group (HAG) and a Low Autistic Group (LAG). The results confirmed that the HAG exhibited greater behavioral emotion switch costs and increased N2 and decreased P3 components when switching to the emotion task. Additionally, we identified an affective asymmetric switch cost in the HAG, where the switch cost for the emotion task was larger than for the gender task at both behavioral and electrophysiological levels. In contrast, a symmetrical switch cost was observed in the LAG. These findings indicate that the HAG experiences difficulties with affective flexibility, particularly in tasks involving emotional processing. The patterns of affective asymmetric switch costs observed in both groups differed from previous results in autistic children and the general population, suggesting that the relative dominance of gender and emotion tasks may vary between the two groups. We propose that the dominance of emotion tasks declines as autistic traits increase.
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Afeto , Eletroencefalografia , Emoções , Potenciais Evocados , Humanos , Masculino , Feminino , Potenciais Evocados/fisiologia , Adulto Jovem , Adulto , Afeto/fisiologia , Emoções/fisiologia , Transtorno Autístico/fisiopatologia , Transtorno Autístico/psicologia , Transtorno do Espectro Autista/fisiopatologia , Reconhecimento Facial/fisiologia , Função Executiva/fisiologia , Adolescente , Expressão FacialRESUMO
Conductive metal-organic frameworks (c-MOFs) hold promise for highly sensitive sensing systems due to their conductivity and porosity. However, the fabrication of c-MOF thin films with controllable morphology, thickness, and preferential orientation remains a formidable yet ubiquitous challenge. Herein, we propose an innovative template-assisted strategy for constructing MOF-on-MOF (Ni3(HITP)2/NUS-8 (HITP: 2,3,6,7,10,11-hexamino-tri (p-phenylene))) systems with good electrical conductivity, porosity, and solution processability. Leveraging the 2D nature and solution processability of NUS-8, we achieve the controllable self-assembly of Ni3(HITP)2 on NUS-8 nanosheets, producing solution-processable Ni3(HITP)2/NUS-8 nanosheets with a film conductivity of 1.55×10-3â S â cm-1 at room temperature. Notably, the excellent solution processability facilitates the fabrication of large-area thin films and printing of intricate patterns with good uniformity, and the Ni3(HITP)2/NUS-8-based system can monitor finger bending. Gas sensors based on Ni3(HITP)2/NUS-8 exhibit high sensitivity (LOD~6â ppb) and selectivity towards ultratrace H2S at room temperature, attributed to the coupling between Ni3(HITP)2 and NUS-8 and the redox reaction with H2S. This approach not only unlocks the potential of stacking different MOF layers in a sequence to generate functionalities that cannot be achieved by a single MOF, but also provides novel avenues for the scalable integration of MOFs in miniaturized devices with salient sensing performance.
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BACKGROUND: Aging skin, exacerbated by external factors like UV radiation and pollutants, is a major cosmetic concern. Taurine, renowned for its antioxidant and anti-inflammatory properties, may combat skin aging. We performed mendelian randomization (MR) analysis to investigate the causal link between taurine and immune cells linked to skin aging. OBJECTIVES: To investigate the association between taurine and immune cells using mendelian randomization, to thereby explore the mechanism through which taurine exerts anti-aging effects on the skin via immune modulation. METHODS: A MR approach was employed using taurine-level data from the Ieu Open GWAS Project and immunocyte traits from a large European cohort. MR-Egger regression, weighted median estimation, and inverse variance weighting all provided statistical insights into causality. Sensitivity analyses assessed the heterogeneity and pleiotropy among the genetic instruments used. RESULTS: MR analysis identified a causal relationship between taurine levels and 10 immunocyte phenotypes, with taurine found to be negatively and positively associated with three and seven phenotypes, respectively. Sensitivity analysis revealed no significant heterogeneity or pleiotropy, suggesting reliable MR findings. CONCLUSION: This study provides insights into the immunological pathways by which taurine contributes to skin anti-aging effects, suggesting that increasing taurine levels could offer a novel strategy for anti-aging skincare.
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Background: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression. Material and methods: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Results: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation. Conclusion: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.
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Carcinoma Basocelular , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/sangue , Carcinoma Basocelular/genética , Carcinoma Basocelular/epidemiologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/epidemiologia , Polimorfismo de Nucleotídeo Único , Feminino , Masculino , Predisposição Genética para Doença , Fatores de Risco , Finlândia/epidemiologiaRESUMO
Vascular remodeling is a dynamic process involving cellular and molecular changes, including cell proliferation, migration, apoptosis and extracellular matrix (ECM) synthesis or degradation, which disrupt the homeostasis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Cigarette smoke exposure (CSE) is thought to promote vascular remodeling, but the components are complex and the mechanisms are unclear. In this review, we overview the progression of major components of cigarette smoke (CS), such as nicotine and acrolein, involved in vascular remodeling in terms of ECs injury, VSMCs proliferation, migration, apoptosis, and ECM disruption. The aim was to elucidate the effects of different components of CS on different cells of the vascular system, to discover the relevance of their actions, and to provide new references for future studies.
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Células Endoteliais , Músculo Liso Vascular , Nicotina , Fumaça , Remodelação Vascular , Humanos , Animais , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Fumaça/efeitos adversos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Nicotina/efeitos adversos , Miócitos de Músculo Liso/fisiologia , Miócitos de Músculo Liso/metabolismo , Apoptose , Proliferação de Células , Movimento Celular , Acroleína , Nicotiana , Matriz Extracelular/metabolismo , Fumar/efeitos adversos , Produtos do Tabaco/efeitos adversosRESUMO
Farm leftovers, particularly crop residues, are a key source of renewable energy in Canada. The nation's robust agricultural industry provides ample biomass, derived from forestry and agriculture resources, for energy generation. Crop residues, such as straws and husks, play a crucial role in this biomass reservoir, contributing to biofuel production and greenhouse gas mitigation efforts. Focusing on supply chains, waste management, and emission reduction, this study evaluates the sustainability of wheat straw, an agricultural biomass by-product. The environmental issues of various approaches to managing agricultural biomass were explored. Following an evaluation of biomass features, conversion methods, and economic and environmental advantages, the results show anaerobic digestion to be the most sustainable approach. Four metrics were examined in relation to social elements, and numerous aspects were considered as inputs in the evaluation of transportation costs. The use of electric trucks versus fuel-based trucks resulted in an 18% reduction in total operating costs and a 58% reduction in consumption costs. This study examined CO2 emissions over four different transportation distances. The data indicate that a significant reduction of 36% in kg CO2 equivalent emissions occurred when the distance was lowered from 100 km to 25 km. These findings offer insights for creating practical plans that should increase the sustainability of agricultural biomass leftovers.
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BACKGROUND: Zishenhuoxue decoction (ZSHX), a Chinese herbal medicine, exhibits myocardial and vascular endothelial protective properties. The intricate regulatory mechanisms underlying myocardial ischemic injury and its association with dysfunctional mitochondrial quality surveillance (MQS) remain elusive. HYPOTHESIS/PURPOSE: To study the protective effect of ZSHX on ischemic myocardial injury in mice using a TMBIM6 gene-modified animal model and mitochondrial quality control-related experiments. STUDY DESIGN: Using model animals and myocardial infarction surgery-induced ischemic myocardial injury TMBIM6 gene-modified mouse models, the pharmacological activity of ZSHX in inhibiting ischemic myocardial injury and mitochondrial homeostasis disorder in vivo was tested. METHODS: Our focal point entailed scrutinizing the impact of ZSHX on ischemic myocardial impairment through the prism of TMBIM6. This endeavor was undertaken utilizing mice characterized by heart-specific TMBIM6 knockout (TMBIM6CKO) and their counterparts, the TMBIM6 transgenic (TMBIM6TG) and VDAC1 transgenic (VDAC1TG) mice. RESULTS: ZSHX demonstrated dose-dependent effectiveness in mitigating ischemic myocardial injury and enhancing mitochondrial integrity. TMBIM6CKO hindered ZSHX's cardio-therapeutic and mitochondrial protective effects, while ZSHX's benefits persisted in TMBIM6TG mice. TMBIM6CKO also blocked ZSHX's regulation of mitochondrial function in HR-treated cardiomyocytes. Hypoxia disrupted the MQS in cardiomyocytes, including calcium overload, excessive fission, mitophagy issues, and disrupted biosynthesis. ZSHX counteracted these effects, thereby normalizing MQS and inhibiting calcium overload and cardiomyocyte necroptosis. Our results also showed that hypoxia-induced TMBIM6 blockade resulted in the over-activation of VDAC1, a major mitochondrial calcium uptake pathway, while ZSHX could increase the expression of TMBIM6 and inhibit VDAC1-mediated calcium overload and MQS abnormalities. CONCLUSIONS: Our findings suggest that ZSHX regulates mitochondrial calcium homeostasis and MQS abnormalities through a TMBIM6-VDAC1 interaction mechanism, which helps to treat ischemic myocardial injury and provides myocardial protection. This study also offers insights for the clinical translation and application of mitochondrial-targeted drugs in cardiomyocytess.
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Cálcio , Medicamentos de Ervas Chinesas , Homeostase , Canal de Ânion 1 Dependente de Voltagem , Animais , Medicamentos de Ervas Chinesas/farmacologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Cálcio/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Masculino , Proteínas de Membrana/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais de Doenças , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Cardiotônicos/farmacologiaRESUMO
OBJECTIVES: To investigate the effect of Peitu Yimu(strengthening spleen and soothing liver) acupuncture on intestinal mucosal barrier function and corticotropin-releasing factor (CRF)/CRF receptor 1 (CRFR1) pathway in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in alleviating IBS-D. METHODS: Forty female SD rats were randomly divided into blank, model, electroacupuncture (EA), and agonist groups, with 10 rats in each group. Except for the blank group, rats in the other groups were given folium sennae infusion by gavage combined with chronic unpredictable mild stress to establish IBS-D model. Rats in the EA group received acupuncture at "Tianshu"(ST25) and EA at "Zusanli"(ST36) and "Taichong"(LR3) (2 Hz/15 Hz) on one side for 20 min, with the side chosen alternately every other day, for 14 days after modeling. Rats in the agonist group received acupuncture 30 min after intravenous injection of CRFR1 agonist urocortin, with the same manipulation method and time as the EA group. Before and after intervention, visceral pain threshold and stool Bristol scores were measured. Elevated plus maze test and open field test were used to detect anxiety and depression like behavior of rats. ELISA was used to detect the contents of CRF and CRFR1 in rats serum. Immunohistochemistry was used to detect the positive expressions of CRF, CRFR1, zonula occludens protein 1(ZO-1), occlusal protein(Occludin), and closure protein 1 (Claudin-1) in colon tissue. RESULTS: Compared with the blank group, the visceral pain threshold, open arm time percentage (OT%), total distance of movement in the open field test, and positive expression of ZO-1, Occludin, and Claudin-1 in colon were decreased (P<0.01, P<0.05), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were increased (P<0.01) in the model group. After intervention and compared with the model group, the visceral pain threshold, OT%, total distance of movement in the open field test, and positive expressions of ZO-1, Occludin, and Claudin-1 in colon were increased (P<0.05, P<0.01), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were decreased (P<0.01) in the EA groupï¼the Bristol stool scores, serum CRF content, and CRF positive expression in colon were significantly decreased in the agonist group (P<0.01). CONCLUSIONS: Peitu Yimu acupuncture can significantly improve visceral hypersensitivity and anxiety-depression state in IBS-D rats. Its mechanism may be related to the inhibition of CRF/CRFR1 pathway and restoration of intestinal tight junction protein expressions.
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Terapia por Acupuntura , Diarreia , Mucosa Intestinal , Síndrome do Intestino Irritável , Receptores de Hormônio Liberador da Corticotropina , Animais , Feminino , Humanos , Ratos , Pontos de Acupuntura , Claudina-1/metabolismo , Claudina-1/genética , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/genética , Diarreia/terapia , Diarreia/metabolismo , Diarreia/genética , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/terapia , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/genética , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores de Hormônio Liberador da Corticotropina/genética , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genéticaRESUMO
The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca2+) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca2+ on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca2+ was not always conducive to structure formation, and excessive Ca2+ addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca2+ and DE. All of these results showed that Ca2+ addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.
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Cálcio , Malus , Pectinas , Reologia , Sacarose , Pectinas/química , Malus/química , Sacarose/química , Cálcio/química , Viscosidade , Géis/química , Esterificação , Água/químicaRESUMO
BACKGROUND: LACS (long-chain acyl-CoA synthetase) genes are widespread in organisms and have multiple functions in plants, especially in lipid metabolism. However, the origin and evolutionary dynamics of the LACS gene family remain largely unknown. RESULTS: Here, we identified 1785 LACS genes in the genomes of 166 diverse plant species and identified the clades (I, II, III, IV, V, VI) of six clades for the LACS gene family of green plants through phylogenetic analysis. Based on the evolutionary history of plant lineages, we found differences in the origins of different clades, with Clade IV originating from chlorophytes and representing the origin of LACS genes in green plants. The structural characteristics of different clades indicate that clade IV is relatively independent, while the relationships between clades (I, II, III) and clades (V, VI) are closer. Dispersed duplication (DSD) and transposed duplication (TRD) are the main forces driving the evolution of plant LACS genes. Network clustering analysis further grouped all LACS genes into six main clusters, with genes within each cluster showing significant co-linearity. Ka/Ks results suggest that LACS family genes underwent purifying selection during evolution. We analyzed the phylogenetic relationships and characteristics of six clades of the LACS gene family to explain the origin, evolutionary history, and phylogenetic relationships of different clades and proposed a hypothetical evolutionary model for the LACS family of genes in plants. CONCLUSIONS: Our research provides genome-wide insights into the evolutionary history of the LACS gene family in green plants. These insights lay an important foundation for comprehensive functional characterization in future research.
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Coenzima A Ligases , Evolução Molecular , Família Multigênica , Filogenia , Plantas , Coenzima A Ligases/genética , Plantas/genética , Plantas/classificação , Proteínas de Plantas/genética , Genes de Plantas , Genoma de Planta , Duplicação GênicaRESUMO
BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.
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Autofagia , Células Estreladas do Fígado , Hidroxicloroquina , Cirrose Hepática , Hidroxicloroquina/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Animais , Autofagia/efeitos dos fármacos , Camundongos , Cirrose Hepática/tratamento farmacológico , Lipossomos , Nanopartículas , Masculino , Modelos Animais de Doenças , Humanos , Tioacetamida , Camundongos Endogâmicos C57BLRESUMO
Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-Hâ§â§â§π interactions. The optimal size matching between the carboxylate AP5As and DMBr was â¼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.
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Bloqueadores Neuromusculares , Fármacos Neuromusculares não Despolarizantes , Organofosfonatos , gama-Ciclodextrinas , Animais , gama-Ciclodextrinas/farmacologia , Sugammadex , Bloqueadores Neuromusculares/farmacologia , BrometosRESUMO
Coastal waters are complex and dynamic areas with unique environmental attributes that complicate the vertical migration of microplastics (MPs). The MPs that enter coastal waters from diverse sources, including terrestrial, riverine, oceanic, and shoreline inputs undergo various aging pathways. In this study, the variations in the physiochemical characteristics of MPs undergoing various aging pathways and their vertical migration under dynamic conditions subjected to the effects of different MP characteristics and coastal environmental features were comprehensively explored. Opposite effects of aging on the vertical migration of hydrophobic and hydrophilic MPs were observed, with aging appearing to promote the dispersion of hydrophobic MPs but enhance the vertical migration of hydrophilic ones. The positive role of salinity and the negative role of humic acid (HA) concentrations on MP vertical migration were identified, and the mechanisms driving these effects were analyzed. Notably, intense turbulence not only promoted the floating of positively buoyant MPs but also reversed the migration direction of negatively buoyant MPs from downward to upward. Aging-induced changes in MP characteristics had a limited effect on MP vertical migration. The inherent characteristics of MPs and the surrounding environmental features, however, played major roles in their vertical migration dynamics. ENVIRONMENTAL IMPLICATION: Microplastics (MPs) have emerged as a significant global environmental concern and the coastal zones are the hotspots for MP pollution due to their high population density. This study comprehensively investigated the variations in the physiochemical characteristics of MPs undergoing various aging pathways. Their vertical migration patterns under dynamic conditions subjected to the effects of different MP characteristics and coastal environmental features were revealed. The roles of turbulence and MP density in their migration were identified. The findings of this study have important implications for understanding the transport and determining the ecological risks of MPs in coastal waters.
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Glioma is easy to develop resistance to temozolomide (TMZ). TMZ-resistant glioma secretes interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß), recruiting regulatory T cell (Treg) and inhibiting the activity of T cells and natural killer cell (NK cell), subsequently forming an immunosuppressive microenvironment. Oxaliplatin (OXA) greatly inhibits the proliferation of TMZ-resistant glioma cells, but the ability of OXA to cross blood-brain barrier (BBB) is weak. Thus, the therapeutic effect of OXA on glioma is not satisfactory. Transferrin receptor 1 (TfR1) is highly expressed in brain capillary endothelial cells and TMZ-resistant glioma cells. In this study, OXA was loaded into ferritin (Fn) to prepare glioma-targeted oxaliplatin/ferritin clathrate OXA@Fn. OXA@Fn efficiently crossed BBB and was actively taken up by TMZ-resistant glioma cells via TfR1. Then, OXA increased the intracellular H2O2 level and induced the apoptosis of TMZ-resistant glioma cells. Meanwhile, Fn increased Fe2+ level in TMZ-resistant glioma cells. In addition, the expression of ferroportin 1 was significantly reduced, resulting in Fe2+ to be locked up inside the TMZ-resistant glioma cells. This subsequently enhanced the Fenton reaction and boosted the ferroptosis of TMZ-resistant glioma cells. Consequently, T cell mediated anti-tumor immune response was strongly induced, and the immunosuppressive microenvironment was significantly reversed in TMZ-resistant glioma tissue. Ultimately, the growth and invasion of TMZ-resistant glioma was inhibited by OXA@Fn. OXA@Fn shows great potential in the treatment of TMZ-resistant glioma and prospect in clinical transformation.
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Células Endoteliais , Glioma , Humanos , Oxaliplatina/farmacologia , Peróxido de Hidrogênio , Glioma/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Ferritinas , Imunossupressores , Microambiente TumoralRESUMO
The estuary is an energetic area connecting the inland, river, and ocean. The migration of microplastics (MPs) in this highly complex area is tied to the entire ecosystem. In this study, the effects of cohesive SPM (clay) and noncohesive SPM (sand) on the vertical migration of positively buoyant MPs, polyethylene (PE), and negatively buoyant MPs, polytetrafluoroethylene (PTFE), in the estuarine environment under hydrodynamic disturbances were investigated. The settling of positively buoyant MPs was more reliant on the cohesive SPM compared to the settling of negatively buoyant MPs. Moreover, MPs interacting with the SPM mixture at a clay-to-sand ratio of 1:9 settled more efficiently than those interacting with clay alone. A significant positive correlation was observed between MP settling percentage and the salinity level. MP settling percentage was significantly negatively correlated with fluid shear stress for both types of MPs, meanwhile, negatively buoyant MPs were able to resist greater hydraulic disturbances. In the low-energy mixing state, for both types of MPs, the settling percentage reached about 50% in only 10 min. The resuspension process of MPs under hydrodynamic disturbances was also uncovered. Additionally, the migration and potential sites of MPs were described in the context of prevalent environmental phenomena in estuaries.
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Material Particulado , Poluentes Químicos da Água , Material Particulado/análise , Microplásticos , Plásticos , Salinidade , Areia , Hidrodinâmica , Argila , Ecossistema , Poluentes Químicos da Água/análise , Monitoramento Ambiental , EstuáriosRESUMO
Objective: Diabetic foot ulcer (DFU) frequently leads to infections, with infected DFUs being a common cause of amputation. Infection by methicillin-resistant Staphylococcus aureus (MRSA) notably increases the necessity for amputation and surgical debridement in affected individuals. Consequently, determining the prevalence and trends of MRSA in patients with DFU is of critical importance. This study aimed to assess the global prevalence and to identify trends in the occurrence of MRSA in tissue or wound swab samples from DFU patients. Methods: We conducted a comprehensive literature search across PubMed, Embase, Scopus, and Ovid, spanning from the inception of these databases to July 2023, imposing no language restrictions. The inclusion criteria required that the studies report on 30 or more patients with DFU. Additionally, we categorized our analysis based on geographic region, publication date, and the economic status of the patient's domicile. Our primary endpoint was to ascertain the prevalence of MRSA in DFUs. This systematic review has been registered at (https://www.crd.york.ac.uk/prospero/), with the identifier CRD 42023444360. Results: Our analysis encompassed 40 studies involving 12,924 patients across 20 countries. We found that the overall prevalence of MRSA in DFU was 17% (95% Confidence Interval [CI] 0.14-0.20). Regional prevalence varied significantly: in South America, it was 61% (95% CI 0.46-0.76), in North America 20% (95% CI 0.12-0.27), in Europe 19% (95% CI 0.14-0.25), in Africa 13% (95% CI 0.06-0.20), and in other subgroups 11% (95% CI 0.08-0.15). The prevalence of MRSA in DFUs also differed according to the economic status of the countries: 19% (95% CI 0.15-0.23) in high-income countries, 24% (95% CI 0.1-0.37) in upper-middle-income countries, 11% (95% CI 0.07-0.15) in lower-middle-income countries, and 20% (95% CI 0.13-0.27) in low-income countries. Notably, there has been a decline in MRSA prevalence, from 25% before 2010 to 9% thereafter. Conclusion: This meta-analysis reveals a decreasing yet still significant global prevalence of MRSA in DFUs. This trend has important implications for antimicrobial resistance and underscores the need for developing targeted programs focusing on infection prevention and exploring alternative therapeutic strategies.