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T cell receptors (TCR) and gene expression provide two complementary and essential aspects in T cell understanding, yet their diversity presents challenges in integrative analysis. We introduce TCRclub, a novel method integrating single-cell RNA sequencing data and single-cell TCR sequencing data using local harmony to identify functionally similar T cell groups, termed 'clubs'. We applied TCRclub to 298,106 T cells across seven datasets encompassing various diseases. First, TCRclub outperforms the state-of-the-art methods in clustering T cells on a dataset with over 400 verified peptide-major histocompatibility complex categories. Second, TCRclub reveals a transition from activated to exhausted T cells in cholangiocarcinoma patients. Third, TCRclub discovered the pathways that could intervene in response to anti-PD-1 therapy for patients with basal cell carcinoma by analyzing the pre-treatment and post-treatment samples. Furthermore, TCRclub unveiled different T-cell responses and gene patterns at different severity levels in patients with COVID-19. Hence, TCRclub aids in developing more effective immunotherapeutic strategies for cancer and infectious diseases.
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The rhizosphere, where plant roots interact intensely with the soil, is a crucial but understudied area in terms of the impact of virus infection. In this study, we investigated the effects of lily symptomless virus (LSV) and cucumber mosaic virus (CMV) on the Lanzhou lily (Lilium davidii var. unicolor) rhizosphere using metagenomics and bioinformatics analysis. We found that virus infection significantly altered soil pH, inorganic carbon, nitrate nitrogen, and total sulfur. Co-infection with LSV and CMV had a greater influence than single infections on the α- and ß-diversity of the rhizosphere viral community in which the absolute abundance of certain virus families (Siphoviridae, Podoviridae, and Myoviridae) increased significantly, whereas bacteria, fungi, and archaea remained relatively unaffected. These altered virus populations influenced the rhizosphere microbial carbon and nitrogen cycles by exerting top-down control on bacteria. Co-infection potentially weakened rhizosphere carbon fixation and promoted processes such as methane oxidation, nitrification, and denitrification. In addition, the co-occurrence network of bacteria and viruses in the rhizosphere revealed substantial changes in microbial community composition under co-infection. Our partial-least-squares path model confirmed that the diversity of the rhizosphere viral community indirectly regulated the carbon and nitrogen cycling functions of the microbial community, thus affecting the accumulation of carbon and nitrogen nutrients in the soil. Our results are the first report of the effects of virus infection on the lily rhizosphere, particularly for co-infection; they therefore complement research on the plant virus pathogenic mechanisms, and increase our understanding of the ecological role of rhizosphere soil viruses.
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Background: The relationship of systolic blood pressure variability (SBPV) with Alzheimer's disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions. Methods: Longitudinal data across 96 months (T0 to T4) were derived from the Alzheimer's disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years). Results: Participants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008). Conclusion: These findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health.
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BACKGROUND AND PURPOSE: Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses. METHODS: Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses. RESULTS: In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes. CONCLUSIONS: Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.
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Histona Desacetilase 1 , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Histona Desacetilase 1/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Ovário/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Ribossômicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally. METHODS: We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990-2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the ageperiodcohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature. RESULTS: In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14-4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019. CONCLUSION: There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations.
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Mudança Climática , Carga Global da Doença , Saúde Global , Temperatura Alta , Doenças não Transmissíveis , Humanos , Doenças não Transmissíveis/mortalidade , Doenças não Transmissíveis/epidemiologia , Masculino , Feminino , Carga Global da Doença/tendências , Pessoa de Meia-Idade , Idoso , Adulto , Saúde Global/estatística & dados numéricos , Temperatura Alta/efeitos adversos , Adulto Jovem , Adolescente , Anos de Vida Ajustados por Deficiência , Criança , Pré-Escolar , Lactente , Idoso de 80 Anos ou mais , Efeitos Psicossociais da DoençaRESUMO
As the most abundant post-transcriptional modification in eukaryotes, N6-methyladenosine (m6A) plays a crucial role in cancer cell proliferation, invasion and chemoresistance. However, its specific effects on chemosensitivity to oxaliplatin-based regimens and the impact of these drugs on m6A methylation levels in colorectal cancer (CRC) remain largely unexplored. In this study, we demonstrated that the m6A methyltransferase Wilms tumor 1-associating protein (WTAP) weakens oxaliplatin chemosensitivity in HCT116 and DLD1 cells. Mechanistically, oxaliplatin treatment upregulated WTAP expression, preventing multiple forms of cell death simultaneously, a process known as PANoptosis, by decreasing intracellular oxidative stress through maintaining the expression of nuclear factor erythroid-2-related factor 2 (NRF2), a major antioxidant response element, in an m6A-dependent manner. In addition, high WTAP expression in CRC patients is associated with a poor prognosis and reduced benefit from standard chemotherapy by clinical data analysis of The Cancer Genome Atlas (TCGA) database and patient cohort study. These findings suggest that targeting WTAP-NRF2-PANoptosis axis could enhance the antitumor efficacy of oxaliplatin-based chemotherapy in CRC treatment.
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Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Fator 2 Relacionado a NF-E2 , Oxaliplatina , Humanos , Oxaliplatina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Células HCT116 , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Adenosina/análogos & derivados , Adenosina/farmacologiaRESUMO
Six Cordyceps militaris polysaccharides (named CMP-1, CMP-2, CMP-3, CMP-4, CMP-9, and CMP-A) were obtained by fractional alcohol precipitation. The experimental results showed that the six Cordyceps militaris polysaccharides had similar chemical composition and spectral features, and different molecular weights, monosaccharide compositions and anti-tumor activities. Purification of CMP-9 yielded the small molecule polysaccharide LMW-CMP (3.06 kDa). Structural experiments showed that LMW-CMP is an α-glucan with (1 â 4)-α-D-Glcp as the main chain and a glucose branched chain attached at the O-6 position. The results of cell experiments showed that LMW-CMP could effectively inhibit the growth and proliferation of HepG2 cells, activate the downstream NF-κB signaling pathway through the MAPK pathway to induce apoptosis of HepG2 cells, and block apoptosis at the G1 phase. Animal experiments showed that LMW-CMP inhibited the proliferation of tumor cells in H22 tumor-bearing mice by improving the state of immune organs, increasing the activity of immune cells and cytokine levels in the body, and regulating the distribution of lymphocyte subpopulations, with a tumor inhibition rate of 45.70 % (200 mg/kg).
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Antineoplásicos , Apoptose , Proliferação de Células , Cordyceps , Etanol , Polissacarídeos Fúngicos , Cordyceps/química , Animais , Humanos , Camundongos , Etanol/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Peso Molecular , NF-kappa B/metabolismo , Monossacarídeos/análiseRESUMO
BACKGROUND: Asymptomatic bacteriuria (ASB) - the presence of bacteria in urine without urinary tract infection (UTI) related signs & symptoms (S&S) - is common in the elderly bladder and is not considered pathogenic for UTI. We hypothesise that colonisation with non-uropathogenic bacteria could protect the bladder from invasion of more harmful bacteria. The exact role and dynamics of bacteriuria in the relation to the development of a UTI is still unknown. We aim to provide insight into the course of bacteriuria in the elderly bladder and its relation to UTI in frail older adults. METHODS AND ANALYSIS: A prospective observational cohort study is being conducted in Dutch nursing homes (NHs) between February 2024 and December 2025. Urine samples and case report forms (CRF) on UTI-related S&S will be collected from each consenting NH resident every 3 months for a follow-up period of 18 months. Whenever a UTI-suspicion occurs in between the 3 monthly time points, additional data and a urine sample will be collected. Urine samples undergo several urinalyses (e.g. dipstick and bacterial culture). Additional molecular analysis will be conducted on a selection of cultured Escherichia coli (E. coli) for virulence genes. Primary analyses will be conducted between residents with and without ASB at each time point. The primary outcome is UTI incidence during follow-up. In secondary analyses we will also take into account the low versus high presence of virulence genes of the E. coli. DISCUSSION: The combination of high ASB prevalence and a reduced ability of frail older adults to express UTI-related S&S may lead to UTI misdiagnosis and inappropriate antibiotic use. To our knowledge, this is the first study to investigate the dynamics and role of bacteriuria in the elderly bladder and their potential protective effect on the development of UTI. The study findings with comprehensive analysis of epidemiological, clinical and molecular data could set the fundamental base for future guidelines and studies, and contribute to improving prevention, diagnosis and treatment of UTI in frail older adults, in addition to contributing to antibiotic stewardship in NHs.
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Bacteriúria , Bexiga Urinária , Infecções Urinárias , Humanos , Estudos Prospectivos , Idoso , Bacteriúria/microbiologia , Bacteriúria/epidemiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Bexiga Urinária/microbiologia , Países Baixos/epidemiologia , Feminino , Masculino , Casas de Saúde , Escherichia coli/isolamento & purificação , Escherichia coli/genética , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Idoso Fragilizado , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/epidemiologiaRESUMO
Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.
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The use of green methods to treat industrial waste and waste reuse has become a key environmental issue. In order to achieve this goal, this study treated waste phosphogypsum (PG) and produced modified PG biochar to adsorb and remove phosphorus from PG leachate, so that the PG pollution problem was controlled. In this study, PG was modified with sodium carbonate (Na2CO3) to prepare a modified PG biochar that was used for the removal of phosphorus-containing wastewater. An X-ray diffraction (XRD) analysis of the modified PG revealed that the main component was calcium carbonate (CaCO3), and a suitable amount of modified PG could load calcium oxide (CaO) onto the biochar and improve its physical properties. The experimental results showed that the modified PG biochar had a maximum phosphorus adsorption capacity of 132 mg/g. A further investigation of the mechanism of adsorption revealed the importance of electrostatic attraction and chemical precipitation, and it was found that the CaO in the modified PG biochar could effectively facilitate the conversion of phosphate to hydroxylapatite (Ca5(PO4)3OH) in water. The phosphorus removal rate from leachate obtained from a landfill containing PG was 99.38% for a specific dose of the modified PG biochar. In this study, a PG pollution control technology was developed to realize the goal of replacing waste with waste.
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Sulfato de Cálcio , Carvão Vegetal , Fosfatos , Fósforo , Adsorção , Carvão Vegetal/química , Fósforo/química , Sulfato de Cálcio/química , Fosfatos/química , Poluentes Químicos da Água/química , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Difração de Raios XRESUMO
The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.
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The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.
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Diagnosis of tuberculosis remains a challenge when microbiological tests are negative. Immune cell atlas of patients with tuberculosis and healthy controls were established by single-cell transcriptome. Through integrated analysis of scRNA-seq with microarray and bulk RNA sequencing data, a ferroptosis-related gene signature containing ACSL4, CTSB, and TLR4 genes that were associated with tuberculosis disease was identified. Four gene expression datasets from blood samples of patients with tuberculosis, latent tuberculosis infection, and healthy controls were used to assess the diagnostic value of the gene signature. The areas under the ROC curve for the combined gene signature were 1.000, 0.866, 0.912, and 0.786, respectively, in differentiating active tuberculosis from latent infection. During anti-tuberculosis treatment, the expression of the gene signature decreased significantly in cured patients with tuberculosis. In conclusion, the ferroptosis-related gene signature was associated with tuberculosis treatment efficacy and was a promising biomarker for differentiating active tuberculosis from latent infection.
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An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).
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Catequina , Proliferação de Células , Triptofano , Catequina/química , Catequina/farmacologia , Catequina/isolamento & purificação , Triptofano/química , Triptofano/farmacologia , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Antifibróticos/farmacologia , Antifibróticos/química , Antifibróticos/isolamento & purificação , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Relação Dose-Resposta a Droga , Movimento Celular/efeitos dos fármacos , Animais , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Humanos , Raízes de Plantas/químicaRESUMO
Background: The causal relationships of late-life body mass index (BMI) with Alzheimer's disease (AD) remains debated. Objective: We aimed to assess the associations of dynamic BMI features (ΔBMIs) with cognitive trajectories, AD biomarkers, and incident AD risk. Methods: We analyzed an 8-year cohort of 542 non-demented individuals who were aged ≥65 years at baseline and had BMI measurements over the first 4 years. ΔBMIs were defined as changing extent (change ≤ or >5%), variability (standard deviation), and trajectories over the first 4 years measured using latent class trajectory modeling. Linear mixed-effect models were utilized to examine the influence of ΔBMIs on changing rates of AD pathology biomarkers, hippocampus volume, and cognitive functions. Cox proportional hazards models were used to test the associations with AD risk. Stratified analyzes were conducted by the baseline BMI group and age. Results: Over the 4-year period, compared to those with stable BMI, individuals who experienced BMI decreases demonstrated accelerated declined memory function (pâ=â0.006) and amyloid-ß deposition (pâ=â0.034) while BMI increases were associated with accelerated hippocampal atrophy (pâ=â0.036). Three BMI dynamic features, including stable BMI, low BMI variability, and persistently high BMI, were associated with lower risk of incident AD (pâ<â0.005). The associations were validated over the 8-year period after excluding incident AD over the first 4 years. No stratified effects were revealed by the BMI group and age. Conclusions: High and stable BMI in late life could predict better cognitive trajectory and lower risk of AD.
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Doença de Alzheimer , Índice de Massa Corporal , Humanos , Masculino , Feminino , Idoso , Estudos Longitudinais , Hipocampo/patologia , Cognição/fisiologia , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Imageamento por Ressonância Magnética , Progressão da Doença , Estudos de Coortes , Disfunção CognitivaRESUMO
Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.
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Antineoplásicos , Neoplasias da Mama , Cumarínicos , Cumarínicos/farmacologia , Cumarínicos/química , Cumarínicos/síntese química , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Feminino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Relação Estrutura-AtividadeRESUMO
Understanding the influences of climate change and human activities on vegetation change is the foundation for effective ecosystem management. Based on the 250 m MODIS-NDVI data from 2002 to 2020, we employed Theil-Sen Median trend analysis and the Mann-Kendall test to quantify vegetation change in Hunan Province. By combining with meteorological, nighttime light index, land cover and other data, residual analysis and correlation analysis, we examined the impacts of human activities and climate change on vegetation dynamics at both the pixel level and the county level. The results showed that the normalized difference vegetation index (NDVI) in Hunan Province exhibited a spatial pattern of "overall improvement with localized degradation" during 2002-2020. Approximately 64.9% of the study area experienced significant vegetation improvement, mainly occurring in the western and central-southern parts of Hunan Province. 1.4% of the study area experienced significant vegetation degradation, mostly in the newly developed urban areas and the farmland in the Dongting Lake Plain. Human activities and climate change jointly promoted vegetation improvement in 67.9% of the study area. Human activities and climate contributed to 96% and 4% of the NDVI change, respectively. At the county level, human activities contributed to over 80% of the NDVI change in each district or county. The impacts of human activities on vegetation change exhibited significant spatial heterogeneity. Urban expansion led to vegetation degradation in the newly developed areas, while vegetation growth appeared in the old developed urban areas. The ecological restoration projects promoted vegetation restoration in the western part of Hunan Province. This study could help us better understand the spatiotemporal variations of vegetation and their responses to climate change and human activities, which would offer scientific basis for effective ecological restoration policy.
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Mudança Climática , Ecossistema , Monitoramento Ambiental , China , Monitoramento Ambiental/métodos , Conservação dos Recursos Naturais , Imagens de Satélites , Atividades Humanas , Desenvolvimento Vegetal , Árvores/crescimento & desenvolvimentoRESUMO
We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.