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1.
J Environ Manage ; 370: 122585, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303595

RESUMO

An industrial-scale experiment on dairy manure composting with the control group (Ctrl) and the membrane covering group (CM) was conducted to explore the effects of functional membrane covering on gas emissions, the conversion of carbon and nitrogen, and revealing the underlying mechanisms. Results indicated that CM achieved the synergistic effects on gas mitigation and improved compost product quality. CO2, CH4, N2O, and NH3 emissions were reduced by 81.8%, 87.0%, 82.6%, and 82.2%, respectively. The micro-aerobic condition formed in membrane covering compost pile together with the covering inhibiting effect dominated the mitigation effect. CM significantly downregulated the mcrA gene copies and the value of mcrA/pmoA (p < 0.01), which reduced CH4 emission. CM decreased the nirS and nirK gene copies and increased the nosZ gene copies to reduce N2O emission. Functional Annotation of Prokaryotic Taxa showed that membrane covering effectively amended part of carbon and nitrogen cycles, which stimulated the degradation of organic matter, accelerated compost maturity and reduced the gaseous emissions.

2.
Sci Total Environ ; 952: 176019, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39236827

RESUMO

This comprehensive two-year investigation in the coastal South China Sea has advanced our understanding of marine microbes at both community and genomic levels. By combining metagenomics and metatranscriptomics, we have revealed the intricate temporal dynamics and remarkable adaptability of microbial communities and phytoplankton metagenome-assembled genomes (MAGs) in response to environmental fluctuations. We observed distinct seasonal shifts in microbial community composition and function: cyanobacteria were predominant during warmer months, whereas photosynthetic protists were more abundant during colder seasons. Notably, metabolic marker KOs of photosynthesis were consistently active throughout the year, underscoring the persistent role of these processes irrespective of seasonal changes. Our analysis reveals that environmental parameters such as temperature, salinity, and nitrate concentrations profoundly influence microbial community composition, while temperature and silicate have emerged as crucial factors shaping their functional traits. Through the recovery and analysis of 37 phytoplankton MAGs, encompassing nine prokaryotic cyanobacteria and 28 eukaryotic protists from diverse phyla, we have gained insights into their genetic diversity and metabolic capabilities. Distinct profiles of photosynthesis-related pathways including carbon fixation, carotenoid biosynthesis, photosynthesis-antenna proteins, and photosynthesis among the MAGs indicated their genetic adaptations to changing environmental conditions. This study not only enhances our understanding of microbial dynamics in coastal marine ecosystems but also sheds light on the ecological roles and adaptive responses of different microbial groups to environmental changes.


Assuntos
Fitoplâncton , Água do Mar , China , Fitoplâncton/fisiologia , Fitoplâncton/genética , Água do Mar/microbiologia , Microbiota , Cianobactérias/genética , Cianobactérias/fisiologia , Fotossíntese , Estações do Ano , Metagenoma
3.
BMC Public Health ; 24(1): 2484, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267000

RESUMO

BACKGROUND: Chlamydia and gonorrhea notifications are rapidly rising in men who have sex with men (MSM). Currently, there are limited data on the prevalence of chlamydia and gonorrhea across various anatomical sites. Our study aimed to explore the prevalence, association and changing trends of urethral and rectal chlamydia and gonorrhea among MSM in Guangdong Province, China. METHODS: We analyzed data among MSM attending sexually transmitted infections (STI) clinics in the Guangdong governmental sentinel network between 2018 and 2022. Chi-square tests were used to compare the difference, Join-point regressions for analyzing changing trends, and multivariate logistic regressions for examining associated factors. RESULTS: We included 4856 men in the analysis. Rectal chlamydia significantly increased from 13.8% to 26.4% over the past 5 years (average annual percentage change [AAPC] 19.2%, 95%CI 1.0-40.6, p = 0.043). After adjusting for covariates, chlamydia infection positively associated with main venue used to seek sexual partners (aOR = 2.31, 95%CI 1.17-4.55), having regular sexual partners in the past 6 months (aOR = 3.32, 95%CI 1.95-5.64), receiving HIV counselling and testing services (aOR = 2.94, 95%CI 1.67-5.17), receiving peer education (aOR = 1.80, 95%CI 1.14-2.83), infection with syphilis (aOR = 2.02, 95%CI 1.02-4.01) and infection with gonorrhea (aOR 7.04, 95% CI 3.01-16.48). Gonorrhea infection positively associated with having regular sexual partners in the past 6 months (aOR = 3.48.95%CI 1.16-10.49), and infection with chlamydia (aOR 7.03, 95% CI 2.99-16.51). CONCLUSIONS: To conclude, our findings reveal a high prevalence of chlamydia infections among MSM, particularly in the rectal area. Comprehensive chlamydia and gonorrhea health services are necessary for MSM to improve sexual health.


Assuntos
Infecções por Chlamydia , Gonorreia , Homossexualidade Masculina , Humanos , Gonorreia/epidemiologia , Masculino , Infecções por Chlamydia/epidemiologia , China/epidemiologia , Adulto , Homossexualidade Masculina/estatística & dados numéricos , Adulto Jovem , Prevalência , Adolescente , Pessoa de Meia-Idade , Uretra/microbiologia
4.
Ecotoxicol Environ Saf ; 284: 116912, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39181073

RESUMO

Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and even death in livestock. However, the mechanism by swainsonine induced systemic inflammatory responses remained unclear, especially the effects of swainsonine on intestinal permeability, lipopolysaccharide (LPS) level and oxidative stress response were unknown. In this study, swainsonine increased intestinal permeability as evidenced by the significant down-regulation of colonic goblet cells, Akkermansia muciniphila and intestinal tight junction protein Occludin, Claudin 1 and ZO-1, and the significant up-regulation of mRNA expression level of the intestinal permeability indicator protein tyrosine phosphatase receptor type H (Ptprh) in the ileum of mice. Simultaneously, the elevated LPS biosynthetic genes in intestinal microbiota and increased intestinal permeability facilitated more bacterial endotoxin LPS to enter the blood. High concentration of free-form LPS induced high levels of proinflammatory cytokines and oxidative stress response, thereby causing the systemic inflammation. These findings provided a new perspective on swainsonine-induced systemic inflammation, suggesting that intestinal permeability and free-form LPS level may be the potential trigger factors.


Assuntos
Inflamação , Lipopolissacarídeos , Estresse Oxidativo , Permeabilidade , Swainsonina , Animais , Lipopolissacarídeos/toxicidade , Camundongos , Inflamação/induzido quimicamente , Permeabilidade/efeitos dos fármacos , Swainsonina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Masculino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Citocinas/metabolismo , Função da Barreira Intestinal
5.
Nat Nanotechnol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164411

RESUMO

Microstrain and the associated surface-to-bulk propagation of structural defects are known to be major roadblocks to developing high-energy and long-life batteries. However, the origin and effects of microstrain during the synthesis of battery materials remain largely unknown. Here we perform microstrain screening during real-time and realistic synthesis of sodium layered oxide cathodes. Evidence gathered from multiscale in situ synchrotron X-ray diffraction and microscopy characterization collectively reveals that the spatial distribution of transition metals within individual precursor particles strongly governs the nanoscale phase transformation, local charge heterogeneity and accumulation of microstrain during synthesis. This unexpected dominance of transition metals results in a counterintuitive outward propagation of defect nucleation and growth. These insights direct a more rational synthesis route to reduce the microstrain and crystallographic defects within the bulk lattice, leading to significantly improved structural stability. The present work on microstrain screening represents a critical step towards synthesis-by-design of defect-less battery materials.

6.
Chem Commun (Camb) ; 60(66): 8764-8767, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39073564

RESUMO

Cytochrome c (CytC) is conjugated with a small molecule TG6 to give TG6-CytC, which is directly delivered into cytosol, triggering the release of endogenous CytC from mitochondria, and inducing a caspase-3-dependent apoptosis with an IC50 down to 2.4 nM. This work shows an efficient strategy for intracellular protein delivery.


Assuntos
Apoptose , Caspase 3 , Citocromos c , Citosol , Citocromos c/metabolismo , Citocromos c/química , Apoptose/efeitos dos fármacos , Citosol/metabolismo , Caspase 3/metabolismo , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Células HeLa
7.
ACS Omega ; 9(27): 29917-29927, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005807

RESUMO

Two-layered metal oxides (LiCoO2 and cobalt-doped K n MnO2, n < 1) were explored as precatalysts for nanoconfined cobalt-based Fischer-Tropsch catalysts for conversion of syngas (CO and H2) to hydrocarbons. Ex situ, in situ, and PDF XRD analyses are presented. Based on in situ XRD analysis, LiCoO2 underwent reduction to predominantly cubic and hexagonal phases of cobalt metal. Reaction with syngas resulted in the generation of carbon, cobalt carbide, and lithium carbonate, in addition to the metallic cobalt phases. In the case of cobalt-doped birnessite, catalyst activation converted the birnessite phase to manganite and the cobalt to elemental cobalt, along with similar lithium and carbon phases. Conversion of syngas to C1 through C7 products was observed. The best conversions were observed for the LiCoO2 precursor catalyst, with generally a low olefin-to-paraffin ratio. While the conversions for the cobalt-doped birnessite precatalyst were generally lower, with lower chain lengths (up to C5), these catalysts gave a strikingly high olefin-to-paraffin ratio: in the best case, greater than 20:1.

8.
Chem Sci ; 15(26): 10126-10134, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38966377

RESUMO

Metal-organic frameworks (MOFs) show remarkable potential in a broad array of applications given their physical and chemical versatility. Classical synthesis of MOFs is performed using solution chemistry at elevated temperatures to achieve reversible metal-ligand bond formation. These harsh conditions may not be suitable for chemical species sensitive to high temperature or prone to deleterious reactions with solvents. For instance, Pd(ii) is susceptible to reduction under solvothermal conditions and is not a common metal node of MOFs. We report a generic and facile mechanochemical strategy that directly incorporates a series of Pd(ii)-based heterobimetallic clusters into MOFs as metal nodes without Pd(ii) being reduced to Pd(0). Mechanochemistry features advantages of short reaction time, minimum solvent, high reaction yield, and high degree of synthetic control. Catalytic performances of lattice-confined heterobimetallic sites are examined for nitrene transfer reactions and we demonstrate that the chemoselectivity for allylic amination versus olefin aziridination is readily tuned by the identity of the first-row metal ion in Pd(ii)-based heterobimetallic clusters.

9.
J Control Release ; 371: 371-385, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849089

RESUMO

The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.


Assuntos
Acroleína , Camptotecina , Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Humanos , Feminino , Linhagem Celular Tumoral , Acroleína/análogos & derivados , Acroleína/administração & dosagem , Acroleína/química , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Camptotecina/farmacologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Ácido Linoleico/química , Ácido Linoleico/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacologia , Triazóis/química , Dano ao DNA/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Camundongos Nus , Camundongos , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição/metabolismo , Inibidores da Topoisomerase I/administração & dosagem , Proteínas que Contêm Bromodomínio , Azepinas
10.
Opt Express ; 32(8): 13208-13223, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859297

RESUMO

Reading with a bit of yellowish or greenish paper, as compared to white paper, is thought to be more comfortable and friendly, and can help decrease eye fatigue to some degree. In this work, we try to map the light of different colors on a given paper within a region of interest to alter the colors presented by the paper and consequently influence the reading experience. We conducted an ergonomic experiment to study the comfort and clarity under consistent illuminance levels. We adopted 6 color series(red, yellow, green, cyan, blue, and magenta), 5 chroma levels(0, 10, 20, 30, 40), and 4 types of paper with the same hue(yellow) but different lightness(the white, light yellow, yellow, and dark yellow), and conducted pairwise selection experiments within each light color series. Results show that white and low chroma (≈10) color characteristics contribute to comfort, while higher chroma blue(30∼40) color benefits clarity. Referring to white, low chroma greenish and yellowish color characteristics are preferred in terms of comfort and clarity. This work proposes the spectrum mapping technology to endow the paper with new color effects and verifies that although spectrum compositions might differ, people's preferences and comfort perception are consistent with the same object color.

11.
J Agric Food Chem ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847775

RESUMO

Liver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus Akkermansia alleviating inflammation and genus Lactobacillus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.

12.
EPMA J ; 15(2): 233-259, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841616

RESUMO

A natural "medicine and food" plant, Rhodiola rosea (RR) is primarily made up of organic acids, phenolic compounds, sterols, glycosides, vitamins, lipids, proteins, amino acids, trace elements, and other physiologically active substances. In vitro, non-clinical and clinical studies confirmed that it exerts anti-inflammatory, antioxidant, and immune regulatory effects, balances the gut microbiota, and alleviates vascular circulatory disorders. RR can prolong life and has great application potential in preventing and treating suboptimal health, non-communicable diseases, and COVID-19. This narrative review discusses the effects of RR in preventing organ damage (such as the liver, lung, heart, brain, kidneys, intestines, and blood vessels) in non-communicable diseases from the perspective of predictive, preventive, and personalised medicine (PPPM/3PM). In conclusion, as an adaptogen, RR can provide personalised health strategies to improve the quality of life and overall health status.

13.
BMC Infect Dis ; 24(1): 532, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802750

RESUMO

BACKGROUND: HIV self-testing (HIVST) was recommended to improve HIV testing services. China initiated some of the first HIVST pilots in the world, providing a unique opportunity for implementation research. We aim to investigate HIVST adoption and its following linkage to care among Chinese men who have sex with men (MSM). METHODS: Data were collected using an online questionnaire distributed on major social media platforms in 2018, one year after HIVST was officially endorsed and allowed for sale. MSM who were at least 16 years old, assigned as male at birth, and ever tested for HIV were eligible. Primary outcome, adoption was defined as ever use of HIVST. Bivariate and multivariable logistic regressions were performed to explore the association between HIVST adoption and sociodemographic and behavioral factors. Linkage to care was also described via the following sequential events as indicators: (1) receiving result after recent test (2), seeking care from healthcare facility if test result was positive or indeterminate, and (3) delayed time before seeking care. RESULTS: A total of 540 participants were included with an average age of 27.4 ± 6.6. Most were never married (87.4%) and half completed college (52.2%). Overall, 75.2% had adopted HIVST. Self-test kits were commonly obtained from community-based organizations (54.4%) and from online (46.6%). HIVST adoption was positively associated with having college or higher education (OR = 1.66, 95%CI: 1.07-2.57), and negatively associated with age older than 30 (AOR = 0.52, 95%CI: 0.32-0.84). Adoption was not associated with other socio-demographic or behavioral factors. After receiving HIV-positive or indeterminate results, 25/25 of HIVST adopters sought care while 3 out of 7 (42.9%) non-adopters sought care (p < 0.001). Delays before seeking care were not significantly different between HIVST adopters compared to non-adopters (P = 0.366). CONCLUSION: Many MSM adopted HIVST shortly after its launch. Our findings suggested that HIVST linkage to care is promising among MSM in China. Integration of HIVST with other essential sexual health services is needed.


Assuntos
Infecções por HIV , Teste de HIV , Homossexualidade Masculina , Autoteste , Humanos , Masculino , Adulto , China/epidemiologia , Infecções por HIV/diagnóstico , Estudos Transversais , Homossexualidade Masculina/estatística & dados numéricos , Adulto Jovem , Teste de HIV/estatística & dados numéricos , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente
14.
J Control Release ; 370: 168-181, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643936

RESUMO

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.


Assuntos
Adipócitos , Antineoplásicos , Carcinoma Hepatocelular , Docetaxel , Exossomos , Neoplasias Hepáticas , Nanopartículas , Exossomos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Animais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Humanos , Docetaxel/administração & dosagem , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Adipócitos/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/administração & dosagem , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Camundongos Nus , Fototerapia/métodos , Sistemas de Liberação de Medicamentos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C
15.
Heliyon ; 10(7): e29312, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623210

RESUMO

This research dives into the intricate immune landscape of head and neck cancer (HNC), with a keen focus on the roles of specific immune cell subpopulations and their linked genes. We used tumour RNA-seq (in-house cohort: n = 192, TCGA-HNSC: n = 546) and Mendelian randomization to pinpoint key SNPs in immune cells that have a causal connection to HNC. Our discoveries unveil a spectrum of tumour immune phenotypes that either offer protection against or increase the risk of HNC. We underscore the therapeutic promise of Complement C3d Receptor 2 (CR2), a gene closely tied to immune cells, with its increased expression in tumour tissues linked to a more favourable prognosis. This is correlated with heightened immune pathway activity, stronger resistance to radiochemotherapy, and improved immunotherapy responses. Our research emphasises the pivotal role of CR2 in immune regulation and the significance of immune cells in tumour progression, highlighting the potential of CR2-targeted therapeutic interventions.

16.
Bioorg Chem ; 146: 107331, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579614

RESUMO

Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.


Assuntos
Antineoplásicos , Ferroptose , Neoplasias , Humanos , Apoptose , Morte Celular , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
17.
PLoS One ; 19(4): e0300433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564613

RESUMO

The current study seeks to investigate digital inequality among older adults in China, specifically examining two socially defined age groups: young-old adults (aged 60-74) and old-old adults (aged 75+). Descriptive statistics and multiple regression were used to examine the prevalence of and identify the factors associated with Internet access, usage (frequency and breadth containing 11 activities), skills, and social support. The study used data from the 2018 China Longitudinal Ageing Social Survey (CLASS) which consisted of 11,419 respondents aged 60 years and older. We found that 40.22% of older adults had access to the Internet, and 18.27% used it regularly. Socioeconomic factors played a crucial role in determining Internet access and usage, with young-old adults with higher education using the Internet more frequently, deliberately, and competently. Those with higher economic status had greater social support to use it, and the old-old adults with higher socioeconomic status were more likely to have Internet access. This study has implications for prioritizing targeted policies and interventions aimed at supporting socioeconomically disadvantaged older adults and ensuring equal opportunities for all to access and benefit from the digital world.


Assuntos
Acesso à Internet , Classe Social , Idoso , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Fatores Socioeconômicos , Inquéritos e Questionários , População do Leste Asiático
18.
ACS Appl Mater Interfaces ; 16(22): 29364-29373, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38647175

RESUMO

Efficient separation of Kr from Kr/Xe mixtures is pivotal in nuclear waste management and dark matter research. Thus far, scientists have encountered a formidable challenge: the absence of a material with the ability to selectively adsorb Kr over Xe at room temperature. This study presents a groundbreaking transformation of the renowned metal-organic framework (MOF) CuBTC, previously acknowledged for its Xe adsorption affinity, into an unparalleled Kr-selective adsorbent. This achievement stems from an innovative densification approach involving systematic compression of the MOF, where the crystal size, interparticle interaction, defects, and evacuation conditions are synergistically modulated. The resultant densified CuBTC phase exhibits exceptional mechanical resilience, radiation tolerance, and notably an unprecedented selectivity for Kr over Xe at room temperature. Simulation and experimental kinetic diffusion studies confirm reduced gas diffusion in the densified MOF, attributed to its small pore window and minimal interparticle voids. The lighter Kr element demonstrates facile surface passage and higher diffusivity within the material, while the heavier Xe encounters increased difficulty entering the material and lower diffusivity. This Kr-selective MOF not only represents a significant breakthrough in Kr separation but also demonstrates remarkable processability and scalability to kilogram levels. The findings presented herein underscore the transformative potential of engineered MOFs in addressing complex challenges, heralding a new era of Kr separation technologies.

19.
Haematologica ; 109(8): 2445-2458, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38356460

RESUMO

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechanism of ETV6::ACSL6 action remains unclear. Here, we performed multi-omics analyses of primary leukemia cells and patient-derived xenografts from an acute lymphoblastic leukemia (ALL) patient with ETV6::ACSL6 translocation. We identified a super-enhancer located within the ETV6 gene locus, and revealed translocation and activation of the super-enhancer associated with the ETV6::ACSL6 fusion. The translocated super-enhancer exhibited intense interactions with genomic regions adjacent to and distal from the breakpoint at chromosomes 5 and 12, including genes coding inflammatory factors such as IL-3. This led to modulations in DNA methylation, histone modifications, and chromatin structures, triggering transcription of inflammatory factors leading to eosinophilia. Furthermore, the bromodomain and extraterminal domain (BET) inhibitor synergized with standard-of-care drugs for ALL, effectively reducing IL-3 expression and inhibiting ETV6::ACSL6 ALL growth in vitro and in vivo. Overall, our study revealed for the first time a cis-regulatory mechanism of super-enhancer translocation in ETV6::ACSL6ALL, leading to an ALL-accompanying clinical syndrome. These findings may stimulate novel treatment approaches for this challenging ALL subtype.


Assuntos
Variante 6 da Proteína do Fator de Translocação ETS , Elementos Facilitadores Genéticos , Eosinofilia , Interleucina-3 , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras , Translocação Genética , Animais , Humanos , Camundongos , Eosinofilia/genética , Eosinofilia/metabolismo , Eosinofilia/patologia , Regulação Leucêmica da Expressão Gênica , Interleucina-3/genética , Interleucina-3/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
20.
Int J Biol Macromol ; 261(Pt 2): 129917, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309407

RESUMO

Echinacea purpurea polysaccharide (EPP) exhibit various pharmacological activities, including immunomodulatory, anti-inflammatory, and anti-tumor effects. In this study, we investigated the potential mechanism of EPP intervention in hepatocellular carcinoma (HCC). The results demonstrated that EPP effectively mitigated liver injury caused by HCC, inhibited the proliferation of HCC, and induced apoptosis. Following EPP intervention, there was a significant increase in propionic acid and butyric acid-producing gut microbiota such as Coprococcus, Clostridium and Roseburia, leading to enhanced expression of intestinal tight junction proteins and the repair of the intestinal barrier. This controls lipopolysaccharide (LPS) leakage, which in turn inhibits the TLR4/NF-κB pathway and reduces the expression of inflammatory factors such as IL-6, as well as migration factors like MMP-2. Metabolomics revealed the downregulation of pyrimidine metabolism and nucleotide metabolism, along with the upregulation of butyrate metabolism in tumor cells. This study demonstrated that EPP effectively regulated LPS leakage by modulating gut microbes, and this modulation influenced the TLR4/NF-κB pathway, ultimately disrupting tumor cell survival induced by HCC in mice.


Assuntos
Carcinoma Hepatocelular , Echinacea , Microbioma Gastrointestinal , Neoplasias Hepáticas , Animais , Camundongos , NF-kappa B/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico
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