RESUMO
Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.
Assuntos
Endodesoxirribonucleases , Neoplasias , Peptídeos , Poli ADP Ribosilação , RNA Longo não Codificante , Reparo do DNA , Endodesoxirribonucleases/metabolismo , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Peptídeos/farmacologia , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
The future of the global ocean economy is currently envisioned as advancing towards a 'blue economy'-socially equitable, environmentally sustainable and economically viable ocean industries1,2. However, tensions exist within sustainable development approaches, arising from differing perspectives framed around natural capital or social equity. Here we show that there are stark differences in outlook on the capacity for establishing a blue economy, and on its potential outcomes, when social conditions and governance capacity-not just resource availability-are considered, and we highlight limits to establishing multiple overlapping industries. This is reflected by an analysis using a fuzzy logic model to integrate indicators from multiple disciplines and to evaluate their current capacity to contribute to establishing equitable, sustainable and viable ocean sectors consistent with a blue economy approach. We find that the key differences in the capacity of regions to achieve a blue economy are not due to available natural resources, but include factors such as national stability, corruption and infrastructure, which can be improved through targeted investments and cross-scale cooperation. Knowledge gaps can be addressed by integrating historical natural and social science information on the drivers and outcomes of resource use and management, thus identifying equitable pathways to establishing or transforming ocean sectors1,3,4. Our results suggest that policymakers must engage researchers and stakeholders to promote evidence-based, collaborative planning that ensures that sectors are chosen carefully, that local benefits are prioritized, and that the blue economy delivers on its social, environmental and economic goals.
Assuntos
Política Ambiental , Modelos Econômicos , Oceanos e Mares , Desenvolvimento Sustentável/economia , Lógica Fuzzy , ObjetivosRESUMO
Microglial phagocytosis is an energetically demanding process that plays a critical role in the removal of toxic protein aggregates in Alzheimer's disease (AD). Recent evidence indicates that a switch in energy production from mitochondrial respiration to glycolysis disrupts this important protective microglial function and may provide therapeutic targets for AD. Here, we demonstrate that the translocator protein (TSPO) and a member of its mitochondrial complex, hexokinase-2 (HK), play critical roles in microglial respiratory-glycolytic metabolism and phagocytosis. Pharmacological and genetic loss-of-function experiments showed that TSPO is critical for microglial respiratory metabolism and energy supply for phagocytosis, and its expression is enriched in phagocytic microglia of AD mice. Meanwhile, HK controlled glycolytic metabolism and phagocytosis via mitochondrial binding or displacement. In cultured microglia, TSPO deletion impaired mitochondrial respiration and increased mitochondrial recruitment of HK, inducing a switch to glycolysis and reducing phagocytosis. To determine the functional significance of mitochondrial HK recruitment, we developed an optogenetic tool for reversible control of HK localization. Displacement of mitochondrial HK inhibited glycolysis and improved phagocytosis in TSPO-knockout microglia. Mitochondrial HK recruitment also coordinated the inflammatory switch to glycolysis that occurs in response to lipopolysaccharide in normal microglia. Interestingly, cytosolic HK increased phagocytosis independent of its metabolic activity, indicating an immune signaling function. Alzheimer's beta amyloid drastically stimulated mitochondrial HK recruitment in cultured microglia, which may contribute to microglial dysfunction in AD. Thus, targeting mitochondrial HK may offer an immunotherapeutic approach to promote phagocytic microglial function in AD.
Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Microglia/metabolismo , Fagocitose , Mitocôndrias/metabolismoRESUMO
Photocatalytic water splitting represents a leading approach to harness the abundant solar energy, producing hydrogen as a clean and sustainable energy carrier. Zinc indium sulfide (ZIS) emerges as one of the most captivating candidates attributed to its unique physicochemical and photophysical properties, attracting much interest and holding significant promise in this domain. To develop a highly efficient ZIS-based photocatalytic system for green energy production, it is paramount to comprehensively understand the strengths and limitations of ZIS, particularly within the framework of solar-driven water splitting. This review elucidates the three sequential steps that govern the overall efficiency of ZIS with a sharp focus on the mechanisms and inherent drawbacks associated with each phase, including commonly overlooked aspects such as the jeopardising photocorrosion issue, the neglected oxidative counter surface reaction kinetics in overall water splitting, the sluggish photocarrier dynamics and the undesired side redox reactions. Multifarious material design strategies are discussed to specifically mitigate the formidable limitations and bottleneck issues. This review concludes with the current state of ZIS-based photocatalytic water splitting systems, followed by personal perspectives aimed at elevating the field to practical consideration for future endeavours towards sustainable hydrogen production through solar-driven water splitting.
RESUMO
The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ferro , Raízes de Plantas , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Ferro/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Concentração de Íons de Hidrogênio , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Protons (H+) in acidic soils arrest plant growth. However, the mechanisms by which plants optimize their biological processes to diminish the unfavorable effects of H+ stress remain largely unclear. Here, we showed that in the roots of Arabidopsis thaliana, the C2H2-type transcription factor STOP1 in the nucleus was enriched by low pH in a nitrate-independent manner, with the spatial expression pattern of NITRATE TRANSPORTER 1.1 (NRT1.1) established by low pH required the action of STOP1. Additionally, the nrt1.1 and stop1 mutants, as well as the nrt1.1 stop1 double mutant, had a similar hypersensitive phenotype to low pH, indicating that STOP1 and NRT1.1 function in the same pathway for H+ tolerance. Molecular assays revealed that STOP1 directly bound to the promoter of NRT1.1 to activate its transcription in response to low pH, thus upregulating its nitrate uptake. This action improved the nitrogen use efficiency (NUE) of plants and created a favorable rhizospheric pH for root growth by enhancing H+ depletion in the rhizosphere. Consequently, the constitutive expression of NRT1.1 in stop1 mutants abolished the hypersensitive phenotype to low pH. These results demonstrate that STOP1-NRT1.1 is a key module for plants to optimize NUE and ensure better plant growth in acidic media.
Assuntos
Proteínas de Transporte de Ânions/genética , Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Nitratos/metabolismo , Proteínas de Plantas/genética , Rizosfera , Solo/química , Fatores de Transcrição/genética , Adaptação Fisiológica/genética , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Concentração de Íons de Hidrogênio , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.
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Dermatite Atópica , Eczema , Terapia Ultravioleta , Humanos , Dermatite Atópica/radioterapia , Estudos Prospectivos , Método Duplo-Cego , Qualidade de Vida , Terapia Ultravioleta/efeitos adversos , Fototerapia , Prurido/etiologia , Prurido/radioterapia , Resultado do TratamentoRESUMO
Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.
Assuntos
Parede Celular , Melatonina , Óxido Nítrico , Oryza , Fósforo , Raízes de Plantas , Oryza/metabolismo , Fósforo/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/efeitos dos fármacos , Óxido Nítrico/metabolismoRESUMO
Iron deficiency is a major constraint for plant growth in calcareous soils. The interplay between NO3 - and Fe nutrition affects plant performance under Fe-deficient conditions. However, how NO3 - negatively regulates Fe nutrition at the molecular level in plants remains elusive. Here, we showed that the key nitrate transporter NRT1.1 in Arabidopsis plants, especially in the shoots, was markedly downregulated at post-translational levels by Fe deficiency. However, loss of NRT1.1 function alleviated Fe deficiency chlorosis, suggesting that downregulation of NRT1.1 by Fe deficiency favors plant tolerance to Fe deficiency. Further analysis showed that although disruption of NRT1.1 did not alter Fe levels in both the shoots and roots, it improved the reutilization of apoplastic Fe in shoots but not in roots. In addition, disruption of NRT1.1 prevented Fe deficiency-induced apoplastic alkalization in shoots by inhibiting apoplastic H+ depletion via NO3 - uptake. In vitro analysis showed that reduced pH facilitates release of cell wall-bound Fe. Thus, foliar spray with an acidic buffer promoted the reutilization of Fe in the leaf apoplast to enhance plant tolerance to Fe deficiency, while the opposite was true for the foliar spray with a neutral buffer. Thus, downregulation of the shoot-part function of NRT1.1 prevents apoplastic alkalization to ensure the reutilization of apoplastic Fe under Fe-deficient conditions. Our findings may provide a basis for elucidating the link between N and Fe nutrition in plants and insight to scrutinize the relevance of shoot-expressed NRT1.1 to the plant response to stress.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ferro/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Arabidopsis/metabolismo , Solo , Regulação da Expressão Gênica de Plantas , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Transporte de Ânions/genéticaRESUMO
Interim analysis of the National Skin Centre Singapore Psoriasis Biologics Registry (SINGPSOR) from August 2017 to May 2021, in which 58 patients were analysed, showing that those receiving biologic treatment had significantly more severe psoriasis based on PASI (Psoriasis Area and Severity Index), BSA (body surface area) and PGA (Physician Global Assessment) measures at baseline, demonstrated a statistically non-significant trend towards greater improvement with treatment, and had a lower percentage of adverse events compared to those receiving conventional systemic therapy. Future analyses of SINGPSOR, with larger sample size and longer follow-up, will be invaluable to further characterize these patients and their treatment outcomes.
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Produtos Biológicos , Psoríase , Humanos , Singapura , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Resultado do Tratamento , Sistema de Registros , Produtos Biológicos/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Adalimumab/uso terapêuticoRESUMO
BACKGROUND: Previous studies regarding the risk of skin malignancy with NBUVB have been performed in Caucasian patients, but few studies have been conducted in Asians. AIM: The aim of the study was to determine the risk of skin cancer in Asian patients with psoriasis and vitiligo receiving NBUVB phototherapy. METHODS: We performed a 9-year retrospective study including all patients with psoriasis and vitiligo receiving NBUVB (either 311 nm wavelength through cabin phototherapy or 308 nm through excimer lamp phototherapy) at the National Skin Centre. We matched the identification numbers of patients to the National Registry of Diseases Office database and collected data on all skin cancers diagnosed. RESULTS: A total of 3730 patients were included. During the course of the study, 12 cases of skin cancer were diagnosed, of which 10 were basal cell carcinomas, and 2 were squamous cell carcinomas. No cases of melanoma were detected in the study. The age-standardized incidence of skin cancer in psoriasis and vitiligo patients who received phototherapy was 47.5 and 26.5, respectively, which is higher than the incidence of skin cancers in the general population. Risk of skin malignancy was positively correlated with the cumulative (p = .008) and maximum dose of phototherapy (p = .011) as well as previous systemic treatments (p = .006). LIMITATIONS: Limitations include a relatively short follow-up period as well as the lack of quantification of solar exposure. CONCLUSIONS: NBUVB phototherapy in Asian skin increases the risk of skin malignancy. The risk of skin malignancy is higher with psoriasis patients, greater cumulative and maximal dose of phototherapy as well as the use of systemic therapy. Despite the increased risk, the absolute number of skin malignancies remains low, especially for vitiligo patients, with no cases of melanoma diagnosed-a reassuring finding that phototherapy remains a safe alternative in the treatment of psoriasis and vitiligo.
Assuntos
Melanoma , Psoríase , Neoplasias Cutâneas , Terapia Ultravioleta , Vitiligo , Humanos , Estudos Retrospectivos , Vitiligo/epidemiologia , Incidência , Terapia Ultravioleta/efeitos adversos , Fototerapia/efeitos adversos , Psoríase/complicações , Psoríase/epidemiologia , Psoríase/radioterapia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Melanoma/epidemiologia , Melanoma/radioterapia , Resultado do TratamentoRESUMO
BACKGROUND: There is increasing intervention activities provided during pharmacist-led diabetes management. Nevertheless, there is an unclear definition of the activities involved during the intervention. Thus, this study aimed to describe the type of intervention strategies and service model provided during pharmacist-led type 2 diabetes management and service outcomes. METHODS: This study utilized the scoping review methodology of the Joanna Briggs Institute Reviewers' Manual 2015. Articles on pharmacist-led diabetes management focusing on the service content, delivery methods, settings, frequency of appointments, collaborative work with other healthcare providers, and reported outcomes were searched and identified from four electronic databases: Ovid Medline, PubMed, Scopus, and Web of Science from 1990 to October 2020. Relevant medical subject headings and keywords, such as "diabetes," "medication adherence," "blood glucose," "HbA1c," and "pharmacist," were used to identify published articles. RESULTS: The systematic search retrieved 4,370 articles, of which 61 articles met the inclusion criteria. The types of intervention strategies and delivery methods were identified from the studies based on the description of activities reported in the articles and were tabulated in a summary table. CONCLUSION: There were variations in the descriptions of intervention strategies, which could be classified into diabetes education, medication review, drug consultation/counseling, clinical intervention, lifestyle adjustment, self-care, peer support, and behavioral intervention. In addition, most studies used a combination of two or more intervention strategy categories when providing services, with no specific pattern between the service model and patient outcomes.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Farmacêuticos , Adesão à Medicação , Educação em SaúdeRESUMO
Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as "Paku Pedang") against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography-high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11-43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.
Assuntos
Anti-Infecciosos , Gleiquênias , Animais , Cromatografia Líquida de Alta Pressão , Anti-Infecciosos/farmacologia , Antiparasitários/farmacologia , Antibacterianos/farmacologiaRESUMO
OBJECTIVES: Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). METHODS: Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. RESULTS: The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. CONCLUSIONS: Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.
Assuntos
Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Lactente , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Contagem de Linfócitos , Subpopulações de Linfócitos , Estudos RetrospectivosRESUMO
Toxic and odorous iodophenols are commonly identified as disinfection by-products (DBPs) in drinking water. Herein, ng/L levels of iodophenols were identified in river water, wastewater treatment plant effluent, and medical wastewater, with the simultaneous identification of µg/L to mg/L levels of iodide (I-) and total organic iodine (TOI). Oxidation experiment suggested that the I-, TOI, and iodophenols could be oxidized by ferrate [Fe(VI)], and more than 97% of TOI had been transformed into stable and nontoxic IO3-. Fe(VI) initially cleaved the C-I bond of iodophenols and led to the deiodination of iodophenols. The resulted I- was swiftly oxidized into HOI and IO3-, with the intermediate phenolic products be further oxidized into lower molecular weight products. The Gibbs free energy change (ΔG) of the overall reaction was negative, indicating that the deiodination of iodophenols by Fe(VI) was spontaneous. In the disinfection of iodine-containing river water, ng/L levels of iodophenols and chloro-iodophenols formed in the reaction with NaClO/NH2Cl, while Fe(VI) preoxidation was effective for inhibiting the formation of iodinated DBPs. Fe(VI) exhibited multiple functions for oxidizing organic iodine, abating their acute toxicity/cytotoxicity and controlling the formation of iodinated DBPs for the treatment of iodide/organic iodine-containing waters.
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Desinfetantes , Água Potável , Iodo , Poluentes Químicos da Água , Purificação da Água , Iodetos , Halogenação , Poluentes Químicos da Água/química , Purificação da Água/métodos , Desinfecção/métodosRESUMO
BACKGROUND: Studies suggest excessive screen time (use of smartphones, televisions, computers and/or video games) is linked to speech and language delay. This study explored the sociodemographic characteristics of children with speech delay in Kuantan, Malaysia, and the association of screen time with speech and other developmental delays. METHODS: This cross-sectional study was conducted between July and November 2019 at the child psychiatry and speech therapy clinics, at Kuantan Hospital, Pahang, Malaysia. Parents of children with speech delay aged <72 months provided information on their children's and their own screen times. Speech and other developmental skills were assessed using the Schedule of Growing Skills II with scores reported as developmental quotient (DQ) level. RESULTS: The study included 91 children (67 boys, 24 girls) of whom 54.9% had primary speech delay and 45.1% had neurodevelopmental disorders; their mean age was 39.9 ± 11.52 months. The children's mean screen time was 2.26 ± 1.98 h daily, with 36.3% exceeding 2 h. Higher children's screen time was moderately correlated with higher parental screen time (rs = 0.479, P < 0.01). Household income was positively correlated with screen times of the children and the parents (rs = 0.243, P = 0.02 and rs = 0.390, p < 0.01, respectively). Parents who intended to reduce their children's screen time reported higher screen time in their children (t(89) = 2.322, P = 0.023). Children's age was positively correlated with the number of types of screen media (rs = 0.225, P = 0.032). The mean speech DQ was 54.76 ± 24.06%. Lower speech DQ was associated with lower DQs in other skills (P < 0.01). No significant correlation was shown between children's and parents' screen time with DQs of speech and other skills (P > 0.05). CONCLUSION: The correlation between parent and child screen time provides an opportunity for possible intervention, where necessary. Larger studies are required to examine this correlation further.
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Transtornos do Desenvolvimento da Linguagem , Tempo de Tela , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/epidemiologia , Malásia/epidemiologia , Masculino , Pais , TelevisãoRESUMO
Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.
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Vesículas Extracelulares/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transporte Biológico , Biomarcadores , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Fracionamento Químico , Gerenciamento Clínico , Progressão da Doença , Suscetibilidade a Doenças , Portadores de Fármacos , Resistência a Medicamentos , Exossomos/metabolismo , Humanos , Imunoterapia , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/terapia , Microambiente Tumoral/efeitos dos fármacosRESUMO
K+ and NO3 - are the major forms of potassium and nitrogen that are absorbed by the roots of most terrestrial plants. In this study, we observed that a close relationship between NO3 - and K+ in Arabidopsis (Arabidopsis thaliana) is mediated by NITRATE TRANSPORTER1.1 (NRT1.1). The nrt1.1 knockout mutants showed disturbed K+ uptake and root-to-shoot allocation, and were characterized by growth arrest under K+-limiting conditions. The K+ uptake and root-to-shoot allocation of these mutants were partially recovered by expressing NRT1.1 in the root epidermis-cortex and central vasculature using SULFATE TRANSPORTER1;2 and PHOSPHATE1 promoters, respectively. Two-way analysis of variance based on the K+ contents in nrt1.1-1/K + transporter1, nrt1.1-1/high-affinity K + transporter5-3, nrt1.1-1/K + uptake permease7, and nrt1.1-1/stelar K + outward rectifier-2 double mutants and the corresponding single mutants and wild-type plants revealed physiological interactions between NRT1.1 and K+ channels/transporters located in the root epidermis-cortex and central vasculature. Further study revealed that these K+ uptake-related interactions are dependent on an H+-consuming mechanism associated with the H+/NO3 - symport mediated by NRT1.1. Collectively, these data indicate that patterns of NRT1.1 expression in the root epidermis-cortex and central vasculature are coordinated with K+ channels/transporters to improve K+ uptake and root-to-shoot allocation, respectively, which in turn ensures better growth under K+-limiting conditions.
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Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Transporte Biológico/fisiologia , Nitratos/metabolismo , Deficiência de Potássio/metabolismo , Arabidopsis/genética , Transporte Biológico/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Mutação , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Deficiência de Potássio/genéticaRESUMO
The present study explored the modulating apoptosis effect of hydrogen sulfide (H2S) in subarachnoid hemorrhage (SAH) rats and its exact mechanism. A rat SAH model established by intravascular puncturing was used for the present study. After giving NaHS (donor of H2S), an L-type calcium channel opener (Bay K8644), or a calcium channel agonist (nifedipine), the neurological function of the rats, associated pathological changes, and expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and microtubule-associated protein (MAP-2) were examined. The concentration of H2S and expression of cystathionine beta synthase in the hippocampus changed upon early brain injury (EBI) after SAH. Compared with the SAH group, the neurological function of the rats and microstructure observed by electron microscopy were better in the SAH + NaHS group and SAH + Bay K8644 group. It was observed that apoptosis was more obvious in the SAH group than in the control group and was alleviated in the SAH + NaHS group. Furthermore, the alleviating effect of NaHS was partially weakened by nifedipine, indicating that the effect of anti-apoptosis in H2S might be correlated with the calcium channel. The expression of Bax and caspase-3 was elevated, while the expression of Bcl-2 decreased in the SAH group but improved in the SAH + NaHS and SAH + Bay K8644 group. Compared with the SAH + NaHS group, the expression of pro-apoptotic proteins was higher in the SAH + NaHS + nifedipine group. Therefore, upon EBI following SAH, the H2S system plays an important neurological protective effect by modulating the function of the L-type calcium channel and inhibiting apoptosis.
Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Canais de Cálcio Tipo L/metabolismo , Sulfeto de Hidrogênio/metabolismo , Neuroproteção/fisiologia , Hemorragia Subaracnóidea/metabolismo , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/prevenção & controle , Agonistas dos Canais de Cálcio/farmacologia , Masculino , Neuroproteção/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/prevenção & controle , Sulfitos/farmacologiaRESUMO
A unique metal-organic framework (MOF) with tetrazole-padded helical channels has been successfully synthesized in one pot from iron(II) trifluoromethanesulfonate, 4-formylimidazole, hydrazine, and sodium azide under solvothermal conditions and features a rare unh topology and porous structure for gas adsorption. Transformations of condensation, cycloaddition, and coordination occurred during the synthetic process, in which a 1,5-disubstituted tetrazole ligand was formed in situ.