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1.
Nat Commun ; 15(1): 5154, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886378

RESUMO

Cancer incidence escalates exponentially with advancing age; however, the underlying mechanism remains unclear. In this study, we build a chronological molecular clock at single-cell transcription level with a mammary stem cell-enriched population to depict physiological aging dynamics in female mice. We find that the mammary aging process is asynchronous and progressive, initiated by an early senescence program, succeeded by an entropic late senescence program with elevated cancer associated pathways, vulnerable to cancer predisposition. The transition towards senescence program is governed by a stem cell factor Bcl11b, loss of which accelerates mammary ageing with enhanced DMBA-induced tumor formation. We have identified a drug TPCA-1 that can rejuvenate mammary cells and significantly reduce aging-related cancer incidence. Our findings establish a molecular portrait of progressive mammary cell aging and elucidate the transcriptional regulatory network bridging mammary aging and cancer predisposition, which has potential implications for the management of cancer prevalence in the aged.


Assuntos
Envelhecimento , Neoplasias da Mama , Senescência Celular , Feminino , Animais , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Humanos , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Animais/metabolismo , Células-Tronco/metabolismo
2.
Environ Res ; 257: 119250, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844031

RESUMO

Aquatic ecosystems are being increasingly polluted by microplastics (MPs), which calls for an understanding of how MPs affect microbially driven biogenic element cycling in water environments. A 28-day incubation experiment was conducted using freshwater lake water added with three polymer types of MPs (i.e., polyethylene, polypropylene, polystyrene) separately or in combination at a concentration of 1 items/L. The effects of various MPs on microbial communities and functional genes related to carbon, nitrogen, phosphorus, and sulfur cycling were analyzed using metagenomics. Results showed that Sphingomonas and Novosphingobium, which were indicator taxa (genus level) in the polyethylene treatment group, made the largest functional contribution to biogenic element cycling. Following the addition of MPs, the relative abundances of genes related to methane oxidation (e.g., hdrD, frhB, accAB) and denitrification (napABC, nirK, norB) increased. These changes were accompanied by increased relative abundances of genes involved in organic phosphorus mineralization (e.g., phoAD) and sulfate reduction (cysHIJ), as well as decreased relative abundances of genes involved in phosphate transport (phnCDE) and the SOX system. Findings of this study underscore that MPs, especially polyethylene, increase the potential of greenhouse gas emissions (CO2, N2O) and water pollution (PO43-, H2S) in freshwater lakes at the functional gene level.

3.
J Sci Food Agric ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873964

RESUMO

BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

4.
Mol Cell ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38838666

RESUMO

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

5.
Biosci Rep ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828664

RESUMO

Increasing cadmium (Cd) pollution has negative effects on quinoa growth and production. Gamma-aminobutyric acid (GABA) confers plants with stress resistance to heavy metals; however, the mechanism remains unclear. We explored the effects of exogenous GABA on the physiological characteristics, antioxidant capacity, and Cd accumulation of quinoa seedlings under Cd stress using hydroponic experiments. Partial least-squares regression was used to identify key physical and chemical indices of seedlings affecting Cd accumulation. Compared with those of the CK group, exposure to 10 µmol·L-1 and 25 µmol·L-1 Cd significantly reduced the photosynthetic pigment contents, photosynthesis, and biomass accumulation of quinoa seedlings; resulted in shorter and thicker roots; decreased the length of the lateral roots; decreased the activities of superoxide dismutase (SOD) and peroxide (POD); and increased H2O2 and malondialdehyde (MDA) contents. Exogenous GABA reduced the Cd content in the stem/leaves and roots of quinoa seedlings under Cd stress by 13.22-21.63% and 7.92-28.32%, decreased Cd accumulation by 5.37-6.71% and 1.91-4.09%, decreased the H2O2 content by 38.21-47.46% and 45.81-55.73%, and decreased the MDA content by 37.65-48.12% and 29.87-32.51%, respectively. GABA addition increased the SOD and POD activities in the roots by 2.78-5.61% and 13.81-18.33%, respectively, under Cd stress. Thus, exogenous GABA can reduce the content and accumulation of Cd in quinoa seedlings by improving the photosynthetic characteristics and antioxidant enzyme activity and reducing the degree of lipid peroxidation in the cell membrane to alleviate the toxic effect of Cd stress on seedling growth.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38829052

RESUMO

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

7.
Adv Mater ; : e2405170, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838950

RESUMO

High-entropy strategies are regarded as a powerful means to enhance performance in energy storage fields. The improved properties are invariably ascribed to entropy stabilization or synergistic cocktail effect. Therefore, the manifested properties in such multicomponent materials are usually unpredictable. Elucidating the precise correlations between atomic structures and properties remains a challenge in high-entropy materials (HEMs). Herein, atomic-resolution scanning transmission electron microscopy annular dark field (STEM-ADF) imaging and four dimensions (4D)-STEM are combined to directly visualize atomic-scale structural and electric information in high-entropy FeMnNiVZnPS3. Aperiodic stacking is found in FeMnNiVZnPS3 accompanied by high-density strain soliton boundaries (SSBs). Theoretical calculation suggests that the formation of such structures is attributed to the imbalanced stress of distinct metal-sulfur bonds in FeMnNiVZnPS3. Interestingly, the electric field concentrates along the two sides of SSBs and gradually diminishes toward the two-dimensional (2D) plane to generate a unique electric field gradient, strongly promoting the ion-diffusion rate. Accordingly, high-entropy FeMnNiVZnPS3 demonstrates superior ion-diffusion coefficients of 10-9.7-10-8.3 cm2 s-1 and high-rate performance (311.5 mAh g-1 at 30 A g-1). This work provides an alternative way for the atomic-scale understanding and design of sophisticated HEMs, paving the way for property engineering in multi-component materials.

8.
Mar Pollut Bull ; 204: 116536, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850760

RESUMO

In this study, we examined the persistent pollutant contents [harmful elements (HEs), cadmium (Cd, 0.1 mg/kg) âˆ¼ barium (Ba, 881.1 mg/kg)] and polycyclic aromatic hydrocarbons [PAHs; Acenaphthylene (Acy), Acenaphthene (Ace), Fluorene (Flu), Benzo(k)fluoranthene (BkF), Benzo(a)pyrene (BaP) (0 mg/kg) âˆ¼ BaP (10.2 mg/kg)] in bus stop dust (BSD) from Qingyang, Northwest China. The Nemerow composite pollution index of the eight types of PAHs and ∑16PAHs indicated severe pollution. The carcinogenic risk of the persistent pollutant in BSD to adults was 1.6 times greater than the acceptable upper limit for the human body, while the noncarcinogenic risk was small to five daily bus passenger groups. Clustering and principal component analysis showed that 12 kinds of HEs were mainly derived from coal and fuel combustion and 16 kinds of PAHs were mainly derived from biomass combustion, organic matter decomposition, and chemical applications.


Assuntos
Poeira , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , China , Hidrocarbonetos Policíclicos Aromáticos/análise , Poeira/análise , Humanos , Medição de Risco , Cidades , Poluentes Orgânicos Persistentes , Florestas , Poluentes Atmosféricos/análise
9.
Redox Biol ; 74: 103236, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875958

RESUMO

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.


Assuntos
Glucosefosfato Desidrogenase , Espécies Reativas de Oxigênio , Receptores de N-Metil-D-Aspartato , Fator de Transcrição STAT1 , Convulsões , Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/antagonistas & inibidores , Glucosefosfato Desidrogenase/genética , Espécies Reativas de Oxigênio/metabolismo , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Convulsões/metabolismo , Convulsões/tratamento farmacológico , Fator de Transcrição STAT1/metabolismo , Epilepsia/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/genética , Transdução de Sinais/efeitos dos fármacos , Camundongos , Humanos , Neurônios/metabolismo , Masculino , Ratos , Modelos Animais de Doenças
10.
JAMA Netw Open ; 7(5): e2413708, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809553

RESUMO

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.


Assuntos
Predisposição Genética para Doença , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/complicações , China/epidemiologia , Estudo de Associação Genômica Ampla , Estudos de Casos e Controles , Adulto , Fatores de Risco , Suplementos Nutricionais , Estudos de Coortes , Idoso , Antibacterianos/uso terapêutico
11.
Neurobiol Dis ; 197: 106534, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759931

RESUMO

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.


Assuntos
Esclerose Lateral Amiotrófica , Modelos Animais de Doenças , Camundongos Transgênicos , Proteínas Mitocondriais , Mitofagia , Neurônios Motores , Animais , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Mitofagia/fisiologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Camundongos , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Humanos , Medula Espinal/metabolismo , Medula Espinal/patologia
12.
Int Immunopharmacol ; 134: 112141, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733819

RESUMO

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.


Assuntos
Anticorpos Antivirais , Inteligência Artificial , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Vacinas contra COVID-19/imunologia , Masculino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/sangue , Estudos Prospectivos , Imunidade Humoral , Anticorpos Neutralizantes/sangue , Eficácia de Vacinas , Imunização Secundária , Aprendizado de Máquina , Idoso , Adulto Jovem , Imunidade Celular
13.
Biochem Pharmacol ; 225: 116320, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38801927

RESUMO

TMP269, a class IIA histone deacetylase inhibitor with selectivity, that has a protective effect on the central nervous system, yet its specific mechanism of action remains ambiguous. Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that histone deacetylase 5 plays a key role in the pathological process of depression and the fact that preclinical studies have shown HDAC5 to be a potential antidepressant target, the search for natural drugs or small molecule compounds that can target HDAC5 may be a potential therapeutic strategy for the treatment of depression. In addition, we examined the role of the Brain-derived neurotrophic factor (BDNF), an important neurotrophic factor for neuronal survival and growth, as a potential downstream target of HDAC5. We found downward revision of HDAC5 levels in the hippocampus ameliorated depressive-like behavior in LH (Learned helplessness) mice. Furthermore, injection of HDAC5 overexpressing adenoviral vectors in the hippocampal dentate gyrus of wild-type mice produced a somewhat depressive-like phenotype. Pharmacological, immunofluorescence and biochemical experiments showed that TMP269 could produce antidepressant effects by inhibiting mouse hippocampal HDAC5 and thus modulating its downstream BDNF. Over all, TMP269 mitigated LH-induced depressive-like behaviors and abnormalities in synapse formation and neurogenesis within the hippocampus. These findings suggest potential beneficial effects of TMP269 on depression.


Assuntos
Antidepressivos , Depressão , Camundongos Endogâmicos C57BL , Estresse Psicológico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Camundongos , Masculino , Depressão/tratamento farmacológico , Depressão/metabolismo , Estresse Psicológico/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Histona Desacetilases/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Comportamento Animal/efeitos dos fármacos
14.
Cortex ; 176: 1-10, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723449

RESUMO

Recognizing talkers' identity via speech is an important social skill in interpersonal interaction. Behavioral evidence has shown that listeners can identify better the voices of their native language than those of a non-native language, which is known as the language familiarity effect (LFE). However, its underlying neural mechanisms remain unclear. This study therefore investigated how the LFE occurs at the neural level by employing functional near-infrared spectroscopy (fNIRS). Late unbalanced bilinguals were first asked to learn to associate strangers' voices with their identities and then tested for recognizing the talkers' identities based on their voices speaking a language either highly familiar (i.e., native language Chinese), or moderately familiar (i.e., second language English), or completely unfamiliar (i.e., Ewe) to participants. Participants identified talkers the most accurately in Chinese and the least accurately in Ewe. Talker identification was quicker in Chinese than in English and Ewe but reaction time did not differ between the two non-native languages. At the neural level, recognizing voices speaking Chinese relative to English/Ewe produced less activity in the inferior frontal gyrus, precentral/postcentral gyrus, supramarginal gyrus, and superior temporal sulcus/gyrus while no difference was found between English and Ewe, indicating facilitation of voice identification by the automatic phonological encoding in the native language. These findings shed new light on the interrelations between language ability and voice recognition, revealing that the brain activation pattern of the LFE depends on the automaticity of language processing.


Assuntos
Idioma , Reconhecimento Psicológico , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala , Voz , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Feminino , Masculino , Reconhecimento Psicológico/fisiologia , Adulto Jovem , Voz/fisiologia , Percepção da Fala/fisiologia , Adulto , Multilinguismo , Mapeamento Encefálico , Tempo de Reação/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem
15.
J Leukoc Biol ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753658

RESUMO

Extracellular vesicles (EVs) are the nano-sized membrane particles secreted by various cell types, which are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells (CAR-T) and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8 + T cells (caCD8) and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokines cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30-200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e., granzyme B and perforin), but also significantly enrich IFNγ compared to caCD8 cells. The EVs-derived IFNγ participates in EVs-induced apoptosis in cancer cells. Therefore, our data reveal an antitumor effects of EVs secreted from caCD8 cells and the potential role of the EVs-derived IFNγ.

16.
Front Neurosci ; 18: 1386108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765671

RESUMO

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi. Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making.

17.
Curr Med Sci ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38802649

RESUMO

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

18.
Water Res ; 257: 121683, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703542

RESUMO

Efficient uranium capture from wastewater holds great importance for the environmental remediation and sustainable development of nuclear energy, but it is a tremendous challenge. Herein, a facile and scalable approach is reported to fabricate functionalized hierarchical porous polymers (PPN-3) decorated with high density of phosphate groups for uranium adsorption. The as-constructed hierarchical porous structure could allow rapid diffusion of uranyl ions, while abundant phosphate groups that serve as adsorption sites could provide the high affinity for uranyl. Consequently, PPN-3 shows a high uranium adsorption uptake of 923.06 mg g-1 and reaches adsorption equilibrium within simply 10 min in uranium-spiked aqueous solution. Moreover, PPN-3 affords selective adsorption of uranyl over multiple metal ions and possesses a rapid and high removal rate of U(VI) in real water systems. Furthermore, this study offers direct polymerization strategy for the cost-effective fabrication of phosphate-functionalized porous organic polymers, which may provide promising application potential for uranium extraction.


Assuntos
Polímeros , Urânio , Urânio/química , Adsorção , Polímeros/química , Porosidade , Purificação da Água/métodos , Poluentes Radioativos da Água
19.
Nano Lett ; 24(21): 6441-6449, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757836

RESUMO

In the realm of condensed matter physics and materials science, charge density waves (CDWs) have emerged as a captivating way to modulate correlated electronic phases and electron oscillations in quantum materials. However, collectively and efficiently tuning CDW order is a formidable challenge. Herein, we introduced a novel way to modulate the CDW order in 1T-TaS2 via stacking engineering. By introducing shear strain during the electrochemical exfoliation, the thermodynamically stable AA-stacked TaS2 consecutively transform into metastable ABC stacking, resulting in unique 3a × 1a CDW order. By decoupling atom coordinates, we atomically deciphered the 3D subtle structural variations in trilayer samples. As suggested by density functional theory (DFT) calculations, the origin of CDWs is presumably due to collective excitations and charge modulation. Therefore, our works shed light on a new avenue to collectively modulate the CDW order via stackingtronics and unveiled novel mechanisms for triggering CDW formation via charge modulation.

20.
BMC Plant Biol ; 24(1): 432, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773389

RESUMO

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.


Assuntos
Regulação da Expressão Gênica de Plantas , Gossypium , Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Salino , Gossypium/genética , Gossypium/fisiologia , Estresse Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Genes de Plantas , Tolerância ao Sal/genética
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