Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 724
Filtrar
1.
Small ; : e2404099, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940444

RESUMO

The chemically pre-intercalated lattice engineering is widely applied to elevate the electronic conductivity, expand the interlayer spacing, and improve the structural stability of layered oxide cathodes. However, the mainstream unitary metal ion pre-intercalation generally produces the cation/vacancy ordered superstructure, which astricts the further improvement of lattice respiration and charge-carrier ion storage and diffusion. Herein, a multiple metal ions pre-intercalation lattice engineering is proposed to break the cation/vacancy ordered superstructure. Taking the bilayer V2O5 as an example, Ni, Co, and Zn ternary ions are simultaneously pre-intercalated into its interlayer space (NiCoZnVO). It is revealed that the Ni─Co neighboring characteristic caused by Ni(3d)-O(2p)-Co(3d) orbital coupling and the Co-Zn/Ni-Zn repulsion effect due to chemical bond incompatibility, endow the NiCoZnVO sample with the cation/vacancy disordered structure. This not only reduces the Li+ diffusion barrier, but also increases the diffusion dimension of Li+ (from one-dimension to two-dimension). Particularly, Ni, Co, and Zn ions co-pre-intercalation causes a prestress, which realizes a quasi-zero-strain structure at high-voltage window upon charging/discharging process. The functions of Ni ion stabilizing the lattice structure and Co or Zn ions activating more Li+ reversible storage reaction of V5+/V4+ are further revealed. The cation/vacancy disordered structure significantly enhances Li+ storage properties of NiCoZnVO cathode.

2.
BMC Med ; 22(1): 223, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831366

RESUMO

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Adolescente , Masculino , Feminino , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Neuroimagem , Estudos de Coortes
3.
Mol Cell Biochem ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38879838

RESUMO

As the world's aging population increases, cardiovascular diseases (CVDs) associated with aging deserve increasing attention. CVD in association with age is considered a major cause of morbidity and mortality worldwide. In this review, we provide an overview of the key molecular pathways, cellular processes such as autophagy, oxidative stress, inflammatory responses, myocardial remodeling and ischemia-refocused injury that accompany CVD as well as the natural products of targeting these mechanisms and some of the dietary habits that have been studied in cardiovascular-related diseases. The potential preventive and therapeutic avenues resulting from these dietary habits and natural products related to animal models and clinical studies can help us to better understand the processes involved in cardiovascular diseases and provide recommendations to reduce the cardiovascular burden associated with aging heart.

4.
Food Chem ; 457: 140143, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38901339

RESUMO

The Hippophae rhamnoides L. pomace was generated in the production process for juice, wine of food industry. To expand the application of pomace, the extraction process optimization, enrichment and identification of triterpene acids were performed in this study. The extraction yield was 14.87% under optimal ultrasound-assisted extraction techniques performed via response surface methodology. The extract was subsequently purified to obtain the triterpenoid acid enrichment fraction (TPF) with the content of 75.23% ± 1.45%. 13 triterpenoid acids were identified via UPLC-Triple-TOF MS/MS and further semi-quantified through comparison with triterpenoid acid standards. TPF exhibited a strong inhibitory effect on α-glucosidase with IC50 value of 5.027 ± 0.375 µg/mL, as determined via enzyme inhibition experiment and molecular docking. Additionally, the TPF significantly reduced postprandial glucose levels, as revealed via carbohydrate tolerance tests, as well as ameliorate serum lipid profiles. Therefore, pomace may be a promising resource of functional food components with therapeutic and commercial values.

5.
Ultrasonics ; 142: 107359, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38823151

RESUMO

Conventional surface acoustic wave (SAW) atomizers require a direct water supply on the surface, which can be complex and cumbersome. This paper presents a novel SAW atomizer that uses lateral acoustic wetting to achieve atomization without a direct water supply. The device works by simply pressing a piece of wetted paper strip against the bottom of an excited piezoelectric transducer. The liquid then flows along the side to the unmodified surface edge, where it is atomized into a well-converging mist in a stable and sustainable manner. We identified this phenomenon as the edge effect, using numerical simulation results of surface displacement mode. The feasibility of the prototype design was demonstrated by observing and investigating the integrated process of liquid extraction, transport, and atomization. We further explored the hydrodynamic principles of the change and breakup in liquid film geometry under different input powers. Experiments demonstrate that our atomizer is capable of generating high-quality fine liquid particles stably and rapidly even at very high input power. Compared to conventional SAW atomizer, the dispersion of mist width can be scaled down by 70%, while the atomization rate can be increased by 37.5%. Combined with the advantages of easy installation and robustness, the edge effect-based atomizer offers an attractive alternative to current counterparts for applications requiring high efficiency and miniaturization, such as simultaneous synthesis and encapsulation of nanoparticles, pulmonary drug delivery and portable inhalation therapy.

6.
Int J Biol Macromol ; 272(Pt 2): 132930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848843

RESUMO

The rapid absorption of water from the blood to concentrate erythrocytes and platelets, thus triggering quick closure, is important for hemostasis. Herein, expansion-clotting chitosan fabrics are designed and fabricated by ring spinning of polylactic acid (PLA) filaments as the core layer and highly hydrophilic carboxyethyl chitosan (CECS) fibers as the sheath layer, and subsequent knitting of obtained PLA@CECS core spun yarns. Due to the unidirectional fast-absorption capacity of CECS fibers, the chitosan fabrics can achieve erythrocytes and platelets aggregate quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the loop structure of coils formed in the knitted fabric can help them to expand by absorbing water to close their pores, providing effective sealing for bleeding. Besides, They have enough mechanical properties, anti-penetrating ability, and good tissue-adhesion ability in wet conditions, which can form a physical barrier to resist blood pressure during hemostasis and prevent them from falling off the wound, thus enhancing hemostasis synergistically. Therefore, the fabrics exhibit superior hemostatic performance in the rabbit liver, spleen, and femoral artery puncture injury model compared to the gauze group. This chitosan fabric is a promising hemostatic material for hemorrhage control.


Assuntos
Quitosana , Hemorragia , Hemostáticos , Quitosana/química , Animais , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Coelhos , Hemostáticos/química , Hemostáticos/farmacologia , Poliésteres/química , Têxteis , Coagulação Sanguínea/efeitos dos fármacos , Hemostasia/efeitos dos fármacos
7.
Chem Biodivers ; : e202400145, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738490

RESUMO

As a medicinal and edible resource, Hippophae rhamnoides Linn. subsp. sinensis Rousi is rich in bioactive secondary metabolites, including flavonoids and their derivatives, which offer protective effects against oxidative damage. This study reported the isolation of three new kaempferol derivatives from the seed residue of H. rhamnoides - Hippophandine A, B, and C (compounds 1-3). Their structures were elucidated by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), and chemical analyses. The compounds were evaluated for their ability to mitigate hydrogen peroxide (H2O2)-induced cell death in SH-SY5Y cells. The results elucidated that Hippophandine A-C at concentrations of 1, 5, and 10 µM reduced the levels of malondialdehyde (MDA) and increased the activity of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, they significantly altered the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1), which is an indicator of redox detection in H2O2-induced SH-SY5Y.

8.
Biol Psychiatry ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718879

RESUMO

BACKGROUND: The right middle frontal gyrus (MFG) has been proposed as a convergence site for the dorsal attention network (DAN) and ventral attention network (VAN), regulating both networks and enabling flexible modulation of attention. However, it is unclear whether the connections between the right MFG and these networks can predict changes in attention-deficit/hyperactivity disorder (ADHD) symptoms. METHODS: This study used data from the Children School Functions and Brain Development project (N = 713, 56.2% boys). Resting-state functional magnetic resonance imaging was employed to analyze the connections of the right MFG with the DAN/VAN; connectome-based predictive modeling was applied for longitudinal prediction, and ADHD polygenic risk scores were used for genetic analysis. RESULTS: ADHD symptoms were associated with the connections between the right MFG and DAN subregion, including the frontal eye field, as well as the VAN subregions, namely the inferior parietal lobule and inferior frontal gyrus. Furthermore, these connections of the right MFG with the frontal eye field, the inferior parietal lobule, and the inferior frontal gyrus could significantly predict changes in ADHD symptoms over 1 year and mediate the prediction of ADHD symptom changes by polygenic risk scores for ADHD. Finally, the validation samples confirmed that the functional connectivity between the right MFG and the frontal eye field/inferior parietal lobule in patients with ADHD was significantly weaker than that in typically developing control participants, and this difference disappeared after medication. CONCLUSIONS: The connection of the right MFG with the DAN and VAN can serve as a predictive indicator for changes in ADHD symptoms over the following year, while also mediating the prediction of ADHD symptom changes by a polygenic risk score for ADHD. These findings hold promise as potential biomarkers for early identification of children who are at risk of developing ADHD.

9.
Cancer Lett ; 594: 216991, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38797232

RESUMO

Genetic interactions (GIs) refer to two altered genes having a combined effect that is not seen individually. They play a crucial role in influencing drug efficacy. We utilized CGIdb 2.0 (http://www.medsysbio.org/CGIdb2/), an updated database of comprehensively published GIs information, encompassing synthetic lethality (SL), synthetic viability (SV), and chemical-genetic interactions. CGIdb 2.0 elucidates GIs relationships between or within protein complex models by integrating protein-protein physical interactions. Additionally, we introduced GENIUS (GENetic Interactions mediated drUg Signature) to leverage GIs for identifying the response signature of immune checkpoint inhibitors (ICIs). GENIUS identified high MAP4K4 expression as a resistant signature and high HERC4 expression as a sensitive signature for ICIs treatment. Melanoma patients with high expression of MAP4K4 were associated with decreased efficacy and poorer survival following ICIs treatment. Conversely, overexpression of HERC4 in melanoma patients correlated with a positive response to ICIs. Notably, HERC4 enhances sensitivity to immunotherapy by facilitating antigen presentation. Analyses of immune cell infiltration and single-cell data revealed that B cells expressing MAP4K4 may contribute to resistance to ICIs in melanoma. Overall, CGIdb 2.0, provides integrated GIs data, thus serving as a crucial tool for exploring drug effects.


Assuntos
Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Imunoterapia/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas
10.
Sci Data ; 11(1): 463, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714688

RESUMO

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Assuntos
Encéfalo , Desenvolvimento Infantil , Criança , Pré-Escolar , Humanos , Encéfalo/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , China , Cognição , Bases de Dados Factuais , Neuroimagem
11.
J Am Chem Soc ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788197

RESUMO

Molecular rearrangement occupies a pivotal position among fundamental transformations in synthetic chemistry. Radical translocation has emerged as a prevalent synthetic tool, efficiently facilitating the migration of diverse functional groups. In contrast, the development of di-π-methane rearrangement remains limited, particularly in terms of the translocation of cyano functional groups. This is primarily attributed to the energetically unfavorable three-membered-ring transition state. Herein, we introduce an unprecedented di-π-ethane rearrangement enabled by energy-transfer catalysis under visible light conditions. This innovative open-shell rearrangement boasts broad tolerance toward a range of functional groups, encompassing even complex drug and natural product derivatives. Overall, the reported di-π-ethane rearrangement represents a complementary strategy to the development of radical translocation enabled by energy-transfer catalysis.

12.
Nephrology (Carlton) ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716715

RESUMO

AIM: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. METHODS: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. RESULTS: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ2 = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD). CONCLUSION: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN.

13.
BMC Psychol ; 12(1): 286, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778400

RESUMO

BACKGROUND: Mothers of children with autism reported higher levels of anxiety than mothers of typical children. This study revealed the relationship between parent-child conflict, children's problem behavior, parenting stress, and maternal anxiety from the perspective of the relationship within the family. METHODS: The State-Trait Anxiety Inventory (STAI) and Caregiver Strain Questionnaire (CGSQ) were used to measure maternal anxiety and parenting stress respectively from 102 mothers of children with autism. We also collected information on parent-child relationships and children's problem behaviors by using the Child-Parent Relationship Scale (CPRS) and Conners Parent Symptom Questionnaire (PSQ). RESULTS: Parent-child conflict positively predicted state and trait anxiety in mothers of children with autism. The severity of children's psychosomatic disorders fully mediated the positive association between parent-child conflict and state-trait anxiety in mothers of children with autism. Parenting stress significantly moderated the impact of parent-child conflict on maternal state anxiety and trait anxiety. CONCLUSION: In the case of children with autism spectrum disorders, parent-child conflict can directly affect maternal anxiety levels, especially when mothers have low levels of parenting stress. Parent-child conflict can also affect children's problem behaviors and thus indirectly affect maternal anxiety. Therefore, this study is of great significance for the alleviation of anxiety of mothers of autistic children and the family intervention for the early rehabilitation of autistic children.


Assuntos
Ansiedade , Mães , Estresse Psicológico , Humanos , Feminino , Ansiedade/psicologia , Mães/psicologia , Masculino , Adulto , Criança , Estresse Psicológico/psicologia , Poder Familiar/psicologia , Pré-Escolar , Transtorno Autístico/psicologia , China , Inquéritos e Questionários , Relações Mãe-Filho/psicologia , Relações Pais-Filho , Comportamento Problema/psicologia , Pessoa de Meia-Idade , População do Leste Asiático
14.
Nat Commun ; 15(1): 4303, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773073

RESUMO

Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI- anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm-2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

15.
Small ; : e2400408, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709208

RESUMO

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

16.
Small ; : e2401443, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38676339

RESUMO

The as-reported doping entropy engineering of electrode materials that are usually realized by the sharing of multiple metal elements with the metal element from the lattice body, potentially has three shortages of stringent synthesis conditions, large active element loss, and serious lattice distortion. Herein, an interlayer entropy engineering of layered oxide cathodes is proposed, where the multiple metal ions are simultaneously intercalated into the same interlayer sites, thus avoiding the three shortages. Concretely, a novel interlayer medium-entropy V2O5 ((MnCoNiMgZn)0.26V2O5∙0.84H2O) is successfully constructed by a one-step hydrothermal method. The interlayer medium-entropy effect is revealed to be that five metal ions pre-intercalation induces the local symmetry-broken [VO6] octahedra in bilayer V2O5, thus activating the reversible high-voltage redox reaction, inhibiting the layer slip and following phase transformation by its pinning effect, and enhancing the charge transfer kinetics. As a result, the medium-entropy cathode realizes the trade-off between specific capacity and structural stability with a discharge capacity of 152 mAh g-1 at 0.1 A g-1 after 100 cycles, and a capacity retention rate of 98.7% at 0.5 A g-1 after 150 cycles for Li+ storage. This engineering provides a new guideline for the rational design of high-performance layered oxide cathodes.

17.
Free Radic Biol Med ; 218: 166-177, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582229

RESUMO

BACKGROUND: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated. METHODS: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl4) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte. RESULTS: Herein, we report that the expression level of ENPP1 are increased in patients with NAFLD liver tissue and in mouse model of NAFLD. Hypomethylation of ENPP1, is associated with the perpetuation of hepatocyte autophagy and liver fibrosis in the NAFLD. ENPP1 hypomethylation is mediated by the DNA demethylase TET3 in NAFLD liver fibrosis and hepatocyte autophagy. Additionally, knockdown of TET3 methylated ENPP1 promoter, reduced the ENPP1 expression, ameliorated the experimental NAFLD. Mechanistically, TET3 epigenetically promoted ENPP1 expression via hypomethylation of the promoter. Knocking down TET3 can inhibit the hepatocyte autophagy but an overexpression of ENPP1 showing rescue effect. CONCLUSIONS: We describe a novel epigenetic mechanism wherein TET3 promoted ENPP1 expression through promoter hypomethylation is a critical mediator of NAFLD. Our findings provide new insight into the development of preventative measures for NAFLD.


Assuntos
Autofagia , Metilação de DNA , Dioxigenases , Modelos Animais de Doenças , Epigênese Genética , Hepatócitos , Hepatopatia Gordurosa não Alcoólica , Diester Fosfórico Hidrolases , Regiões Promotoras Genéticas , Pirofosfatases , Animais , Humanos , Masculino , Camundongos , Autofagia/genética , Tetracloreto de Carbono/toxicidade , Dieta Hiperlipídica/efeitos adversos , Dioxigenases/genética , Dioxigenases/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Pirofosfatases/genética , Pirofosfatases/metabolismo
18.
BMJ Open ; 14(4): e079354, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569706

RESUMO

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.


Assuntos
Terapia por Acupuntura , Diabetes Mellitus , Neuropatias Diabéticas , Eletroacupuntura , Humanos , Neuropatias Diabéticas/terapia , Dor , China , Pequim , Resultado do Tratamento , Eletroacupuntura/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
19.
Sci Rep ; 14(1): 7088, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38528143

RESUMO

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein-protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.


Assuntos
Doenças Ósseas Metabólicas , Medicamentos de Ervas Chinesas , Osteoporose , Humanos , Metaloproteinase 9 da Matriz , Quempferóis/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Osteoporose/tratamento farmacológico
20.
Small ; : e2400108, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38511540

RESUMO

Aqueous rechargeable proton batteries are attractive due to the small ionic radius, light mass, and ultrafast diffusion kinetics of proton as charge carriers. However, the commonly used acidic electrolyte is usually very corrosive to the electrode material, which seriously affects the cycle life of the battery. Here, it is proposed that decreasing water activity and limiting proton concentration can effectively prevent side reactions of the MoO3 anode such as corrosion and hydrogen precipitation by using a lean-water hydrogel electrolyte. The as-prepared polyacrylamide (PAAM)-poly2-acrylamide-2-methylpropanesulfonic acid (PAMPS)/MnSO4 (PPM) hydrogel electrolyte not only has abundant hydrophilic groups that can form hydrogen bonds with free water and inhibit solvent-electrode interaction, but also has fixed anions that can maintain a certain interaction with protons. The assembled MoO3||MnO2 full battery can stably cycle over 500 times for ≈350 h with an unprecedented capacity retention of 100% even at a low current density of 0.5 A g-1. This work gives a hint that limiting free water as well as proton concentration is important for the design of electrolytes or interfaces in aqueous proton batteries.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA