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1.
Adv Sci (Weinh) ; : e2401730, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696659

RESUMO

Sodium ion batteries (SIBs) are considered as the ideal candidates for the next generation of electrochemical energy storage devices. The major challenges of anode lie in poor cycling stability and the sluggish kinetics attributed to the inherent large Na+ size. In this work, Bi nanosphere encapsulated in N-doped carbon nanowires (Bi@N-C) is assembled by facile electrospinning and carbonization. N-doped carbon mitigates the structure stress/strain during alloying/dealloying, optimizes the ionic/electronic diffusion, and provides fast electron transfer and structural stability. Due to the excellent structure, Bi@N-C shows excellent Na storage performance in SIBs in terms of good cycling stability and rate capacity in half cells and full cells. The fundamental mechanism of the outstanding electrochemical performance of Bi@N-C has been demonstrated through synchrotron in-situ XRD, atomic force microscopy, ex-situ scanning electron microscopy (SEM) and density functional theory (DFT) calculation. Importantly, a deeper understanding of the underlying reasons of the performance improvement is elucidated, which is vital for providing the theoretical basis for application of SIBs.

2.
Dev Cell ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38640925

RESUMO

Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways.

3.
Metallomics ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658185

RESUMO

This study reports the toxicity of Pb exposure on systemic inflammation in high-fat diet (HFD) mice and the potential mechanisms. Results indicated that Pb exacerbated intestinal barrier damage and increased serum levels of lipopolysaccharide (LPS) and diamine oxidase in HFD mice. Elevated LPS activates the colonic and ileal LPS-TLR4 inflammatory signaling pathway and further induces hepatic and adipose inflammatory expression. The 16S rRNA gene sequencing results showed that Pb promoted the abundance of potentially harmful and LPS-producing bacteria such as Coriobacteriaceae_UCG-002, Alloprevotella and Oscillibacter in the intestines of HFD mice, and their abundance was positively correlated with LPS levels. Additionally, Pb inhibited the abundance of the beneficial bacteria Akkermansia, resulting in lower levels of the metabolite SCFAs. Meanwhile, Pb inhibited adenosine 5'-monophosphate-activated protein kinase signaling-mediated lipid metabolism pathways promoting hepatic lipid accumulation. The above results suggest that Pb exacerbates systemic inflammation and lipid disorders in HFD mice by altering the gut microbiota, intestinal barrier and the mediation of metabolites LPS and SCFAs. Our study provides potential novel mechanisms of human health related to Pb-induced metabolic damage and offers new evidence for a comprehensive assessment of Pb risk.

4.
Nanoscale Horiz ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602167

RESUMO

Solution-processable semiconductor heterostructures enable scalable fabrication of high performance electronic and optoelectronic devices with tunable functions via heterointerface control. In particular, artificial optical synapses require interface manipulation for nonlinear signal processing. However, the limited combinations of materials for heterostructure construction have restricted the tunability of synaptic behaviors with simple device configurations. Herein, MAPbBr3 nanocrystals were hybridized with MgAl layered double hydroxide (LDH) nanoplates through a room temperature self-assembly process. The formation of such heterostructures, which exhibited an epitaxial relationship, enabled effective hole transfer from MAPbBr3 to LDH, and greatly reduced the defect states in MAPbBr3. Importantly, the ion-conductive nature of LDH and its ability to form a charged surface layer even under low humidity conditions allowed it to attract and trap holes from MAPbBr3. This imparted tunable synaptic behaviors and short-term plasticity (STP) to long-term plasticity (LTP) transition to a two-terminal device based on the LDH-MAPbBr3 heterostructures. The further neuromorphic computing simulation under varying humidity conditions showcased their potential in learning and recognition tasks under ambient conditions. Our work presents a new type of epitaxial heterostructure comprising metal halide perovskites and layered ion-conductive materials, and provides a new way of realizing charge-trapping induced synaptic behaviors.

5.
Adv Mater ; : e2403476, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666554

RESUMO

In organic photovoltaic cells, the solution-aggregation effect (SAE) is long considered a critical factor in achieving high power-conversion efficiencies for polymer donor (PD)/non-fullerene acceptor (NFA) blend systems. However, the underlying mechanism has yet to be fully understood. Herein, based on an extensive study of blends consisting of the representative 2D-benzodithiophene-based PDs and acceptor-donor-acceptor-type NFAs, it is demonstrated that SAE shows a strong correlation with the aggregation kinetics during solidification, and the aggregation competition between PD and NFA determines the phase separation of blend film and thus the photovoltaic performance. PDs with strong SAEs enable earlier aggregation evolutions than NFAs, resulting in well-known polymer-templated fibrillar network structures and superior PCEs. With the weakening of PDs' aggregation effects, NFAs, showing stronger tendencies to aggregate, tend to form oversized domains, leading to significantly reduced external quantum efficiencies and fill factors. These trends reveal the importance of matching SAE between PD and NFA. The aggregation abilities of various materials are further evaluated and the aggregation ability/photovoltaic parameter diagrams of 64 PD/NFA combinations are provided. This work proposes a guiding criteria and facile approach to match efficient PD/NFA systems.

6.
Pathol Res Pract ; 256: 155270, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38552564

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignancy with high mortality. Immediate early response 5 like (IER5L) has been found to associate with worse prognosis in colorectal cancer patients. However, its role in the prognosis prediction of NSCLC has remained largely unknown. METHODS: The IER5L expression in NSCLC and normal tissues was analyzed in two public cohorts: TCGA-LUAD-LUSC and GSE159857. Additionally, functional enrichment, survival analysis, CIBERSORT and tumor mutation burden (TMB) were investigated between low- and high-IER5L level groups. The in vitro IER5L mRNA and protein levels were determined using RT-qPCR and western blot, respectively. RESULTS: The data from TCGA-LUAD-LUSC and GSE159857 cohorts showed a high IER5L mRNA expression in NSCLC tissue samples compared to normal controls. The increased expression of IER5L in NSCLC cells were also validated by RT-qPCR and western blot analysis. Additionally, NSCLC patients with high-IER5L level had significantly worse prognosis and IER5L could be used as an independent prognostic factor for NSCLC patients. Meanwhile, patients in the high-IER5L group had higher TMB level. IER5L expression was negatively correlated with the proportion of Monocytes and T cells CD4 memory resting, and was positively related to the proportion of Tregs and M0 macrophages in tumor tissues. Besides, transcription factors TFAP4 and ZNF692 may bind to the promoter region of IER5L, and then modulate IER5L gene transcription, thereby affecting IER5L gene expression. Furthermore, GSEA results showed that IER5L gene was closely related to MAPK, PI3K-Akt, NF-kappaB signaling pathways in NSCLC. CONCLUSION: Collectively, high IER5L expression may be a promising unfavorable prognostic biomarker and therapeutic target for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico , Fosfatidilinositol 3-Quinases , Neoplasias Pulmonares/genética , Prognóstico , RNA Mensageiro , Proteínas de Ligação a DNA , Fatores de Transcrição
7.
J Biochem Mol Toxicol ; 38(3): e23681, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444083

RESUMO

Recent studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in paraquat (PQ)-induced tissue fibrosis, which is the main cause of death in patients with PQ poisoning. However, no effective treatment for pulmonary interstitial fibrosis caused by PQ poisoning exists. It is of great significance for us to find new therapeutic targets through bioinformatics in PQ-induced EMT. We conducted transcriptome sequencing to determine the expression profiles of 1210 messenger RNAs (mRNAs), 558 long noncoding RNAs, 28 microRNAs (miRNAs), including 18 known-miRNAs, 10 novel-miRNAs and 154 circular RNAs in the PQ-exposed EMT group mice. Using gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses, we identified the pathways associated with signal transduction, cancers, endocrine systems and immune systems were involved in PQ-induced EMT. Furthermore, we constructed long noncoding RNA-miRNA-mRNA interrelated networks and found that upregulated genes included Il22ra2, Mdm4, Slc35e2 and Angptl4, and downregulated genes included RGS2, Gabpb2, Acvr1, Prkd3, Sp100, Tlr12, Syt15 and Camk2d. Thirteen new potential competitive endogenous RNA targets were also identified for further treatment of PQ-induced pulmonary tissue fibrosis. Through further study of the pathway and networks, we may identify new molecular targets in PQ-induced pulmonary EMT.


Assuntos
MicroRNAs , Fibrose Pulmonar , RNA Longo não Codificante , Humanos , Animais , Camundongos , MicroRNAs/genética , Paraquat/toxicidade , RNA Endógeno Competitivo , Sequenciamento de Nucleotídeos em Larga Escala , Transição Epitelial-Mesenquimal , RNA Mensageiro
8.
Front Pharmacol ; 15: 1287262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464724

RESUMO

Background: The CONSORT Extension for Chinese Herbal Medicine Formula 2017 (CONSORT-CHM Formula 2017) has established a reporting standard for randomized controlled trials (RCTs) of Chinese Herbal Medicine Formula (CHMF) interventions; however, its adherence and implications for the design and execution of study design remain ambiguous. It is necessary to evaluate the level of compliance with the CONSORT-CHM Formula 2017 in RCTs conducted over the past 5 years, and to determine the reporting quality of clinical trials in this field. Methods: First, a systematic search is conducted for RCTs on CHMF in EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid-MEDLINE(R), Wanfang data, China National Knowledge Infrastructure (CNKI), VIP Chinese Medical Journal Database (VIP) and Chinese Biomedical Literature (CBM) database, that encompassed CHMF interventional RCTs published from 1 January 2018 to 8 June 2022, with language restriction to English or Chinese. Second, a descriptive analysis will be performed regarding the study design and general characteristics of the included trials. Third, for the quality assessment, we have subdivided the CONSORT-CHM Formula 2017 checklist (consisting of 22 extended items) into a total of 42 sub-questions to facilitate scoring, with a specific focus on the description, quality control, and safety assessment of CHMF interventions. Professional training and a pilot test on 100 randomly selected articles will be provided for all reviewers. Throughout this process, a standard operating procedure (SOP) for quality assessment will be developed to ensure consistency. Each item will be assessed by two reviewers in a paired back-to-back manner, and the compliance rate will be calculated to assess inter-rater agreement. Discussion: This review will identify the current reporting characteristics and quality of CHMF interventional studies and further evaluate the impact of CONSORT-CHM Formula 2017. The results may provide suggestions for future application or promotion of the guideline. Registration: The study has been registered on Open Science Framework (https://osf.io/xpn7f).

9.
Cell Mol Life Sci ; 81(1): 128, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472451

RESUMO

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.


Assuntos
Transtornos Motores , Doença de Parkinson , Animais , Camundongos , Histonas/metabolismo , Metilação , Neurônios/metabolismo , alfa-Sinucleína/metabolismo
10.
ACS Nano ; 18(12): 8673-8682, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38471123

RESUMO

Developing green perovskite light-emitting diodes (PeLEDs) with a high external quantum efficiency (EQE) and low efficiency roll-off at high brightness remains a critical challenge. Nanostructured emitter-based devices have shown high efficiency but restricted ascending luminance at high current densities, while devices based on large-sized crystals exhibit low efficiency roll-off but face great challenges to high efficiency. Herein, we develop an all-inorganic device architecture combined with utilizing tens-of-nanometers-sized CsPbBr3 (TNS-CsPbBr3) emitters in a carrier-confined heterostructure to realize green PeLEDs that exhibit high EQEs and low efficiency roll-off. A typical type-I heterojunction containing TNS-CsPbBr3 crystals and wide-bandgap Cs4PbBr6 within a grain is formed by carefully controlling the precursor ratio. These heterostructured TNS-CsPbBr3 emitters simultaneously enhance carrier confinement and retain low Auger recombination under a large injected carrier density. Benefiting from a simple device architecture consisting of an emissive layer and an oxide electron-transporting layer, the PeLEDs exhibit a sub-bandgap turn-on voltage of 2.0 V and steeply rising luminance. In consequence, we achieved green PeLEDs demonstrating a peak EQE of 17.0% at the brightness of 36,000 cd m-2, and the EQE remained at 15.7% and 12.6% at the brightness of 100,000 and 200,000 cd m-2, respectively. In addition, our results underscore the role of interface degradation during device operation as a factor in device failure.

11.
J Agric Food Chem ; 72(12): 6509-6518, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488047

RESUMO

Limosilactobacillus reuteri 121 4,6-α-glucanotransferase GtfB (Lr 121 GtfB), belonging to glycoside hydrolase family 70 (GH70), synthesizes linear isomalto/malto polysaccharides having (α1→6) linkages attached to the nonreducing ends of (α1→4) linked maltose oligosaccharide segments using starch or maltodextrin as a substrate. Since Lr 121 GtfB has low catalytic activity and efficiency, it leads to substrate regeneration and reduced substrate utilization. In this study, we superimposed the crystal structure of Lr 121 GtfB-ΔNΔV with that of L. reuteri NCC 2613 GtfB-ΔNΔV (Lr 2613 GtfB-ΔNΔV) to identify the acceptor binding subsites +1 to +3 and constructed five single-residue mutants and a random mutagenesis of N1019. Compared with the wild-type, N1019D Lr 121 GtfB-ΔN did not alter the product specificity, increased the catalytic activity and efficiency by 420 and 590%, respectively, and maintained >80% relative activity in the pH 3.5-6.5 interval. The findings will contribute to the industrial application of Lr 121 GtfB and provide new solutions for starch synthesis of higher value derivatives.


Assuntos
Sistema da Enzima Desramificadora do Glicogênio , Limosilactobacillus reuteri , Sistema da Enzima Desramificadora do Glicogênio/química , Amido/metabolismo , Oligossacarídeos
12.
Chem Sci ; 15(9): 3071-3092, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38425533

RESUMO

Aqueous zinc-iodine batteries stand out as highly promising energy storage systems owing to the abundance of resources and non-combustible nature of water coupled with their high theoretical capacity. Nevertheless, the development of aqueous zinc-iodine batteries has been impeded by persistent challenges associated with iodine cathodes and Zn anodes. Key obstacles include the shuttle effect of polyiodine and the sluggish kinetics of cathodes, dendrite formation, the hydrogen evolution reaction (HER), and the corrosion and passivation of anodes. Numerous strategies aimed at addressing these issues have been developed, including compositing with carbon materials, using additives, and surface modification. This review provides a recent update on various strategies and perspectives for the development of aqueous zinc-iodine batteries, with a particular emphasis on the regulation of I2 cathodes and Zn anodes, electrolyte formulation, and separator modification. Expanding upon current achievements, future initiatives for the development of aqueous zinc-iodine batteries are proposed, with the aim of advancing their commercial viability.

13.
Adv Mater ; : e2401916, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531655

RESUMO

The iodide vacancy defects generated during the perovskite crystallization process are a common issue that limits the efficiency and stability of perovskite solar cells (PSCs). Although excessive ionic iodides have been used to compensate for these vacancies, they are not effective in reducing defects through modulating the perovskite crystallization. Moreover, these iodide ions present in the perovskite films can act as interstitial defects, which are detrimental to the stability of the perovskite. Here, an effective approach to suppress the formation of vacancy defects by manipulating the coordination chemistry of lead polyhalides during perovskite crystallization is demonstrated. To achieve this suppression, an α-iodo ketone is introduced to undergo a process of Kornblum oxidation reaction that releases halide ions. This process induces a rapid collective transformation of lead polyhalides during the nucleation process and significantly reduces iodide vacancy defects. As a result, the ion mobility is decreased by one order of magnitude in perovskite film and the PSC achieves significantly improved thermal stability, maintaining 82% of its initial power conversion efficiency at 85 °C for 2800 h. These findings highlight the potential of halide ions released by the Kornblum oxidation reaction, which can be widely used for achieving high-performance perovskite optoelectronics.

14.
Geriatr Nurs ; 56: 100-107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38340431

RESUMO

Nursing assistants are strategically positioned to detect and interpret behavioral alterations indicative of pain in residents suffering from dementia. Despite this, extant literature is scarce regarding their experiences in administering pain care to this demographic. Utilizing a phenomenological approach, this study engaged 17 nursing assistants selected via purposive sampling for semi-structured interviews. Data analysed by the Colaizzi 7-step method. Four emergent themes were discerned: perception of pain; strategies for coping with pain; emotional and psychological responses to pain-related caregiving; challenges and needs in pain-related caregiving. Nursing assistants play a unique and crucial role in the identification of pain, reporting and providing feedback to healthcare professionals, and implementing non-pharmacological interventions. However, these roles have not been fully utilized. Enhancements in pain management could be facilitated by decreasing staff turnover, augmenting educational and training programs, and incorporating empathy-focused situational training. The provision of mental health services is also recommended to ameliorate caregiving-induced stress.


Assuntos
Demência , Assistentes de Enfermagem , Humanos , Idoso , Dor/psicologia , Assistentes de Enfermagem/psicologia , Manejo da Dor , Pesquisa Qualitativa , Percepção
15.
Nano Lett ; 24(9): 2681-2688, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408023

RESUMO

Perovskite light-emitting diodes (PeLEDs) have emerged as promising candidates for lighting and display technologies owing to their high photoluminescence quantum efficiency and high carrier mobility. However, the performance of planar PeLEDs is limited by the out-coupling efficiency, predominantly governed by photonic losses at device interfaces. Most notably, the plasmonic loss at the metal electrode interfaces can account for up to 60% of the total loss. Here, we investigate the use of plasmonic nanostructures to improve the light out-coupling in PeLEDs. By integrating these nanostructures with PeLEDs, we have demonstrated an effectively reduced plasmonic loss and enhanced light out-coupling. As a result, the nanostructured PeLEDs exhibit an average 1.5-fold increase in external quantum efficiency and an ∼20-fold improvement in device lifetime. This finding offers a generic approach for enhancing light out-coupling, promising great potential to go beyond existing performance limitations.

16.
Sci Total Environ ; 918: 170672, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38316306

RESUMO

Aminium ions, as crucial alkaline components within fine atmospheric particles, have a notable influence on new particle formation and haze occurrence. Their concentrations within coastal atmosphere depict considerable variation due to the interplay of distinctive marine and terrestrial sources, further complicated by dynamic meteorological conditions. This study conducted a comprehensive examination of aminiums ions concentrations, with a particular focus on methylaminium (MMAH+), dimethylaminium (DMAH+), trimethylaminium (TMAH+), and triethylaminium (TEAH+) within PM2.5, over varying seasons (summer, autumn, and winter of 2019 and summer of 2021), at an urban site in the coastal megacity of Qingdao, Northern China. The investigations revealed that the total concentration of particulate aminium ions (∑Aminium) was 21.6 ± 23.6 ng/m3, exhibiting higher values in the autumn and winter compared to the two summer periods. Considering diurnal variations during autumn and winter, concentrations of particulate aminium ions (excluding TEAH+) exhibited a slight increase during the day compared to night, with a notable peak during the morning hours. However, it was not the case for TEAH+, which was argued to be readily oxidized by ambient oxidants in the afternoon. Additionally, the ∑Aminium within the summer demonstrated markedly elevated levels during the day compared to night, potentially attributed to daytime sea fog associated with sea-land breeze interactions. Positive matrix factorization results indicate terrestrial anthropogenic emissions, including vehicle emission mixed with road dust and primary pollution, as the primary sources of MMAH+ and DMAH+. Conversely, TMAH+ was predominantly emitted from agricultural and marine sources. With the dominance of sea breeze in summer, TMAH+ was identified as a primary marine emission correlated with sea salt, while MMAH+, DMAH+, and TEAH+ were postulated to undergo secondary formation. Furthermore, a notable inverse correlation was observed between TMAH+ and methanesulfonate in PM2.5, consistent with dynamic emissions of sulfur-content and nitrogen-content gases reported in the literature.

17.
Nano Lett ; 24(7): 2299-2307, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38334593

RESUMO

Organic-inorganic hybrid perovskites have attracted tremendous attention owing to their fascinating optoelectronic properties. However, their poor air stability seriously hinders practical applications, which becomes more serious with thickness down to the nanoscale. Here we report a one-step vapor phase growth of HC(NH2)2PbBr3 (FAPbBr3) single-crystalline nanosheets of tunable size up to 50 µm and thickness down to 20 nm. The FAPbBr3 nanosheets demonstrate high stability for over months of exposure to air with no degradation in surface roughness and photoluminescence efficiency. Besides, the FAPbBr3 photodetectors exhibit superior overall performance as compared to previous devices based on nonlayered perovskite nanosheets, such as an ultralow dark current of 24 pA, an ultrahigh responsivity of 1033 A/W, an external quantum efficiency over 3000%, a rapid response time around 25 ms, and a high on/off ratio of 104. This work provides a strategy to tackle the challenges of hybrid perovskites toward integrated optoelectronics with requirements of nanoscale thickness, high stability, and excellent performance.

18.
Nanoscale ; 16(8): 4239-4248, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38348473

RESUMO

Activatable photodynamic therapy (PDT) has shown great potential in cancer therapy owing to its high tumor specificity and minimized side effect. However, the relatively low level of biomarkers within tumor tissue rescricts the photosensitizer to get thoroughly activated. In this study, we design a self-amplified activatable nanophotosensitizer (CPPa NP) for enhanced PDT. CPPa NP is prepared by encapsulating a hypoxia-inducible factor 1α (HIF-1α) inhibitor CI-994 with an amphiphilic hydrogen peroxide (H2O2) responsive copolymer PPa-CA-PEG. Upon the addition of H2O2, the thioketal linker within CPPa NP is cleaved, resulting in the simultaneous release of thiol-modified pyropheophorbide a (PPa-SH), cinnamic aldehyde (CA), and CI-994. PPa-SH can be encapsulated by albumin to turn on its photodynamic efficiency, while CI-994 may inhibit the expression of HIF-1α to improve the PDT efficacy. CA is able to deplete glutathione (GSH) and upregulate reactive oxygen species (ROS) within tumor cells, accelerating the dissociation of nanoparticles and disrupting the redox balance of tumor cells. In vitro and in vivo studies showed that CPPa NP can successfully elevate the ROS level within 4T1 cells and has a better anticancer efficacy than PPa NP without CI-994 under laser irradiation. This study thus provides an effective approach to develop self-amplified activatable nanoparticles for enhanced PDT.


Assuntos
Benzamidas , Nanopartículas , Fenilenodiaminas , Fotoquimioterapia , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular Tumoral
19.
Food Funct ; 15(6): 3060-3075, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38414441

RESUMO

Lead (Pb) is a widespread toxic endocrine disruptor that could cause liver damage and gut microbiota dysbiosis. However, the causal relationship and underlying mechanisms between the gut microbiota and Pb-induced liver injury are unclear. In this study, we investigated the metabolic toxicity caused by Pb exposure in normal chow (Chow) and high-fat diet (HFD) mice and confirmed the causal relationship by fecal microbial transplantation (FMT) and antibiotic cocktail experiments. The results showed that Pb exposure exacerbated HFD-induced hepatic lipid deposition, fibrosis, and inflammation, but it had no significant effect on Chow mice. Pb increased serum lipopolysaccharide (LPS) levels and induced intestinal inflammation and barrier damage by activating TLR4/NFκB/MLCK in HFD mice. Furthermore, Pb exposure disrupted the gut microbiota, reduced short-chain fatty acid (SCFA) concentrations and the colonic SCFA receptors, G protein-coupled receptor (GPR) 41/43/109A, in HFD mice. Additionally, Pb significantly inhibited the hepatic GPR109A-mediated adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway, resulting in hepatic lipid accumulation. FMT from Pb-exposed HFD mice exacerbated liver damage, disturbed lipid metabolic pathways, impaired intestinal barriers, and altered the gut microbiota and metabolites in recipient mice. However, mice exposed to HFD + Pb and HFD mice had similar levels of these biomarkers in microbiota depleted by antibiotics. In conclusion, our study provides new insights into gut microbiota dysbiosis as a potential novel mechanism for human health related to liver function impairment caused by Pb exposure.


Assuntos
Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Chumbo/toxicidade , Dieta Hiperlipídica/efeitos adversos , Disbiose , Inflamação , Antibacterianos , Lipopolissacarídeos , Fígado
20.
BMC Anesthesiol ; 24(1): 78, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408918

RESUMO

BACKGROUND: Modern perioperative guidelines encourage drinking oral carbohydrates 2 h before management. Nevertheless, research on the safety of preoperative carbohydrate drinks, particularly in extremely elderly patients is lacking. We aimed to evaluate the safety of carbohydrate drinks 2 h before surgery in extremely elderly patients (≥ 80 years) using gastric ultrasonography. METHODS: We conducted a randomized prospective comparative study of 70 patients aged over 80 years who were scheduled for total knee arthroplasty, hip fracture or humerus fracture surgery. These patients were randomly assigned to the carbohydrate group (n = 35), which fasted from midnight, except for drinking 355 mL of a carbohydrate-containing fluid 2 h before surgery, or the fasting group (n = 35), which fasted from midnight and drank no fluid before surgery. The primary outcome of the study was the cross-sectional area (CSA) of the gastric antrum in the right lateral decubitus position (RLDP) before surgery. The secondary outcomes included CSA in the supine position, intraoperative blood glucose levels and their variability coefficients, Perlas grade, and the visual analog scale of subjective feelings. RESULTS: The CSA in the RLDP and supine positions revealed no differences between the carbohydrate and fasting groups at 0 h preoperatively (P > 0.05). In the qualitative assessment, preoperative 0-h Perlas grading did not differ significantly between the groups (P > 0.05). From 2 h before surgery to transfer out of the post-anesthesia care unit, the average blood glucose level of patients in the carbohydrate group was significantly higher than that in the fasting group (P < 0.001) but remained within the normal range. Moreover, the blood glucose variability coefficient was significantly lower in the carbohydrate group than in the fasting group (P = 0.009). Oral intake of 355 mL carbohydrates before surgery significantly relieved patients' feelings (P < 0.001). CONCLUSION: Preoperative consumption of carbohydrate drinks 2 h before surgery is safe in "healthy" extremely elderly patients. In addition, preoperative drinking has potential value in maintaining ideal blood glucose levels and stable blood glucose fluctuations perioperatively and improving subjective perceptions of preoperative preparation. This finding warrants further investigation in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number ChiCTR1900024812), first registered on 29/07/2019.


Assuntos
Glicemia , Estômago , Idoso de 80 Anos ou mais , Humanos , Jejum , Cuidados Pré-Operatórios , Estudos Prospectivos , Estômago/diagnóstico por imagem , Ultrassonografia
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