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1.
Chem Soc Rev ; 53(15): 7828-7874, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-38962926

RESUMO

Rechargeable sodium-ion batteries (SIBs) have emerged as an advanced electrochemical energy storage technology with potential to alleviate the dependence on lithium resources. Similar to Li-ion batteries, the cathode materials play a decisive role in the cost and energy output of SIBs. Among various cathode materials, Na layered transition-metal (TM) oxides have become an appealing choice owing to their facile synthesis, high Na storage capacity/voltage that are suitable for use in high-energy SIBs, and high adaptivity to the large-scale manufacture of Li layered oxide analogues. However, going from the lab to the market, the practical use of Na layered oxide cathodes is limited by the ambiguous understanding of the fundamental structure-performance correlation of cathode materials and lack of customized material design strategies to meet the diverse demands in practical storage applications. In this review, we attempt to clarify the fundamental misunderstandings by elaborating the correlations between the electron configuration of the critical capacity-contributing elements (e.g., TM cations and oxygen anion) in oxides and their influence on the Na (de)intercalation (electro)chemistry and storage properties of the cathode. Subsequently, we discuss the issues that hinder the practical use of layered oxide cathodes, their origins and the corresponding strategies to address their issues and accelerate the target-oriented research and development of cathode materials. Finally, we discuss several new Na layered cathode materials that show prospects for next-generation SIBs, including layered oxides with anion redox and high entropy and highlight the use of layered oxides as cathodes for solid-state SIBs with higher energy and safety. In summary, we aim to offer insights into the rational design of high-performance Na layered oxide cathode materials towards the practical realization of sustainable electrochemical energy storage at a low cost.

2.
Small ; : e2400498, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863125

RESUMO

Sodium-ion battery (SIB) is a candidate for the stationary energy storage systems because of the low cost and high abundance of sodium. However, the energy density and lifespan of SIBs suffer severely from the irreversible consumption of the Na-ions for the formation of the solid electrolyte interphase (SEI) layer and other side reactions on the electrodes. Here, Na3.5C6O6 is proposed as an air-stable high-efficiency sacrificial additive in the cathode to compensate for the lost sodium. It is characteristic of low desodiation (oxidation) potential (3.4-3.6 V vs. Na+/Na) and high irreversible desodiation capacity (theoretically 378 mAh g-1). The feasibility of using Na3.5C6O6 as a sodium compensation additive is verified with the improved electrochemical performances of a Na2/3Ni1/3Mn1/3Ti1/3O2ǀǀhard carbon cells and cells using other cathode materials. In addition, the structure of Na3.5C6O6 and its desodiation path are also clarified on the basis of comprehensive physical characterizations and the density functional theory (DFT) calculations. This additive decomposes completely to supply abundant Na ions during the initial charge without leaving any electrochemically inert species in the cathode. Its decomposition product C6O6 enters the carbonate electrolyte without bringing any detectable negative effects. These findings open a new avenue for elevating the energy density and/or prolonging the lifetime of the high-energy-density secondary batteries.

3.
Bioinformatics ; 39(10)2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37851384

RESUMO

SUMMARY: The PacBio High-Fidelity (HiFi) sequencing technology produces long reads of >99% in accuracy. It has enabled the development of a new generation of de novo sequence assemblers, which all have sequencing error correction (EC) as the first step. As HiFi is a new data type, this critical step has not been evaluated before. Here, we introduced hifieval, a new command-line tool for measuring over- and under-corrections produced by EC algorithms. We assessed the accuracy of the EC components of existing HiFi assemblers on the CHM13 and the HG002 datasets and further investigated the performance of EC methods in challenging regions such as homopolymer regions, centromeric regions, and segmental duplications. Hifieval will help HiFi assemblers to improve EC and assembly quality in the long run. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/magspho/hifieval.


Assuntos
Algoritmos , Software , Análise de Sequência de DNA/métodos , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
4.
J Transl Med ; 22(1): 557, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858729

RESUMO

BACKGROUND: Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment. METHODS: We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes' expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR. RESULTS: Twenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies. CONCLUSIONS: By employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.


Assuntos
Proteínas Sanguíneas , Análise da Randomização Mendeliana , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Sanguíneas/metabolismo , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Genômica , Terapia de Alvo Molecular , Multiômica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Proteômica , Locos de Características Quantitativas , Reprodutibilidade dos Testes
5.
BMC Cancer ; 24(1): 581, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741043

RESUMO

OBJECTIVES: To explore the effects of a 'Rebuilding Myself' intervention on enhancing the adaptability of cancer patients to return to work. METHODS: A single-center, single-blind, randomized controlled trial design was used. Eligible patients who were receiving routine hospital treatment were recruited from the university-affiliated hospital in our city. Patients in the control group only received usual care, while patients in the intervention group received additional 'Rebuilding Myself' intervention. Adaptability to return to work, self-efficacy of returning to work, mental resilience, quality of life and work ability were measured at baseline, the 6th and 12th of the intervention. The general estimation equations were used to compare the overall changes of each outcome index between the two groups at different time points. Considering that there may be patient shedding and rejection, Per-Protocol and Intention-to-Treat analysis were used to analyze the data in this study. RESULTS: There were statistically significant differences between the two groups of patients in the cancer patients' adaptability to return to work, self-efficacy to return to work, mental resilience, work abilities, the physical, emotional, cognitive function, fatigue, insomnia and overall health status dimensions of quality of life (P < 0.05). And no significant difference was found in other dimensions (P > 0.05). The group effect, time effect, and interaction effect of patients' return to work adaptability and return to work self-efficacy were statistically significant in both groups (P < 0.05). Mental resilience, working ability, and quality of life had obvious time effect and interaction effect (P < 0.05). CONCLUSION: This intervention could improve cancer patients' adaptability to return to work, self-efficacy to return to work, mental resilience, work abilities and quality of life. And it can be further expanded to improve the adaptability of patients to return to work, then to help patients achieve comprehensive rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: The application of 'Rebuilding Myself' interventions can effectively improve the adaptability of cancer patients returning to work. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2200057943) on 23 March, 2022.


Assuntos
Adaptação Psicológica , Neoplasias , Qualidade de Vida , Resiliência Psicológica , Retorno ao Trabalho , Autoeficácia , Humanos , Masculino , Feminino , Neoplasias/reabilitação , Neoplasias/psicologia , Adulto , Pessoa de Meia-Idade , Retorno ao Trabalho/psicologia , Retorno ao Trabalho/estatística & dados numéricos , Método Simples-Cego
6.
Anal Biochem ; 694: 115626, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032527

RESUMO

Chimeric-antigen-receptor-T (CAR-T) have heralded a paradigm shift in the landscape of cancer immunotherapy. Retrovirus-mediated gene transfer serves to deliver the specific CAR expressing cassette into T cells across a spectrum of basic research and clinical contests in cancer therapy. However, it is necessary to devise a precise and validated quantitative methodology tailored to the diverse CAR constructs. In the investigation, a TaqMan real-time qPCR method was developed, utilizing primers targeting ψ gene sequence. This method offers a swift, sensitive, reproducible, and accurate tool for evaluating retroviral copy numbers at the integrated DNA level. Importantly, the established qPCR exhibits no cross-reactivity with non-transduced T cells or tissues. The regression equation characterizing TaqMan real-time PCR dynamics is y = -3.3841x + 41.402 (R2 = 0.999), showing an amplification efficiency of 97.47 %. Notably, the established qPCR method achieves a minimum detection of 43.1 copies/µL. Furthermore, both intra- and inter-group discrepancies remain below 4 %, underscoring the good repeatability of the established method. Our in vitro and in vivo results also support its sensitivity, specificity, and stability. Consequently, this method offers researchers with a cost-effective tool to quantify CAR copies both in vitro and in vivo.

7.
Support Care Cancer ; 32(7): 454, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913103

RESUMO

PURPOSE: Employers play an important role in the return-to-work (RTW) of cancer survivors (CSs), and recently a substantial number of qualitative studies from the employers' perspective have emerged. This meta-synthesis aims to systematically review these qualitative studies regarding employers' experiences with CSs' RTW. METHODS: Five electronic databases were searched from inception to January 2024 to identify the studies. Three researchers conducted quality assessment of included. Subsequent, we performed thematic integration of the included studies with the NVivo 11 software. RESULTS: Thirteen qualitative studies were included, and 16 topics were finally extracted and summarized into seven categories to form three integrated themes: employers' perspective on facilitators and obstacles for CSs' RTW, employers' response including negative emotion and positive behavior, and employers' need resources from different aspects. CONCLUSION: CSs' RTW is influenced by many factors; the support employers need is also extensive and complex. Employers need more support beyond healthcare.


Assuntos
Sobreviventes de Câncer , Pesquisa Qualitativa , Retorno ao Trabalho , Humanos , Sobreviventes de Câncer/psicologia , Emprego , Neoplasias/psicologia , Neoplasias/terapia , Retorno ao Trabalho/psicologia
8.
J Clin Nurs ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661107

RESUMO

BACKGROUND: Advance care planning is a process through which people communicate their goals and preferences for future medical care. Due to the complexity of the decision-making process, decision aids can assist individuals in balancing potential benefits and risks of treatment options. OBJECTIVE: While decision aids have the potential to better promote advance care planning, their characteristics, content and application effectiveness are unclear and lack systematic review. Therefore, we aimed to explore these three aspects and establish a foundation for future research. DESIGN: Scoping review. METHODS: This scoping review adheres to the framework proposed by Arksey and O'Malley and the PRISMA-ScR list. Six English-language databases were systematically searched from the time of construction until 1 December 2023. Two researchers conducted the article screening and data extraction, and the extracted data was presented in written tables and narrative summaries. RESULTS: Of the 1479 titles and abstracts, 20 studies fulfilled the inclusion criteria. Types of decision aids were employed, mainly websites and videos. Decision aid's primary components center around 11 areas, such as furnishing information, exploring treatment and care preferences. The main manifestations were a significant increase in knowledge and improved recognition of patients' target value preferences. Among the aids, websites and videos for advance care planning have relatively high content acceptability and decision-making process satisfaction, but their feasibility has yet to be tested. CONCLUSIONS: Decision aids were varied, with content focused on describing key information and exploring treatment and care preferences. Regarding application effects, the aids successfully facilitated the advance care planning process and improved the quality of participants' decisions. Overall, decision aids are efficient in improving the decision-making process for implementing advance care planning in cancer and geriatric populations. In the future, personalised decision aids should be developed based on continuous optimization of tools' quality and promoted for clinical application. REPORTING METHOD: The paper has adhered to the EQUATOR guidelines and referenced the PRISMAg-ScR checklist. NO PATIENT OR PUBLIC CONTRIBUTION: This is a review without patient and public contribution. REGISTRATION: https://doi.org/10.17605/OSF.IO/YPHKF, Open Science DOI: 10.17605/OSF.IO/YPHKF.

9.
Molecules ; 29(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893565

RESUMO

L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases.


Assuntos
Caenorhabditis elegans , Glutamatos , Longevidade , Mitocôndrias , Raios Ultravioleta , Animais , Caenorhabditis elegans/efeitos dos fármacos , Glutamatos/farmacologia , Raios Ultravioleta/efeitos adversos , Longevidade/efeitos dos fármacos , Longevidade/efeitos da radiação , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Autofagia/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos da radiação , Trifosfato de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética
10.
BMC Genomics ; 24(1): 98, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864386

RESUMO

BACKGROUND: Serum biochemical indicators are often regarded as direct reflections of animal metabolism and health. The molecular mechanisms underlying serum biochemical indicators metabolism of chicken (Gallus Gallus) have not been elucidated. Herein, we performed a genome-wide association study (GWAS) to identify the variation associated with serum biochemical indicators. The aim of this research was to broaden the understanding of the serum biochemical indicators in chickens. RESULTS: A GWAS of serum biochemical indicators was carried out on 734 samples from an F2 Gushi× Anka chicken population. All chickens were genotyped by sequencing, 734 chickens and 321,314 variants were obtained after quality control. Based on these variants, a total of 236 single-nucleotide polymorphisms (SNPs) on 9 chicken chromosomes (GGAs) were identified to be significantly (-log10(P) > 5.72) associated with eight of seventeen serum biochemical indicators. Ten novel quantitative trait locis (QTLs) were identified for the 8 serum biochemical indicator traits of the F2 population. Literature mining revealed that the ALPL, BCHE, GGT2/GGT5 genes at loci GGA24, GGA9 and GGA15 might affect the alkaline phosphatase (AKP), cholinesterase (CHE) and γ-glutamyl transpeptidase (GGT) traits, respectively. CONCLUSION: The findings of the present study may contribute to a better understanding of the molecular mechanisms of chicken serum biochemical indicator regulation and provide a theoretical basis for chicken breeding programs.


Assuntos
Galinhas , Estudo de Associação Genômica Ampla , Animais , Galinhas/genética , Fosfatase Alcalina , Genótipo , Fenótipo
11.
J Am Chem Soc ; 145(29): 15809-15815, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37458572

RESUMO

Methods capable of controlling synthesis at the level of an individual nanoparticle are a key step toward improved reproducibility and scalability in engineering complex nanomaterials. To address this, we combine the spatially patterned activation of the photoreductant sodium pyruvate with interferometric scattering microscopy to achieve fast, label-free monitoring and control of hundreds of gold nanoparticles in real time. Individual particle growth kinetics are well-described by a two-step nucleation-autocatalysis model but with a distribution of individual rate constants that change with reaction conditions.

12.
J Am Chem Soc ; 145(47): 25643-25652, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37970704

RESUMO

Anode-free rechargeable sodium batteries represent one of the ultimate choices for the 'beyond-lithium' electrochemical storage technology with high energy. Operated based on the sole use of active Na ions from the cathode, the anode-free battery is usually reported with quite a limited cycle life due to unstable electrolyte chemistry that hinders efficient Na plating/stripping at the anode and high-voltage operation of the layered oxide cathode. A rational design of the electrolyte toward improving its compatibility with the electrodes is key to realize the battery. Here, we show that by refining the volume ratio of two conventional linear ether solvents, a binary electrolyte forms a cation solvation structure that facilitates flat, dendrite-free, planar growth of Na metal on the anode current collector and that is adaptive to high-voltage Na (de)intercalation of P2-/O3-type layered oxide cathodes and oxidative decomposition of the Na2C2O4 supplement. Inorganic fluorides, such as NaF, show a major influence on the electroplating pattern of Na metal and effective passivation of plated metal at the anode-electrolyte interface. Anode-free batteries based on the refined electrolyte have demonstrated high coulombic efficiency, long cycle life, and the ability to claim a cell-level specific energy of >300 Wh/kg.

13.
Mol Microbiol ; 118(6): 731-743, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36308071

RESUMO

Acute respiratory infection by influenza virus is a persistent and pervasive public health problem. Antiviral innate immunity initiated by type I interferon (IFN) is the first responder to pathogen invasion and provides the first line of defense. We discovered that Axin1, a scaffold protein, was reduced during influenza virus infection. We also found that overexpression of Axin1 and the chemical stabilizer of Axin1, XAV939, reduced influenza virus replication in lung epithelial cells. This effect was also observed with respiratory syncytial virus and vesicular stomatitis virus. Axin1 boosted type I IFN response to influenza virus infection and activated JNK/c-Jun and Smad3 signaling. XAV939 protected mice from influenza virus infection. Thus, our studies provide new mechanistic insights into the regulation of the type I IFN response and present a new potential therapeutic of targeting Axin1 against influenza virus infection.


Assuntos
Proteína Axina , Influenza Humana , Interferons , Animais , Humanos , Camundongos , Proteína Axina/metabolismo , Células Epiteliais , Imunidade Inata , Influenza Humana/imunologia , Influenza Humana/metabolismo , Interferons/metabolismo , Replicação Viral
14.
Neuropathol Appl Neurobiol ; 49(1): e12855, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36259948

RESUMO

AIMS: The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain ß-amyloid (Aß) and lipid levels. METHOD: A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE-/- ) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aß1-40 and Aß1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aß and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. RESULTS: DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE-/- mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE-/- mice. In comparison with C57 wt mice, the content of cortical soluble Aß1-42 , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE-/- mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. CONCLUSION: DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aß levels in ApoE-/- and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aß metabolism to DHA treatment.


Assuntos
Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Camundongos , Animais , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Apolipoproteínas E/genética , Colesterol
15.
Mol Psychiatry ; 27(1): 758-770, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561613

RESUMO

The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson's disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.


Assuntos
Doença de Parkinson , Sinucleinopatias , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo
16.
Cell Commun Signal ; 21(1): 66, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36998049

RESUMO

BACKGROUND: Sepsis is a life-threatening organ dysfunction syndrome resulted from severe infection with high morbidity and mortality. Cluster of differentiation 38 (CD38) is a multifunctional type II transmembrane glycoprotein widely expressed on the surface of various immunocytes membranes that mediates host immune response to infection and plays an important role in many inflammatory diseases. Daphnetin (Daph), isolated from the daphne genus plant, is a natural coumarin derivative that possesses anti-inflammatory and anti-apoptotic effects. The current study aimed to investigate the role and mechanism of Daph in alleviating lipopolysaccharide (LPS)-induced septic lung injury, and to explore whether the protective effect of Daph in mice and cell models was related to CD38. METHODS: Firstly, network pharmacology analysis of Daph was performed. Secondly, LPS-induced septic lung injury in mice were treated with Daph or vehicle control respectively and then assessed for survival, pulmonary inflammation and pathological changes. Lastly, Mouse lung epithelial cells (MLE-12 cells) were transfected with CD38 shRNA plasmid or CD38 overexpressed plasmid, followed by LPS and Daph treatment. Cells were assessed for viability and transfection efficiency, inflammatory and signaling. RESULTS: Our results indicated that Daph treatment improved survival rate and alleviated pulmonary pathological damage of the sepsis mice, as well as reduced the excessive release of pro-inflammatory cytokines IL-1ß, IL-18, IL-6, iNOS and chemokines MCP-1 regulated by MAPK/NF-κB pathway in pulmonary injury. Daph treatment decreased Caspase-3 and Bax, increased Bcl-2, inhibited nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis in lung tissues of septic lung injury. Also, Daph treatment reduced the level of excessive inflammatory mediators, inhibited apoptosis and pyroptosis in MLE-12 cells. It is noteworthy that the protective effect of Daph on MLE-12 cells damage and death was assisted by the enhanced expression of CD38. CONCLUSIONS: Our results demonstrated that Daph offered a beneficial therapeutic effect for septic lung injury via the up-regulation of CD38 and inhibition of MAPK/NF-κB/NLRP3 pathway. Video Abstract.


Assuntos
Lesão Pulmonar , Sepse , Umbeliferonas , Animais , Camundongos , Lipopolissacarídeos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sepse/metabolismo , Umbeliferonas/farmacologia
17.
Eur Radiol ; 33(5): 3521-3531, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36695903

RESUMO

OBJECTIVES: To develop and validate a two-stage deep learning model for automatic detection and segmentation of brain metastases (BMs) in MRI images. METHODS: In this retrospective study, T1-weighted (T1) and T1-weighted contrast-enhanced (T1ce) MRI images of 649 patients who underwent radiotherapy from August 2019 to January 2022 were included. A total of 5163 metastases were manually annotated by neuroradiologists. A two-stage deep learning model was developed for automatic detection and segmentation of BMs, which consisted of a lightweight segmentation network for generating metastases proposals and a multi-scale classification network for false-positive suppression. Its performance was evaluated by sensitivity, precision, F1-score, dice, and relative volume difference (RVD). RESULTS: Six hundred forty-nine patients were randomly divided into training (n = 295), validation (n = 99), and testing (n = 255) sets. The proposed two-stage model achieved a sensitivity of 90% (1463/1632) and a precision of 56% (1463/2629) on the testing set, outperforming one-stage methods based on a single-shot detector, 3D U-Net, and nnU-Net, whose sensitivities were 78% (1276/1632), 79% (1290/1632), and 87% (1426/1632), and the precisions were 40% (1276/3222), 51% (1290/2507), and 53% (1426/2688), respectively. Particularly for BMs smaller than 5 mm, the proposed model achieved a sensitivity of 66% (116/177), far superior to one-stage models (21% (37/177), 36% (64/177), and 53% (93/177)). Furthermore, it also achieved high segmentation performance with an average dice of 81% and an average RVD of 20%. CONCLUSION: A two-stage deep learning model can detect and segment BMs with high sensitivity and low volume error. KEY POINTS: • A two-stage deep learning model based on triple-channel MRI images identified brain metastases with 90% sensitivity and 56% precision. • For brain metastases smaller than 5 mm, the proposed two-stage model achieved 66% sensitivity and 22% precision. • For segmentation of brain metastases, the proposed two-stage model achieved a dice of 81% and a relative volume difference (RVD) of 20%.


Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Humanos , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Radiologistas
18.
J Nat Prod ; 86(5): 1179-1188, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37115657

RESUMO

Apigenin (APG) is a well-known dietary flavonoid with multiple bioactivities, but its poor aqueous solubility may result in low oral bioavailability and thus compromised therapeutic effects. In the present study, APG was complexed with oxymatrine (OMT), a natural quinolizidine alkaloid, for enhanced anti-inflammatory activity, and the related mechanisms in the interaction of APG with OMT were investigated. Fourier transform-infrared spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and proton nuclear magnetic resonance spectroscopy characterizations demonstrated the occurrence of an APG-OMT complex formed at a molar ratio of 1:2. Then, molecular dynamics simulations and quantum chemical calculations were utilized to elucidate that hydrogen bonding, van der Waals forces, and hydrophobic effects were the main forces acting in the formation of the APG-OMT complex. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of APG in the APG-OMT complex was significantly higher than that of APG alone. Finally, bioactivity evaluation in the lipopolysaccharide-induced acute inflammatory injury mouse models showed that the APG-OMT complex exhibited more potent anti-inflammatory effects than APG alone. This study confirmed that APG and OMT exerted enhanced anti-inflammatory effects through self-complexation, which may provide a novel strategy for improving the bioavailability and bioactivity of natural product mixtures.


Assuntos
Alcaloides , Apigenina , Camundongos , Ratos , Animais , Apigenina/farmacologia , Apigenina/química , Alcaloides/farmacocinética , Matrinas , Anti-Inflamatórios/farmacologia , Quinolizinas/farmacocinética
19.
Support Care Cancer ; 31(5): 302, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37099274

RESUMO

OBJECTIVES: To clarify the adaptability of cancer patients to return to work and explore its influencing factors. DESIGN: A cross-sectional study. SETTINGS/PARTICIPANTS: From March to October 2021, 283 cancer patients in the follow-up period were recruited from the oncology departments of four secondary and above hospitals and cancer friendship associations in Nantong city using self-developed scale of adaptability to return to work for cancer patients by convenience sampling method. METHODS: The contents included general sociodemographic data, disease-related data, cancer patients' readability to work Scale, Medical Coping Style Questionnaire, Social Support Rating Scale, Family Closeness and Readability Scale, General self-efficacy Scale and Social impact Scale. Paper questionnaires were used for face-to-face data collection, and SPSS17.0 was used for statistical analysis. Univariable analyses and multiple linear regression analysis were conducted. RESULTS: The overall score of cancer patients' adaptability to return to work was (87.05±20.255), (22.54±4.234) for the dimension of focused rehabilitation, (32.02±9.013) for the dimension of reconstruction effectiveness, and (32.49±9.023) for the dimension of adjustment planning. Multiple linear regression analysis showed that the current return to full-time work (ß =0.226, P 0.05), the current return to non-full-time work (ß =0.184, P 0.05), yield response (ß = -0.132, P 0.05), and general self-efficacy (ß =0.226, P 0.05) could affect their return to work adaptation. CONCLUSION: The results of status quo and influencing factors showed that the adaptability of cancer patients to return to work was generally higher in this study. Cancer patients who had participated in work, had lower yield coping scores and stigma scores, and higher self-efficacy scores and family adjustment and intimacy scores had better adaptability to return to work again. ETHICAL APPROVAL: It has been approved by the Human Research Ethics Committee of the Affiliated Hospital of Nantong University (Project No.202065).


Assuntos
Neoplasias , Retorno ao Trabalho , Humanos , Estudos Transversais , Adaptação Psicológica , Inquéritos e Questionários
20.
Environ Res ; 219: 115017, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36495959

RESUMO

With the implementation of the 'Grain-for-Green' program on the Chinese Loess Plateau (CLP), drought-tolerant deep-rooted plants have been increasingly introduced to the northwest in China. However, the vertical features of dissolved organic matter (DOM) in deep soil profiles on CLP during the 'Grain-for-Green' program is still not well understood. In the study, ultraviolet-visible (UV-Vis) spectroscopy and three-dimensional fluorescence excitation-emission matrices (3D-EEMs) with parallel factor analysis (PARAFAC) were used to characterize DOM in 5-m profile of farmland and forestland (Pinus tabulaeformis and Robinia pseudoacacia) in the southern CLP. The results demonstrated that the average dissolved organic carbon (DOC) content of the surface layer of farmland (119.3 mg kg-1 soil) was lower than that of forestland (Pinus tabulaeformis 175.5 mg kg-1 soil; Robinia pseudoacacacia 166.4 mg kg-1 soil). The DOC content gradually decreased with increasing soil depth and reached stability after 2 m depth. Three substances, including tryptophan-like substances (C1) and two humic acid-like substances (C2, C3), were detected from all samples. Tryptophan-like substances (C1) significantly increased with soil depth while humic acid-like substances (C2, C3) significantly decreased particularly in farmland. The humic acid-like content of surface soils (Robinia pseudoacacia) was relatively higher, but the difference between the two vegetation soils was not significant. The freshness index (ß/α) values of DOM as well as biological index (BIX) values were significantly higher in farmland than that in forestland, and the humification index (HIX) values were lower than in forestland soils, indicating that the change of soil DOM in farmland was more active than that in forestland and more dependent on local terrestrial sources. These results could contribute to a better understanding of the vertical distribution and features of soil DOM during the 'Grain-for-Green' program of CLP.


Assuntos
Substâncias Húmicas , Solo , Solo/química , Substâncias Húmicas/análise , Matéria Orgânica Dissolvida , Fazendas , Triptofano , Florestas , Espectrometria de Fluorescência/métodos
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