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1.
Sci Rep ; 14(1): 7740, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565888

RESUMO

Analyzing the important nodes of complex systems by complex network theory can effectively solve the scientific bottlenecks in various aspects of these systems, and how to excavate important nodes has become a hot topic in complex network research. This paper proposes an algorithm for excavating important nodes based on the heat conduction model (HCM), which measures the importance of nodes by their output capacity. The number and importance of a node's neighbors are first used to determine its own capacity, its output capacity is then calculated based on the HCM while considering the network density, distance between nodes, and degree density of other nodes. The importance of the node is finally measured by the magnitude of the output capacity. The similarity experiments of node importance, sorting and comparison experiments of important nodes, and capability experiments of multi-node infection are conducted in nine real networks using the Susceptible-Infected-Removed model as the evaluation criteria. Further, capability experiments of multi-node infection are conducted using the Independent cascade model. The effectiveness of the HCM is demonstrated through a comparison with eight other algorithms for excavating important nodes.

2.
BMC Med ; 22(1): 154, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609982

RESUMO

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.


Assuntos
Apoptose , Neoplasias Colorretais , Animais , Camundongos , Humanos , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Expressão Gênica , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Fatores de Troca do Nucleotídeo Guanina
3.
Int J Biol Macromol ; 267(Pt 2): 131375, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604424

RESUMO

Compostable zein-polycaprolactone (PZ) electrospun nanofiber integrated with different concentrations of Aster yomena extract loaded halloysite nanotubes (A. yomena-HNT) as bioactive nanofibrous food packaging is reported. SEM micrographs reveal heterogeneous nanofibers. A. yomena extract used in the study showed weak antioxidant activity with AAI and TEAC values of 0.229 and 0.346. In vitro, release profile over 7 days of A. yomena indicates a controlled, sustained, and prolonged release. The prepared nanofibers were effective against both gram-positive and gram-negative bacteria. The prepared composite nanofibers were rendered biocompatible and nontoxic when subjected to WST-1 and LDH assay after incubating with NIH 3T3 mouse fibroblast cell line. PZ-15 nanofiber packaging showed the best postharvest quality preservation in Black mulberry fruits after 4 days of storage at 25 °C and 85 % Rh. Moreover, the in vitro decomposition test reveals that the fabricated nanofibers decompose in the soil and do not pose as a threat to the environment.

4.
Sci Total Environ ; : 172575, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641105

RESUMO

Phosphorus (P) plays an important role in regulating primary production in estuarine environments. However, knowledge of the P-functional gene composition of microbial communities and the mechanisms of microbial adaptation to changes in available P in estuaries remain limited. This study coupling 16 s rDNA and metagenomics sequencing was conducted to reveal the relationship between P cycling functional genes, microbial interactions, and P availability in the Jiulong River Estuary. The results showed that the relative abundance of P cycling functions genes was highest in winter, and lowest in summer. Spatially, the total relative abundance of P cycling functions genes was higher in the riverward than that in the seaward. P cycling functional microbial interactions and P cycling gene coupling were strongest in summer and in the seaward. Changes in both temperature and salinity had significant direct and indirect effects on P cycling function, and the influence of salinity on P cycling function was greater than that on the microbial community in the estuary. Salinity had significant direct negative effects on inorganic P-solubilization (IP), organic P-mineralization (OP), and P uptake and transport functions (PT). Whereas, salinity had a significant positive effect on P-starvation response regulation (PR) function. Thus, salinity and microbial communities regulate the soluble reactive phosphate concentrations in estuarine environments by strengthening internal coupling among P cycling functions, promoting PR function, and facilitating PT gene expression. PR is the most important predictors, PR, PT, and PR-PT together explained 38.56 % of the overall soluble reactive phosphorus (SRP) variation. Over 66 % of the explained SRP variations can be predicted by the PR, PT, and PR-PT functional genes. This finding improves the knowledge base of the microbial processes for P cycling and provides a foundation for eutrophication management strategies in the estuary.

6.
Skin Res Technol ; 30(4): e13692, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650354

RESUMO

OBJECTIVE: To compare emotional responses elicited by four cosmetic products on different sensory modalities (smell, visual, and touch), and analyze the link between objective instrumental analysis results and subjective evaluation of participants occurring within dimensional valence-arousal model of emotions. METHODS: In this study, four cream products exhibiting variations in olfactory perception, visual appearance and perception usability were selected. Electroencephalography (EEG) and a subjective emotion scale were used to assess participants' emotional responses during the sensory experience of utilizing the creams. RESULTS: The study revealed that the objective emotional valence and arousal of different cream products exhibited certain variations at distinct stages of usage. The trend of valence differences induced by different products measured by EEG at the same stage was almost as same as measured by subjective evaluation. The correspondence between the valence measured by EEG closely approximated that obtained through subjective evaluation across various products at distinct stages of usage. These findings demonstrate a significant correlation between EEG-based valence and subjective valence, however, no such relationship was observed for arousal. CONCLUSION: This study demonstrates the feasibility of using EEG as a method to assess emotions elicited by various stages of cosmetics application, including smelling, looking, rubbing, and afterfeel. This technique serves as a valuable supplement to traditional methods for examining emotional responses by providing more objective evidence.

7.
Front Psychol ; 15: 1293845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495419

RESUMO

Background: Positive psychology is a vibrant field of study, and conceptualizations of the components of well-being have received a great deal of attention from researchers. The study of well-being literacy thus provides an innovative perspective for enhancing and sustaining individuals' experiences of well-being. Objective: This study aimed to examine the psychometric properties of the wellbeing literacy 6-item (Well-Lit 6) scale in Chinese military academy cadets. Methods: A total of 3,218 undergraduate students from five military academies in China were recruited to complete questionnaires online. Results: (1) The items of the scale showed high discrimination; (2) The alpha coefficient of the scale was 0.986 and the split-half reliability was 0.981, indicating high homogeneous reliability and split-half reliability; (3) The scale model fitted well and displayed structural validity; (4) The correlation between well-being literacy and related indicators was significant, and the calibration correlation and convergent-discriminant validity of the scale were high; (5) After gradually adding demographic variables, known predictors factors and well-being literacy, the ∆R2 for subjective well-being, life satisfaction, depression, and anxiety ranged from 0.036 to 0.067, 0.184 to 0.340, and 0.009 to 0.017, respectively, showing high incremental validity; (6) the total well-being literacy scores differed significantly by gender, grade, and parenting style. Conclusion: The Chinese version of the Well-Lit 6 is reliable and valid in predicting and accessing the subjective well-being, life satisfaction, emotion regulation, and psychological resilience of Chinese military academy cadets.

8.
Langmuir ; 40(14): 7723-7732, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38554094

RESUMO

Liquid crystal emulsion is a new type of emulsion, in which the emulsifier molecules are located at the oil/water (O/W) interface and form a long-range ordered and short-range disordered lamellar liquid crystal. The lamellar liquid crystal formed by the emulsifier is similar to the skin stratum corneum lipid structure, which enables it to have a broad application prospect in the fields of cosmetics, pharmaceuticals, etc. In this work, a liquid crystal nanoemulsion was obtained by passing a liquid crystal emulsion stabilized by hydrogenated lecithin and phytosterol combination through a microfluidizer. The microstructure of the prepared liquid crystal nanoemulsion was investigated experimentally by dynamic light scattering, transmission electron microscopy, and small-angle X-ray scattering. The results have shown that the nanoemulsion inherited the liquid crystal emulsion property, namely, the long-range ordered and short-range disordered lamellar structure still existed at the oil/water interface even though they underwent extrusion, friction, and acceleration. At the same time, the underlying mechanisms of the existence of lamellar liquid crystal between the oil phase and the water phase for the nanoemulsion were explored theoretically by molecular dynamics simulations. The simulation results elucidated that the hydrogenated lecithin and phytosterol combination improved the flexibility of the bilayer structure composed of emulsifiers. The bilayers were the basic structure units of lamellar liquid crystals, and thus, the improved flexibility of bilayers provided insurance for the existence of lamellar liquid crystals with larger curvature around the oil droplets. In addition, the applicable properties of liquid crystal nanoemulsion were studied, and the results have shown that the liquid crystal nanoemulsion presented better slow-release and moisturizing properties than traditional nanoemulsions due to the existence of multilayers between oil and water phases. This work not only provides necessary information for the development and effective application of liquid crystal emulsions but also is helpful for in-depth understanding the inner properties of lamellar liquid crystal at molecular level.

9.
Skin Res Technol ; 30(3): e13653, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488420

RESUMO

BACKGROUND: During the coronavirus disease 2019 pandemic, wearing medical respirators and masks was essential to prevent transmission. OBJECTIVE: To quantify the effects of N95 mask usage by measuring facial skin biophysical characteristics and changes in the lipidome. METHODS: Sixty healthy volunteers wore N95 respirators for 3 or 6 h. Facial images were acquired and physiological parameters were measured in specific facial areas, before and after mask-wearing. Lipidome analysis was also performed. RESULTS: After N95 respirator usage, facial erythema was observed in both the 3 and 6 h groups. Both sebum secretion and trans-epidermal water loss increased significantly in mask-covered cheeks and chins after 6 h of mask wearing compared with before mask wearing (p < 0.05). Principal component analysis revealed significant differences in lipid composition after mask wearing compared with before. The ceramide subclass NS exhibited a positive correlation with stratum corneum hydration, whereas the AP subclass was negatively correlated with trans-epidermal water loss in the 6 h group. CONCLUSION: Prolonged wear of N95 respirators may impair facial skin function and alter lipidome composition.


Assuntos
Respiradores N95 , Dispositivos de Proteção Respiratória , Humanos , Lipidômica , Máscaras , Água , Atenção à Saúde
10.
Food Res Int ; 182: 114176, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519189

RESUMO

In this work, the effects of Maillard reaction of different monosaccharide-modified fish gelatin were studied. The changes of gel properties, rheology and structure of fish gelatin before and after modification were compared and analyzed, and oil-in-woter emulsions were prepared. The results showed that the five-carbon monosaccharide had stronger modification ability than the six-carbon monosaccharide, which was mainly due to the different steric hindrance of the amino acids in the nuclear layer and the outer layer to the glycosylation reaction. With the progress of the Maillard reaction, the color of fish gelatin gradually became darker. The attachment of sugar chains inhibited the gelation process of fish gelatin, decreased the gelation rate, changed the secondary structure, increased the content of ß-turn or α-helix, increased the degree of fluorescence quenching, and enhanced the emulsifying properties and emulsion stability. This study provides useful information for the preparation of different types of monosaccharide-modified proteins and emulsions.


Assuntos
Gelatina , Monossacarídeos , Animais , Gelatina/química , Reação de Maillard , Emulsões/química , Carbono
11.
Environ Int ; 185: 108546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38458116

RESUMO

Mangrove wetlands are hotspots of the global nitrogen (N) cycle and important sinks of microplastics (MPs) due to their ecotone location between terrestrial and marine ecosystems. However, the effects of MPs on N cycle processes in mangrove ecosystems are still poorly understood. Thus, the present study assessed the impacts by adding MPs to mangrove sediments in a microcosm incubation experiment. The results showed that MPs increased dissolved organic carbon and nitrate but reduced ammonium contents in the sediments. MPs increased C:N stoichiometric and N:C-acquiring enzymatic ratios, indicating an intensified N limitation in mangrove sediments following exposure of MPs. MPs decreased microbial community diversity and shifted sediment microbial communities from r- to K-strategists, consistent with the intensified N limitation. In response, dissimilatory nitrate reduction to ammonium (DNRA) rates increased while nitrous oxide (N2O) production reduced suggesting more efficient N utilization in MPs treatments. The MPs with heteroatoms such as PLA- and PVC-MPs, increased DNRA rates by 67.5-78.7%, exhibiting a stronger impact than PE-MPs. The variation partitioning analysis revealed that the variances of DNRA rates and N2O production could be attributed to synergistic effects of physicochemical properties, nutrient limitation, and microbial community in mangrove sediments. Overall, this study provides pertinent insights into the impacts of MPs as a new carbon source on nutrient limitation and N turnover in mangrove ecosystems.


Assuntos
Compostos de Amônio , Ecossistema , Nitratos/análise , Microplásticos , Plásticos , Nitrogênio/análise , Compostos Orgânicos , Sedimentos Geológicos/química
12.
J Pharm Anal ; 14(2): 177-195, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38464781

RESUMO

Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-ß-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.

13.
Cancer Immunol Immunother ; 73(5): 81, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554184

RESUMO

Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.


Assuntos
Células Matadoras Naturais , Neoplasias , Humanos , Ligantes , Imunoterapia , Linfócitos do Interstício Tumoral , Neoplasias/metabolismo
14.
Dalton Trans ; 53(15): 6507-6514, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38512102

RESUMO

Calix[8]arene has been used as a promising type of macrocyclic ligand for the construction of multinuclear metal-oxo clusters (MOCs), but not for zirconium/hafnium-oxo clusters (Zr/HfOCs). In this paper, we report the first series of ZrOCs (HfOCs) based on calix[8]arene: Zr4, Zr8, Hf4, and Hf8. Zr8/Hf8 has a rhombohedral conformation and can be regarded as a derivative of the octahedral Zr6 cluster. Remarkably, I2 adsorption experiments indicate that Zr4 (Zr8) adsorbs much faster than Hf4 (Hf8). Density functional theory (DFT) calculations show that metallic Zr atoms interact more strongly with I2 than metallic Hf atoms. The successful application of calix[8]arene for the synthesis of well-defined ZrOCs (HfOCs) shows a bright future for MOCs protected by macrocyclic ligands.

15.
J Ethnopharmacol ; 328: 118021, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38492793

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, also known as the Anas fruit, is a unique perennial woody oil plant from Yunnan Province, China. In the ancient texts of Dongba sutras and Yunnan Southern Materia Medica, it has been documented that the local Naxi, Tibetan, and Mosuo communities extensively utilize the root and leaf fruits of green thorns for various purposes. These include treating mild-to-moderate specific dermatitis, moisturising the skin, providing protection against UV damage, aiding childbirth in pregnant women, safeguarding stomach health, reducing the risk of arteriosclerosis, and delaying aging. AIM OF THE STUDY: In this study, leftover residues from oil extraction were efficiently reused, and flavonoids were identified during subsequent extraction and separation processes. The anti-senescent effects of flavonoids in P. utilis Royle have not been systematically studied. Therefore, the objective of this study was to explore the anti-senescent properties of the flavonoids obtained from P. utilis Royle. METHODS: First, HPLC and other analytical techniques were used to identify the components of the P. utilis Royle flavonoid (PURF). Next, DPPH, hydroxyl radicals, superoxide anion O2-, collagenase, and elastase were initially detected using in vitro biochemical assays. To examine its antioxidant properties, a zebrafish model was used, and to confirm its anti-senescent effects, a d-galactose-induced mouse aging model was employed. The anti-senescent mechanism of PURF was examined using a natural senescence HFF model. Furthermore, the anti-senescent target was confirmed using a 3D full T-Skin™ model. RESULTS: In vitro biochemical assays demonstrated that flavones exhibited potent antioxidant activity and anti-senescent potential by inhibiting DPPH, hydroxyl radicals, superoxide anion O2-, collagenase, and elastase. It significantly enhanced the antioxidant effect on zebrafish while suppressing ROS and inflammatory injury, up-regulating COL1A1, COL3A1, AMPK, and mTOR gene expression and down-regulating MMP-9, TGF-ß, p21, and p16 gene expression suggesting its potential anti-senescent ability. Findings from the D-galactose-induced aging mouse model showed that PURF greatly increased SOD levels, while simultaneously decreasing HYP and MDA levels. In addition, when PURF was given to the HFF cell and 3D full T-Skin™ model, consistent trends were observed in gene and protein expression, with up-regulation of COL1A1, COL3A1, AMPK, and mTOR genes and down-regulation of TGF-ß, MMP-1, MMP-9, p21, and p16 genes. Therefore, these preliminary findings indicate that flavones can modulate AMPK/mTOR/TGF-ß signalling pathways to exert its influence. CONCLUSION: The kernel residue of natural P. utilis Royle oil extracted from Yunnan province was previously considered agricultural waste, but we successfully extracted and isolated its flavonoid components. Our preliminary studies demonstrated its potential as an environmentally friendly anti-senescent raw material.


Assuntos
Flavonas , Gravidez , Animais , Camundongos , Humanos , Feminino , Flavonas/farmacologia , Metaloproteinase 9 da Matriz , Peixe-Zebra , Superóxidos , Galactose , Proteínas Quinases Ativadas por AMP , China , Antioxidantes/farmacologia , Flavonoides/farmacologia , Sementes , Elastase Pancreática , Fator de Crescimento Transformador beta , Serina-Treonina Quinases TOR
16.
PeerJ ; 12: e16984, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426132

RESUMO

Background: Wheat (Tritium aestivum L.) production is critical for global food security. In recent years, due to climate change and the prolonged growing period of rice varieties, the delayed sowing of wheat has resulted in a loss of grain yield in the area of the middle and lower reaches of the Yangtze River. It is of great significance to screen for natural germplasm resources of wheat that are resistant to late sowing and to explore genetic loci that stably control grain size and yield. Methods: A collection of 327 wheat accessions from diverse sources were subjected to genome-wide association studies using genotyping-by-sequencing. Field trials were conducted under normal, delayed, and seriously delayed sowing conditions for grain length, width, and thousand-grain weight at two sites. Additionally, the additive main effects and multiplicative interaction (AMMI) model was applied to evaluate the stability of thousand-grain weight of 327 accessions across multiple sowing dates. Results: Four wheat germplasm resources have been screened, demonstrating higher stability of thousand-grain weight. A total of 43, 35, and 39 significant MTAs were determined across all chromosomes except for 4D under the three sowing dates, respectively. A total of 10.31% of MTAs that stably affect wheat grain size could be repeatedly identified in at least two sowing dates, with PVE ranging from 0.03% to 38.06%. Among these, six were for GL, three for GW, and one for TGW. There were three novel and stable loci (4A_598189950, 4B_307707920, 2D_622241054) located in conserved regions of the genome, which provide excellent genetic resources for pyramid breeding strategies of superior loci. Our findings offer a theoretical basis for cultivar improvement and marker-assisted selection in wheat breeding practices.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Fenótipo , Triticum/genética , Melhoramento Vegetal , Grão Comestível/genética
17.
J Control Release ; 368: 157-169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367861

RESUMO

Gene delivery to macrophages holds great promise for cancer immunotherapy. However, traditional gene delivery methods exhibit low transfection efficiency in macrophages. The star-shaped topological structure of polymers is known to encapsulate genes inside their cores, thereby facilitating sustained release of the genetic material. Herein, combining the structural advantages of star polymers and the transfection advantages of poly (ß-amino ester)s (PAEs), we developed a novel linear oligomer grafting-onto strategy to synthesize a library of multi-terminal star structured PAEs (SPAEs), and evaluated their gene delivery efficiency in various tissue cells. The transfection with human hepatocellular carcinoma cells (HepG2, HCC-LM3 cells and MHCC-97H cells), rat normal liver cells (BRL-3 A cells), human ovarian cancer cells (A2780 cells), African green monkey kidney cells (Vero cells), human cervical cancer cells (HeLa cells), human chondrosarcoma cells (SW1353 cells), and difficult-to-transfect human epidermal keratinocytes (HaCaT cells) and normal human fibroblast cells (NHF cells) showed that SPAEs exhibited superior transfection profile. The GFP transfection efficiency of top-performing SPAEs in HeLa cells (96.1%) was 2.1-fold, and 3.2-fold higher compared to jetPEI and Lipo3000, respectively, indicating that the star-shaped topological structure can significantly enhance the transfection efficiency of PAEs. More importantly, the top-performing SPAEs could efficiently deliver Nod2 DNA to difficult-to-transfect RAW264.7 macrophages, with a high transfection efficiency of 33.9%, which could promote macrophage M1 polarization and enhanced CD8+ T cell response in co-incubation experiments. This work advances gene therapy by targeting difficult-to-transfect macrophages and remodeling the tumor immune microenvironment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Ovarianas , Ratos , Humanos , Animais , Chlorocebus aethiops , Feminino , Células HeLa , Linhagem Celular Tumoral , Células Vero , Ésteres , Transfecção , Terapia Genética , Polímeros/química , Macrófagos , Microambiente Tumoral
18.
Artigo em Inglês | MEDLINE | ID: mdl-38397692

RESUMO

Traditional assessments of anxiety and depression face challenges and difficulties when it comes to understanding trends in-group psychological characteristics. As people become more accustomed to expressing their opinions online, location-based online media and cutting-edge algorithms offer new opportunities to identify associations between group sentiment and economic- or healthcare-related variables. Our research provides a novel approach to analyzing emotional well-being trends in a population by focusing on retrieving online information. We used emotionally enriched texts on social media to build the Public Opinion Dictionary (POD). Then, combining POD with the word vector model and search trend, we developed the Composite Anxiety and Depression Index (CADI), which can reflect the mental health level of a region during a specific time period. We utilized the representative external data by CHARLS to validate the effectiveness of CADI, indicating that CADI can serve as a representative indicator of the prevalence of mental disorders. Regression and subgroup analysis are employed to further elucidate the association between public mental health (measured by CADI) with economic development and medical burden. The results of comprehensive regression analysis show that the Import-Export index (-16.272, p < 0.001) and average cost of patients (4.412, p < 0.001) were significantly negatively associated with the CADI, and the sub-models stratificated by GDP showed the same situation. Disposable income (-28.389, p < 0.001) became significant in the subgroup with lower GDP, while the rate of unemployment (2.399, p < 0.001) became significant in the higher subgroup. Our findings suggest that an unfavorable economic development or unbearable medical burden will increase the negative mental health of the public, which was consistent across both the full and subgroup models.


Assuntos
Depressão , Mídias Sociais , Humanos , Depressão/epidemiologia , Ferramenta de Busca , Emoções , Ansiedade/epidemiologia , Internet
19.
Transl Psychiatry ; 14(1): 120, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409093

RESUMO

It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Ratos , Masculino , Animais , Dopamina , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/genética , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Recompensa , Perfilação da Expressão Gênica , Autoadministração
20.
Soft Robot ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407844

RESUMO

Soft underwater swimming robots actuated by smart materials have unique advantages in exploring the ocean, such as low noise, high flexibility, and friendly environment interaction ability. However, most of them typically exhibit limited swimming speed and flexibility due to the inherent characteristics of soft actuation materials. The actuation method and structural design of soft robots are key elements to improve their motion performance. Inspired by the muscle actuation and swimming mechanism of natural fish, a fast-swimming soft robotic fish actuated by a bionic muscle actuator made of dielectric elastomer is presented. The results show that by controlling the two independent actuating units of a biomimetic actuator, the robotic fish can not only achieve continuous C-shaped body motion similar to natural fish but also have a large bending angle (maximum unidirectional angle is about 40°) and thrust force (peak thrust is about 14 mN). In addition, the coupling relationship between the swimming speed and actuating parameters of the robotic fish is established through experiments and theoretical analysis. By optimizing the control strategy, the robotic fish can demonstrate a fast swimming speed of 76 mm/s (0.76 body length/s), which is much faster than most of the reported soft robotic fish driven by nonbiological soft materials that swim in body and/or caudal fin propulsion mode. What's more, by applying programmed voltage excitation to the actuating units of the bionic muscle, the robotic fish can be steered along specific trajectories, such as continuous turning motions and an S-shaped routine. This study is beneficial for promoting the design and development of high-performance soft underwater robots, and the adopted biomimetic mechanisms, as well as actuating methods, can be extended to other various flexible devices and soft robots.

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