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1.
Int J Ophthalmol ; 17(9): 1723-1730, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296574

RESUMO

AIM: To assess the causal link between 211 gut microbiota (GM) taxa and dry age-related macular degeneration (dAMD) risk. METHODS: Mendelian randomization using instrumental factors taken from a genome-wide association study (GWAS) were used. Inverse variance weighted (IVW) analysis and sensitivity analysis were performed on the FinnGen project, which included 5095 cases and 222 590 controls. RESULTS: The IVW analysis showed substantial genus- and family-level relationships between GM taxa and dAMD risk. Specifically, the family Peptococcaceae (P=0.03), genus Bilophila (P=3.91×10-3), genus Faecalibacterium (P=6.55×10-3), and genus Roseburia (P=0.04) were linked to a higher risk of developing dAMD, while the genus Candidatus Soleaferrea (P=7.75×10-4), genus Desulfovibrio (P=0.04) and genus Eubacterium ventriosum group (P=0.04) exhibited a protective effect against dAMD. No significant causal relationships were observed at higher taxonomic levels. Additionally, in the reverse IVW analysis, no meaningful causal effects of the 7 GM taxa. CONCLUSION: These findings give support for the gut-retina axis participation in dAMD and shed light on putative underlying processes. Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.

2.
Biol Trace Elem Res ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320572

RESUMO

Strontium-rich mineral water (strontium > 0.20 mg/L) is the second largest type of mineral water on commercial drinking water market. Exposure to high levels of strontium through drinking water or soil may interfere with calcium metabolism and increase the risk of cardiovascular and skeletal diseases, but no in-depth mechanism has been disclosed to date. Data on liver metabolic alterations in rats resulted from drinking natural high strontium mineral water (strontium 26.06 mg/L, SrHW) or tap water (filtered by activated carbon, strontium 0.49 mg/L, TW) for 3 months were obtained and analyzed with non-targeted metabolomics strategy. Compared with rats drinking TW, those drinking SrHW showed a significant change in 36 liver metabolites. Among them, 33 liver metabolites (including 14 amino acids, 6 carbohydrates, 4 short-chain fatty acids, 4 organic acids, 2 phenylpropanoic acids, 1 fatty acid, 1 peptide, and 1 bile acid) were down-regulated, and 3 (hydroxyphenyllactic acid, propionylcarnitine and S-adenosine homocysteine) were up-regulated. Metabolic pathway analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and alanine, aspartate and glutamate metabolism are most impacted. Furthermore, the serum prealbumin content also significantly decreased in rats drinking SrHW. Therefore, changes in liver metabolites and serum protein levels suggested that high concentration of strontium in water was associated with decreased liver protein synthesis; changes in liver metabolites suggested that high strontium was associated with decreased lipid levels. In conclusion, high strontium in water may exert a negative effect on protein synthesis, and further study on the dose-response relationship is necessary.

3.
Nano Lett ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291795

RESUMO

With high current density, the intense near-electrode CO2 reduction reaction (CO2RR) will cause the concentration gradients of bicarbonate (HCO3-) and hydroxyl (OH-) ions, which affect the selectivity of high-value C2+ products of the CO2RR. In this work, we simulated the near-electrode concentration gradients of electrolyte species with different porous Cu-based CLs (catalyst layers) of GDE (gas diffusion electrode) by COMSOL Multiphysics. The higher porosity CL exhibits a better buffer ability of local alkalinity while ensuring a sufficient supply of H+ and local CO2 concentration. Subsequently, the different porosity CLs were prepared by vacuum-thermal evaporation with different evaporation rate. Structural characterizations and liquid permeability tests confirm the role of the porous CL structure in optimizing concentration gradients. As a result, the high-porosity CL (Cu-HP) exhibits a higher C2+ Faraday efficiency (FE) of ∼79.61% at 500 mA cm-2 under 1 M KHCO3, far more than the FEC2+ ≈ 38.20% with the low-porosity sample (Cu-LP).

4.
Nutrients ; 16(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39275197

RESUMO

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35-40 °C, 70-80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.


Assuntos
Osso e Ossos , Boro , Camundongos Endogâmicos BALB C , Águas Minerais , Água do Mar , Animais , Boro/farmacologia , Masculino , Água do Mar/química , Camundongos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Densidade Óssea/efeitos dos fármacos , Água Potável , Biomarcadores/sangue , Vértebras Lombares/efeitos dos fármacos , Fêmur/efeitos dos fármacos
5.
Nat Commun ; 15(1): 8048, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277619

RESUMO

White organic light-emitting diodes (WOLEDs) hold significant promise in illumination and displays, but achieving high efficiency while maintaining stability is an ongoing challenge. Here, we strategically combine a blue donor-acceptor thermally activated delayed fluorescence (TADF) emitter featuring rapid reverse intersystem crossing rate and a yellow multi-resonance TADF emitter renowned for the fast radiative transition process to achieve warm WOLEDs with exceptional power efficiency exceeding 190 lm W-1 and external quantum efficiency (EQE) of 39%, setting records for WOLEDs. Meanwhile, these devices also exhibit an extended operational lifetime (LT80) of 446 h at an initial luminance of 1000 cd m-2. Another group of blue and yellow emitters based on our strategy achieves a standard white emission and a high EQE of 35.6%, confirming the universality of our strategy. This work presents a versatile strategy to harmonize singlet exciton radiation and triplet exciton up-conversion, thus achieving a win-win situation of efficiency and stability.

6.
Neurol Sci ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39266808

RESUMO

BACKGROUND: Primary Meige syndrome (PMS) is a rare form of dystonia, and comparative analysis of globus pallidus internal deep brain stimulation (GPi-DBS), subthalamic nucleus deep brain stimulation (STN-DBS), and pallidotomy has been lacking. This study aims to compare the efficacy, safety, and psychiatric features of GPi-DBS, STN-DBS, and pallidotomy in patients with PMS. METHODS: This prospective cohort study was divided into three groups: GPi-DBS, STN-DBS, and pallidotomy. Clinical assessments, including motor and non-motor domains, were evaluated at baseline and at 1 year and 3 years after neurostimulation/surgery. RESULTS: Ninety-eight patients were recruited: 46 patients received GPi-DBS, 34 received STN-DBS, and 18 underwent pallidotomy. In the GPi-DBS group, the movement score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) improved from a mean (SE) of 13.8 (1.0) before surgery to 5.0 (0.7) (95% CI, -10.5 to -7.1; P < 0.001) at 3 years. Similarly, in the STN-DBS group, the mean (SE) score improved from 13.2 (0.8) to 3.5 (0.5) (95% CI, -10.3 to -8.1; P < 0.001) at 3 years, and in the pallidotomy group, it improved from 14.9 (1.3) to 6.0 (1.1) (95% CI, -11.3 to -6.5; P < 0.001) at 3 years. They were comparable therapeutic approaches for PMS that can improve motor function and quality of life without non-motor side effects. CONCLUSIONS: DBS and pallidotomy are safe and effective treatments for PMS, and an in-depth exploration of non-motor symptoms may be a new entry point for gaining a comprehensive understanding of the pathophysiology.

7.
J Agric Food Chem ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225681

RESUMO

This study identified genetic mutations linked to resistance to pyrethroid insecticides in the plant pest Lygus pratensis. The voltage-gated sodium channel (VGSC) gene was cloned, revealing two mutations (Met918Thr and Leu1014Phe) in laboratory strains and field populations from Inner Mongolia, resulting in variable pyrethroid resistance. A 3D model of LpVGSC was created using homology modeling, and pyrethroid binding patterns were analyzed via molecular docking. Molecular dynamics simulations confirmed structural stability changes and binding stability of pyrethroids to VGSC sites. Mutation frequencies of homozygous and heterozygous genotypes did not exceed 40 and 20%, respectively. Toxicity tests showed high resistance to λ-cyhalothrin (LC50:401.31 ng/cm2). The kdr (L1014F) and superkdr (M918T) mutations weakened interaction forces, reducing pyrethroid binding. M918T and L1014F mutations are predicted to reduce Type I pyrethroid affinity, suggesting Type II pyrethroids may be more effective against resistant strains. These findings aid in resistance management and insecticide design.

8.
Acta Diabetol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090426

RESUMO

AIMS: Diabetic retinopathy (DR) results from complex genetic and metabolic interactions. Unraveling the links between blood metabolites and DR can advance risk prediction and therapy. METHODS: Leveraging Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC), we analyzed 10,413 DR cases and 308,633 controls. Data was sourced from the Metabolomics GWAS server and the FinnGen project. RESULTS: Our research conducted a comprehensive MR analysis across 486 serum metabolites to investigate their causal role in DR. After stringent selection and validation of instrumental variables, we focused on 480 metabolites for analysis. Our findings revealed 38 metabolites potentially causally associated with DR. Specifically, 4-androsten-3beta,17beta-diol disulfate 2 was identified as significantly associated with a reduced risk of DR (OR = 0.471, 95% CI = 0.324-0.684, p = 7.87 × 10- 5), even after rigorous adjustments for multiple testing. Sensitivity analyses further validated the robustness of this association, and linkage disequilibrium score regression analyses showed no significant genetic correlation between this metabolite and DR, suggesting a specific protective effect against DR. CONCLUSIONS: Our study identifies 4-androsten-3beta,17beta-diol disulfate 2, a metabolite of androgens, as a significant protective factor against diabetic retinopathy, suggesting androgens as potential therapeutic targets.

9.
Heliyon ; 10(13): e33433, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39027515

RESUMO

Objective: This study aims to comprehensively analyze genomic, transcriptomic, proteomic, and single-cell sequencing data to unravel the molecular basis of primary Sjögren's syndrome (pSS) and explore potential therapeutic targets. Methods: Mendelian randomization and single-cell RNA sequencing were employed to analyze pSS data. Differentially expressed genes specific to different blood cell types were identified. Integration of multiomics data facilitated the exploration of genetic regulatory relationships. Results: The analysis revealed distinct cell clusters representing various immune cell subsets. Several genes, including cathepsin S (CTSS) and glutathione S-transferase omega 1 (GSTO1), were identified as potential biomarkers and therapeutic targets for pSS. Diagnostic utility analysis demonstrated the discriminatory power of CTSS and GSTO1 in distinguishing pSS patients from healthy controls. Conclusion: The findings highlight the importance of integrating multiomics data for understanding pSS pathogenesis. CTSS and GSTO1 show promise as diagnostic biomarkers and potential therapeutic targets for pSS. Further investigations are warranted to elucidate the underlying mechanisms and develop targeted therapies for this complex autoimmune disease.

10.
World J Clin Cases ; 12(21): 4789-4793, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070835

RESUMO

BACKGROUND: Peritoneal dialysis (PD) is an important renal replacement therapy in patients with end-stage renal disease. PD catheters remain the lifeline for patients undergoing PD. The catheter technique survival rate is considered a core PD outcome domain. CASE SUMMARY: The PD catheter spontaneously dislodged in a patient undergoing PD during regular fluid exchange without pain. Abdominal computed tomography showed a tunnel infection. A double-cuff straight Tenckhoff catheter had been inserted using the Seldinger technique. Before this incident, the patient had a history of tunnel infections. We speculate that recurrent tunnel infections and catheter insertion using the Seldinger technique may have led to catheter dislodgement. CONCLUSION: The present case suggests that clinicians should more rigorously assess the persistence of catheter-related infections concerning the potential complications arising from catheter dislodgement associated with the Seldinger technique.

11.
Chem Sci ; 15(29): 11382-11390, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39055019

RESUMO

Luminescent metallopolymers have attracted broad interest in the fields of healthcare and organic electronics. However, polymeric emitters based on earth-abundant metal complexes are scarce. Here, two series of Cu(i) polymers, PMAC-x and PCAAC-x (x = 1-3) have been developed using two kinds of Cu(i)-based carbene-metal-amide (CMA) complexes as side-chain emitter units to combine with a nonconjugated polystyrene backbone. These Cu(i) polymers emit via distinct thermally activated delayed fluorescence or dominant phosphorescence, inherited from the grafted Cu(i)-based CMA units. Particularly, the PMAC-x polymers exhibit high photoluminescence quantum efficiencies of up to 0.78, short emission lifetimes of down to 0.66 µs, and fast radiative rates of up to 106 s-1 in neat films. Thanks to the good encapsulation effect of the polystyrene backbone, these Cu(i) polymers not only demonstrate favorable moisture stability but also show significant aggregation-induced emission. The resultant host-free solution-processed organic light-emitting diodes (OLEDs) achieve outstanding electroluminescence performance with a record external quantum efficiency of 13.8% at a practical luminance of ∼100 nits, representing state-of-the-art device efficiency for metallopolymer-based OLEDs. This work not only presents the first example of CMA polymers but also provides the future direction of polymeric emitters from earth-abundant metal complexes for the OLED application.

12.
Adv Mater ; 36(30): e2402893, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38848582

RESUMO

The ability of water droplets to move freely on superrepellent surfaces is a crucial feature that enables effective liquid repellency. Common superrepellent surfaces allow free motion of droplets in the Cassie state, with the liquid resting on the surface textures. However, liquid impalement into the textures generally leads to a wetting transition to the Wenzel state and droplet immobilization on the surface, thereby destroying the liquid repellency. This study reports the creation of a novel type of superrepellent surface through rational structural control combined with liquid-like surface chemistry, which allows for the free movement of water droplets and effective repellency in both the Cassie and Wenzel states. Theoretical guidelines for designing such surfaces are provided, and experimental results are consistent with theoretical analysis. Furthermore, this work demonstrates the enhanced ice resistance of the dually-mobile superrepellent surfaces, along with their distinctive self-cleaning capability to eliminate internal contaminants. This study expands the understanding of superrepellency and offers new possibilities for the development of repellent surfaces with exceptional anti-wetting properties.

13.
Chronobiol Int ; 41(7): 971-986, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38887932

RESUMO

Recently, research on the circadian rhythm of hypertension has gained popularity. However, few bibliometric analyses have been conducted in this field. In this study, CiteSpace 6.1. R6, VOSviewer 1.6.18, R language (version 4.2.3), R package Bibliometrix (4.1.2), and Microsoft Excel 365 were used to conduct the data mining and knowledge visualization analysis. A total of 1,560 papers from 1,825 institutions in 77 countries were included. Research on the role of circadian rhythms in hypertension is increasing annually. Overall, Chronobiology International published the most literature and Hypertension received the most citations. Ramon Hermida from the Universidade de Vigo in Spain published the most papers and had the most citations. The United States of America and Japan have been the most productive countries. The University of Ferrara, Universidade de Vigo, and the University of California system produced the most publications. Amongst authors, Hermida had the most and longest literature bursts. Keywords such as "chronic kidney disease," "oxidative stress," and "gene expression" have been breakout keywords since 2014. This study revealed the dynamic evolution of research on circadian rhythms in hypertension and provides a knowledge base for researchers.


Assuntos
Bibliometria , Ritmo Circadiano , Hipertensão , Ritmo Circadiano/fisiologia , Humanos , Hipertensão/fisiopatologia
14.
Heliyon ; 10(11): e31819, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38845992

RESUMO

Macrophage pyroptosis plays a significant role in the pathogenesis of various diseases, especially acute lung injury, atherosclerosis, and sepsis. Despite its importance, analysis of the existing literature has been limited. Therefore, we conducted a bibliometric analysis to provide a comprehensive overview of research on macrophage pyroptosis and identify the current research foci and trends in this field. We collected articles related to macrophage pyroptosis published between 2001 and 2022 from the Web of Science Core Collection and PubMed. Citespace, VOSviewer, bibliometrix R package, and Microsoft Excel 2019 were used to analyze co-occurrence relationships and the contribution of countries/regions, institutions, journals, authors, references, and keywords. In total, 1321 papers were included. China and the United States of America published the most articles in this field. TD Kanneganti had the most publications; BT Cookson was the most cited. Although China contributed the most publications, it had a relatively low ratio of multiple-country collaborations (0.132). Among journals, Frontiers in Immunology and Cell Death Disease published the most papers; Nature and the Journal of Immunology were frequently co-cited. Frequently occurring keywords included "inflammation," "NLRP3 inflammasome," "apoptosis," "caspase-1," and "cell death." Moreover, with the advancement of gene editing technology and the integration of clinical applications, novel molecules ("caspases," "GSDMD," "ASC"), programmed cell death topics ("pyroptosis," "ferroptosis," "necrosis"), and clinical applications ("alveolar macrophage," "atherosclerosis," "prognosis") emerged as frontiers. The macrophage pyroptosis field is rapidly evolving and holds promise as a potential target for treating macrophage pyroptosis-related diseases.

15.
Neurosci Lett ; 832: 137800, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38697601

RESUMO

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.


Assuntos
Proteínas de Ciclo Celular , Endorribonucleases , Inflamação , Lipopolissacarídeos , Microglia , Transdução de Sinais , Masculino , Camundongos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Endorribonucleases/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/metabolismo , Resveratrol/administração & dosagem , Proteínas de Ciclo Celular/metabolismo
16.
Sci Rep ; 14(1): 10535, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719907

RESUMO

Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality by analyzing pooled data from 7824 iridocyclitis patients in a Genome-Wide Association Study (GWAS) using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Employing rigorous quality control and comprehensive statistical methods, including sensitivity analyses, we examined the influence of 486 serum metabolites on iridocyclitis. Our MR analysis identified 23 metabolites with significant causal effects on iridocyclitis, comprising 17 known and 6 unidentified metabolites. Further refinement using Cochran's Q test and MR-PRESSO indicated 16 metabolites significantly associated with iridocyclitis risk. LDSC highlighted the heritability of certain metabolites, underscoring genetic influences on their levels. Notably, tryptophan, proline, theobromine, and 7-methylxanthine emerged as risk factors, while 3,4-dihydroxybutyrate appeared protective. These findings enhance our understanding of the metabolic interactions in iridocyclitis, offering insights for diagnosis, unraveling pathophysiological mechanisms, and informing potential avenues for prevention and personalized treatment.


Assuntos
Estudo de Associação Genômica Ampla , Iridociclite , Análise da Randomização Mendeliana , Humanos , Iridociclite/genética , Iridociclite/sangue , Fatores de Risco , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Masculino , Feminino , Predisposição Genética para Doença
17.
Metabolites ; 14(5)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38786766

RESUMO

The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl-tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention.

18.
Environ Pollut ; 351: 124081, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697251

RESUMO

Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.


Assuntos
Quimiocina CXCL1 , Neoplasias Colorretais , Transdução de Sinais , Macrófagos Associados a Tumor , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Humanos , Animais , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Camundongos , Macrófagos Associados a Tumor/metabolismo , Microcistinas/toxicidade , Toxinas Marinhas , Linhagem Celular Tumoral , Progressão da Doença , Proliferação de Células/efeitos dos fármacos , Microambiente Tumoral
19.
Chemistry ; 30(36): e202400817, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38654445

RESUMO

Luminescent organometallic complexes of earth-abundant copper(I) have long been studied in organic light-emitting diodes (OLED). Particularly, Cu(I)-based carbene-metal-amide (CMA) complexes have recently emerged as promising organometallic emitters. However, blue-emitting Cu(I) CMA complexes have been rarely reported. Here we constructed two blue-emitting Cu(I) CMA emitters, MAC*-Cu-CF3Cz and MAC*-Cu-2CF3Cz, by introducing one or two CF3 substitutes into carbazole ligands. Both complexes exhibited high thermal stability and blue emission colors. Moreover, two complexes exhibited different emission origins rooting from different donor ligands: a distinct thermally activated delayed fluorescence (TADF) from ligand-to-ligand charge transfer excited states for MAC*-Cu-CF3Cz or a dominant phosphorescence nature from local triplet excited state of the carbazole ligand for MAC*-Cu-2CF3Cz. Inspiringly, MAC*-Cu-CF3Cz had high photoluminescence quantum yields of up to 94 % and short emission lifetimes of down to 1.2 µs in doped films, accompanied by relatively high radiative rates in the 105 s-1 order. The resultant vacuum-deposited OLEDs based on MAC*-Cu-CF3Cz delivered pure-blue electroluminescence at 462 nm together with a high external quantum efficiency of 13.0 %.

20.
Injury ; 55(6): 111568, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38669890

RESUMO

IMPORTANCE: Most patients use a traditional socket prosthesis (TSP) to ambulate independently following transtibial amputation. However, these patients generally require prosthesis repairs more than twice annually and an entirely new prosthesis every two years. Furthermore, transtibial amputation patients have four times the skin ulceration rate of transfemoral patients, prompting more frequent prosthesis refitting and diminished use. Trans-Tibial osseointegration (TTOI) is a promising technique to address the limitations of TSP, but remains understudied with only four cohorts totaling 41 total procedures reported previously. Continued concerns regarding the risk of infection and questions as to functional capacity postoperatively have slowed adoption of TTOI worldwide. OBJECTIVE: This study reports the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TTOI following traumatic amputation. DESIGN: Retrospective observational cohort study. The cohort consisted of patients with data outcomes collected before and after osseointegration intervention. SETTING: A large, tertiary referral, major metropolitan center. PARTICIPANTS: Twenty-one skeletally mature adults who had failed socket prosthesis rehabilitation, with at least two years of post-osseointegration follow-up. MAIN OUTCOMES AND MEASURES: Mobility was evaluated by K-level, Timed Up and Go (TUG), and Six Minute Walk Test (6MWT). QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and Short Form 36 (SF36). Adverse events included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure. RESULTS: All patients demonstrated statistically significant improvement post osseointegration surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF36 Physical Component Score (p < 0.01 for all). Three patients had four unplanned surgeries: two soft tissue refashionings, and one soft tissue debridement followed eventually by implant removal. No deaths, postoperative systemic complications, more proximal amputations, or periprosthetic fractures occurred. CONCLUSIONS AND RELEVANCE: TTOI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic transtibial amputation. Adverse events are relatively infrequent and not further disabling. Judicious use of TTOI seems reasonable for properly selected patients. LEVEL OF EVIDENCE: 2 (Therapeutic investigation, Observational study with dramatic effect).


Assuntos
Amputação Traumática , Membros Artificiais , Osseointegração , Qualidade de Vida , Tíbia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Amputação Traumática/cirurgia , Amputação Traumática/reabilitação , Seguimentos , Tíbia/cirurgia , Resultado do Tratamento , Desenho de Prótese , Implantação de Prótese
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