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1.
Nanoscale ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39290054

RESUMO

Cooperative wrapping of nanoparticles (NPs) with small sizes is an important pathway for the uptake of NPs by cell membranes. However, the cooperative wrapping efficiency and the effects of NPs' rigidity remain ambiguous. With the aid of computer simulations, we show that the complete wrapping mechanism of cooperative endocytosis is that the aggregation of NPs leads to greater wrapping forces than the single NP case, which triggers the increase of the wrapping degree and in turn further increases the wrapping forces until they are finally fully taken up. The effects of the NP size, initial distance, interaction strength, arrangement and stiffness on cooperative endocytosis were systematically studied. The cooperative wrapping efficiency increases as the NP radius increases. Hexagonal close packed NPs have the highest internalization efficiency. When the interactions are strong, softer NPs exhibit higher endocytosis efficiency. We further propose two strategies by combining NPs with different wrapping properties for targeting applications. By combining two NPs decorated with different types of ligands, the combination NPs can only be fully endocytosed by the cell membrane with two cognate types of receptors and adhere to the normal cell membrane with only one type of receptor. We also design composite NPs using a large NP non-covalently decorated with several small NPs. By harnessing the competition between the ligand-receptor interactions and the excluded volume interactions between the small NPs and the lipid membrane, the composite NPs have targeting ability towards the cancer cell membrane. The design concept of combining NPs with different wrapping properties for drug targeting applications may be very promising in biomedicine.

2.
ACS Nano ; 18(37): 25671-25684, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39223995

RESUMO

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.


Assuntos
Ciclobutanos , Fenóis , Fotoquimioterapia , Fármacos Fotossensibilizantes , Terapia Fototérmica , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Ciclobutanos/química , Ciclobutanos/farmacologia , Fenóis/química , Fenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Animais , Sobrevivência Celular/efeitos dos fármacos , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Substâncias Macromoleculares/síntese química
3.
Front Cell Infect Microbiol ; 14: 1397675, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39268487

RESUMO

Background: The infant gut microbiome's establishment is pivotal for health and immune development. Understanding it unveils insights into growth, development, and maternal microbial interactions. Research often emphasizes gut bacteria, neglecting the phageome. Methods: To investigate the influence of geographic or maternal factors (mode of delivery, mode of breastfeeding, gestational diabetes mellitus) on the gut microbiota and phages of newborns, we collected fecal samples from 34 pairs of mothers and their infants within 24 hours of delivery from three regions (9 pairs from Enshi, 7 pairs from Hohhot, and 18 pairs from Hulunbuir) using sterile containers. Gut microbiota analysis by Shotgun sequencing was subsequently performed. Results: Our results showed that geographic location affects maternal gut microbiology (P < 0.05), while the effect on infant gut microbiology was not significant (P = 0.184). Among the maternal factors, mode of delivery had a significant (P < 0.05) effect on the newborn. Specific bacteria (e.g., Bacteroides, Escherichia spp., Phocaeicola vulgatus, Escherichia coli, Staphylococcus hominis, Veillonella spp.), predicted active metabolites, and bacteriophage vOTUs varied with delivery mode. Phocaeicola vulgatus significantly correlated with some metabolites and bacteriophages in the early infant gut (P < 0.05). In the GD group, a strong negative correlation of phage diversity between mother and infants was observed (R = -0.58, P=0.04). Conclusion: In conclusion, neonatal early gut microbiome (including bacteria and bacteriophages) colonization is profoundly affected by the mode of delivery, and maternal gestational diabetes mellitus. The key bacteria may interact with bacteriophages to influence the levels of specific metabolites. Our study provides new evidence for the study of the infant microbiome, fills a gap in the analysis of the infant gut microbiota regarding the virome, and emphasizes the importance of maternal health for the infant initial gut virome.


Assuntos
Bactérias , Diabetes Gestacional , Fezes , Microbioma Gastrointestinal , Humanos , Diabetes Gestacional/microbiologia , Gravidez , Feminino , Recém-Nascido , Fezes/microbiologia , Fezes/virologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Adulto , Bacteriófagos/genética , Parto Obstétrico , Aleitamento Materno
5.
Inorg Chem ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266252

RESUMO

Pollution of surface water by heavy metal hexavalent chromium ions poses a serious threat to human health; herein, a two-dimensional (2D) cationic breathing Ni-MOF with free nitrate ions between the layers was designed and synthesized according to the characteristics of hexavalent chromium ions, {[Ni(L)2](NO3)2·5H2O}n (L = 1,3,5-tris[4-(imidazol-1-yl)phenyl]benzene). The flexible layer spacing of the 2D breathing Ni-MOF allows the exchange of NO3- by CrO42- without destroying the original structure. Electrostatic and hydrogen bonding interactions between CrO42- and Ni-MOF facilitate its exchange with NO3-. Moreover, CrO42- exhibits a higher binding energy with Ni-MOF compared to NO3-, and the hydrophobic channels of Ni-MOF favor CrO42- trapping due to its lower hydration energy. Consequently, Ni-MOF demonstrates both effective sorption and electrochemical sensing of Cr(VI), achieving a sensitivity of 2.091 µA µM-1 and a detection limit of 0.07 µM.

6.
Sci Total Environ ; 953: 176094, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39244055

RESUMO

Elevated ammonium (NH4-N) contents in groundwater are a global concern, yet the mobilization and enrichment mechanisms controlling NH4-N within riverside aquifers (RAS) remain poorly understood. RAS are important zones for nitrogen cycling and play a vital role in regulating groundwater NH4-N contents. This study conducted an integrated assessment of a hydrochemistry dataset using a combination of hydrochemical analyses and multivariate geostatistical methods to identify hydrochemical compositions and NH4-N distribution in the riverside aquifer within Central Yangtze River Basin, ultimately elucidating potential NH4-N sources and factors controlling NH4-N enrichment in groundwater ammonium hotspots. Compared to rivers, these hotspots exhibited extremely high levels of NH4-N (5.26 mg/L on average), which were mainly geogenic in origin. The results indicated that N-containing organic matter (OM) mineralization, strong reducing condition in groundwater and release of exchangeable NH4-N in sediment are main factors controlling these high concentrations of NH4-N. The Eh representing redox state was the dominant variable affecting NH4-N contents (50.17 % feature importance), with Fe2+ and dissolved organic carbon (DOC) representing OM mineralization as secondary but important variables (26 % and 5.11 % feature importance, respectively). This study proposes a possible causative mechanism for the formation of these groundwater ammonium hotspots in RAS. Larger NH4-N sources through OM mineralization and greater NH4-N storage under strong reducing condition collectively drive NH4-N enrichment in the riverside aquifer. The evolution of depositional environment driven by palaeoclimate and the unique local environment within the RAS likely play vital roles in this process.

7.
Sci Rep ; 14(1): 19356, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169075

RESUMO

This study aims to evaluate the biomechanical performance of the Gamma 3 nail with an anti-rotation screw (GNS) and compare it to two established gold-standard methods for treating unstable femoral neck fractures (UFNFs). Synthetic bone models were prepared with Pauwels' type III osteotomy and an additional posterior wedge. Three different implant configurations were tested: three cannulated crews (3CS) in an inverted triangle configuration, a dynamic hip screw with an anti-rotation screw (DHSS), and GNS. Non-destructive cyclic axial loading was applied at 7° adduction, with 1000 cycles ranging from 100 to 1000 N. Subsequently, a construct failure test was conducted using progressive axial compression, and fracture reduction loss was recorded. The average axial stiffness was 321 ± 52 N/mm for 3CS, 430 ± 71 N/mm for DHSS, and 519 ± 104 N/mm for GNS. The average ultimate failure loads were 2699.3 N for 3CS, 3427.1 N for DHSS, and 3758.9 N for GNS. GNS demonstrated significantly greater axial stiffness compared to the other two groups (P < 0.05). Both DHSS and GNS exhibited similar failure loading, which were greater than those of 3CS (P < 0.05). GNS offers the advantages of a minimally invasive and intramedullary implant with comparable stability to the DHSS system. Moreover, GNS demonstrated superior biomechanical performance compared to 3 CS configuration.


Assuntos
Pinos Ortopédicos , Parafusos Ósseos , Fraturas do Colo Femoral , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/fisiopatologia , Humanos , Fenômenos Biomecânicos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação
8.
Soft Robot ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140862

RESUMO

Due to their exceptional adaptability, inherent compliance, and high flexibility, soft actuators have significant advantages over traditional rigid actuators in human-machine interaction and in grasping irregular or fragile objects. Most existing soft actuators are designed using preprogramming methods, which schedule complex motions into flexible structures by correctly designing deformation constraints. These constraints restrict undesired deformation, allowing the actuator to achieve the preprogrammed motion when stimulated. Therefore, these actuators can only achieve a certain type of motion, such as extension, bending, or twisting, since it is impossible to adjust the deformation constraints once they are embedded into the structures. In this study, we propose the use of variable stiffness materials, such as shape memory polymer (SMP), in the structural design of soft actuators to achieve variable stiffness constraints. A reconfigurable soft helical actuator with a variable stiffness skeleton is developed based on this concept. The skeleton, made of SMP, is encased at the bottom of a fiber-reinforced chamber. In its high-stiffness state, the SMP constrains the deformation toward the skeleton when the actuator is pressurized. This constraint is removed once the SMP skeleton is heated, endowing the actuator with the ability to switch between bending and helical motion in real-time. A theoretical model is proposed to predict the behavior of the actuator when driven by pressure, and experiments are conducted to verify the model's accuracy. In addition, the influence of different design parameters is investigated based on experimental results, providing reference guidelines for the design of the actuator.

9.
Nat Commun ; 15(1): 6823, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122704

RESUMO

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.


Assuntos
Diarreia , Probióticos , Humanos , Diarreia/microbiologia , Diarreia/terapia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Método Duplo-Cego , Masculino , Adulto Jovem , Adulto , Feminino , Doença Crônica , Resultado do Tratamento , Lactobacillus plantarum , Adolescente
10.
Gut Microbes ; 16(1): 2395092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39189588

RESUMO

Chronic diarrhea has a considerable impact on quality of life. This randomized, double-blind, placebo-controlled crossover intervention trial was conducted with 69 participants (36 in Group A, 33 in Group B), aiming to investigate the potential of postbiotics in alleviating diarrhea-associated symptoms. Participants received postbiotic Probio-Eco® and placebo for 21 days each in alternating order, with a 14-day washout period between interventions. The results showed that postbiotic intake resulted in significant improvements in Bristol stool scale score, defecation frequency, urgency, and anxiety. Moreover, the postbiotic intervention increased beneficial intestinal bacteria, including Dysosmobacter welbionis and Faecalibacterium prausnitzii, while reducing potential pathogens like Megamonas funiformis. The levels of gut Microviridae notably increased. Non-targeted metabolomics analysis revealed postbiotic-driven enrichment of beneficial metabolites, including α-linolenic acid and p-methoxycinnamic acid, and reduction of diarrhea-associated metabolites, including theophylline, piperine, capsaicin, and phenylalanine. Targeted metabolomics confirmed a significant increase in fecal butyric acid after postbiotic intervention. The levels of aromatic amino acids, phenylalanine and tryptophan, and their related metabolites, 5-hydroxytryptophan and kynurenine, decreased after the postbiotic intervention, suggesting diarrhea alleviation was through modulating the tryptophan-5-hydroxytryptamine and tryptophan-kynurenine pathways. Additionally, chenodeoxycholic acid, a diarrhea-linked primary bile acid, decreased substantially. In conclusion, postbiotics have shown promise in relieving chronic diarrhea.


Assuntos
Estudos Cross-Over , Diarreia , Fezes , Microbioma Gastrointestinal , Humanos , Diarreia/microbiologia , Diarreia/metabolismo , Diarreia/terapia , Método Duplo-Cego , Masculino , Feminino , Adulto Jovem , Adulto , Doença Crônica , Fezes/microbiologia , Fezes/química , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Probióticos/administração & dosagem , Qualidade de Vida
11.
Vascul Pharmacol ; 156: 107417, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39159737

RESUMO

Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of these disorders. Alterations in mitochondrial homeostasis have been reported to be involved in the pathogenesis of various cardiovascular diseases (CVDs). In this regard, perturbations to mitochondrial dynamics leading to impaired clearance of dysfunctional mitochondria have been previously established to be a crucial trigger for MI/HF. In this study, we found that MI patients could be classified into three clusters based on the expression levels of mitophagy-related genes and consensus clustering. We identified a mitophagy-related diagnostic 5-genes signature for MI using support vector machines-Recursive Feature Elimination (SVM-RFE) and random forest, with the area under the ROC curve (AUC) value of the predictive model at 0.813. Additionally, the single-cell transcriptome and pseudo-time analyses showed that the mitoscore was significantly upregulated in macrophages, endothelial cells, pericytes, fibroblasts and monocytes in patients with ischemic cardiomyopathy, while sequestosome 1 (SQSTM1) exhibited remarkable increase in the infarcted (ICM) and non-infarcted (ICMN) myocardium samples dissected from the left ventricle compared with control samples. Lastly, through analysis of peripheral blood from MI patients, we found that the expression of SQSTM1 is positively correlated with troponin-T (P < 0.0001, R = 0.4195, R2 = 0.1759). Therefore, this study provides the rationale for a cell-specific mitophagy-related gene signature as an additional supporting diagnostic for CVDs.


Assuntos
Perfilação da Expressão Gênica , Mitofagia , Infarto do Miocárdio , Valor Preditivo dos Testes , Transcriptoma , Mitofagia/genética , Humanos , Infarto do Miocárdio/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/genética , Idoso , Máquina de Vetores de Suporte , Marcadores Genéticos , Estudos de Casos e Controles
12.
ACS Appl Mater Interfaces ; 16(36): 48094-48102, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39189509

RESUMO

Lead halide perovskite anion exchange reactions tend to be spontaneous and rapid. To achieve precise control of anion exchange and modulate the bandgaps of perovskites to meet the demands in full-color displays, a laser-induced liquid-phase anion exchange method is developed in this paper. CsPbBr3 perovskites embedded in a polymer matrix are converted to CsPb(BrxCl1-x)3 and CsPb(BrxI1-x)3 perovskites, realizing the shift from green fluorescence to blue and red fluorescence. By changing the laser parameters, the anion exchange extent and luminescence wavelength are precisely tuned, with the maximum tuning wavelength range of 431-696 nm. Due to the focusing properties of the laser, the spatial position of anion exchange can be precisely controlled, which is significant for realizing fast and accurate patterning without masks. Based on this method, blue patterns with different light-emitting wavelengths are fabricated. RGB three-color patterns on a single perovskite composite film are successfully prepared by further replacement of halogen ions. More importantly, the polymer matrix provides ultraflexibility and good stability for the films; even if the composite films are arbitrarily folded or repeatedly bent, they can still maintain good luminous intensity. This method will show great potential in the field of flexible, full-color displays.

13.
Adv Exp Med Biol ; 1445: 47-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967749

RESUMO

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.


Assuntos
Regulação da Expressão Gênica , Imunoglobulinas , Transcrição Gênica , Humanos , Animais , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Rearranjo Gênico , Linfócitos B/metabolismo , Linfócitos B/imunologia
14.
Endocrine ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982023

RESUMO

BACKGROUND: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. AIMS: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). METHODS: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. RESULTS: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). CONCLUSIONS: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

15.
Nat Commun ; 15(1): 6317, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060314

RESUMO

Aerosol jet printing has the potential to fabricate fine features on various substrates due to its large stand-off distance. However, the presence of overspray and instability, particularly at high printing resolutions, has limited its widespread application. In this study, we introduce an efficient approach called annular acoustic focusing for aerosol jet printing. By determining the optimal focusing frequency (5.8 MHz) for silver nanoparticles using a particle ejection model, we achieve precise and stable printing. We also propose a modified print nozzle geometry, resulting in ultrafine traces (line width < 6 µm, overspray < 0.1 µm). Compared to printing without acoustic focusing, the line width of the traces decreases to 60 ± 5% while their conductivity increases to 180 ± 5%. Additionally, several 8 h experiments demonstrate excellent printing stability. This research opens up possibilities for the fabrication of conformal electronics with high precision and improved conductivity using aerosol jet printing.

16.
Small ; : e2401020, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012061

RESUMO

Scaffolds have garnered considerable attention for enhancing neural repairment for spinal cord injury (SCI) treatment. Both microstructural features and biochemical modifications play pivotal roles in influencing the interaction of cells with the scaffold, thereby affecting tissue regeneration. Here, a scaffold is designed with spiral structure and gradient peptide modification (GS) specifically for SCI treatment. The spiral structure provides crucial support and space, while the gradient peptide isoleucine-lysine-valine-alanine-valine (IKVAV) modification imparts directional guidance for neuronal and axonal extension. GS scaffold shows a significant nerve extension induction effect through its interlayer gap and gradient peptide density to dorsal root ganglia in vitro, while in vivo studies reveal its substantial promotion for functional recovery and neural repair. Additionally, the GS scaffold displays impressive drug-loading capacity, mesenchymal stem cell-derived exosomes can be efficiently loaded into the GS scaffold and delivered to the injury site, thereby synergistically promoting SCI repair. Overall, the GS scaffold can serve as a versatile platform and present a promising multifunctional approach for SCI treatment.

17.
JACC Basic Transl Sci ; 9(5): 557-573, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38984045

RESUMO

Recent evidence demonstrates that low engraftment rates limit the efficacy of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac repair after myocardial infarction. In this study, we attempted to overcome this limitation by enhancing the proliferative capacity of transplanted hiPSC-CMs. We found that miR-590-3p overexpression increased the proliferative capacity of hiPSC-CMs. miR-590-3p overexpression increased the number of engrafted cells and had a higher efficacy for myocardial repair than control cells. Moreover, we confirmed the safety of using miR-590-3p-overexpressing hiPSC-CMs in pig hearts. These results indicated that miR-590-3p overexpression stimulated hiPSC-CM cell cycle re-entry to induce cell proliferation and increased the therapeutic efficacy in MI.

18.
J Neurointerv Surg ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39084858

RESUMO

BACKGROUND: Hyperperfusion-induced cerebral hemorrhage (HICH) is a rare but severe complication in patients with carotid stenosis undergoing stent placement for which predictive models are lacking. Our objective was to develop a nomogram to predict such risk. METHODS: We included a total of 1226 patients with carotid stenosis who underwent stenting between June 2015 and December 2022 from three medical centers, divided into a development cohort of 883 patients and a validation cohort of 343 patients. The model used LASSO regression for feature optimization and multivariable logistic regression to develop the predictive model. Model accuracy was assessed via the receiver operating characteristic curve, with further evaluation of calibration and clinical utility through calibration curves and decision curve analysis (DCA). The model underwent internal validation using bootstrapping and external validation with the validation cohort. RESULTS: Older age (OR 1.07, p=0.005), higher degrees of carotid stenosis (OR 1.07, p=0.006), poor collateral circulation (OR 6.26, p<0.001), elevated preoperative triglyceride levels (OR 1.27, p=0.041) and neutrophil counts (OR 1.36, p<0.001) were identified as independent risk factors for HICH during hospitalization. The nomogram constructed based on these predictive factors demonstrated an area under the curve (AUC) of 0.817. The AUCs for internal and external validation were 0.809 and 0.783, respectively. Calibration curves indicated good model fit, and DCA confirmed substantial clinical net benefit in both cohorts. CONCLUSION: We developed and validated a nomogram to predict HICH in patients with carotid stenosis post-stenting, facilitating early identification and preventive intervention in high-risk individuals.

19.
Hum Cell ; 37(5): 1446-1461, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39014290

RESUMO

Cervical cancer poses a significant health burden for women globally, and the rapid proliferation of cervical cancer cells greatly worsens patient prognosis. Long non-coding RNAs (lncRNAs) play a crucial role in regulating tumor cell proliferation. However, the involvement of lncRNAs in cervical cancer cell proliferation remains unclear. In this study, we investigated the lncRNA SIX1-1, which was found to be upregulated in cervical cancer tissues and cell lines. Functional assays revealed that knockdown of SIX1-1 inhibited cell proliferation in vitro and reduced tumor growth in vivo. Mechanistically, SIX1-1 was predominantly localized in the nucleus and could bind with DNMT1 protein. The expression of SIX1-1 enhanced the interaction of DNMT1 with RASD1 promoter, leading to the methylation of the promoter and decreased mRNA transcription. Then RASD1 downregulation activated the cAMP/PKA/CREB signaling pathway, promoting cell proliferation. Rescue experiments showed that knockdown of RASD1 restored the inhibited cell proliferation caused by decreased expression of SIX1-1, indicating that RASD1 acted as the functional mediator of SIX1-1. In conclusion, SIX1-1 promoted cervical cancer cell proliferation by modulating RASD1 expression. This suggests that targeting the SIX1-1/RASD1 axis could be a potential antitumor strategy for cervical cancer.


Assuntos
Proliferação de Células , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Humanos , Proliferação de Células/genética , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular Tumoral , Transcrição Gênica/genética , Transdução de Sinais/genética , Proteínas ras/genética , Proteínas ras/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Expressão Gênica/genética
20.
J Affect Disord ; 363: 239-248, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39038625

RESUMO

With increasing prevalence rate of depression by years, more attention has been paid to the influence of environmental pollutants on depression, but relationship between exposure to volatile organic compounds (VOCs) and depression is rarely studied. Therefore, this cross-sectional study use the National Center for Health Statistics (NHANES) database (2013-2016 years) to explore association between exposure to multiple VOCs and depression in general population. Multiple linear and logistic regression models were used to analyze the association between urinary VOC metabolism (mVOCs) and depression. To further analyze effect of multiple mVOCs mixed exposure, Bayesian kernel machine regression (BKMR) models were performed. A total of 3240 participants and 16 mVOCs were included in the analysis. Results showed that 10 mVOCs exposure were positively correlated with depression by multiple linear and logistic regression models, especially CYMA and MHBMA3, which also showed significant positive association with depression in BKMR model. Mixed exposure of multiple mVOCs was significantly positively correlated with depression. Gender differences were existed in effects of some VOCs concentrations on depression. AAMA, CYMA and MA had significant positive correlations with depression by women, and DHBMA had significant positive correlations with depression by men. Hence, this study showed that exposing to VOCs might have negative impacts on depression, and impact of CYMA and MHBMA3 on depression may be more evident, which provide new ideas for prevention and control of depression. But further research and exploration are needed to clarify the mechanism and influence factors of this relationship, to demonstrate the reliability of these relationship.


Assuntos
Depressão , Compostos Orgânicos Voláteis , Humanos , Masculino , Feminino , Compostos Orgânicos Voláteis/urina , Compostos Orgânicos Voláteis/efeitos adversos , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Depressão/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Teorema de Bayes , Inquéritos Nutricionais , Fatores Sexuais
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