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1.
J Chem Theory Comput ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747149

ABSTRACT

The field of computer-aided synthesis planning (CASP) has witnessed significant growth in recent years. Still, many CASP programs rely on large data sets to train neural networks, resulting in limitations due to the data quality and prior knowledge from chemists. In response, we propose Retrosynthesis Zero (ReSynZ), a reaction template-based method that combines Monte Carlo Tree Search with reinforcement learning inspired by AlphaGo Zero. Unlike other single-step reaction template-based CASP methods, ReSynZ takes complete synthesis paths for complex molecules, determined by reaction rules, as input for training the neural network. ReSynZ enables neural networks trained with relatively small reaction data sets (tens of thousands of data) to generate multiple synthesis pathways for a target molecule and suggest possible reaction conditions. On multiple data sets of molecular retrosynthesis, ReSynZ demonstrates excellent predictive performance compared to existing algorithms. The advantages, such as self-improving model features, flexible reward settings, the potential to surpass human limitations in chemical synthesis route planning, and others, make ReSynZ a valuable tool in chemical synthesis design.

2.
Nano Lett ; 24(19): 5831-5837, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38708822

ABSTRACT

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

3.
J Am Chem Soc ; 146(19): 13488-13498, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38709095

ABSTRACT

Self-assembling peptides represent a captivating area of study in nanotechnology and biomaterials. This interest is largely driven by their unique properties and the vast application potential across various fields such as catalytic functions. However, design complexities, including high-dimensional sequence space and structural diversity, pose significant challenges in the study of such systems. In this work, we explored the possibility of self-assembled peptides to catalyze the hydrolysis of hydrosilane for hydrogen production using ab initio calculations and carried out wet-lab experiments to confirm the feasibility of these catalytic reactions under ambient conditions. Further, we delved into the nuanced interplay between sequence, structural conformation, and catalytic activity by combining modeling with experimental techniques such as transmission electron microscopy and nuclear magnetic resonance and proposed a dual mode of the microstructure of the catalytic center. Our results reveal that although research in this area is still at an early stage, the development of self-assembled peptide catalysts for hydrogen production has the potential to provide a more sustainable and efficient alternative to conventional hydrogen production methods. In addition, this work also demonstrates that a computation-driven rational design supplemented by experimental validation is an effective protocol for conducting research on functional self-assembled peptides.


Subject(s)
Hydrogen , Peptides , Hydrogen/chemistry , Catalysis , Peptides/chemistry , Models, Molecular , Hydrolysis
4.
Food Chem X ; 22: 101404, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38707784

ABSTRACT

2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP) is one of the higher levels of HAAs produced in protein foods during heating. The effects of heating temperature, time, and concentration of precursors on PhIP and related substances in the chemical model system and roast pork patty were studied using HPLC-Q-Orbitrap-HRMS and GC-MS. Results showed that the heating temperature, time, and concentration of four precursors significantly affected PhIP and its related substances (P < 0.05) in the chemical model system. Among them, PhIP production was greatest when heating at 200 min with 220 °C, and the concentrations of phenylalanine, creatinine, glucose, and creatine added were 10, 20, 20, and 20 mmol/L, respectively. Moreover, as the fat proportion of roast pork patties increased, PhIP and its intermediate-phenylacetaldehyde concentrations increased substantially (P < 0.05). PCA results showed that the samples of PhIP and related substances gradually dispersed as the temperature and time increased, and there were obvious effects among them.

5.
World J Orthop ; 15(3): 215-229, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38596190

ABSTRACT

BACKGROUND: In recent years, the use of Magnesium alloy implants have gained renewed popularity, especially after the first commercially available Conformité Européenne approved Magnesium implant became available (MAGNEZIX® CS, Syntellix) in 2013. AIM: To document our clinical and radiographical outcomes using magnesium implants in treating peri-articular elbow fractures. METHODS: Our paper was based on a retrospective case series design. Intra-operatively, a standardized surgical technique was utilized for insertion of the magnesium implants. Post - operatively, clinic visits were standardized and physical exam findings, functional scores, and radiographs were obtained at each visit. All complications were recorded. RESULTS: Five patients with 6 fractures were recruited (2 coronoid, 3 radial head and 1 capitellum). The mean patient age and length of follow up was 54.6 years and 11 months respectively. All fractures healed, and none exhibited loss of reduction or complications requiring revision surgery. No patient developed synovitis of the elbow joint or suffered electrolytic reactions when titanium implants were used concurrently. CONCLUSION: Although there is still a paucity of literature available on the subject and further studies are required, magnesium implants appear to be a feasible tool for fixation of peri-articular elbow fractures with promising results in our series.

6.
Biomed Phys Eng Express ; 10(4)2024 May 14.
Article in English | MEDLINE | ID: mdl-38670076

ABSTRACT

In this paper, we propose a novel multi-scale 3D-CRU model, with the goal of extracting more discriminative emotion feature from EEG signals. By concurrently exploiting the relative electrode locations and different frequency subbands of EEG signals, a three-dimensional feature representation is reconstructed wherein the Delta (δ) frequency pattern is included. We employ a multi-scale approach, termed 3D-CRU, to concurrently extract frequency and spatial features at varying levels of granularity within each time segment. In the proposed 3D-CRU, we introduce a multi-scale 3D Convolutional Neural Network (3D-CNN) to effectively capture discriminative information embedded within the 3D feature representation. To model the temporal dynamics across consecutive time segments, we incorporate a Gated Recurrent Unit (GRU) module to extract temporal representations from the time series of combined frequency-spatial features. Ultimately, the 3D-CRU model yields a global feature representation, encompassing comprehensive information across time, frequency, and spatial domains. Numerous experimental assessments conducted on publicly available DEAP and SEED databases provide empirical evidence supporting the enhanced performance of our proposed model in the domain of emotion recognition. These findings underscore the efficacy of the features extracted by the proposed multi-scale 3D-GRU model, particularly with the incorporation of the Delta (δ) frequency pattern. Specifically, on the DEAP dataset, the accuracy of Valence and Arousal are 93.12% and 94.31%, respectively, while on the SEED dataset, the accuracy is 92.25%.


Subject(s)
Electroencephalography , Emotions , Neural Networks, Computer , Signal Processing, Computer-Assisted , Humans , Electroencephalography/methods , Algorithms , Brain/physiology , Brain/diagnostic imaging , Databases, Factual
7.
Int J Mol Sci ; 25(7)2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38612440

ABSTRACT

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.


Subject(s)
Arabidopsis , Morus , Salt Tolerance/genetics , Morus/genetics , Plant Breeding , Salt Stress , Agriculture , Plants, Genetically Modified
8.
Food Chem X ; 22: 101361, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38633738

ABSTRACT

The changes in the qualities and sweet-substance levels of Junzao jujube during variable-temperature drying (VTD) were investigated. The results showed that VTD retains the original color of jujube, reduces its hardness and chewiness, and decreases its wrinkling while shortening the drying time by 13.2% compared with that of constant temperature drying (CTD). "Electronic-tongue" taste analysis showed that the sweetness of VTD jujube is significantly higher than that for CTD. This is shown to be related to the contents of sucrose, fructose, and glucose, as well as the activities of invertase and sucrose synthase enzymes. In addition, the content trends for sweet amino acids are correlated with the temperature gradient used in VTD. Thus, the present study elucidates the factors governing the transformation of sugar substances in jujube during VTD, as well as providing a practical reference for the application of VTD in the jujube industry.

9.
Article in English | MEDLINE | ID: mdl-38676843

ABSTRACT

PURPOSE: Male cancer survivors experience confusion about fertility following cancer treatment. The aims of this study were to evaluate survivors' semen quality in different tumor type groups in China and to analyze the current situation and challenges of male cancer patients with sperm cryopreservation. METHODS: This was a multicenter retrospective study of male patients with cancer who underwent sperm cryopreservation in 16 regions of the national sperm banks over an 11-year period from 2010 to 2020. RESULTS: The number of male cancer patients with sperm cryopreservation showed an overall upward trend. The development of male cancer fertility preservation (FP) in the eastern, central, and western regions of Chinese displayed imbalance. There are seven tumor types for sperm preservation in the top incidence ten tumor types, including lymphoma, leukemia, nasopharyngeal carcinoma, sarcoma, thyroid cancer, and brain tumor. Moreover, nasopharyngeal carcinoma is a high incidence rate in China, which is related to high sperm preservation rate, different from other countries. The most percentage of males receiving sperm cryopreservation in the testicular cancers (15-39 years old) of China in 2020 was 5.55%, 1.29% in the lymphoma, and 0.39% in the leukemia. According to the type of cancer, a statistically significant lower pre-sperm density, total sperm output, and post-sperm density was observed in testicular cancers. It is worth noting that the prevalence of azoospermia 22.2% in leukemia patients attribute to urgent treatment before sperm cryopreservation. Disposition of cryopreserved sperm categories included continued storage (47.2%), discarded (9%), death (0.9%), and use (3.7%). CONCLUSION: This study provides the first comprehensive national statistical census and review of fertility preservation in male cancer patients with respect to trends, prevalence, and cancer types. The development of male cancer fertility preservation in China is imbalanced and percentage of males receiving sperm cryopreservation in the adolescent and young adult cancers was low. Sixteen human sperm banks from China analyze current problems and challenges, and then prioritize steps toward the achievement of the FP strategy framework for Healthy China 2030.

10.
Cell Death Dis ; 15(4): 295, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664392

ABSTRACT

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.


Subject(s)
Adenocarcinoma of Lung , Disease Progression , Lung Neoplasms , MAP Kinase Signaling System , Membrane Proteins , STAT3 Transcription Factor , Vascular Endothelial Growth Factor A , Animals , Female , Humans , Male , Mice , Middle Aged , A549 Cells , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/genetics , STAT3 Transcription Factor/metabolism , Vascular Endothelial Growth Factor A/metabolism
11.
Food Chem X ; 22: 101357, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38623517

ABSTRACT

The combination of pretreatment and vacuum freeze-drying (VFD) technology is an effective technique for extending the shelf life of apricots, reducing costs and energy consumption. However, the impact of pretreatment on the freeze-drying and quality characteristics of apricots is still unclear. The effects of ultrasound (US), freeze-thaw (FT), and their combination (FT-US) on water migration and quality characteristics of apricot slices on VFD were studied. LR-NMR and SEM showed that pretreatment significantly reduced the time (19.05%-33.33%) and energy consumption (17.67%-35.66%) of the VFD process. Compared with the control group, the US, FT, and FT-US improved the color, texture, rehydration ability, and flavor of apricot slices. Among them, FT-US retained the most biologically active substances and antioxidant capacity, with the highest sensory score. Overall, FT-US pretreatment induced changes in the microstructure and chemistry of apricots, which contributed to the production of high-quality VFD apricot slices.

12.
Ann Nutr Metab ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38631305

ABSTRACT

BACKGROUND: A major risk factor for neurodegenerative disorders is old age. Nutritional interventions that delay aging, such as calorie restriction (CR) and intermittent fasting (IF), as well as pharmaceuticals that affect the pathways linking nutrition and aging processes, have been developed in recent decades and have been shown to alleviate the effects of aging on the brain. SUMMARY: CR is accomplished by alternating periods of ad libitum feeding and fasting. In animal models, IF has been shown to increase lifespan and slow the progression and severity of age-related pathologies such as cardiovascular and neurodegenerative diseases and cancer. According to recent research, dietary changes can help older people with dementia retain brain function. However, the mechanisms underlying the neuroprotective effect of IF on the aging brain and related questions in this area of study (i.e., the potential of IF to treat neurodegenerative disorders) remain to be examined. KEY MESSAGES: This review addresses the hypothesis that IF may have translational potential in protecting the aged brain while summarizing the research supporting the putative neuroprotective mechanisms of IF in animal models. Additionally, given the emerging understanding of the connection between aging and dementia, our investigations may offer a fresh perspective on the use of dietary interventions for enhancing brain function and preventing dementia in elderly individuals. Finally, the absence of guidelines regarding the application of IF in patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge of the long-term effects of IF on dementia before it can be widely prescribed. In conclusion, IF may be an ancillary intervention for preserving memory and cognition in elderly individuals.

13.
Angew Chem Int Ed Engl ; : e202405255, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682659

ABSTRACT

Precise regulation of the active site structure is an important means to enhance the activity and selectivity of catalysts in CO2 electroreduction. Here, we creatively introduce anionic groups, which can not only stabilize metal sites with strong coordination ability but also have rich interactions with protons at active sites to modify the electronic structure and proton transfer process of catalysts. This strategy helps to convert CO2 into fuel chemicals at low overpotentials. As a typical example, a composite catalyst, CuO/Cu-NSO4/CN, with highly dispersed Cu(II)-SO4 sites has been reported, in which CO2 electroreduction to formate occurs at a low overpotential with a high Faradaic efficiency (-0.5 V vs. RHE, FEHCOO-=87.4%). Pure HCOOH is produced with an energy conversion efficiency of 44.3% at a cell voltage of 2.8 V. Theoretical modeling demonstrates that sulfate promotes CO2 transformation into a carboxyl intermediate followed by HCOOH generation, whose mechanism is significantly different from that of the traditional process via a formate intermediate for HCOOH production.

14.
Front Endocrinol (Lausanne) ; 15: 1379607, 2024.
Article in English | MEDLINE | ID: mdl-38686204

ABSTRACT

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.


Subject(s)
Biliary Tract Neoplasms , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Thyroxine , Humans , Biliary Tract Neoplasms/genetics , Biliary Tract Neoplasms/blood , Biliary Tract Neoplasms/epidemiology , Biliary Tract Neoplasms/prevention & control , Thyroxine/blood , Mediation Analysis , Risk Factors , Hypothyroidism/genetics , Hypothyroidism/blood , Female , Male , Hyperthyroidism/genetics , Hyperthyroidism/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/prevention & control , Carcinoma, Hepatocellular/etiology
15.
Eur J Pharmacol ; 972: 176553, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38574838

ABSTRACT

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.


Subject(s)
Benzamides , Ferroptosis , Microglia , NF-E2-Related Factor 2 , Pyrroles , Reperfusion Injury , Animals , Ferroptosis/drug effects , NF-E2-Related Factor 2/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Mice , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Male , Mice, Inbred C57BL , Signal Transduction/drug effects , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Neuroprotective Agents/pharmacology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Cell Nucleus/metabolism , Cell Nucleus/drug effects , Disease Models, Animal , Brain Ischemia/metabolism , Brain Ischemia/drug therapy , Brain Ischemia/pathology , Cell Line , Active Transport, Cell Nucleus/drug effects
16.
Chem Biodivers ; : e202400507, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606561

ABSTRACT

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.

17.
Cell Signal ; 119: 111182, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38640983

ABSTRACT

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.


Subject(s)
Breast Neoplasms , Cancer-Associated Fibroblasts , Cell Movement , Epithelial-Mesenchymal Transition , Exosomes , Gene Expression Regulation, Neoplastic , MicroRNAs , Neoplasm Invasiveness , MicroRNAs/metabolism , MicroRNAs/genetics , Humans , Exosomes/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Female , Animals , Mice , Cell Line, Tumor , Mice, Nude , Mice, Inbred BALB C , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , Carrier Proteins/metabolism , Carrier Proteins/genetics , Neoplasm Metastasis , Twist-Related Protein 1/metabolism , Twist-Related Protein 1/genetics , RNA-Binding Proteins/metabolism
18.
ACS Appl Mater Interfaces ; 16(17): 22055-22065, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38636080

ABSTRACT

Nb2O5 has been viewed as a promising anode material for lithium-ion batteries by virtue of its appropriate redox potential and high theoretical capacity. However, it suffers from poor electric conductivity and low ion diffusivity. Herein, we demonstrate the controllable fabrication of Cu-doped Nb2O5 with orthorhombic (T-Nb2O5) and monoclinic (H-Nb2O5) phases through annealing the solvothermally presynthesized Nb2O5 precursor under different temperatures in air, and the Cu doping amount can be readily controlled by the concentration of the precursor solution, whose effect on the lithium storage behaviors of the Cu-doped Nb2O5 is thoroughly investigated. H-Nb2O5 shows obvious redox peaks (Nb5+/Nb4+ and Nb4+/Nb3+) with much higher capacity and better cycling stability than those for the widely investigated T-Nb2O5. When introducing appropriate Cu doping, the optimized H-Cu0.1-Nb2O5 electrode shows greatly enhanced conductivity and lower diffusion barrier as revealed by the theoretical calculations and electrochemical characterizations, delivering a high reversible capacity of 203.6 mAh g-1 and a high capacity retention of 140.8 mAh g-1 after 5000 cycles at 1 A g-1, with a high initial Coulombic efficiency of 91% and a high rate capacity of 144.2 mAh g-1 at 4 A g-1. As a demonstration for full-cell application, the H-Cu0.1-Nb2O5||LiFePO4 cell displays good cycling performance, exhibiting a reversible capacity of 135 mAh g-1 after 200 cycles at 0.2 A g-1. More importantly, this work offers a new synthesis protocol of the monoclinic Nb2O5 phase with high capacity retention and improved reaction kinetics.

19.
Adv Sci (Weinh) ; : e2307487, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520715

ABSTRACT

Collective cells, a typical active matter system, exhibit complex coordinated behaviors fundamental for various developmental and physiological processes. The present work discovers a collective radial ordered migration behavior of NIH3T3 fibroblasts that depends on persistent top-down regulation with 2D spatial confinement. Remarkably, individual cells move in a weak-oriented, diffusive-like rather than strong-oriented ballistic manner. Despite this, the collective movement is spatiotemporal heterogeneous and radial ordering at supracellular scale, manifesting as a radial ordered wavefront originated from the boundary and propagated toward the center of pattern. Combining bottom-up cell-to-extracellular matrix (ECM) interaction strategy, numerical simulations based on a developed mechanical model well reproduce and explain above observations. The model further predicts the independence of geometric features on this ordering behavior, which is validated by experiments. These results together indicate such radial ordered collective migration is ascribed to the couple of top-down regulation with spatial restriction and bottom-up cellular endogenous nature.

20.
Micromachines (Basel) ; 15(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38542585

ABSTRACT

Technological advancements across various sectors are driving a growing demand for large-scale three-degree-of-freedom micro-nano positioning platforms, with substantial pressure to reduce footprints while enhancing motion range and accuracy. This study proposes a three-prismatic-revolute-revolute (3-PRR) parallel mechanism based on biomimetic variable-diameter helical flexible hinges. The resulting platform achieves high-precision planar motion along the X- and Y-axes, a centimeter-level translation range, and a rotational range of 35° around the Z-axis by integrating six variable-diameter flexible helical hinges that serve as rotational joints when actuated by three miniature linear servo drives. The drives are directly connected to the moving platform, thereby enhancing the compactness of the system. A kinematic model of the motion platform was established, and the accuracy and effectiveness of the forward and inverse kinematic solutions were validated using finite element analysis. Finally, a prototype of the 3-PRR parallel platform was fabricated, and its kinematic performance was experimentally verified visually for improved endpoint displacement detection. The assessment results revealed a maximum displacement error of 9.5% and confirmed that, judging by its favorable workspace-to-footprint ratio, the final system is significantly more compact than those reported in the literature.

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