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1.
J Biol Chem ; : 107256, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569937

RESUMO

Transforming growth factor ß (TGF-ß) is a pleiotropic cytokine that is widely distributed throughout the body. Its receptor proteins, TGF-ß type I and type II receptors, are also ubiquitously expressed. Therefore, the regulation of various signaling outputs in a context-dependent manner is a critical issue in this field. Smad proteins were originally identified as signal-activated transcription factors similar to signal transducer and activator of transcription proteins. Smads are activated by serine phosphorylation mediated by intrinsic receptor dual specificity kinases of the TGF-ß family, indicating that Smads are receptor-restricted effector molecules downstream of ligands of the TGF-ß family. Smad proteins have other functions in addition to transcriptional regulation, including post-transcriptional regulation of micro-RNA processing, pre-mRNA splicing, and m6A methylation. Recent technical advances have identified a novel landscape of Smad-dependent signal transduction, including regulation of mitochondrial function without involving regulation of gene expression. Therefore, Smad proteins are receptor-activated transcription factors and also act as intracellular signaling modulators with multiple modes of function. In this review, we discuss the role of Smad proteins as receptor-activated transcription factors and beyond. We also describe the functional differences between Smad2 and Smad3, two receptor-activated Smad proteins downstream of TGF-ß, activin, myostatin, growth and differentiation factor (GDF) 11, and Nodal.

2.
J Colloid Interface Sci ; 664: 423-432, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484511

RESUMO

Prussian Blue analogs (PBAs) are a suitable aqueous zinc-ion batteries (AZIBs) cathode material, but they face issues related to low specific capacity and cycling lifespan due to insufficient active sites and poor ion de-intercalation structural stability. In this study, Mn-Prussian Blue Analog (Mn-PBA) is fabricated using a simple co-precipitation method and the morphology of Mn-PBA is further optimized through artificially manipulating concentration gradients strategy, effectively enhancing the structural stability of Zn2+ de-intercalation. Furthermore, the introduction of Mn established dual Zn2+ active centers in Mn-PBA (Mn-O and Fe(CN)6]4-/[Fe(CN)6]3-), leading to an increased specific capacity. As a proof of concept for AZIBs, the optimized Mn-PBA-3 cathode exhibits a high reversible specific capacity of 143.5 mAh/g and maintains a capacity retention of 88.5 % after 250 cycles at 1 A/g, surpassing commercial MnO2 (30.5 mAh/g after 100 cycles). Mn-PBA-3 also delivers a high capacity of 79.0 mA h g-1 after 2000 cycles of 10 A/g. The mechanism of the Zn2+ double redox reaction of Mn-PBA-3 has been revealed in detail by in situ Raman and a series of ex situ techniques. Under a high operating voltage window of 0-1.9 V, Zn//Mn-PBA-3 demonstrates a capacity of 99.3 mAh/g after 800 cycles (5 A/g) by assembling zinc ion button battery. This work has reference significance for structurally modulated PBAs used in high performance AZIBs.

3.
Sci Rep ; 14(1): 6276, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491102

RESUMO

The morphological, physiological, and biochemical characteristics of leaves result from the long-term adaptation of plants to their environment and are closely related to plant growth and development. In this study, 37 prickly ash germplasm resources from 18 production areas were utilized as the subjects of research. Logistic equations, principal component analysis, and cluster analysis were employed to comprehensively evaluate the leaf traits of prickly ash germplasm resources, with an analysis of their correlation with ecological and geographical factors in the production areas. The results showed that the leaf traits of prickly ash germplasms of different origins are substantially different and diverse. The coefficient of variation for the 14 leaf traits was greater than 10%. The coefficient of variation of the compound leaflet number was the highest among all the considered leaf traits, and the coefficient of variation of leaf thickness was the lowest, at 49.86% and 11.37%, respectively. The leaf traits of the prickly ash germplasm originating from Chongqing in Yongchuan, Chongqing in Rongchang, and Yunnan in Honghe ranked highest, whereas the leaf traits of the prickly ash germplasm from Henan in Jiaozuo, Gansu in Tianshui, and Shanxi in Yuncheng ranked lowest. The results of the correlation analysis showed that among the ecological and geographical factors of the origins, latitude had the strongest correlation with the leaf traits of the prickly ash germplasm. As latitude increased, the leaves of prickly ash gradually decreased in size, weight, and leaf shape index. The factor with the second strongest correlation was temperature. The leaves of the prickly ash germplasm originating from warmer climate areas were larger and heavier than those from areas with colder climates. Altitude and longitude did not significantly affect the leaf traits of the prickly ash germplasm, but at similar latitudes, the leaves of the prickly ash germplasm in high-altitude areas were smaller, and the leaves of the prickly ash germplasm in low-altitude areas were larger. These findings can provide valuable references for breeding and the sustainable utilization of new varieties of prickly ash resources.


Assuntos
Altitude , Melhoramento Vegetal , Humanos , China , Geografia , Folhas de Planta
5.
J Am Chem Soc ; 146(13): 9012-9025, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38516778

RESUMO

The development of efficient and stable catalysts for hydrogen production from electrolytic water in a wide pH range is of great significance in alleviating the energy crisis. Herein, Pt nanoparticles (NPs) anchored on the vacancy of high entropy rare earth oxides (HEREOs) were prepared for the first time for highly efficient hydrogen production by water electrolysis. The prepared Pt-(LaCeSmYErGdYb)O showed excellent electrochemical performances, which require only 12, 57, and 77 mV to achieve a current density of 100 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS environments, respectively. In addition, Pt-(LaCeSmYErGdYb)O has successfully worked at 400 mA cm-2 @ 60 °C for 100 h in 0.5 M H2SO4, presenting the high mass activity of 37.7 A mg-1Pt and turnover frequency (TOF) value of 38.2 s-1 @ 12 mV, which is far superior to the recently reported hydrogen evolution reaction (HER) catalysts. Density functional theory (DFT) calculations have revealed that the interactions between Pt and HEREO have optimized the electronic structures for electron transfer and the binding strength of intermediates. This further leads to optimized proton binding and water dissociation, supporting the highly efficient and robust HER performances in different environments. This work provides a new idea for the design of efficient RE-based electrocatalysts.

6.
Front Immunol ; 15: 1308068, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524138

RESUMO

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.


Assuntos
Disartria , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Masculino , Humanos , Adulto , Disartria/complicações , Tremor/complicações , Contactina 1 , Ataxia
7.
Environ Res ; 251(Pt 1): 118596, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38442810

RESUMO

n-Caproic acid is a widely used biochemical that can be produced from organic waste through chain elongation technology. This study aims to evaluate the environmental impacts of n-caproic acid production through chain elongation by two processes (i.e., shunting and staged technology). The Open-life cycle assessment (LCA) model was used to calculate the environmental impacts of both technologies based on experimental data. Results showed that the shunting technology had higher environmental impacts than the staged technology. Water and electricity made bigger contribution to the environmental impacts of both technologies. Reusing chain elongation effluent substituting for water and using electricity produced by wind power could reduce the environmental impacts of water and electricity effectively. Using ethanol from food waste had higher global warming potential than fossil ethanol, which suggested that a cradle-to-grave LCA is needed to be carried out for specific raw materials and chain elongation products in the future.

8.
Clin Ophthalmol ; 18: 799-807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495679

RESUMO

Purpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses. Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction. Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months. Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.

9.
Prog Brain Res ; 283: 193-229, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38538188

RESUMO

Prior research has highlighted the potential impact of aerobic exercise on cognitive functioning, particularly in situations demanding heightened cognitive control. However, the mechanism underlying this cognitive enhancement has remained unknown. To address this issue, this study examined the impact of a 4-week aerobic exercise program on cognitive control processes in young male adults (aerobic exercise group: n=36, aged 21.42±1.13years) in comparison to a control group that received no treatment (n=33, aged 21.82±1.76years). We employed the redundant-target Stroop task to investigate inhibition processes at both perceptual and semantic stages. Utilizing systems factorial technology and the drift diffusion model, we assessed changes in resilience capacity and the underlying cognitive mechanisms. Our primary findings revealed a significant reduction in mean response times (RTs) in the aerobic exercise group, accompanied by a decrease in RT variability when inhibiting semantic processing. Resilience capacity significantly declined in both groups at similar levels. Notably, the aerobic exercise group exhibited an enhanced drift rate during automatic response inhibition and reduced non-decision time in the condition involving the inhibition of perceptual information. This study deepens our understanding of how a 4-week aerobic exercise program enhances cognitive control, affecting distinct cognitive processes, including processing speed, information accumulation during automatic response inhibition, and sensory and motor processes in perceptual conflicts. Our research underscores the potential of aerobic exercise as a means to boost cognitive control among young adults.


Assuntos
Cognição , Exercício Físico , Humanos , Masculino , Adulto Jovem , Exercício Físico/fisiologia , Cognição/fisiologia , Terapia por Exercício , Tempo de Reação/fisiologia
10.
Antioxidants (Basel) ; 13(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38539915

RESUMO

This study takes the fruit of Rosa roxburghii Tratt (RRT) as a fermentation substrate and carries out a quantitative visual analysis of the domestic and foreign literature on screenings of five different lactic acid bacteria to obtain a fermentation broth. Systemic anti-photoaging effects are analyzed at the biochemical, cellular, and molecular biological levels. DPPH and ABTS free radical scavenging activities are used to verify the antioxidant capacity of the RRT fruit fermentation broth in vitro. Human embryonic skin fibroblasts (HESs) are used to establish a UVA damage model, and the antioxidant capacity of the RRT fruit fermentation broth is verified in terms of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. RT-qPCR and ELISA are used to detect the expression of TGF-ß/Smad, MMPs, and the MAPK/AP-1 and Nrf2/Keap-1 signaling pathways in order to explore the anti-oxidation and anti-photoaging effects of the RRT fruit fermentation broth by regulating different signaling pathways. The results show that an RRT fruit fermentation broth can effectively protect cells from oxidative stress caused by UVA and has significant anti-photoaging effects, with the co-cultured Lactobacillus Yogurt Starter LYS-20297 having the highest overall effect.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38526879

RESUMO

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

12.
ChemSusChem ; 17(6): e202301771, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385812

RESUMO

Optimized catalytic properties and reactant adsorption energy played a crucial role in promoting CO2 electrocatalysis. Herein, Cu7S4/Cu underwent in situ dynamic restructuring to generate S-Cu2O/Cu hybrid catalyst for effective electrochemical CO2 reduction to formate that outperformed Cu2O/Cu and Cu7S4. Thermodynamic and in situ Raman spectra revealed that the optimized adsorption of the HCOO* intermediate on S-Cu2O/Cu was regulated and the H2 pathway (surface H) was suppressed by S-doping. Meanwhile, Cu7S4/Cu nanoflowers created abundant boundaries for ECR and strengthened the CO2 adsorption by inducing Cu. These findings provide a new perspective on synthetic methods for various electrocatalytic reduction processes.

13.
Nanomicro Lett ; 16(1): 112, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334816

RESUMO

The undesirable dendrite growth induced by non-planar zinc (Zn) deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries (ZMBs). Herein, we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium (Zn-In) interface in the microchannels. The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities. Meanwhile, electron aggregation accelerates the dissolution of non-(002) plane Zn atoms on the array surface, thereby directing the subsequent homoepitaxial Zn deposition on the array surface. Consequently, the planar dendrite-free Zn deposition and long-term cycling stability are achieved (5,050 h at 10.0 mA cm-2 and 27,000 cycles at 20.0 mA cm-2). Furthermore, a Zn/I2 full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C, demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38412702

RESUMO

This study compares the skin structures of Rana kukunoris with two different skin colors living in the same area of Haibei in the Northeastern Qinghai-Tibet Plateau. The skin thickness of the khaki R. kukunoris was significantly greater than that of the brown R. kukunoris (P < 0.01), and significantly more mucous and granular glands were present on the dorsal skin of the khaki frog (P < 0.05). Meanwhile, the melanocytes on the dorsal skin of the brown frog were significantly larger than those on the khaki one (P < 0.05). Morphological changes in the expansion and aggregation of melanocytes seemed to deepen the skin color of R. kukunoris. Moreover, transcriptome sequencing identified tyrosine metabolism, melanogenesis, and riboflavin metabolism as the main pathways involved in melanin formation and metabolism in brown R. kukunoris. TYR, MC1R was upregulated as the skin color of R. kukunoris was deepened and contributed to melanin production and metabolism. In contrast, the khaki frog had significantly more upregulated genes and metabolic pathways related to autoimmunity. The khaki frog appeared to defend against ultraviolet (UV) radiation-induced damage by secreting mucus and small molecular peptides, whereas the brown frog protected itself by distributing a large amount of melanin. Hence, the different skin colors of R. kukunoris might represent different adaptation strategies for survival in the intense UV radiation environment of the Qinghai-Tibet Plateau.

16.
J Neurosci Res ; 102(2): e25309, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400573

RESUMO

Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.


Assuntos
Sinapses , Transmissão Sináptica , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Mitocôndrias/metabolismo , Plasticidade Neuronal/fisiologia , Autofagia
17.
Front Plant Sci ; 15: 1276799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362453

RESUMO

To address the problem that the low-density canopy of greenhouse crops affects the robustness and accuracy of simultaneous localization and mapping (SLAM) algorithms, a greenhouse map construction method for agricultural robots based on multiline LiDAR was investigated. Based on the Cartographer framework, this paper proposes a map construction and localization method based on spatial downsampling. Taking suspended tomato plants planted in greenhouses as the research object, an adaptive filtering point cloud projection (AF-PCP) SLAM algorithm was designed. Using a wheel odometer, 16-line LiDAR point cloud data based on adaptive vertical projections were linearly interpolated to construct a map and perform high-precision pose estimation in a greenhouse with a low-density canopy environment. Experiments were carried out in canopy environments with leaf area densities (LADs) of 2.945-5.301 m2/m3. The results showed that the AF-PCP SLAM algorithm increased the average mapping area of the crop rows by 155.7% compared with that of the Cartographer algorithm. The mean error and coefficient of variation of the crop row length were 0.019 m and 0.217%, respectively, which were 77.9% and 87.5% lower than those of the Cartographer algorithm. The average maximum void length was 0.124 m, which was 72.8% lower than that of the Cartographer algorithm. The localization experiments were carried out at speeds of 0.2 m/s, 0.4 m/s, and 0.6 m/s. The average relative localization errors at these speeds were respectively 0.026 m, 0.029 m, and 0.046 m, and the standard deviation was less than 0.06 m. Compared with that of the track deduction algorithm, the average localization error was reduced by 79.9% with the proposed algorithm. The results show that our proposed framework can map and localize robots with precision even in low-density canopy environments in greenhouses, demonstrating the satisfactory capability of the proposed approach and highlighting its promising applications in the autonomous navigation of agricultural robots.

18.
Biol Trace Elem Res ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38388752

RESUMO

Magnesium (Mg), iron (Fe), copper (Cu), and zinc (Zn) are indispensable elements in children's growth and development. However, epidemiological evidence regarding essential elements and their mixed exposure to behavior problems remains in its infancy. The objective of the present study was to evaluate the association between essential elements and the manifestation of behavior problems, with an additional focus on the implications of their mixture. An electronic medical records review was performed among 4122 subjects aged 6-18 years who underwent examinations at Children's Hospital, Zhejiang University School of Medicine, between January 2019 and July 2022. The concentrations of essential elements were measured by atomic absorption spectrometry, and behavior problems were assessed by using the Conners' Parent Rating Scale (CPRS). A total of 895 (21.7%) children and adolescents were identified as having behavior problems. For single exposure, inversely linear dose-response relationships were identified between continuous Mg and Zn levels and the prevalence of behavior problems, and the prevalence ratios (PRs) in the categorical lowest tertile were 1.28 (95% confidence interval, CI: 1.07-1.54) for Mg and 1.31 (95% CI: 1.05-1.63) for Zn compared to the highest tertile. For mixture exposure, an inverse association between essential elements and behavior problems was also found, mainly contributed by Mg (posterior inclusion probability, PIP = 0.854). Whole blood levels of Mg and Zn were significantly inversely associated with behavior problems. The findings highlight the pivotal role of essential elements in behavior problems and emphasize the importance of maintaining adequate levels of essential elements during children's maturation.

19.
J Cancer ; 15(6): 1770-1778, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370378

RESUMO

Bladder cancer (BCa) is one of the most common malignancies affecting men. Oncogenic transcription factors function as an important regulator in the progression of human cancer. In our study, we aimed to construct artificial circular non-coding RNAs (acircRNAs) consisting of three functional units that mimic the CRISPR-Cas system and elucidate its therapeutic role in bladder cancer. Additionally, the compare of the efficiency in regulating gene expression between acircRNA and CRISPR-dCas systems was performed. We connected the cDNA sequences of TFs aptamer and constructed a circRNA. To demonstrate the platform's practicality, ß-catenin and NF-κB were chosen as functional targets, while T24 and 5637 cell lines served as test models. Real-time Quantitative PCR (qPCR), double luciferase assay and related phenotype assay were used to detect the expression of related genes and the therapeutic effect. To elucidate the functionality of acircRNAs, luciferase vectors capable of detecting ß-catenin and NF-κB expression were employed to assess the inhibitory impact of acircRNA on ß-catenin and NF-κB. Consequently, the optimal combination involving acircRNA-3 was determined. Next, qPCR assay was employed to assess the relative expression levels of target downstream genes following acircRNA treatment. The expression of c-myc and cyclin D1 were used to determine the function of ß-catenin, while Bcl-XL and TRAF1 were used to determine that of NF-κB. The acircRNAs inhibited the ß-catenin and NF-κB related signaling in BCa cells specifically. CD63-HuR fusion protein was used to loading acircRNA into exosomes. The results showed that acircRNA could inhibit the activity of the target transcription factors, and the inhibitory effect was better than that of CRIPSR-dCas9-KRAB. Furthermore, functional experiments demonstrated that the transfection of acircRNA in bladder cells resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. In conclusion, our synthetic gene device exhibited anti-tumor regulatory capabilities and showed greater efficiency in tumor suppression compared to the CRISPR-dCas9-KRAB system. Therefore, our device provides a new strategy for cancer treatment and could be a useful strategy for cancer cells.

20.
J Microbiol Immunol Infect ; 57(2): 300-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38350840

RESUMO

PURPOSES: This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB). METHODS: We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays. RESULTS: Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL. CONCLUSION: Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Colistina/farmacologia , Colistina/uso terapêutico , Polimixina B/farmacologia , Sinergismo Farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla
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