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1.
Light Sci Appl ; 13(1): 264, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39300062

RESUMEN

Higher-order topological insulators (HOTIs) are unique materials hosting topologically protected states, whose dimensionality is at least by 2 lower than that of the bulk. Topological states in such insulators may be strongly confined in their corners which leads to considerable enhancement of nonlinear processes involving such states. However, all nonlinear HOTIs demonstrated so far were built on periodic bulk lattice materials. Here, we demonstrate the first nonlinear photonic HOTI with the fractal origin. Despite their fractional effective dimensionality, the HOTIs constructed here on two different types of the Sierpinski gasket waveguide arrays, may support topological corner states for unexpectedly wide range of coupling strengths, even in parameter regions where conventional HOTIs become trivial. We demonstrate thresholdless spatial solitons bifurcating from corner states in nonlinear fractal HOTIs and show that their localization can be efficiently controlled by the input beam power. We observe sharp differences in nonlinear light localization on outer and multiple inner corners and edges representative for these fractal materials. Our findings not only represent a new paradigm for nonlinear topological insulators, but also open new avenues for potential applications of fractal materials to control the light flow.

2.
Opt Lett ; 49(15): 4110-4113, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090871

RESUMEN

The type-II Dirac cone is a special feature of the band structure, whose Fermi level is represented by a pair of crossing lines. It has been demonstrated that such a structure is useful for investigating topological edge solitons and, more specifically, for mimicking the Klein tunneling. However, it is still not clear what the interplay between type-II Dirac cones and the non-Hermiticity mechanism will result in. Here, this question is addressed; in particular, we report the P T-symmetric photonic lattices with type-II Dirac cones for the first time to our knowledge. We identify a slope-exceptional ring and name it the type-II exceptional ring. We display the restoration of the P T symmetry of the lattice by reducing the separation between the sites in the unit cell. Curiously, the amplitude of the beam during propagation in the non-Hermitian lattice with P T symmetry only decays because of diffraction, whereas in the P T symmetry-broken lattice it will be amplified, even though the beam still diffracts. This work establishes the link between the non-Hermiticity mechanism and the violation of Lorentz invariance in these physical systems.

3.
BMC Microbiol ; 24(1): 314, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187803

RESUMEN

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within  30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.


Asunto(s)
Técnicas de Amplificación de Ácido Nucleico , Pneumocystis carinii , Sensibilidad y Especificidad , Pneumocystis carinii/genética , Pneumocystis carinii/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/microbiología , Técnicas de Diagnóstico Molecular/métodos , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Proteínas Asociadas a CRISPR/genética , ADN de Hongos/genética , Recombinasas/metabolismo , Recombinasas/genética , Proteínas Bacterianas
4.
Front Neurol ; 15: 1407516, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39022730

RESUMEN

Background and objective: To investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients. Methods: A retrospective analysis was conducted on 180 patients with HR-NICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected. The culprit plaques were analyzed using VesselExplorer2 software. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for recurrence, and a nomogram was constructed using R software to evaluate the discrimination of the model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the model performance. Calibration curves and Decision Curve Analysis (DCA) were used to evaluate the model efficacy. Results: Intra-plaque hemorrhage (OR = 3.592, 95% CI = 1.474-9.104, p = 0.006), homocysteine (OR = 1.098, 95% CI = 1.025-1.179, p = 0.007), and normalized wall index (OR = 1.114, 95% CI = 1.027-1.222, p = 0.015) were significantly higher in the recurrent stroke group than in the non-recurrent stroke group, and were independent risk factors for recurrent stroke. The performance of the nomogram model (AUC = 0.830, 95% CI: 0.769-0.891; PR-AUC = 0.628) was better than that of the modified Essen scoring model (AUC = 0.660, 95% CI: 0.583-0.738) and the independent risk factor combination model (AUC = 0.827, 95% CI: 0.765-0.889). The nomogram model still had good model performance in the validation group (AUC = 0.785, 95% CI: 0.671-0.899), with a well-fitting calibration curve and a DCA curve indicating good net benefit efficacy for patients. Conclusion: High-resolution vessel wall imaging combined with a modified Essen score can effectively assess the recurrence risk of HR-NICE patients, and the nomogram model can provide a reference for identifying high-risk populations with good clinical application prospects.

5.
Chem Biol Drug Des ; 103(4): e14517, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38610074

RESUMEN

The epidermal growth factor receptor (EGFR) has been well validated as a therapeutic target for anticancer drug discovery. Osimertinib has become the first globally accessible third-generation EGFR inhibitor, representing one of the most advanced developments in non-small-cell lung cancer (NSCLC) therapy. However, a tertiary Cys797 to Ser797 (C797S) point mutation has hampered osimertinib treatment in patients with advanced EGFR-mutated NSCLC. Several classes of fourth-generation EGFR inhibitors were consequently discovered with the aim of overcoming the EGFRC797S mutation-mediated resistance. However, no clinical efficacy data of the fourth-generation EGFR inhibitors were reported to date, and EGFRC797S mutation-mediated resistance remains an "unmet clinical need." Proteolysis-targeting chimeric molecules (PROTACs) obtained from EGFR-TKIs have been developed to target drug resistance EGFR in NSCLC. Some PROTACs are from nature products. These degraders compared with EGFR inhibitors showed better efficiency in their cellular potency, inhibition, and toxicity profiles. In this review, we first introduce the structural properties of EGFR, the resistance, and mutations of EGFR, and then mainly focus on the recent advances of EGFR-targeting degraders along with its advantages and outstanding challenges.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Receptores ErbB/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico
6.
Microb Cell Fact ; 23(1): 107, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609931

RESUMEN

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.


Asunto(s)
Chalconas , Criptococosis , Cryptococcus neoformans , Animales , Cryptococcus neoformans/genética , Antifúngicos/farmacología , RNA-Seq , Simulación del Acoplamiento Molecular , Biopelículas , Caenorhabditis elegans
7.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38535487

RESUMEN

The miniaturization, lightweight, and solidification of pulse forming lines (PFLs) are of prime significance during the evolution of pulsed power technology. In this paper, an all-solid-state annular pulse forming line (APFL) based on film-insulated coaxial transmission lines is developed to generate fast-rise time quasi-square pulses. First, a coiled coaxial transmission line (CCTL) comprised of multilayer polypropylene films with outstanding insulating properties is constructed. It can withstand direct current voltages up to 200 kV, with a cross section diameter of 7.4 mm. In addition, in order to turn the pulse transmission direction from circumferential to axial, a compact insulated terminal with a 90° bend structure is designed for CCTL. Although single terminal inductance can slow down the rising edge of the output pulse, their parallel connection in an APFL can weaken such an effect. The APFL, with a characteristic impedance of 2.95 Ω and a transmission time of 13 ns, is composed of three CCTLs with six terminals, which can run over 100 thousand times under the pulse voltage of 75 kV. Finally, 15 series APFL modules are employed to assemble a multi-stage PFL for the Tesla-type pulse generator. When charged to a voltage of 1 MV, the mixed PFL consisting of a coaxial line and the multi-stage PFL outputs quasi-square pulses with a voltage amplitude, rise time, and width of 510 kV, 4 ns, and 41.5 ns, respectively, and the fluctuation of the flat top is about 6%.

8.
ACS Omega ; 9(8): 9702-9713, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38434859

RESUMEN

Potassium ion channels are the structural basis for excitation transmission, heartbeat, and other biological processes. The selectivity filter is a critical structural component of potassium ion channels, whose structure is crucial to realizing their function. As biomolecules vibrate and rotate at frequencies in the terahertz band, potassium ion channels are sensitive to terahertz waves. Therefore, it is worthwhile to investigate how the terahertz wave influences the selectivity filter of the potassium channels. In this study, we investigate the structure of the selectivity filter of Kv1.2 potassium ion channels using molecular dynamics simulations. The effect of an electric field on the channel has been examined at four different resonant frequencies of the carbonyl group in SF: 36.75 37.06, 37.68, and 38.2 THz. As indicated by the results, 376GLY appears to be the critical residue in the selectivity filter of the Kv1.2 channel. Its dihedral angle torsion is detrimental to the channel structural stability and the transmembrane movement of potassium ions. 36.75 THz is the resonance frequency of the carbonyl group of 376GLY. Among all four frequencies explored, the applied terahertz electric field of this frequency has the most significant impact on the channel structure, negatively impacting the channel stability and reducing the ion permeability by 20.2% compared to the absence of fields. In this study, we simulate that terahertz waves in the mid-infrared frequency region can significantly alter the structure and function of potassium ion channels and that the effects of terahertz waves differ greatly based on frequency.

9.
Pol J Microbiol ; 73(1): 39-48, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437470

RESUMEN

Feline parvovirus (FPV) is highly infectious for cats and other Felidae and often causes severe damage to young kittens. In this study, we incorporated recombinase polymerase amplification (RPA) and Cas12a-mediated detection and developed an RPA-Cas12a-based real-time or end-point fluorescence detection method to identify the NS1 gene of FPV. The total time of RPA-Cas12a-based fluorescence assay is approximately 25 min. The assay presented a limit of detection (LOD) of 1 copies/µl (25 copies/per reaction), with no cross-reactivity with several feline pathogens. The clinical performance of the assay was examined using total genomic DNA purified from 60 clinical specimens and then compared to results obtained with qPCR detection of FPV with 93.3% positive predictive agreement and 100% negative predictive agreement. Together, the rapid reaction, cost-effectiveness, and high sensitivity make the RPA-Cas12a-based fluorescence assay a fascinating diagnostic tool that will help minimize infection spread through instant detection of FPV.


Asunto(s)
Virus de la Panleucopenia Felina , Recombinasas , Gatos , Animales , Femenino , Sistemas CRISPR-Cas , Límite de Detección
10.
Cell Death Discov ; 10(1): 71, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341418

RESUMEN

Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

11.
Front Plant Sci ; 15: 1334189, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410728

RESUMEN

Leucine-rich repeat receptor-like kinases (LRR-RLKs) can participate in the regulation of plant growth and development, immunity and signal transduction. Sesamum indicum, one of the most important oil crops, has a significant role in promoting human health. In this study, 175 SiLRR-RLK genes were identified in S. indicum, and they were subdivided into 12 subfamilies by phylogenetic analysis. Gene duplication analysis showed that the expansion of the SiLRR-RLK family members in the sesame was mainly due to segmental duplication. Moreover, the gene expansion of subfamilies IV and III contributed to the perception of stimuli under M. phaseolina stress in the sesame. The collinearity analysis with other plant species revealed that the duplication of SiLRR-RLK genes occurred after the differentiation of dicotyledons and monocotyledons. The expression profile analysis and functional annotation of SiLRR-RLK genes indicated that they play a vital role in biotic stress. Furthermore, the protein-protein interaction and coexpression networks suggested that SiLRR-RLKs contributed to sesame resistance to Macrophomina phaseolina by acting alone or as a polymer with other SiLRR-RLKs. In conclusion, the comprehensive analysis of the SiLRR-RLK gene family provided a framework for further functional studies on SiLRR-RLK genes.

12.
BMC Microbiol ; 23(1): 333, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951882

RESUMEN

Human rhinovirus B (HRV-B) is a major human viral pathogen that can be responsible for various kinds of infections. Due to the health risks associated with HRV-B, it is therefore crucial to explore a rapid, specific, and sensitive method for surveillance. Herein, we exploited a novel detection method for HRV-B by combining reverse-transcription recombinase polymerase amplification (RT-RPA) of nucleic acids isothermal amplification and the trans-cleavage activity of Cas12a. Our RT-RPA-Cas12a-based fluorescent assay can be completed within 35-45 min and obtain a lower detection threshold to 0.5 copies/µL of target RNA. Meanwhile, crRNA sequences without a specific protospacer adjacent motif can effectively activate the trans-cleavage activity of Cas12a. Moreover, our RT-RPA-Cas12a-based fluorescent method was examined using 30 clinical samples, and exhibited high accuracy with positive and negative predictive agreement of 90% and 100%, respectively. Taken together, a novel promising, rapid and effective RT-RPA-Cas12a-based detection method was explored and shows promising potential for on-site HRV-B infection in resource-limited settings.


Asunto(s)
Bioensayo , Sistemas CRISPR-Cas , Humanos , Colorantes , Nucleotidiltransferasas , Recombinasas
13.
Nanomaterials (Basel) ; 13(18)2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37764579

RESUMEN

Secondary electron emission (SEE) is a fundamental phenomenon of particle/surface interaction, and the multipactor effect induced by SEE can result in disastrous impacts on the performance of microwave devices. To suppress the SEE-induced multipactor, an Ni (111) surface covered with a monolayer of graphene was proposed and studied theoretically via the density functional theory (DFT) method. The calculation results indicated that redistribution of the electron density at the graphene/Ni (111) interface led to variations in the work function and the probability of SEE. To validate the theoretical results, experiments were performed to analyze secondary electron yield (SEY). The measurements showed a significant decrease in the SEY on an Ni (111) surface covered with a monolayer of graphene, accompanied by a decrease in the work function, which is consistent with the statistical evidence of a strong correlation between the work function and SEY of metals. A discussion was given on explaining the experimental phenomenon using theoretical calculation results, where the empty orbitals lead to an electron trapping effect, thereby reducing SEY.

14.
Comp Immunol Microbiol Infect Dis ; 100: 102024, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37487313

RESUMEN

Monkeypox virus (Mpox) is a zoonotic infectious disease that threatens human and animal health, with a global outbreak of the low-pathogenic Mpox beginning from 2022. In this study, we analyzed the codon usage of Mpox between two clades, Clade-I and Clade-IIb-B, to understand changes in host adaptation. Clade-IIb-B of the Mpox genome underwent non-adaptive evolution making it less adapted to its host than Clade-I. The analysis of individual genes revealed that 48 genes exhibited non-adaptive mutation, while 38 genes underwent adaptive mutations. Genes involved in replication, transcription, and host-modulation exhibited a mix of adaptive and non-adaptive evolutionary patterns. This study also found that the mutations of Mpox led to changes in non-adaptative genes in different organs. Additionally, we found that codon usage of Mpox was less similar to that of up-regulated host genes and more similar to that of down-regulated host genes post-infection, indicating that codon usage affects host gene expression. Overall, the study highlights the non-adaptive changes in codon usage as a potential cause of differences in Mpox virulence and provides insights into the evolutionary and adaptive mechanisms of Mpox and its potential impact on pathogenicity and host adaptation.


Asunto(s)
Uso de Codones , Mpox , Humanos , Animales , Genoma Viral , Codón/genética , Monkeypox virus/genética , Mpox/genética , Mpox/veterinaria , Evolución Molecular
15.
J Cardiovasc Pharmacol ; 82(5): 350-363, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37523690

RESUMEN

ABSTRACT: Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m 2 , and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the T rs4897367 A rs2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.


Asunto(s)
Enfermedad Coronaria , Proteínas de Unión al ADN , Predisposición Genética a la Enfermedad , Humanos , Masculino , Estudios de Casos y Controles , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Proteínas de Unión al ADN/genética , Pueblos del Este de Asia , Genotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Persona de Mediana Edad
16.
J Chem Phys ; 159(4)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37486058

RESUMEN

As biomolecules vibrate and rotate in the terahertz band, the biological effects of terahertz electromagnetic fields have drawn considerable attention from the physiological and medical communities. Ion channels are the basis of biological electrical signals, so studying the effect of terahertz electromagnetic fields on ion channels is significant. In this paper, the effect of a terahertz electromagnetic field with three different frequencies, 6, 15, and 25 THz, on the Kv1.2 potassium ion channel was investigated by molecular dynamics simulations. The results show that an electromagnetic field with a 15 THz frequency can significantly enhance the permeability of the Kv1.2 potassium ion channel, which is 1.7 times higher than without an applied electric field. By analyzing the behavior of water molecules, it is found that the electromagnetic field with the 15 THz frequency shortens the duration of frozen and relaxation processes when potassium ions pass through the channel, increases the proportion of the direct knock-on mode, and, thus, enhances the permeability of the Kv1.2 potassium ion channel.

17.
CNS Neurosci Ther ; 29(12): 3756-3773, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37309294

RESUMEN

AIM: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2-like polarization of tumor-associated macrophages (TAMs). However, the exact mechanisms by which GSCs-derived exosomes (GSCs-exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated. METHODS: Transmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs-derived exosomes. Sphere formation assays, flow cytometry, and tumor xenograft transplantation assays were performed to identify the exact roles of exosomal miR-6733-5p. Then, the mechanisms of miR-6733-5p and its downstream target gene regulating crosstalk between GSCs cells and M2 macrophages were further investigated. RESULTS: GSCs-derived exosomal miR-6733-5p induce macrophage M2 polarization of TAMs by positively targeting IGF2BP3 to activate the AKT signaling pathway, which further facilitates the self-renewal and stemness of GSCs. CONCLUSION: GSCs secrete miR-6733-5p-rich exosomes to induce M2-like polarization of macrophages, as well as enhance GSCs stemness and promote malignant behaviors of GBM through IGF2BP3 activated AKT pathway. Targeting GSCs exosomal miR-6733-5p may provide a potential new strategy against GBM.


Asunto(s)
Glioblastoma , MicroARNs , Humanos , Glioblastoma/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Macrófagos/patología , Células Madre/metabolismo , Línea Celular Tumoral , Microambiente Tumoral
18.
Opt Express ; 31(13): 20812-20824, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37381196

RESUMEN

Topological edge states have recently garnered a lot of attention across various fields of physics. The topological edge soliton is a hybrid edge state that is both topologically protected and immune to defects or disorders, and a localized bound state that is diffraction-free, owing to the self-balance of diffraction by nonlinearity. Topological edge solitons hold great potential for on-chip optical functional device fabrication. In this report, we present the discovery of vector valley Hall edge (VHE) solitons in type-II Dirac photonic lattices, formed by breaking lattice inversion symmetry with distortion operations. The distorted lattice features a two-layer domain wall that supports both in-phase and out-of-phase VHE states, appearing in two different band gaps. Superposing soliton envelopes onto VHE states generates bright-bright and bright-dipole vector VHE solitons. The propagation dynamics of such vector solitons reveal a periodic change in their profiles, accompanied by the energy periodically transferring between the layers of the domain wall. The reported vector VHE solitons are found to be metastable.

19.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-37373419

RESUMEN

In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the Kv1.2 voltage-gated potassium ion channel on the nerve cell membrane was studied using the combined model of the "Constant Electric Field-Ion Imbalance" method by molecular dynamics. We found that although the applied terahertz electric field does not produce strong resonance with the -C=O groups of the conservative sequence T-V-G-Y-G amino acid residue of the selective filter (SF) of the channel, it would affect the stability of the electrostatic bond between potassium ions and the carbonyl group of T-V-G-Y-G of SF, and it would affect the stability of the hydrogen bond between water molecules and oxygen atoms of the hydroxyl group of the 374THR side chain at the SF entrance, changing the potential and occupied states of ions in the SF and the occurrence probability of the permeation mode of ions and resulting in the change in the permeability of the channel. Compared with no external electric field, when the external electric field with 15 THz frequency is applied, the lifetime of the hydrogen bond is reduced by 29%, the probability of the "soft knock on" mode is decreased by 46.9%, and the ion flux of the channel is activated by 67.7%. Our research results support the view that compared to "direct knock-on", "soft knock-on" is a slower permeation mode.


Asunto(s)
Campos Electromagnéticos , Canales de Potasio con Entrada de Voltaje , Canales de Potasio con Entrada de Voltaje/metabolismo , Simulación de Dinámica Molecular , Iones/metabolismo , Permeabilidad , Potasio/metabolismo , Canal de Potasio Kv.1.2/química , Canal de Potasio Kv1.5/metabolismo
20.
Pathol Res Pract ; 246: 154481, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37121053

RESUMEN

Glioblastoma multiforme (GBM) is one of the most malignant tumors of the central nervous system, and its treatment has always been a difficult clinical problem. Here, we evaluated HDAC1 expression patterns and their effect on prognosis based on GBM cases from TCGA and CGGA databases. Expression was compared between GBM samples and normal controls. High HDAC1 expression was found to be an indicator of poor prognosis in glioblastoma. We also established a protein-protein interaction network to explore HDAC1-related interacting proteins, including the epithelial-mesenchymal transition (EMT)-related protein VIM, which is closely associated with HDAC1. Consistently, functional enrichment analysis showed that several GBM tissues with high HDAC1 were enriched in the expression of cancer markers, such as those involved in glycolysis, hypoxia, inflammation, and some signaling pathways. Next, this study analyzed the effect of HDAC1 on invasive ability and the EMT signaling pathway in GBM cells in vitro. The results showed that an HDAC1 inhibitor (RGFP109) could inhibit the EMT process in glioma cells in vitro, thereby affecting the invasion and migration of cells. Similar results were obtained based on in vivo studies. Our data suggest that HDAC1 has the potential to be a powerful prognostic biomarker, which might provide a basis for developing therapeutic targets for GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/patología , Transición Epitelial-Mesenquimal/fisiología , Glioma/metabolismo , Procesos Neoplásicos , Invasividad Neoplásica , Línea Celular Tumoral , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 1/farmacología
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