Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 357
Filtrar
1.
Opt Express ; 32(4): 4987-4997, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439236

RESUMO

We propose a scheme to achieve nonreciprocal parity-time (P T)-symmetric magnon laser in a P T-symmetric cavity optomagnonical system. The system consists of active and passive optical spinning resonators. We demonstrate that the Fizeau light-dragging effect induced by the spinning of a resonator results in significant variations in magnon gain and stimulated emitted magnon numbers for different driving directions. We find that utilizing the Fizeau light-dragging effect allows the system to operate at ultra-low thresholds even without reaching gain-loss balance. A one-way magnon laser can also be realized across a range of parameters. High tunability of the magnon laser is achieved by changing the spinning speed of the resonators and driving direction. Our work provides a new way to explore various nonreciprocal effects in non-Hermitian magnonic systems, which may be applied to manipulate photons and magnons in multi-body non-Hermitian coupled systems.

2.
Opt Express ; 32(8): 13562-13573, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859323

RESUMO

We propose a method for simulating a 1D non-Hermitian Su-Schrieffer-Heeger model with modulated nonreciprocal hopping using a cyclic three-mode optical system. The current system exhibits different localization of topologically nontrivial phases, which can be characterized by the winding number. We find that the eigenenergies of such a system undergo a real-complex transition as the nonreciprocal hopping changes, accompanied by a non-Bloch parity-time symmetry breaking. We explain this phase transition by considering the evolution of saddle points on the complex energy plan and the ratio of complex eigenenergies. Additionally, we demonstrate that the skin states resulting from the non-Hermitian skin effect possess higher-order exceptional points under the critical point of the non-Bloch parity-time phase transition. Furthermore, we investigate the non-Hermitian skin phase transition by the directional mean inverse participation ratio and the generalized Brillouin zone. This work provides an alternative way to investigate the novel topological and non-Hermitian effects in nonreciprocal optical systems.

3.
Qual Life Res ; 33(3): 745-752, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38064016

RESUMO

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.


Assuntos
Nefrologia , Humanos , Reprodutibilidade dos Testes , Qualidade de Vida/psicologia , Inquéritos e Questionários , Diálise Renal , Fadiga/terapia , China , Psicometria , Traduções
4.
J Ultrasound Med ; 43(9): 1723-1732, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38975721

RESUMO

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.


Assuntos
Meniscos Tibiais , Ultrassonografia , Humanos , Masculino , Feminino , Ultrassonografia/métodos , Adulto , Reprodutibilidade dos Testes , Meniscos Tibiais/diagnóstico por imagem , Valores de Referência , Adulto Jovem , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Voluntários Saudáveis
5.
Phytochem Anal ; 35(5): 1186-1196, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38639052

RESUMO

INTRODUCTION: Smilacis Glabrae Rhizoma (SGR) is rich in chemical constituents with a variety of pharmacological activities. However, in-depth research has yet to be conducted on the chemical and pharmacodynamic constituents of SGR. MATERIALS AND METHODS: In this study, the chemical constituents of SGR were analyzed using liquid chromatography-mass spectrometry, and the pharmacodynamic compounds responsible for the medicinal effects of SGR were elucidated through a literature review. RESULTS: In total, 20 potentially new compounds, including 16 flavonoids (C19, C20, and C27-C40) and four phenylpropanoids (C107, C112, C113, and C118), together with 161 known ones were identified in the ethanol extract of SGR using liquid chromatography-mass spectrometry, and 25 of them were unequivocally identified by comparison with reference compounds. Moreover, 17 known constituents of them were identified in the plants of genus Smilax for the first time, and 16 were identified in the plant Smilax glabra Roxb. for the first time. Of 161 known compounds, 84 constituents (including isomers) have been reported to have 17 types of pharmacological activities, covering all known pharmacological activities of SGR; among these 84 bioactive constituents, six were found in the plants of genus Smilax for the first time and five were found in S. glabra for the first time, which are new bioactive constituents found in the plants of genus Smilax and the plant S. glabra, respectively. CONCLUSION: The results provide further information on the chemical composition of SGR, laying the foundation for the elucidation of the pharmacodynamic substances of SGR.


Assuntos
Rizoma , Smilax , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Líquida de Alta Pressão/métodos , Rizoma/química , Smilax/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Flavonoides/análise , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estrutura Molecular
6.
Clin Genet ; 103(1): 87-92, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36046950

RESUMO

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disease characterized by progressive lower limb spasticity. Recent studies revealed that biallelic variants in RNF170 gene cause autosomal recessive complicated HSP with infancy onset. Here, we report an adolescent-onset HSP patient from a consanguineous Chinese family, with lower extremity stiffness, spastic gait, and unstable straight-line walking as the main manifestations. Whole-exome sequencing identifies a novel RNF170 mutation c.190C>T (p.R64*), which co-segregates with the disease in this pedigree. Functional analysis, including quantitative real-time PCR (RT-qPCR) and Western blot, indicates that both the mRNA and protein levels of mutant RNF170 are significantly reduced, which confirms the loss-of-function mechanism. Our study expands the spectrum of RNF170-associated HSP, while the RNF170 protein-involved degradation of the inositol 1,4,5-trisphosphate receptor in neurodegenerative motor neuron disorders deserves further investigation.


Assuntos
Doenças Neurodegenerativas , Paraplegia Espástica Hereditária , Ubiquitina-Proteína Ligases , Adolescente , Humanos , População do Leste Asiático , Paraplegia Espástica Hereditária/genética , Ubiquitina-Proteína Ligases/genética
7.
Opt Express ; 31(8): 12847-12864, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157436

RESUMO

A scheme is presented to achieve quantum nonreciprocity by manipulating the statistical properties of the photons in a composite device consisting of a double-cavity optomechanical system with a spinning resonator and nonreciprocal coupling. It can be found that the photon blockade can emerge when the spinning device is driven from one side but not from the other side with the same driving amplitude. Under the weak driving limit, to achieve the perfect nonreciprocal photon blockade, two sets of optimal nonreciprocal coupling strengths are analytically obtained under different optical detunings based on the destructive quantum interference between different paths, which are in good agreement with the results obtained from numerical simulations. Moreover, the photon blockade exhibits thoroughly different behaviors as the nonreciprocal coupling is altered, and the perfect nonreciprocal photon blockade can be achieved even with weak nonlinear and linear couplings, which breaks the orthodox perception.

8.
Opt Express ; 31(26): 43506-43517, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38178442

RESUMO

We propose a scheme to achieve a tunable nonreciprocal magnon laser with parametric amplification in a hybrid cavity optomagnonical system, which consists a yttrium iron garnet (YIG) sphere and a spinning resonator. We demonstrate the control of magnon laser can be enhanced via parametric amplification, which make easier and more convenient to control the magnon laser. Moreover, we analyze and evaluate the effects of pump light input direction and amplification amplitude on the magnon gain and laser threshold power. The results indicate that we can obtian a higher magnon gain and a broader range of threshold power of the magnon laser. In our scheme both the nonreciprocity and magnon gain of the magnon laser can be increased significantly. Our proposal provides a way to obtain a novel nonreciprocal magnon laser and offers new possibilities for both nonreciprocal optics and spin-electronics applications.

9.
Opt Express ; 31(15): 24939-24951, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37475309

RESUMO

In the dispersive limit, the conventional photon blockade effect cannot be realized due to the absence of photon nonlinearity. We propose a scheme to recover the photon blockade effect of the dispersive Tavis-Cummings model, which makes it possible to realize the conventional photon blockade effect in the dispersive limit. It is shown that both single-photon and two-photon blockade effects can be recovered at appropriate qubit driving strength. The optimal qubit drive strength and cavity field drive detuning are given analytically. All analyses can be verified by numerical simulation, and the strongest photon blockade effect with the largest average photon number can be produced when the single excitation resonance condition is satisfied. Moreover, we find that the achieved two-photon blockade effect is relatively robust to thermal noise. Our proposal is able to obtain single-photon sources with high purity and high brightness and has great potential for applications in quantum communication processing.

10.
Opt Express ; 31(14): 22343-22357, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475347

RESUMO

We propose a scheme to generate nonreciprocal photon blockade in a stationary whispering gallery microresonator system based on two physical mechanisms. One of the two mechanisms is inspired by recent work [Phys. Rev. Lett.128, 083604 (2022)10.1103/PhysRevLett.128.083604], where the quantum squeezing caused by parametric interaction not only shifts the optical frequency of propagating mode but also enhances its optomechanical coupling, resulting in a nonreciprocal conventional photon blockade phenomenon. On the other hand, we also give another mechanism to generate stronger nonreciprocity of photon correlation according to the destructive quantum interference. Comparing these two strategies, the required nonlinear strength of parametric interaction in the second one is smaller, and the broadband squeezed vacuum field used to eliminate thermalization noise is no longer needed. All analyses and optimal parameter relations are further verified by numerically simulating the quantum master equation. Our proposed scheme opens a new avenue for achieving the nonreciprocal single photon source without stringent requirements, which may have critical applications in quantum communication, quantum information processing, and topological photonics.

11.
Opt Express ; 31(8): 13243-13254, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157465

RESUMO

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

12.
Phys Chem Chem Phys ; 25(40): 27427-27437, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37795706

RESUMO

Herein, we studied the combined effects of the magnetic field and the alternating current driven air surface dielectric barrier discharge on ozone production, and found that a 0.13 T perpendicular magnetic field introduced into the discharge area significantly enhanced the ozone generation performance with a 36-108% increase in ozone number density and 24-80% increase in ozone yield depending on discharge voltage and frequency differences. To reveal the micro physico-chemical mechanism of the influence of a magnetic field and discharge parameters of discharge voltage and frequency on ozone generation, a plasma chemical reaction network involving electron collision-chain reactions was considered. The results show that these parameters jointly influence ozone generation by affecting electron collision reactions and chain chemical reactions by changing the mean electron energy and plasma gas temperature. In this study, both the experimental results and mechanism analysis suggested that an optimal discharge parameter for ozone generation is the magnetic field assisted, low frequency, high voltage (6.5 kHz, 6.5 kV) surface dielectric barrier discharge. These insights provide guidance for optimizing the discharge parameters of the magnetic field assisted discharge to increase ozone production and reduce energy consumption.

13.
Ren Fail ; 45(1): 2215334, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37345712

RESUMO

OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.


Assuntos
Hiperparatireoidismo Secundário , Complicações Pós-Operatórias , Ablação por Radiofrequência , Insuficiência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Hipocalcemia/epidemiologia , Fósforo , Ablação por Radiofrequência/efeitos adversos , Traumatismos do Nervo Laríngeo Recorrente/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Terapia de Substituição Renal , Distribuição por Idade
14.
Clin Anat ; 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37681447

RESUMO

This study aimed to validate and compare the anatomical variations of the superior intercostal veins, focusing on their origin, course, anastomoses, and destination. In addition, the results were compared with findings from other relevant studies. Fifty Korean and 16 Chinese adult cadavers were dissected for this study. The superior intercostal veins were dissected and measured. In our study of 66 specimens, the right superior intercostal vein was observed in 92.3% of cases, while the left superior intercostal vein was observed in 50%. The right superior intercostal vein was subdivided into six types based on its composition, which mainly drained the second and third right posterior intercostal veins. Similarly, the left superior intercostal vein was subdivided into eight types, primarily involving the second to fourth left posterior intercostal veins. This detailed anatomical study successfully identified and classified the various morphologic types of the superior intercostal vein and reviewed the clinical significance of this vein. The findings of this study can offer valuable anatomical evidence to physicians, aiding in their understanding and utilization of the superior intercostal vein.

15.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985654

RESUMO

Polysaccharides from the species of Boletaceae (Boletales, Agaricomycetes, Basidiomycota) are economically significant to both functional foods and medicinal industries. The crude polysaccharide from Butyriboletus pseudospeciosus (BPP) was prepared, and its physicochemical properties were characterized through the use of consecutive experimental apparatus, and its impact on the gut microbiota of Kunming mice was evaluated. Analyses of the structure characteristics revealed that BPP was mainly composed of Man, Glc, and Gal, possessing the pyranose ring and ß/α-glycosidic linkages. TG analysis exhibited that BPP had great heat stability. The SEM observation performed demonstrated that BPP appeared with a rough, dense, and porous shape. Through the BPP intervention, the serum and fecal biochemical index in mice can be improved obviously (p < 0.05). The abundance of beneficial microbiota in the BPP-treated group was significantly increased, while the abundance of harmful microbiota was significantly decreased (p < 0.05). Based on the Tax4Fun, we also revealed the relationship between the species of gut microbiota and showed that the high dose of BPP has significantly changed the functional diversities compared with those in other groups (p < 0.05). The results suggest that B. pseudospeciosus could serve as potential functional food or medicine.


Assuntos
Ascomicetos , Basidiomycota , Microbioma Gastrointestinal , Camundongos , Animais , Polissacarídeos/química , Basidiomycota/química , Carpóforos/química
16.
Angew Chem Int Ed Engl ; 62(49): e202313016, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37823882

RESUMO

Both the regional isomerization and selenium-substitution of the small molecular acceptors (SMAs) play significant roles in developing efficient organic solar cells (OSCs), while their synergistic effects remain elusive. Herein, we developed three isomeric SMAs (S-CSeF, A-ISeF, and A-OSeF) via subtly manipulating the mono-selenium substituted position (central, inner, or outer) and type of heteroaromatic ring on the central core by synergistic strategies for efficient OSCs, respectively. Crystallography of asymmetric A-OSeF presents a closer intermolecular π-π stacking and more ordered 3-dimensional network packing and efficient charge-hopping pathways. With the successive out-shift of the mono-selenium substituted position, the neat films give a slightly wider band gap and gradually higher crystallinity and electron mobility. The PM1 : A-OSeF afford favourable fibrous phase separation morphology with more ordered molecular packing and efficient charge transportation compared to the other two counterparts. Consequently, the A-OSeF-based devices achieve a champion efficiency of 18.5 %, which represents the record value for the reported selenium-containing SMAs in binary OSCs. Our developed precise molecular engineering of the position and type of selenium-based heteroaromatic ring of SMAs provides a promising synergistic approach to optimizing crystal stacking and boosting top-ranked selenium-containing SMAs-based OSCs.

17.
Opt Express ; 30(7): 10969-10980, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473050

RESUMO

We propose a simple scheme to generate quantum entanglement and one-way steering between distinct mode pairs in a generic cavity magnomechanical system, which is composed of a microwave cavity and a yttrium iron garnet sphere supporting magnon and phonon modes. The microwave cavity is pumped by a weak squeezed vacuum field, which plays an important role for establishing quantum entanglement and steering. It is found that when the magnon mode is driven by the red-detuned laser, the maximum entanglement between cavity mode and phonon mode and the maximum phonon-to-photon one-way steering can be effectively generated via adjusting the ratio of two coupling rates. While under the much weaker magnomechanical coupling, the quantum entanglement and one-way steering between cavity mode and magnon mode can be achieved, where the steering direction is determined merely by the relative dissipation strength of the cavity to the magnon mode. More interestingly, we reveal that the robustness to the temperature for entanglement and steering between any mode pairs can be evidently enhanced by selecting the squeezing parameter appropriately.

18.
Mov Disord ; 37(3): 608-613, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35083789

RESUMO

BACKGROUND: Mutations in proline-rich transmembrane protein 2 (PRRT2) are the major cause of paroxysmal kinesigenic dyskinesia (PKD). We recently reported transmembrane protein 151A (TMEM151A) mutations caused PKD. Herein, we aimed to conduct phenotypic comparisons of patients with PKD carrying PRRT2 variants, carrying TMEM151A variants, and carrying neither the PRRT2 nor TMEM151A variant. METHODS: Sanger sequencing of PRRT2 and TMEM151A was performed, and phenotypic characteristics were analyzed. RESULTS: In a cohort of 131 PKD probands (108 without PRRT2 variants and 23 newly recruited), five novel TMEM151A variants were identified and one (c.647C > A) occurred de novo. Together with our previous studies, PRRT2 and TMEM151A variants accounted for 34.7% (85/245) and 6.9% (17/245) of PKD probands, respectively. Compared with patients carrying PRRT2 variants, those with TMEM151A variants tended to exbibit dystonia with shorter durations, have no history of benign infantile epilepsy, and have residual attacks/aura when treated with carbamazepine/oxcarbazepine. CONCLUSIONS: Patients with TMEM151A variants have different features from patients with PRRT2 variants. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Coreia , Distonia , Epilepsia , Humanos , Coreia/genética , Estudos de Coortes , Distonia/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética
19.
Cell Biol Int ; 46(2): 213-221, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34719075

RESUMO

Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Sorafenibe/farmacologia
20.
Brain ; 144(8): 2457-2470, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-33751098

RESUMO

Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A>G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient's fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients' fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.


Assuntos
Deficiência de Citocromo-c Oxidase/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Perda de Heterozigosidade , Mitocôndrias/genética , Adolescente , Adulto , Proliferação de Células/genética , Criança , Pré-Escolar , Deficiência de Citocromo-c Oxidase/fisiopatologia , Feminino , Neuropatias Hereditárias Sensoriais e Autônomas/fisiopatologia , Humanos , Masculino , Nervo Mediano/fisiopatologia , Mutação , Condução Nervosa/fisiologia , Linhagem , Nervo Radial/fisiopatologia , Nervo Ulnar/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA