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1.
Nucleic Acids Res ; 52(5): 2212-2230, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38364871

RESUMO

Nonreference sequences (NRSs) are DNA sequences present in global populations but absent in the current human reference genome. However, the extent and functional significance of NRSs in the human genomes and populations remains unclear. Here, we de novo assembled 539 genomes from five genetically divergent human populations using long-read sequencing technology, resulting in the identification of 5.1 million NRSs. These were merged into 45284 unique NRSs, with 29.7% being novel discoveries. Among these NRSs, 38.7% were common across the five populations, and 35.6% were population specific. The use of a graph-based pangenome approach allowed for the detection of 565 transcript expression quantitative trait loci on NRSs, with 426 of these being novel findings. Moreover, 26 NRS candidates displayed evidence of adaptive selection within human populations. Genes situated in close proximity to or intersecting with these candidates may be associated with metabolism and type 2 diabetes. Genome-wide association studies revealed 14 NRSs to be significantly associated with eight phenotypes. Additionally, 154 NRSs were found to be in strong linkage disequilibrium with 258 phenotype-associated SNPs in the GWAS catalogue. Our work expands the understanding of human NRSs and provides novel insights into their functions, facilitating evolutionary and biomedical researches.


Assuntos
Genoma Humano , Estudo de Associação Genômica Ampla , Grupos Populacionais , Humanos , Diabetes Mellitus Tipo 2/genética , Desequilíbrio de Ligação , Fenótipo , Polimorfismo de Nucleotídeo Único , Genética Populacional , Grupos Populacionais/genética
2.
Opt Express ; 32(10): 16732-16745, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858872

RESUMO

The orbital angular momentum (OAM) of vortex beams has great potential in optical communications due to its communication confidentiality and low crosstalk. It is necessary to design a plausible OAM pattern recognition mechanism. Abandoning AI models that require large datasets, a single passive all-dielectric metasurface consisting of TiO2 nanopillars on a SiO2 substrate is used to recognize high-order optical vortexes. In this configuration, the proposed device is capable of simultaneously encoding the wavefront and the transmission paths in different incident OAM beams. Due to the presence of spin angular momentum (SAM), the vortex beam to be identified is spatially separated after passing through the metasurface. As a proof of concept, 14 signal channels are considered in the constructed metasurface, 12 of them can be encoded at will for the detection of any vortex beam with a predefined topological charge. These results make use of metasurfaces to enable OAM pattern recognition in an effective way, which may open avenues for the ultimate miniaturization of optical vortex communication and advanced OAM detection technologies.

3.
Opt Express ; 32(7): 12092-12103, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571042

RESUMO

To achieve an autonomously controlled reconfigurable microwave waveform generator, this study proposes and demonstrates a self-adjusting synthesis method based on a photonic delay reservoir computer with ring resonator. The proposed design exploits the ring resonator to configure the reservoir, facilitating a nonlinear transformation and providing delay space. A theoretical analysis is conducted to explain how this configuration addresses the challenges of microwave waveform generation. Considering the generalization performance of waveform generation, the simulations demonstrate the system's capability to produce six distinct representative waveforms, all exhibiting a highly impressive root mean square error (RMSE) of less than 1%. To further optimize the system's flexibility and accuracy, we explore the application of various artificial intelligence algorithms at the reservoir computer's output layer. Furthermore, our investigation delves deeply into the complexities of system performance, specifically exploring the influence of reservoir neurons and micro-ring resonator parameters on calculation performance. We also delve into the scalability of reservoirs, considering both parallel and cascaded arrangements.

4.
Opt Express ; 32(2): 1406-1420, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297693

RESUMO

The noise figure (NF) of a fiber amplifier is one of the key measures of amplification performance, which characterizes the quality of the amplified signal. Residual stresses are inevitably generated during the manufacturing process of optical fibers, and this can lead to changes in the refractive index (RI) distribution of the fiber. Further, the change in RI distribution causes the mode-field characteristics of the fiber to change as well, and this ultimately has an impact on the NF performance of the amplifier. However, until now, there have been fewer studies on the effect of residual stress on the NF of the fiber amplifiers. In this work, we took a commercial single-mode bismuth-doped fiber (BDF) as an example and used a self-developed stress test device to measure its residual stress and refractive index distribution and compare it with that of a passive fiber. We also comprehensively compared the distribution of residual stress and refractive index of the fiber at different pump powers and pump wavelengths. Finally, we performed numerical simulations of the bismuth-doped fiber amplifier (BDFA) based on the BDF under the theoretical mode field area and BDF after the expansion of the mode field area due to stresses to compare the NF performance. The results demonstrate that: the entire cross-section (core and cladding) of the BDF exhibits tensile stress (>0 MPa), where the residual stress at the core of the BDF is nearly 9.8 MPa higher than that of the passive fiber; The residual stress makes the mode-field area of the BDF expand by 26.7% compared with the theoretical values, which ultimately makes the NF of the BDFA rise from 4.6 dB to 4.7 dB; The stress at the BDF core is exacerbated by pump excitation, where it is elevated by about 26% and 5% compared to vacancy at 1240 nm and 1310 nm pumps, which is most likely attributed to thermal effects. Therefore, it is necessary to consider the effect of residual stresses in the fabrication of optical fibers to better achieve the radius of the expected indicators. This work contributes to the better development of O-band BDFAs, especially for pre-simulation of the actual performance of BDFAs with a practical reference.

5.
Opt Express ; 32(12): 21007-21016, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859466

RESUMO

Finding suitable fiber amplifiers is one of the key strategies to increase the transmission capacity of fiber links. Recently, bismuth-doped fiber amplifiers (BDFAs) have attracted much attention due to their distinctive ultra-wideband luminescence properties. In this paper, we propose a linear cavity double pass structure for BDFA operating in the O and E bands. The design creates a linear cavity within the amplifier by combining a fiber Bragg grating (FBG) and a fiber mirror to achieve dual-wavelength pump at 1240 nm and 1310 nm. Meanwhile, the configuration of a circulator and mirror facilitates bidirectional signal propagation through the BDFA, resulting in a double-pass amplification structure. We have tested and analyzed the performance of the linear cavity double pass structure BDFA under different pump schemes and compared it with the conventional structure BDFA. The results show that the gain spectrum of the new structure is shifted toward longer wavelengths, and the gain band is extended from the O band to the O and E bands compared with the conventional structure. In particular, the linear cavity double pass structure BDFA has more relaxed requirements on the stability of the pump and signal power. This work provides a positive reference for the design, application, and development of BDFAs.

6.
Cell Commun Signal ; 22(1): 279, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773637

RESUMO

O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O­GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.


Assuntos
Acetilglucosamina , N-Acetilglucosaminiltransferases , Humanos , Animais , N-Acetilglucosaminiltransferases/metabolismo , Acetilglucosamina/metabolismo , Osso e Ossos/metabolismo , Processamento de Proteína Pós-Traducional , Doenças Ósseas/metabolismo
7.
Mol Cell Biochem ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503948

RESUMO

NEK2 is a serine/threonine protein kinase that is involved in regulating the progression of various tumors. Our previous studies have found that NEK2 is highly expressed in gastric cancer and suggests that patients have a worse prognosis. However, its role and mechanism in gastric cancer are only poorly studied. In this study, we established a model of ferroptosis induced by RSL3 or Erastin in AGS cells in vitro, and konckdown NEK2, HOMX1, Nrf2 by siRNA. The assay kit was used to analyzed cell viability, MDA levels, GSH and GSSG content, and FeRhoNox™-1 fluorescent probe, BODIPY™ 581/591 C11 lipid oxidation probe, CM-H2DCFDA fluorescent probe were used to detected intracellular Fe2+, lipid peroxidation, and ROS levels, respectively. Calcein-AM/PI staining was used to detect the ratio of live and dead cells, qRT-PCR and Western blot were used to identify the mRNA and protein levels of genes in cells, immunofluorescence staining was used to analyze the localization of Nrf2 in cells, RNA-seq was used to analyze changes in mRNA expression profile, and combined with the FerrDb database, ferroptosis-related molecules were screened to elucidate the impact of NEK2 on the sensitivity of gastric cancer cells to ferroptosis. We found that inhibition of NEK2 could enhance the sensitivity of gastric cancer cells to RSL3 and Erastin-induced ferroptosis, which was reflected in the combination of inhibition of NEK2 and ferroptosis induction compared with ferroptosis induction alone: cell viability and GSH level were further decreased, while the proportion of dead cells, Fe2+ level, ROS level, lipid oxidation level, MDA level, GSSG level and GSSG/GSH ratio were further increased. Mechanism studies have found that inhibiting NEK2 could promote the expression of HMOX1, a gene related to ferroptosis, and enhance the sensitivity of gastric cancer cells to ferroptosis by increasing HMOX1. Further mechanism studies have found that inhibiting NEK2 could promote the ubiquitination and proteasome degradation of Keap1, increase the level of Nrf2 in the nucleus, and thus promote the expression of HMOX1. This study confirmed that NEK2 can regulate HMOX1 expression through Keap1/Nrf2 signal, and then affect the sensitivity of gastric cancer cells to ferroptosis, enriching the role and mechanism of NEK2 in gastric cancer.

8.
Cell Mol Biol (Noisy-le-grand) ; 70(1): 128-133, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372108

RESUMO

The purpose of this study was to analyze the correlation between vaginal flora and immune function Type 1 helper T cells/Type 2 helper T cells imbalance in females having HPV infections at high risk within the female reproductive tract. We selected 150 female patients who visited our hospital for reproductive tract inflammation between March 2019 and March 2021. They were divided into high-risk HPV-positive and high-risk HPV-negative groups according to the results of the HPV tests. Vaginal flora composition, density, diversity, and Th1/Th2 immune cell cytokine expression were assessed, and their correlations were analyzed. Compared to the HPV-negative group at high risk, the HPV-positive group at high risk exhibited significantly higher rates of Lactobacillius abnormalities, Chlamydia trachomatis and Mycoplasma urealyticum positivity(P<0.05). However, no statistically significant differences in the rates of Neisseria gonorrhoeae, bacterial vaginosis, mould, and trichomonad positivity were observed in both groups (P>0.05). The high-risk HPV-positive group displayed significantly higher rates of abnormal vaginal flora density and diversity compared to the HPV-negative group at high risk (P < 0.05). Compared to the HPV-negative group at high risk, the HPV-positive group at high risk exhibited significantly lower expression levels of Th1, Th1/Th2, IFN-γ, and IL-2 and higher expression levels of Th2, IL-4, and IL-10(P<0.05). Among patients having HPV infections at high risk, those with abnormal vaginal flora had lower expression levels of Th1, Th1/Th2, IFN-γ, and IL-2 and higher expression levels of Th2, IL-4, and IL-10 compared to those with normal vaginal flora, all of which were statistically significant(P<0.05). Vaginal flora dysbiosis was correlated with Th1/Th2 imbalance (P<0.05). Women with high-risk HPV infections in the female reproductive tract exhibit abnormal vaginal flora and immune function Th1/Th2 imbalance, characterized by a shift from Th1 to Th2. Moreover, there is a close correlation between vaginal flora dysbiosis and immune function Th1/Th2 imbalance.


Assuntos
Interleucina-10 , Infecções por Papillomavirus , Humanos , Feminino , Interleucina-10/metabolismo , Interleucina-2 , Disbiose/metabolismo , Interleucina-4/metabolismo , Células Th1/metabolismo , Imunidade , Células Th2/metabolismo
9.
J Chem Phys ; 160(14)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38597307

RESUMO

A new multiple-time scale integration method is presented that propagates ab initio path integral molecular dynamics (PIMD). This method uses a large time step to generate an approximate geometrical configuration whose energy and gradient are evaluated at the level of an ab initio method, and then, a more precise integration scheme, e.g., the Bulirsch-Stoer method or velocity Verlet integration with a smaller time step, is used to integrate from the previous step using the computationally efficient interpolated potential energy surface constructed from two consecutive points. This method makes the integration of PIMD more efficient and accurate compared with the velocity Verlet integration. A Nosé-Hoover chain thermostat combined with this new multiple-time scale method has good energy conservation even with a large time step, which is usually challenging in velocity Verlet integration for PIMD due to the very small chain mass when a large number of beads are used. The new method is used to calculate infrared spectra and free energy profiles to demonstrate its accuracy and capabilities.

10.
J Am Chem Soc ; 145(27): 14686-14696, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37392183

RESUMO

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

11.
Appl Opt ; 62(6): 1567-1574, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821318

RESUMO

A step index few-mode erbium-doped fiber (FM-EDF) for mode gain equalization is designed and proposed in this paper, which uses the layered-doping method to reduce the differential mode gain (DMG). The optimum structure of FM-EDF is obtained by adjusting the doping radius and doping concentration. When this structure is applied to a few-mode erbium-doped fiber amplifier (FM-EDFA), the DMG in the range of 1550-1565 nm is ∼0.28d B, and the DMG of the whole C-band is usually less than 0.5 dB. At the same time, the gain of each mode in 1530-1555 nm is ∼20d B, while the gain decreases gradually in the 1555-1565 nm due to the absorption characteristics of erbium ions. In addition, the minimum refractive index difference (Δ n eff) between modes is 1.29∗10-3 due to the selection of the refractive index and radius of the fiber core, which will greatly reduce the coupling between modes in practical application. Tolerances in the fiber manufacturing process are also considered for reliable FM-EDFA performance. When the doping concentration or the doping radius changes based on the precise value, the DMG will increase to a certain extent. In general, the DMG can maintain a small value, which is beneficial to applications in optical communication systems.

12.
Appl Opt ; 62(24): 6366-6374, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706828

RESUMO

A symmetry tunable triangular waveform photonic generator based on channelized frequency synthesis is proposed and studied. The generator adopts a multichannel system architecture and harmonic amplitude control algorithm to physically isolate each subchannel. In a single subchannel, quadrature phase shift keying modulation and coherent dual-wavelength balanced detection are used to realize optical upconversion and suppress mixing interference in the process of frequency conversion. Therefore, the model has the characteristics of a high-order Fourier series fitting tunable function waveform output. The analysis results show that the Fourier series harmonic coefficients can be adjusted flexibly by the multivariable joint regulation algorithm. The relationship between the variables is analyzed and discussed. The feasibility of the scheme is verified by optical simulation; when the rms error (RMSE)≤0.03, a 20%-80% tunable symmetry triangular waveform can be obtained.

13.
Oral Dis ; 29(4): 1439-1453, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35286741

RESUMO

This systematic review was aimed to comprehensively evaluate the clinicopathological and prognostic value of dysregulated expression of circRNAs in OSCC. The research was carried out by searching mainstream electronic databases including PubMed, Embase, Web of Science, Scopus, LILACS, and Cochrane Library to collect relevant studies on prognostic role of circRNAs in OSCC. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, overall survival (OS), disease/recurrence/progression survival (DFS/RFS/PFS), and clinical parameters. This research included 1813 patients from 26 selected articles. The pooled HR values (95% CIs) in OS were 2.38 (1.92-2.93) for oncogenic circRNAs and 0.43 (0.28-0.66) for tumor-suppressor circRNAs, respectively, in DFS/RFS/PFS were 2.34 (1.73-3.17). The meta-analysis on clinicopathology features showed higher level of oncogenic circRNAs is related to advanced TNM stage, tumor stage, worse histological differentiation, positive lymph node and distant metastasis, while enforced expression of tumor-suppressor circRNAs is related to inferior TNM stage, tumor stage and lymphatic metastasis. In conclusion, our meta-analysis implies that circRNAs may be candidate biomarkers for the prognosis and clinicopathology of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Prognóstico , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço , Recidiva Local de Neoplasia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
14.
Altern Ther Health Med ; 29(7): 316-321, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37499146

RESUMO

Context: Facet joint disorder is a series of clinical syndromes that lumbar trauma or degenerative disease can cause, and it can result in lumbar pain and restricted movement. Despite use of conventional Western and traditional Chinese treatments, patients can still experience many clinical symptoms, with no effective improvements in lumbar-spine movement or quality of life. Objective: The study intended to investigate the effects of spinal, fixed-point, rotating reduction on the pain levels and daily living abilities of patients with facet joint disorders. Design: The research team performed a prospective, randomized controlled study. Setting: The study took place at Wuhan Central Hospital, Affiliated to Tongji Medical College, at Huazhong University of Science and Technology in Wuhan, China. Participants: Participants were 88 patients with facet joint disorders who had been admitted to the hospital between June 2021 and August 2022. Intervention: The research team randomly divided participants into two groups, with 44 participants in each group, using the numerical table method: (1) the intervention group, who received treatment using the spinal, fixed-point, rotating reduction method, and (2) the control group, treated who received treatment using conventional tui-na, acupuncture, and traction. Outcome Measures: The research team measured changes: (1) in pain, (2) in lumbar mobility, (3) in lumbar-spine function, and (4) in daily living abilities. Results: In the comparisons between the groups at baseline, no significant differences existed: (1) in pain levels (P = .656); (2) in forward flexion (P = .982), extension (P = .887), lateral flexion (P = .408), or rotation (P = .888); (3) in the scores for clinical symptoms (P = .982), subjective symptoms (P = .887), or limitations in daily activities (P = .408); or (4) in the scores for daily living abilities (P = .427). In the comparisons between the groups at two weeks postintervention, the intervention group's: (1) pain levels were significantly lower than those of the control group (P < .001); (2) forward flexion, extension, lateral flexion, and rotation were significantly higher than those of the control group (all P < .001); (3) scores for clinical symptoms, subjective symptoms, and limitations in daily activities were significantly better than those of the control group (all P < .001); and (4) scores for daily living abilities were subjective higher than those of the control group (P < .001). Conclusion: Spinal, fixed-point, rotating reduction can significantly relieve the pain of patients with facet joint disorders restore their lumbar spine mobility, improve their lumbar spine function, increase their ADL abilities, and facilitate patients' recovery. Practitioners can promote it in clinical practice.


Assuntos
Dor Lombar , Articulação Zigapofisária , Humanos , Qualidade de Vida , Estudos Prospectivos , Dor Lombar/terapia , Vértebras Lombares
15.
Sensors (Basel) ; 23(5)2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36904778

RESUMO

The modal gain equalization (MGE) of few-mode fiber amplifiers (FMFAs) ensures the stability of signal transmission. MGE mainly relies on the multi-step refractive index (RI) and doping profile of few-mode erbium-doped fibers (FM-EDFs). However, complex RI and doping profiles lead to uncontrollable residual stress variations in fiber fabrication. Variable residual stress apparently affects MGE due to its impacts on the RI. So, this paper focuses on the residual stress effects on MGE. The residual stress distributions of passive and active FMFs were measured using a self-constructed residual stress test configuration. As the erbium doping concentration increased, the residual stress of the fiber core decreased, and the residual stress of the active fibers was two orders of magnitude lower than that of the passive fiber. Compared with the passive FMF and the FM-EDFs, the residual stress of the fiber core completely transformed from tensile stress to compressive stress. This transformation led to an obvious smooth RI curve variation. The measurement values were analyzed with FMFA theory, and the results show that the differential modal gain of the FMFA increased from 0.96 to 1.67 dB as the residual stress decreased from 4.86 to 0.01 MPa.

16.
J Mol Cell Cardiol ; 167: 118-128, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35413295

RESUMO

Ryanodine receptor 2 (RyR2) is an ion channel in the heart responsible for releasing into the cytosol most of the Ca2+ required for contraction. Proper regulation of RyR2 is critical, as highlighted by the association between channel dysfunction and cardiac arrhythmia. Lower RyR2 expression is also observed in some forms of heart disease; however, there is limited information on the impact of this change on excitation-contraction (e-c) coupling, Ca2+-dependent arrhythmias, and cardiac performance. We used a constitutive knock-out of RyR2 in rabbits (RyR2-KO) to assess the extent to which a stable decrease in RyR2 expression modulates Ca2+ handling in the heart. We found that homozygous knock-out of RyR2 in rabbits is embryonic lethal. Remarkably, heterozygotes (KO+/-) show ~50% loss of RyR2 protein without developing an overt phenotype at the intact animal and whole heart levels. Instead, we found that KO+/- myocytes show (1) remodeling of RyR2 clusters, favoring smaller groups in which channels are more densely arranged; (2) lower Ca2+ spark frequency and amplitude; (3) slower rate of Ca2+ release and mild but significant desynchronization of the Ca2+ transient; and (4) a significant decrease in the basal phosphorylation of S2031, likely due to increased association between RyR2 and PP2A. Our data show that RyR2 deficiency, although remarkable at the molecular and subcellular level, has only a modest impact on global Ca2+ release and is fully compensated at the whole-heart level. This highlights the redundancy of RyR2 protein expression and the plasticity of the e-c coupling apparatus.


Assuntos
Adrenérgicos , Canal de Liberação de Cálcio do Receptor de Rianodina , Animais , Arritmias Cardíacas/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Acoplamento Excitação-Contração , Miócitos Cardíacos/metabolismo , Coelhos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo
17.
Am J Physiol Heart Circ Physiol ; 322(2): H269-H284, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34951544

RESUMO

The atrial myocardium demonstrates the highly heterogeneous organization of the transversal-axial tubule system (TATS), although its anatomical distribution and region-specific impact on Ca2+ dynamics remain unknown. Here, we developed a novel method for high-resolution confocal imaging of TATS in intact live mouse atrial myocardium and applied a custom-developed MATLAB-based computational algorithm for the automated analysis of TATS integrity. We observed a twofold higher (P < 0.01) TATS density in the right atrial appendage (RAA) than in the intercaval regions (ICR, the anatomical region between the superior vena cava and atrioventricular junction and between the crista terminalis and interatrial septum). Whereas RAA predominantly consisted of well-tubulated myocytes, ICR showed partially tubulated/untubulated cells. Similar TATS distribution was also observed in healthy human atrial myocardium sections. In both mouse atrial preparations and isolated mouse atrial myocytes, we observed a strong anatomical correlation between TATS distribution and Ca2+ transient synchronization and rise-up time. This region-specific difference in Ca2+ transient morphology disappeared after formamide-induced detubulation. ICR myocytes showed a prolonged action potential duration at 80% of repolarization as well as a significantly lower expression of RyR2 and Cav1.2 proteins but similar levels of NCX1 and Cav1.3 compared with RAA tissue. Our findings provide a detailed characterization of the region-specific distribution of TATS in mouse and human atrial myocardium, highlighting the structural foundation for anatomical heterogeneity of Ca2+ dynamics and contractility in the atria. These results could indicate different roles of TATS in Ca2+ signaling at distinct anatomical regions of the atria and provide mechanistic insight into pathological atrial remodeling.NEW & NOTEWORTHY Mouse and human atrial myocardium demonstrate high variability in the organization of the transversal-axial tubule system (TATS), with more organized TATS expressed in the right atrial appendage. TATS distribution governs anatomical heterogeneity of Ca2+ dynamics and thus could contribute to integral atrial contractility, mechanics, and arrhythmogenicity.


Assuntos
Sinalização do Cálcio , Átrios do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Potenciais de Ação , Animais , Canais de Cálcio Tipo L/metabolismo , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Átrios do Coração/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Trocador de Sódio e Cálcio/metabolismo
18.
Opt Express ; 30(22): 39932-39945, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36298935

RESUMO

A novel physics- and data-driven deep-learning (PDDL) method is proposed to execute complete mode decomposition (MD) for few-mode fibers (FMFs). The PDDL scheme underlies using the embedded beam propagation model of FMF to guide the neural network (NN) to learn the essential physical features and eliminate unexpected features that conflict with the physical laws. It can greatly enhance the NN's robustness, adaptability, and generalization ability in MD. In the case of obtaining the real modal weights (ρ2) and relative phases (θ), the PDDL method is investigated both in theory and experiment. Numerical results show that the PDDL scheme eliminates the generalization defect of traditional DL-based MD and the error fluctuation is alleviated. Compared with the DL-based MD, in the 8-mode case, the errors of ρ2 and θ can be reduced by 12 times and 100 times for beam patterns that differ greatly from the training dataset. Moreover, the PDDL maintains high accuracy even in the 8-mode MD case with a practical maximum noise factor of 0.12. In terms of adaptation, with a large variation of the core radius and NA of the FMF, the error keeps lower than 0.43% and 2.08% for ρ2 and θ, respectively without regenerating new dataset and retraining NN. The experimental configuration is set up and verifies the accuracy of the PDDL-based MD. Results show that the correlation factor of the real and reconstructed beam patterns is higher than 98%. The proposed MD-scheme shows much potential in the application of practical modal coupling characterization and laser beam quality analysis.

19.
Opt Express ; 30(26): 47659-47671, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558689

RESUMO

Dispersion characteristic could be a significant factor, which impacts the beat frequency of Multi-longitudinal mode fiber laser (MMFL). In this paper, the mechanism of beat frequency generation in inhomogeneous medium Multi-longitudinal mode fiber laser is discussed. Compared with cavity length-dependent fiber laser sensing system, the proposed model uses a several-millimeter-Fiber-Bragg-Grating (FBG) as the sensing head, which features both high sensitivity and compact size. We designed an experiment to exhibit possible sensing application based on the proposed theory as well.

20.
J Chem Inf Model ; 62(15): 3676-3684, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35838124

RESUMO

Noncoding RNA(ncRNA) is closely related to drug resistance. Identifying the association between ncRNA and drug resistance is of great significance for drug development. Methods based on biological experiments are often time-consuming and small-scale. Therefore, developing computational methods to distinguish the association between ncRNA and drug resistance is urgent. We develop a computational framework called GSLRDA to predict the association between ncRNA and drug resistance in this work. First, the known ncRNA-drug resistance associations are modeled as a bipartite graph of ncRNA and drug. Then, GSLRDA uses the light graph convolutional network (lightGCN) to learn the vector representation of ncRNA and drug from the ncRNA-drug bipartite graph. In addition, GSLRDA uses different data augmentation methods to generate different views for ncRNA and drug nodes and performs self-supervised learning, further improving the quality of learned ncRNA and drug vector representations through contrastive learning between nodes. Finally, GSLRDA uses the inner product to predict the association between ncRNA and drug resistance. To the best of our knowledge, GSLRDA is the first to apply self-supervised learning in association prediction tasks in the field of bioinformatics. The experimental results show that GSLRDA takes an AUC value of 0.9101, higher than the other eight state-of-the-art models. In addition, case studies including two drugs further illustrate the effectiveness of GSLRDA in predicting the association between ncRNA and drug resistance. The code and data sets of GSLRDA are available at https://github.com/JJZ-code/GSLRDA.


Assuntos
Redes Neurais de Computação , RNA não Traduzido , Biologia Computacional/métodos , Resistência a Medicamentos , RNA não Traduzido/genética , Aprendizado de Máquina Supervisionado
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