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Metal-metal bonding is crucial in chemistry for advancing our understanding of the fundamental aspects of chemical bonds. Metal-metal bonds based on alkaline-earth (Ae) elements, especially the heavier Ae elements (Ca, Sr, and Ba), are rarely reported due to their high electropositivity. Herein, we report two heteronuclear di-EMFs CaY@Cs(6)-C82 and CaY@C2v(5)-C80, which contain unprecedented single-electron Ca-Y metal-metal bonds. These compounds were characterized by single-crystal X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and DFT calculations. The crystallographic study of CaY@Cs(6)-C82 shows that Ca and Y are successfully encapsulated into the carbon cage with a Ca-Y distance of 3.691 Å. The CW-EPR study of both CaY@Cs(6)-C82 and CaY@C2v(5)-C80 exhibits a doublet, suggesting the presence of an unpaired electron located between Ca and Y. The combined experimental and theoretical results confirm the presence of a Ca-Y single-electron metal-metal bond with substantial covalent interaction, attributed to significant overlap between the 4s4p orbitals of Ca and the 5s5p4d orbitals of Y. Furthermore, pulse EPR spectroscopy was used to investigate the quantum coherence of the electron spin within this bond. The unpaired electron, characterized by its s orbital nature, is effectively protected by the carbon cage, resulting in efficient suppression of both spin-lattice relaxation and decoherence. CaY@Cs(6)-C82 behaves as an electron spin qubit, displaying a maximum decoherence time of 7.74 µs at 40 K. This study reveals an unprecedented Ae-rare-earth metal-metal bond stabilized by the fullerene cages and elucidates the molecular qubit properties stemming from their unique bonding character, highlighting their potential in quantum information processing applications.
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We demonstrate a unique pulse-splitting mechanism dominated by the linear coupling between two vector modes in a mode-locked fiber laser using polarization-maintaining fiber. As the linear coupling strength increases, the pulse experiences larger perturbations and manifests as stronger spectral sidebands. Correspondingly, the temporal pedestals possessing a higher intensity become untrapped and eventually evolve into a stable pulse. Such linear coupling-related pulse splitting is ubiquitous both in normal- and anomalous-dispersion regimes, fundamentally differing from that induced by the excessive nonlinear phase shift. Experimental observations fully sustain numerical results and provide a flexible approach to managing the number and energy of vector solitons.
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According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by inâ vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC50 values of 15.12â µM and 12.33â µM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100â µM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100â µM. The toxicity analysis inâ vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100â µM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders.
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Doença de Alzheimer , Butirilcolinesterase , Humanos , Butirilcolinesterase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Monoaminoxidase , Benzotiazóis/farmacologia , Morfolinas , Relação Estrutura-Atividade , Estrutura Molecular , Simulação de Acoplamento MolecularRESUMO
In a nonlinear optical system with birefringence such as fiber lasers, soliton trapping can be achieved when the fast (slow) component experiences blueshift (redshift) at normal dispersion to compensate for polarization-mode dispersion (PMD). In this Letter, we demonstrate an anomalous vector soliton (VS) whose fast (slow) component shifts to the red (blue) sides, which is opposite to traditional soliton trapping. It is found that the repulsion between the two components is induced by net-normal dispersion and PMD, while the attraction is ascribed to linear mode coupling and saturable absorption. The equilibrium of attraction and repulsion permits the self-consistent evolution of VSs circulating in the cavity. Our results indicate that the stability and dynamics of VSs are worth revisiting and studying in-depth, especially in lasers with complex configurations, despite it being a well-known object in nonlinear optics.
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Ultrafast few-mode fiber lasers have received increasing attention from basic research to practical applications due to their unique pulse performance and intriguing nonlinear dynamics. Here, we experimentally and numerically reveal the formation and evolution behaviors of a soliton in a mode-locked fiber laser composed of two-mode and single-mode fibers. The LP11 pulse walks away from the LP01 pulse in the two-mode fiber due to modal dispersion and then transforms into an auxiliary LP01 pulse after entering the single-mode fiber. After re-entering the two-mode fiber, the LP01 pulse excites the LP11 pulse via mode coupling; therefore, the LP11 pulse also consists of dominant and auxiliary pulses. Such a soliton fiber laser converges to an asymptotic steady state with unlocked spatial modes arising from the interplay between the strong modal dispersion and weak mode coupling.
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Pulsating solitons are intriguing objects in laser physics and nonlinear science. Recently, emerging works on the pulsating multi-solitons have raised interest in interactions and synchronizations within multiple breathers. However, with their separation of the order of nanoseconds, the evolution and underlying dynamics of multiple pulsating solitons remain uncharted. In this work, we bring initial insights into the pulsating dual-soliton (PDS) with a separation of three orders of magnitude of the pulse duration. Chaotic, synchronous, and asynchronous pulsations are revealed to be controlled by the pump power. Specifically, two solitons can pulsate synchronously in the form of a frozen limit cycle. The asynchronous PDS at a high pump power brings the rotating limit cycle in the phase space. Unveiling the evolutionary dynamics of PDS, this work has potential in all-optical storage, signal encoding, and time division multiplexing communications.
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The bound states (BSs) of solitons are found to have intriguing internal dynamics in ultrafast lasers. Here, we explore the binding mechanism and internal motions of asymmetric bound state (ABS) solitons constituted by unequal solitons at short-range with their tails directly overlapped. Experiments and simulations show that the periodic energy flux between two solitons, mediated by their overlapped tails, gives rise to a balanced separation and energy distribution across the ABS. The motion mechanisms of strong and weak solitons are discussed in detail. This work provides insights into the binding mechanism and internal dynamics of BSs.
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A series of chalcone derivatives (3a-3m) containing 4-phenylquinoline and benzohydrazide were designed and synthesized, and their anti-inflammatory, analgesic, and antidepressant activities were evaluated. Using the classic antidepressant model, except for compounds 3a and 3d, 11 compounds all showed certain antidepressant activity at a dose of 100â mg/kg, among which compounds 3f, 3h, and 3m showed good antidepressant activity (inhibition rate, respectively 63.0 %, 73.2 %, and 76.4 %), which was equivalent to the positive control fluoxetine (inhibition rate of 70.0 %). Secondly, the inhibitory activity of these compounds on mouse MAOA was evaluated. At 10â mM, compounds 3f and 3j showed a certain selective inhibitory effect on mouse MAOA , while compounds 3b, 3d, 3g, 3i, and 3m had a good inhibitory effect on mouse MAOA (inhibition rate is 42.3-71.4 %). The mouse ear edema model was used to evaluate the anti-inflammatory activity of compounds 3a-3m. At 30â mg/kg, compounds 3b, 3c, 3e, 3f, 3g, and 3m showed certain anti-inflammatory effects (inhibition rate of 51.5-99.9 %), which was equivalent to the positive control indomethacin (inhibition rate of 69.7 %). Results of the acetic acid-induced abdominal writhing test showed that, at 30â mg/kg, excepted for compounds 3a, 3b and 3d, all the other 10 compounds can show certain analgesic activity (inhibition rate 67-99.9 %). The use of Auto dock Vina (simina) to simulate molecular target docking shows that the development of quinoline and benzohydrazide groups is of great significance to MAOA inhibitors.
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Chalcona , Chalconas , Animais , Anti-Inflamatórios/farmacologia , Chalcona/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.
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Butirilcolinesterase , Inibidores da Monoaminoxidase , Humanos , Inibidores da Monoaminoxidase/farmacologia , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Butirilcolinesterase/metabolismo , Monoaminoxidase/metabolismo , Benzotiazóis/farmacologia , Isoquinolinas , Inibidores da Colinesterase/farmacologia , Estrutura MolecularRESUMO
BACKGROUND: Bladder cancer is one of the most commonly diagnosed urological malignant tumor. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in bladder cancer remains to be characterized. METHODS: Western blot was used to measure the expression of MINDY1 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect the cell viability. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between MINDY1 and YAP. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. RESULTS: In the present study, we identified MINDY1, a DUB enzyme in the motif interacting with ubiquitin-containing novel DUB family, as a bona fide deubiquitylase of YAP in bladder cancer. MINDY1 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. MINDY1 depletion significantly decreased bladder cancer cell proliferation. The effects induced by MINDY1 depletion could be rescued by further YAP overexpression. Depletion of MINDY1 decreased the YAP protein level and the expression of YAP/TEAD target genes in bladder cancer, including CTGF, ANKRD1 and CYR61. CONCLUSION: In general, our findings establish a previously undocumented catalytic role for MINDY1 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of bladder cancer.
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BACKGROUND: As a pivotal regulator, cyclin D3 gives play to a crucial value in conversion from the G1 stage to the S stage of cell cycle, which is implicated in tumor progression, especially proliferation and migration. Recent literatures have reported that cyclin D3 could predict survival time of malignancy patients. But, its prognostic role of cyclin D3 in neoplasms remains controversial. METHODS: Databases involving EMBASE, PubMed and Web of Science were carefully searched, and literatures investigating the prognostic effect of aberrantly expressing cyclin D3 among human cancers were collected for further analysis. We used both hazards ratios and its corresponding 95% confidence intervals to evaluate the connection among the survival rate of malignancy patients and the expression of cyclin D3. RESULTS: There were 13 eligible researches involving 16 cohorts and 2395 participants which were included in this study. The outcomes suggested that highly expressing cyclin D3 was significantly correlated with worse clinical prognosis of overall survival (HR 1.88; 95% CI 1.31-2.69) and disease specific survival (HR 2.68; 95% CI 1.35-5.31). But there existed no significant connection between the elevated expression of cyclin D3 with disease free survival (HR 2.65; 95% CI 0.83-8.46), recurrence-free survival (HR 2.86; 95% CI 0.82-9.96) and progression-free survival (HR 5.24; 95% CI 0.46-60.25) of diffident kinds of malignancy patients. Moreover, we discovered that elevated cyclin D3 expression was significantly connected with decreased overall survival in lymphoma (HR 3.72; 95% CI 2.18-6.36) while no significant relevance between highly expressing cyclin D3 and the overall survival in breast cancer was obtained (HR 2.12; 95% CI 0.76-5.91). CONCLUSIONS: This meta-analysis demonstrated that highly expressing cyclin D3 might be an unfavorable prognostic biomarker for various malignancy patients, which can make great contributions to the clinical diagnosis and treatment.
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OBJECTIVE: The aim of this study was to evaluate the effectiveness of virtual reality interventions for improving balance and gait in people with Parkinson's disease. DESIGN: This is a systematic review and meta-analysis of randomized controlled trials. METHODS: Databases of MEDLINE, Cochran Central Register of Controlled Trials, EMBASE, PEDro, Web of Science and China Biology Medicine disc were searched from their inception up to 1 March 2019. Two reviewers individually appraised literatures for inclusion, extracted data and evaluated trial quality. RESULTS: A total of 12 studies with a median PEDro score of 6.4 and involving 419 participants were included. This review first demonstrated significant improvements in Berg Balance Scale (mean difference = 2.69; 95% confidence interval = 1.37 to 4.02; p < 0.0001), Timed Up and Go Test (mean difference = -2.86; 95% confidence interval = -5.60 to -0.12; p = 0.04) and stride length (mean difference = 9.65; 95% confidence interval = 4.31 to 14.98; p = 0.0004) in Parkinson patients who received virtual reality compared with controls. However, there was no significant difference in gait velocity and walk distance. CONCLUSION: This systematic review and meta-analysis supports the use of virtual reality to enhance the balance of patients with Parkinson's disease. However, the review does not find any definite effect upon gait by the use of virtual reality.
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Marcha/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/reabilitação , Equilíbrio Postural/fisiologia , Terapia de Exposição à Realidade Virtual , HumanosRESUMO
We demonstrate a mode converter with an insertion loss of 0.36 dB based on mode coupling of tapered single-mode and two-mode fibers, and realize all-fiber flexible cylindrical vector lasers at 1550 nm. Attributing to the continuous distribution of a tangential electric field at taper boundaries, the laser is switchable between the radially and azimuthally polarized states by adjusting the input polarization. In the temporal domain, the operation is controllable among continuous-wave, Q-switched, and mode-locked statuses by changing the saturable absorber or pump strength. The duration of Q-switched radially/azimuthally polarized laser spans from 10.4/10.8 to 6/6.4 µs at the pump range of 38 to 58 mW, while that of the mode-locked pulse varies from 39.2/31.9 to 5.6/5.2 ps by controlling the laser bandwidth. The proposed laser combines the features of a cylindrical vector beam, a fiber laser, and an ultrafast pulse, providing a special and cost-effective source for practical applications.
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Reprogramming of energy metabolism is one of the most important characteristics of tumors. Bladder cancer (BLCA) cells contain higher levels of cholesterol content compared to normal cells, and acyl-coenzyme A (CoA): cholesterol acyltransferase-1 (ACAT1) plays a crucial role in the esterification of cholesterol. Avasimibe is a drug that has been used in the treatment of atherosclerosis, and it can effectively inhibit ACAT1. We observed that ACAT1 was significantly up-regulated in BLCA and positively correlated with tumor grade. By avasimibe administration, the proliferation and migration ability of BLCA cells were reduced, while the production of ROS was strongly increased, accompanied by the up-regulated expression of ROS metabolism-related proteins SOD2 and catalase. Furthermore, BLCA cell cycle was arrested at the G1 phase, accompanied by the downregulation of cell cycle-related proteins (CCNA1/2, CCND1, CDK2 and CDK4), while the PPARγ was found to be up-regulated at both transcriptional and protein levels after avasimibe treatment. Then we found that the PPARγ antagonist GW9662 could reverse the effect of avasimibe on the cell cycle. Moreover, xenograft and pulmonary metastasis models further demonstrated that avasimibe could inhibit tumor cell growth and metastasis in vivo. Taken together, our results for the first time revealed that avasimibe can inhibit BLCA progression and metastasis, and PPARγ signaling pathway may play a key role in regulation of cell cycle distribution induced by avasimibe.
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Prostate cancer (PCa) is the most common malignant tumor with a high global incidence in males. The mechanism underlying PCa progression is still not clear. This study observed that NRP1 was highly expressed in PCa and associated with poor prognosis in PCa patients. Functionally, NRP1 depletion attenuated the proliferation and migration ability of PCa cells in vitro and in vivo, while NRP1 overexpression promoted PCa cell proliferation and migration. Moreover, it was observed that NRP1 depletion induced G1 phase arrest in PCa cells. Mechanistically, HIF1α is bound to the specific promoter region of NRP1, thereby regulating its transcriptional activation. Subsequently, NRP1 interacted with EGFR, leading to EGFR phosphorylation. This study also provided evidence that the b1/b2 domain of NRP1 was responsible for the interaction with the extracellular domain of EGFR. Moreover, EGFR mediated NRP1-induced activation of the AKT signaling pathway, which promoted the malignant progression of PCa. In addition, the administration of NRP1 inhibitor EG01377 significantly inactivated the EGFR/AKT signaling axis, thereby suppressing PCa progression. In conclusion, the findings from this study highlighted the molecular mechanism underlying NRP1 expression in PCa and provide a potential predictor and therapeutic target for clinical prognosis and treatment of PCa.
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Neuropilina-1 , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-akt , Humanos , Masculino , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neuropilina-1/metabolismoRESUMO
Enhanced recovery after surgery (ERAS) pathway comprises a set of comprehensive elements which have been reported to enhance patient postoperative prognosis. In the current study, we aimed to evaluate the effectiveness of the ERAS in patients undergoing laparoscopic adrenal resection. A retrospective review was performed to compare the outcomes of patients undergoing adrenalectomy for primary aldosteronism between the pre-ERAS period and the ERAS era. Data was generated from the traditional surgical period (September 1, 2019, to December 31, 2019) and the ERAS period (September 1, 2020, to December 31, 2020), respectively. Forty-seven adrenalectomy patients were enrolled (pre-ERAS, n = 21; ERAS, n = 26) in analysis. The results revealed that both total length of hospital stay and postoperative length of stay decreased in the ERAS period compared with the pre-ERAS period (14.19 ± 4.96 vs 11.27 ± 4.37, p = 0.015; 5.43 ± 1.08 vs 3.31 ± 0.97, p < 0.001). The medical expenses decreased significantly in the ERAS group (p < 0.05). While, the surgery-related complications, including urinary retention, retroperitoneal effusion and gastrointestinal discomfort, possessed no statistical difference. The ERAS pathway was safe and feasible for adrenalectomy in patients with primary aldosteronism. The ERAS could promote patients to quickly recover from the postoperative status to a physiological state, and decrease the length of hospitalization and medical cost after surgery.
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Recuperação Pós-Cirúrgica Melhorada , Hiperaldosteronismo , Laparoscopia , Adrenalectomia , Humanos , Hiperaldosteronismo/cirurgia , Laparoscopia/métodos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
Purpose: To assess the impact of enhanced recovery after surgery (ERAS) protocols in laparoscopic radical nephrectomy (LRN). Methods: The clinical data of 89 patients underwent LRN in Zhongnan Hospital of Wuhan University from February 2019 to September 2021 were collected (40 in the ERAS group and 49 in the pre-ERAS group). The clinical characteristics, prognosis, and length of hospital stay (LOS) were compared between the two groups using t test, Mann-Whitney test, and chi-square test. Results: Total LOS and postoperative LOS were significantly shorter in ERAS group than in pre-ERAS group [15.0 (13.5-19.5) vs. 12.0 (10.0-14.0), P < 0.001; 8.0 (7.0-10.0) vs. 7.0 (5.0-8.8), P = 0.001]. Compared with the pre-ERAS group, the hospitalization expenses of the ERAS group were also lower (P = 0.023). In addition, the incidence of postoperative complications in the ERAS group also decreased (P = 0.054). Conclusions: ERAS protocol in LRN could help accelerate the recovery of patients and is worthy of clinical promotion.
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BACKGROUND: Denticleless E3 ubiquitin protein ligase homolog (DTL) has been reported to be an important regulator for tumorigenesis and progression. Nonetheless, the biological functions and molecular mechanisms of DTL in BCa remain elusive. METHODS: We implemented integrative bioinformatics analysis to explore the diagnostic and prognostic values of DTL based on The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) databases. Then, we utilized qRT-PCR and immunohistochemistry to verify the clinical significance of DTL expression according to clinical specimens and tissue microarray (TMA). Moreover, the biological functions and underlying mechanisms of DTL in BCa were investigated through in vitro and in vivo experiments. RESULTS: Integrative bioinformatics analysis revealed that DTL was a key gene associated with BCa progression, and increased DTL expression was correlated with malignant biological behavior and poor prognosis. Experiments on clinical specimens and tissue microarray (TMA) further confirmed our findings. Bioinformatics analysis demonstrated that DTL could be associated with cell cycle- and DNA replication-associated pathways in BCa. The suppression of DTL inhibited BCa cell proliferation, migration, and invasion in vivo and in vitro. Mechanistically, DTL may promote BCa progression through the AKT/mTOR pathway. CONCLUSIONS: Increased DTL expression was correlated with malignant biological behavior and poor prognosis of BCa patients, and it may promote BCa progression through the AKT/mTOR pathway. Our research provided a potential predictor and therapeutic target for BCa.
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Biomarcadores Tumorais/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/patologia , Idoso , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Genéticas , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Curva ROC , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genéticaRESUMO
Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare inherited monogenic autoimmune disease characterized by the presence of at least two of three following major clinical features: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Mutations in autoimmune regulator (AIRE) gene have been found to contribute to APS-1. In the present study, we reported a 36-years-old male APS-1 patient who presented with hypoparathyroidism and Addison's disease. The proband underwent complete clinical examinations and mutation screening was performed by Sanger sequencing on AIRE gene. A novel homozygous mutation in exon 9 of the AIRE gene (c.1024C>T) was identified. Based on sequencing findings, HEK293T cell-based assays were conducted to analyze the subcellular localization and mutant transcript processing. Our results revealed that p.Q342X mutant localized in nuclear speckles and exerted a dominant-negative effect on wildtype AIRE function. We reported the c.1024C>T mutation of AIRE gene for the first time, which enriched the AIRE mutation database and contributed to further understanding of APS-1.
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Direct generation of chirp-free solitons without external compression in normal-dispersion fiber lasers is a long-term challenge in ultrafast optics. We demonstrate near-chirp-free solitons with distinct spectral sidebands in normal-dispersion hybrid-structure fiber lasers containing a few meters of polarization-maintaining fiber. The bandwidth and duration of the typical mode-locked pulse are 0.74 nm and 1.95 ps, respectively, giving the time-bandwidth product of 0.41 and confirming the near-chirp-free property. Numerical results and theoretical analyses fully reproduce and interpret the experimental observations, and show that the fiber birefringence, normal-dispersion, and nonlinear effect follow a phase-matching principle, enabling the formation of the near-chirp-free soliton. Specifically, the phase-matching effect confines the spectrum broadened by self-phase modulation and the saturable absorption effect slims the pulse stretched by normal dispersion. Such pulse is termed as birefringence-managed soliton because its two orthogonal-polarized components propagate in an unsymmetrical "X" manner inside the polarization-maintaining fiber, partially compensating the group delay difference induced by the chromatic dispersion and resulting in the self-consistent evolution. The property and formation mechanism of birefringence-managed soliton fundamentally differ from other types of pulses in mode-locked fiber lasers, which will open new research branches in laser physics, soliton mathematics, and their related applications.