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Type 1 interferon (IFN) is a key mediator of organismal responses to pathogens, eliciting prototypical "interferon signature genes" that encode antiviral and inflammatory mediators. For a global view of IFN signatures and regulatory pathways, we performed gene expression and chromatin analyses of the IFN-induced response across a range of immunocyte lineages. These distinguished ISGs by cell-type specificity, kinetics, and sensitivity to tonic IFN and revealed underlying changes in chromatin configuration. We combined 1,398 human and mouse datasets to computationally infer ISG modules and their regulators, validated by genetic analysis in both species. Some ISGs are controlled by Stat1/2 and Irf9 and the ISRE DNA motif, but others appeared dependent on non-canonical factors. This regulatory framework helped to interpret JAK1 blockade pharmacology, different clusters being affected under tonic or IFN-stimulated conditions, and the IFN signatures previously associated with human diseases, revealing unrecognized subtleties in disease footprints, as affected by human ancestry.
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Redes Reguladoras de Genes , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Conjuntos de Dados como Assunto , Humanos , Janus Quinases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Interferon alfa e beta/metabolismoRESUMO
Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA.
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Citidina Desaminase/metabolismo , Switching de Imunoglobulina , RNA Guia de Cinetoplastídeos/metabolismo , Animais , Quadruplex G , Íntrons , Proteínas Ligantes de Maltose/metabolismo , Camundongos , Processamento Pós-Transcricional do RNA , RNA Guia de Cinetoplastídeos/genéticaRESUMO
Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.
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Wilms' tumour 1 (WT1) can function as an oncogene or a tumour suppressor. Our previous clinical cohort studies showed that low WT1 expression at diagnosis independently predicted poor outcomes in acute myeloid leukaemia (AML) with RUNX1::RUNX1T1, whereas it had an opposite role in AML with non-favourable cytogenetic risk (RUNX1::RUNX1T1-deficient). The molecular mechanism by which RUNX1::RUNX1T1 affects the prognostic significance of WT1 in AML remains unknown. In the present study, first we validated the prognostic significance of WT1 expression in AML. Then by using the established transfected cell lines and xenograft tumour model, we found that WT1 suppresses proliferation and enhances effect of cytarabine in RUNX1::RUNX1T1(+) AML but has opposite functions in AML cells without RUNX1::RUNX1T1. Furthermore, as a transcription factor, WT1 physically interacts with RUNX1::RUNX1T1 and acts as a co-factor together with RUNX1::RUNX1T1 to activate the expression of its target gene DUSP6 to dampen extracellular signal-regulated kinase (ERK) activity. When RUNX1::RUNX1T1-deficient, WT1 can activate the mitogen-activated extracellular signal-regulated kinase/ERK axis but not through targeting DUSP6. These results provide a mechanism by which WT1 together with RUNX1::RUNX1T1 suppresses cell proliferation through WT1/DUSP6/ERK axis in AML. The current study provides an explanation for the controversial prognostic significance of WT1 expression in AML patients.
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Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2)-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H2O2) will be decomposed by CAT to produce O2, which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen (1O2). The 1O2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.
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Membrana Eritrocítica , Fotoquimioterapia , Porfirinas , Nanomedicina Teranóstica , Fotoquimioterapia/métodos , Membrana Eritrocítica/química , Animais , Nanomedicina Teranóstica/métodos , Porfirinas/química , Porfirinas/uso terapêutico , Nanopartículas/química , Oxigênio/química , Imagem Óptica/métodos , Clorofilídeos , Imagem Molecular/métodos , Catalase/metabolismo , Camundongos , Humanos , Estruturas Metalorgânicas/química , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Oxigênio Singlete/metabolismoRESUMO
A narrow-linewidth and low relative intensity noise (RIN) Tm/Ho co-doped fiber laser based on a saturable absorber and self-injection locking was demonstrated for the first time. Utilizing self-injection locking technology, the frequency noise power spectral density is remarkably reduced by more than 17.1â dB from 1.21 × 106 Hz2/Hz to 7.30 × 103 Hz2/Hz when the frequency is approximately 1 kHz. Furthermore, a laser with a linewidth compressed to a quarter of the original linewidth from 44.386 kHz to 2.850 kHz, a RIN of less than -127.74â dB/Hz, and an optical signal-to-noise ratio of more than 71.6â dB can be obtained. Using a delay fiber, the relaxation oscillation peak frequencies move to lower frequencies, from 27.9 kHz to 15.8 kHz. The proposed laser is highly competitive in advanced coherent light detection fields, including coherent Doppler wind lidar, high-speed coherent optical communication, and precise absolute distance coherent measurement.
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On-chip Bragg gratings with high reflectivities have been found to have widespread applications in filters, resonators, and semiconductor lasers. However, achieving strong Bragg reflections with flat response across a broad bandwidth on the popular 220â nm silicon-on-insulator (SOI) platform still remains a challenge. In this paper, such a high performance device is proposed and fabricated, which is based on a slot waveguide with gratings etched on the inner sidewalls of the slot. By manipulating the local field in the slot region using a chirped and tapered grating-based mode transition, the device achieves a flat response with ultra-high reflection and low transmission for the TE mode across a broad operating bandwidth. Leveraging the ultra-high birefringence of the SOI waveguide, the device functions both as a TE slot waveguide reflector and a TM pass polarizer. Simulation results demonstrate that the device exhibits an ultra-high rejection of more than 50â dB and a reflectivity exceeding 0.99 for the TE mode across a 91â nm wavelength range, while maintaining a high transmittance of larger than 0.98 for the TM mode. Experimental results validate that the device performance is consistent with the simulation results. A fabricated device based on such a gratings exhibits a low insertion loss (<0.8â dB) and high polarization extinction ratio (>30â dB) over 100â nm bandwidth (1484â nm-1584â nm), demonstrating that the performance of the present design is competitive with that of the state-of-the-art SOI Bragg gratings.
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We present what we believe is the first report on a polarization-insensitive 3 × 3 silicon star-crossing utilizing a composite subwavelength metamaterial waveguide structure. Two different types of subwavelength grating metamaterials (nanohole grating and fan-shaped bent subwavelength grating) are respectively used to address diffraction issues in the crossing region and mode interference issues caused by a compact non-adiabatic design. This approach results in a device with an ultra-compact footprint of 12.68 × 10.98â µm2 on a standard 220â nm silicon-on-insulator (SOI) platform. Simulation results show low insertion loss (IL) values of <0.2â dB/0.3â dB and suppressed cross talk (CT) levels of <-27.2â dB/-23.6â dB for TE/TM polarizations across a wavelength range of 100â nm (1500-1600â nm). Experimental measurements of the fabricated devices confirm outstanding performance, with IL values of <0.35â dB/0.4â dB and CT levels of <-31.5â dB/-28.6â dB for TE/TM polarization in the C-band.
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Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Cobre , Neoplasias Hepáticas/tratamento farmacológico , Ionóforos , ApoptoseRESUMO
Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.
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Angiotensina II , Proteína Forkhead Box O3 , Hipertensão , Camundongos Knockout , Músculo Liso Vascular , Transdução de Sinais , Remodelação Vascular , Proteína Quinase 1 Deficiente de Lisina WNK , Animais , Músculo Liso Vascular/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Camundongos , Proteína Quinase 1 Deficiente de Lisina WNK/metabolismo , Proteína Quinase 1 Deficiente de Lisina WNK/genética , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/genética , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Células CultivadasRESUMO
BACKGROUND: Hepatic steatosis and its related complications are risk factors for multiple respiratory diseases; however, the causal relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and pulmonary function remains controversial. We aimed to identify it using a national cohort and Mendelian randomization (MR). METHODS: We enrolled 30,442 participants from the 2007 to 2012 National Health and Nutrition Examination Survey. Demographics, pulmonary function indices (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC]), and variables used to calculate the liver fat score (LFS) were collected. A two-sample MR analysis employing the summary data of genome-wide association studies on MASLD and FEV1/FVC, chronic obstructive pulmonary disease (COPD), and asthma from the Finngen Biobank and Medical Research Council Integrative Epidemiology Unit was performed. RESULTS: A total of 3,462 participants, 1,335 of whom had MASLD (LFS > -0.640), were finally included in the study. The FEV1 (3,204.7 vs. 3,262.5 ml, P = 0.061), FVC (4,089.1 vs. 4,143.8 ml, P = 0.146), FEV1/FVC ratio (78.5% vs. 78.8%, P = 0.233), and FEV1/predicted FEV1 ratio (146.5% vs. 141.7%, P = 0.366) were not significantly different between people with MASLD and those without. Additionally, the MR analysis suggested no causal correlation between MASLD and FEV1/FVC (P = 0.817), MASLD and COPD (P = 0.407), and MASLD and asthma (P = 0.808). Reverse MR studies showed no causal relationships yet (all P > 0.05). CONCLUSION: Our study provides convincing evidence that there is no causal association between MASLD and pulmonary function.
Assuntos
Asma , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Asma/genética , Asma/fisiopatologia , Asma/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Capacidade Vital , Volume Expiratório Forçado , Idoso , Adulto , Fatores de Risco , Pulmão/fisiopatologia , Fígado Gorduroso/genética , Fígado Gorduroso/fisiopatologia , Testes de Função RespiratóriaRESUMO
The co-culture strategy, which mimics natural ecology by constructing an artificial microbial community, is a useful tool for the activation of biosynthetic gene clusters (BGCs) to generate new metabolites, as well as to increase the yield of respective target metabolites. As part of our project aiming at the discovery of structurally novel and biologically active natural products from mangrove endophytic fungi, we selected the co-culture of a strain of Phomopsis asparagi DHS-48 with another Phomopsis genus fungus DHS-11, both endophyted in mangrove Rhizophora mangle considering the impart of the taxonomic criteria and ecological data. The competition interaction of the two strains was investigated through morphology observation and scanning electron microscopy (SEM), and it was found that the mycelia of the DHS-48 and DHS-11 compacted and tangled with each other with an interwoven pattern in the co-culture system. A new approach that integrates HPLC chromatogram, 1HNMR spectroscopy, UPLC-MS-PCA, and molecular networking enabled the targeted isolation of the induced metabolites, including three new dimeric xanthones phomoxanthones L-N (1-3), along with six known analogs (4-9). Their planar structures were elucidated by an analysis of their HRMS, MS/MS, and NMR spectroscopic data and the absolute configurations based on ECD calculations. These metabolites showed broad cytotoxic activity against the cancer cells assessed, of which compounds 7-9 displayed significant cytotoxicity towards human liver cells HepG-2 with IC50 values ranging from 4.83 µM to 12.06 µM. Compounds 1-6 exhibited weak immunosuppressive activity against the proliferation of ConA-induced (T-cell) and LPS-induced (B-cell) murine splenic lymphocytes. Therefore, combining co-cultivation with a metabolomics-guided strategy as a discovery tool will be implemented as a systematic strategy for the quick discovery of target bioactive compounds.
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Phomopsis , Espectrometria de Massas em Tandem , Humanos , Animais , Camundongos , Cromatografia Líquida , Técnicas de Cocultura , FungosRESUMO
Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1-3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5-17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 µM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 µg/mL to 256 µg/mL.
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Antibacterianos , Benzopiranos , Testes de Sensibilidade Microbiana , Pigmentos Biológicos , Peixe-Zebra , Animais , Benzopiranos/farmacologia , Benzopiranos/química , Benzopiranos/isolamento & purificação , Humanos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/química , Pigmentos Biológicos/farmacologia , Pigmentos Biológicos/isolamento & purificação , Pigmentos Biológicos/química , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Organismos Aquáticos , Escherichia coli/efeitos dos fármacos , China , Linhagem CelularRESUMO
Five new naphthalene derivatives dalesconosides A-D, F (1-4, 6), a known synthetic analogue named dalesconoside E (5), and eighteen known compounds (7-24) were isolated from Daldinia eschscholzii MCZ-18, which is an endophytic fungus obtained from the Chinese mangrove plant Ceriops tagal. Differing from previously reported naphthalenes, compounds 1 and 2 were bearing a rare ribofuranoside substituted at C-1 and the 5-methyltetrahydrofuran-2,3-diol moiety, respectively. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. Compounds 1, 3, 13-17 and 19 showed broad ranges of antimicrobial spectrum against five indicator test microorganisms (Enterococcus faecalis, Methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans); especially, 1, 16 and 17 were most potent. The variations in structure and attendant biological activities provided fresh insights concerning structure-activity relationships for the naphthalene derivatives.
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Testes de Sensibilidade Microbiana , Naftalenos , Naftalenos/farmacologia , Naftalenos/química , Naftalenos/isolamento & purificação , Relação Estrutura-Atividade , Espectroscopia de Ressonância Magnética , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Candida albicans/efeitos dos fármacos , Estrutura Molecular , Rhizophoraceae/microbiologia , Endófitos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificaçãoRESUMO
Overwhelming evidence points to an aberrant Wnt/ß-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/ß catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/ß-catenin signaling by inhibiting ß-catenin transcriptional activity and abrogating ß-catenin translocated to the nucleus; down-regulating the transcription level of ß-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-ß, ß-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-ß expression, which indicates that DD-9 stabilized the ß-catenin degradation complex, thereby inducing ß-catenin degradation and inactivation of the Wnt/ß-catenin pathway. The possible interaction between DD-9 and ß-catenin and GSK3-ß protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-ß-mediated crosstalk with the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.
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Apoptose , Proliferação de Células , Via de Sinalização Wnt , Humanos , Células HeLa , Apoptose/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , beta Catenina/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Neoplasias Hepáticas/tratamento farmacológico , Xantonas/farmacologia , Xantonas/química , Xantonas/isolamento & purificação , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: The proportion of patients with poor ovarian response (POR) is increasing, but effective treatment remains a challenge. To control the hidden peaks of luteinizing hormone (LH) and premature ovulation for poor responders, this study investigated the efficacy of flexible short protocol (FSP) with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day. METHODS: The 662 cycles of POR patients were retrospectively analyzed. The cohort was divided into control and intervention groups. The intervention group (group A) with 169 cycles received a GnRH-ant given on trigger day. The control (group B) with 493 cycles received only FSP. The clinical outcomes of the two groups were compared. RESULTS: Compared with group B, with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day in group A the incidences of spontaneous premature ovulation decreased significantly (2.37% vs. 8.72%, P < 0.05). The number of fresh embryo-transfer cycles was 45 in group A and 117 in group B. There were no significant differences in clinical outcomes, including implantation rate, clinical pregnancy rate, live birth rate and the cumulative live birth rate (12.0% vs. 9.34%; 22.22% vs. 21.93%; 17.78% vs. 14.91%; 20.51% vs. 20%, respectively; P > 0.05) between the two group. CONCLUSION: FSP with GnRH-ant addition on trigger day had no effect on clinical outcomes, but could effectively inhibit the hidden peaks of luteinizing hormone (LH) and spontaneous premature ovulation in POR. Therefore, it is an advantageous option for POR women.
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Hormônio Liberador de Gonadotropina , Nascimento Prematuro , Gravidez , Feminino , Humanos , Fertilização in vitro/métodos , Estudos Retrospectivos , Indução da Ovulação/métodos , Hormônio Luteinizante/farmacologia , Taxa de Gravidez , Ovulação , Nascimento Prematuro/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Antagonistas de Hormônios/farmacologiaRESUMO
Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich 'hidden' genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future.
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Femtosecond lasers can be used to create many functional devices in silica optical fibers with high designability. In this work, a femtosecond laser-induced high scattering fiber (HSF) with randomly distributed high scattering centers is used to effectively compress the linewidth of a fiber laser for the first time. A dual-wavelength, single-longitudinal-mode (SLM) erbium-doped fiber laser (EDFL) is constructed for the demonstration, which is capable of switching among two single-wavelength operations and one dual-wavelength operation. We find that the delayed self-heterodyne beating linewidth of the laser can be reduced from >1 kHz to <150â Hz when the length of the HSF in the laser cavity increases from 0 m to 20 m. We also find that the intrinsic Lorentzian linewidth of the laser can be compressed to several Hz using the HSF. The efficiency and effectiveness of linewidth reduction are also validated for the case that the laser operates in simultaneous dual-wavelength lasing mode. In addition to the linewidth compression, the EDFL shows outstanding overall performance after the HSF is incorporated. In particular, the optical spectrum and SLM lasing state are stable over long periods of time. The relative intensity noise is as low as <-150â dB/Hz@>3â MHz, which is very close to the shot noise limit. The optical signal-to-noise ratios of >85â dB for single-wavelength operation and >83â dB for dual-wavelength operation are unprecedented over numerous SLM fiber lasers reported previously. This novel method for laser linewidth reduction is applicable across gain-medium-type fiber lasers, which enables low-cost, high-performance, ultra-narrow linewidth fiber laser sources for many applications.
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A TM polarizer working for whole optical communication bands with high performance is proposed on a 220-nm-thick silicon-on-insulator (SOI) platform. The device is based on polarization-dependent band engineering in a subwavelength grating waveguide (SWGW). By utilizing an SWGW with a relatively larger lateral width, an ultra-broad bandgap of â¼476â nm (1238â nm-1714nm) is obtained for the TE mode, while the TM mode is well supported in this range. Then, a novel tapered and chirped grating design is adopted for efficient mode conversion, which results in a polarizer with a compact footprint (3.0â µm × 18 µm), low insertion loss (IL < 1.15â dB) and high polarization extinction ratio (PER > 21â dB) covering O-U bands (1260â nm-1675â nm). Experimental results show that the fabricated device has an IL < 1.0â dB and PER > 22â dB over a 300-â nm bandwidth, which is limited by our measurement setup. To the best of our knowledge, no TM polarizer on the 220-nm SOI platform with comparable performance covering O-U bands has ever been reported.
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Engenharia , SilícioRESUMO
Quick identification of abnormal molecular metabolism of bone tissues is challenging. Photoacoustic (PA) spectroscopy techniques have great potential in molecular imaging. However, most of them are amplitude-dependent and easily affected by the light deposition, especially for bone tissues with high optical scattering. In this Letter, we propose a Nakagami statistics-based PA spectroscopy (NSPS) method for characterizing molecules in bone tissues. We indicate that the NSPS curve can intelligently identify changes in the content of molecules in bone tissues, with a high disturbance-resisting ability. The NSPS has remarkable potential for use in the early and rapid detection of bone diseases.