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Oxidative stress (OS) is crucial in idiopathic pulmonary fibrosis (IPF) pathogenesis, with its genes potentially acting as both causes and consequences of the disease. We identified OS-related genes from GeneCards and performed a meta-analysis on pulmonary transcriptome datasets to discover differentially expressed genes (DEGs) related to OS in IPF. We integrated this data with the largest available IPF GWAS summaries, expression quantitative trait loci (eQTLs), and DNA methylation QTLs (mQTLs) from blood. This approach aimed to identify blood OS genes and regulatory elements linked to IPF risk, incorporating the latest pulmonary eQTLs and bronchoalveolar lavage fluid microbial QTLs (bmQTLs) for a comprehensive view of gene-lung microbiota interactions through SMR and colocalization analyses. Sensitivity analyses were conducted using two additional mendelian randomization (MR) methods. Meta-analysis revealed 1090 differentially expressed OS genes between IPF patients and controls. Integration with IPF GWAS, eQTL, and mQTL data identified key genes and regulatory elements involved in IPF pathogenesis, highlighting the role of specific genes such as KCNMA1 and SLC22A5 in modulating IPF risk through epigenetic mechanisms. Colocalization analysis further identified potential interactions between gene expression and lung microbiota. Our findings elucidate the complex interplay between OS genes and IPF, suggesting potential therapeutic targets and highlighting the importance of considering epigenetic and microbial interactions in the disease's etiology and progression.
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In this work, a double-end diffusion bonded Nd:YVO4 self-Raman laser was designed to drive an intracavity, noncritically-phase-matched KTiOAsO4 (KTA) optical parametric oscillator (OPO). Both conversion efficiency and output power at 1.7â µm (the wavelength of the OPO signal field) were improved by effectively reducing the thermal lens effect and increasing the effective length of self-Raman medium. At an incident pump power of 15.4 W, the output power for 1742 nm output laser reached 2.16 W with a conversion efficiency of 14%, and the output having a pulse width of 10.5â ns and a pulse repetition frequency of 90 kHz. The competition between the OPO and cascaded Raman laser was observed when the incident pump power was above 12.4 W. The results highlight that in order to improve output power at 1742 nm, it is critical that both the cascaded, second-Stokes field at 1313â nm and the signal field generated at 1534â nm from the 1064â nm field driving the KTA-OPO be minimized, if not completely suppressed. This laser system combining the processes of stimulated Raman scattering and optical parametric oscillation for the generation of laser emission at 1742 nm may find significant application across a broad range of fields including biological engineering, laser therapy, optical coherence tomography and for the generation of mid-infrared laser wavelengths.
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The tilted fiber Bragg grating (TFBG) with dense comb-like resonances offers a promising fiber-optic sensing platform but could suffer from cross sensitivity dependent on bulk and surface environment. In this work, the decoupling of bulk and surface characteristics (indicated by bulk refractive index (RI) and surface-localized binding film) from each other is attained theoretically with a bare TFBG sensor. This is realized with the proposed decoupling approach based on differential spectral responses of cut-off mode resonance and mode dispersion represented as wavelength interval between P- and S-polarized resonances of the TFBG to the bulk RI and surface film thickness. The results demonstrate that with this method the sensing performance for decoupling bulk RI and surface film thickness is comparative to the cases in which either the bulk or surface environment of the TFBG sensor changes, with the bulk and surface sensitivities over 540â nm/RIU and 12â pm/nm, respectively.
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Phase evolution of soliton and that of first-order sidebands in a fiber laser are investigated by using nonlinear Fourier transform (NFT). Development from dip-type sidebands to peak-type (Kelly) sidebands is presented. The phase relationship between the soliton and the sidebands calculated by the NFT are in good agreement with the average soliton theory. Our results suggest that NFT can be an effective tool for the analysis of laser pulses.
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We investigate the polarization dynamics of vector solitons in a fiber laser mode-locked by a saturable absorber (SA). Three types of vector solitons were obtained in the laser, including group velocity locked vector solitons (GVLVS), polarization locked vector solitons (PLVS), and polarization rotation locked vector solitons (PRLVS). Their polarization evolution during intracavity propagation is discussed. Pure vector solitons are obtained from the continuous wave (CW) background by soliton distillation, and the characteristics of the vector solitons without and with distillation are analyzed, respectively. Numerical simulations suggest that the features of vector solitons in a fiber laser could be assemble to those generated in fibers.
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Polarization properties of a soliton generated in a fiber laser of zero dispersion are investigated. Similar to the solitons generated in a fiber laser of all anomalous dispersion, the polarization ellipse of the soliton rotated during pulse evolution inside the cavity. The number of rotations relies on the cavity averaged birefringence with nonlinear bias. The larger the cavity averaged birefringence is, the bigger the bias is. When the period multiplying of solitons appears, the number of rotations depends on both multiplying periods and the cavity averaged birefringence. Multiple polarization states can be observed at a fixed position in the cavity depending on the multiplying period. When the cavity length is equal to n times of the averaged beat length, the polarization ellipse of the soliton rotates n∗m times at a fixed position, where m is equal to the multiplying period.
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Transition from a gain-guided soliton (GGS) to a fully developed noise-like pulse (NLP) is numerically demonstrated in fiber lasers operated in the normal dispersion regime, which explains well the experimental observation of spectrum evolution that the bottom of the averaged spectrum gradually broadens with pump power increasing. Numerical results suggest that the transition could also happen under the condition of cavity linear phase delay bias change with fixed pump power. It is demonstrated that the peak power clamping effect and the normal dispersion are the key factors leading to the spectrum evolution. In addition, intermittent meta-stable states between GGS and NLP can be obtained when the cavity dispersion is chosen at small normal dispersion.
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A Nd:YAG single-crystal fiber amplifier for the amplification of continuous-wave single-frequency laser end-pumped by a laser diode (LD) is investigated. With a two-stage amplification configuration, an output power of 60.4 W under the total incident pump power of 200 W is achieved, which is, to our knowledge, the highest power from a continuous-wave single-frequency laser achieved with a single-crystal fiber scheme. The extraction efficiency reaches 41.6% in the second amplification stage, which is comparable with Innoslab amplifiers. The beam quality factors M2 at the maximum output power in the horizontal and vertical direction are measured to be 1.51 and 1.38, respectively. The long-term power instability for 1 hour is 0.97%.
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BACKGROUND: Autophagy has been found to be involved in the multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC. METHODS: We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC. RESULTS: H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 µg/ml for 24 h increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples. CONCLUSIONS: The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.
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An evaluation of combining ability can facilitate the selection of suitable parents and superior F1 hybrids for hybrid cotton breeding, although the molecular genetic basis of combining ability has not been fully characterized. In the present study, 282 female parents were crossed with four male parents in accordance with the North Carolina II mating scheme to generate 1128 hybrids. The parental lines were genotyped based on restriction site-associated DNA sequencing and 306 814 filtered single nucleotide polymorphisms were used for genome-wide association analysis involving the phenotypes, general combining ability (GCA) values, and specific combining ability values of eight fiber quality- and yield-related traits. The main results were: (i) all parents could be clustered into five subgroups based on population structure analyses and the GCA performance of the female parents had significant differences between subgroups; (ii) 20 accessions with a top 5% GCA value for more than one trait were identified as elite parents for hybrid cotton breeding; (iii) 120 significant single nucleotide polymorphisms, clustered into 66 quantitative trait loci, such as the previously reported Gh_A07G1769 and GhHOX3 genes, were found to be significantly associated with GCA; and (iv) identified quantitative trait loci for GCA had a cumulative effect on GCA of the accessions. Overall, our results suggest that pyramiding the favorable loci for GCA may improve the efficiency of hybrid cotton breeding.
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Fibra de Algodão , Gossypium/genética , Polimorfismo de Nucleotídeo Único , Quimera , Regulação da Expressão Gênica de Plantas , Pleiotropia Genética , Genética Populacional , Genoma de Planta , Estudo de Associação Genômica Ampla , Gossypium/fisiologia , Haplótipos , Melhoramento Vegetal , Locos de Características QuantitativasRESUMO
BACKGROUND: Cytoplasmic male sterile (CMS) with cytoplasm from Gossypium Trilobum (D8) fails to produce functional pollen. It is useful for commercial hybrid cotton seed production. The restore line of CMS-D8 containing Rf2 gene can restore the fertility of the corresponding sterile line. This study combined the whole genome resequencing bulked segregant analysis (BSA) with high-throughput SNP genotyping to accelerate the physical mapping of Rf2 locus in CMS-D8 cotton. METHODS: The fertility of backcross population ((sterile line×restorer line)×maintainer line) comprising of 1623 individuals was investigated in the field. The fertile pool (100 plants with fertile phenotypes, F-pool) and the sterile pool (100 plants with sterile phenotypes, S-pool) were constructed for BSA resequencing. The selection of 24 single nucleotide polymorphisms (SNP) through high-throughput genotyping and the development insertion and deletion (InDel) markers were conducted to narrow down the candidate interval. The pentapeptide repeat (PPR) family genes and upregulated genes in restore line in the candidate interval were analysed by qRT-PCR. RESULTS: The fertility investigation results showed that fertile and sterile separation ratio was consistent with 1:1. BSA resequencing technology, high-throughput SNP genotyping, and InDel markers were used to identify Rf2 locus on candidate interval of 1.48 Mb on chromosome D05. Furthermore, it was quantified in this experiment that InDel markers co-segregated with Rf2 enhanced the selection of the restorer line. The qRT-PCR analysis revealed PPR family gene Gh_D05G3391 located in candidate interval had significantly lower expression than sterile and maintainer lines. In addition, utilization of anther RNA-Seq data of CMS-D8 identified that the expression level of Gh_D05G3374 encoding NB-ARC domain-containing disease resistance protein in restorer lines was significantly higher than that in sterile and maintainer lines. CONCLUSIONS: This study not only enabled us to precisely locate the restore gene Rf2 but also evaluated the utilization of InDel markers for marker assisted selection in the CMS-D8 Rf2 cotton breeding line. The results of this study provide an important foundation for further studies on the mapping and cloning of restorer genes.
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Gossypium , Melhoramento Vegetal , Mapeamento Cromossômico , Citoplasma , Gossypium/genética , Humanos , Mutação INDEL , Infertilidade das Plantas/genéticaRESUMO
We carry out a very early theoretical study on surface waveguide modes excited in a long-period fiber grating (LPFG) coated with gold-silicon thin films for refractive index sensing. The surface waveguide modes originate from the intermode transition of EH cladding modes and present a very strong evanescent field penetrating into the surrounding medium, which makes them ultrasensitive to external changes. By tracking the dual resonances of surface waveguide modes, ultrahigh sensitivity up to 7267.7nm/RIU around 1.315 is obtained, which is 76-/4-fold higher than the case of bare LPFG/LPFG-assisted surface plasmon resonance, together with the capability of self-referenced measurement. This new, to the best of our knowledge, concept is expected to find wide applications based on refractive index sensing.
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Conjugated ynones are easily accessible feedstock and the existence of an alkyne bond endows ynones with different attractive reactivities, thus making them unique substrates for catalytic asymmetric reactions. Their compatibility under organocatalytic, metal-catalyzed as well as cooperative catalytic conditions has resulted in numerous enantioselective transformations. Importantly, conjugated ynones can act as nucleophiles or electrophiles, and serve as easily accessed synthons for different cyclization pathways. This review summarizes the recent literature examples of the catalytic reactions of conjugated ynones and related compounds such as alkyne conjugated α-ketoesters, and classifies these reaction types alongside mechanistic insights whenever possible. We aim to trigger more intensive research in the future to render the asymmetric transformation of ynones as a common and reliable tool for asymmetric synthesis.
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We demonstrate the coexisting dynamics of loosely bound solitons and noise-like pulses (NLPs) in a passively mode-locked fiber laser with net-normal dispersion. The total pulse number of the single soliton bunch under the NLP operation regime almost increases linearly with increasing pump power, whereas the average pulse spacing decreases accordingly. Furthermore, pulse-to-pulse separation between adjacent soliton pulses in one soliton bunch keeps in the range of hundreds of picoseconds, which decreases from left to right with the change of time. Besides, the real-time observation has been performed by utilizing the time-stretch method, showing that each one of the loosely bound solitons on the NLP operation is actually composed of chaotic wave packets with random intensities. These findings obtained will facilitate the in-depth understanding of nonlinear pulse behaviors in ultrafast optics.
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We report switchable emission of visible light at five wavelengths generated in a $\text{YVO}_4$YVO4 cascaded Raman cavity driven by an acousto-optic ${Q}$Q-switched Nd:YAP laser at 1080 nm. The second-harmonic generation and sum-frequency generation of the fundamental, first-Stokes, and second-Stokes waves were realized based on the angle-tuned BBO crystal. The phase-match angle tuning span of a BBO crystal is only approximately 2.3° to allow the frequency mixing to produce five visible wavelengths on demand. At an absorbed pump power of 5.96 W and a pulse repetition frequency of 10 kHz, average output powers of 800, 340, 460, 190, and 326 mW were obtained for 539.9, 567.2, 597.4, 631.0, and 668.5 nm lasers, respectively. The results show that the cascaded Raman laser system with an angle-tuned BBO crystal can provide a convenient and efficient method to achieve wavelength-switchable visible emission for multi-wavelength laser applications.
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The cytoplasmic male sterility (CMS) system is a useful tool for commercial hybrid cotton seed production. Two main CMS systems, CMS-D8 and CMS-D2, have been recognized with Rf2 and Rf1 as the restorer genes, respectively. The development of molecular markers tightly linked with restorer genes can facilitate the breeding of restorer lines. In this study, the InDel-1892 marker was developed to distinguish Rf2 and Rf1 simultaneously. Sequence alignment implied that CMS-D8-Rf2 has a 32 bp insertion and that CMS-D2-Rf1 has a 186 bp insertion at the InDel-1892 locus. The codominant marker was co-segregated with Rf1 and Rf2. Hence, this marker can be used for tracing Rf1 and Rf2 simultaneously and identifying the allele status at the restorer gene locus. The results of this study will facilitate efficient marker-assisted selection for restorer lines and hybrids of CMS systems.
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Genes de Plantas , Marcadores Genéticos , Gossypium/genética , Mutação INDEL , Infertilidade das Plantas/genética , Mapeamento Cromossômico , Cruzamentos Genéticos , Loci Gênicos , Reprodutibilidade dos Testes , Análise de Sequência de DNARESUMO
BACKGROUND: Heterosis, a multigenic complex trait extrapolated as sum total of many phenotypic features, is widely utilized phenomenon in agricultural crops for about a century. It is mainly focused on establishing vigorous cultivars with the fact that its deployment in crops necessitates the perspective of genomic impressions on prior selection for metric traits. In spite of extensive investigations, the actual mysterious genetic basis of heterosis is yet to unravel. Contemporary crop breeding is aimed at enhanced crop production overcoming former achievements. Leading cotton improvement programs remained handicapped to attain significant accomplishments. RESULTS: In mentioned context, a comprehensive project was designed involving a large collection of cotton accessions including 284 lines, 5 testers along with their respective F1 hybrids derived from Line × Tester mating design were evaluated under 10 diverse environments. Heterosis, GCA and SCA were estimated from morphological and fiber quality traits by L × T analysis. For the exploration of elite marker alleles related to heterosis and to provide the material carrying such multiple alleles the mentioned three dependent variables along with trait phenotype values were executed for association study aided by microsatellites in mixed linear model based on population structure and linkage disequilibrium analysis. Highly significant 46 microsatellites were discovered in association with the fiber and yield related traits under study. It was observed that two-thirds of the highly significant associated microsatellites related to fiber quality were distributed on D sub-genome, including some with pleiotropic effect. Newly discovered 32 hQTLs related to fiber quality traits are one of prominent findings from current study. A set of 96 exclusively favorable alleles were discovered and C tester (A971Bt) posited a major contributor of these alleles primarily associated with fiber quality. CONCLUSIONS: Hence, to uncover hidden facts lying within heterosis phenomenon, discovery of additional hQTLs is required to improve fibre quality. To grab prominent improvement in influenced fiber quality and yield traits, we suggest the A971 Bt cotton cultivar as fundamental element in advance breeding programs as a parent of choice.
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Heterogeneidade Genética , Gossypium/genética , Vigor Híbrido , Estudos de Associação Genética , Genótipo , Repetições de Microssatélites , Fenótipo , Melhoramento Vegetal , Locos de Características Quantitativas , Característica Quantitativa HerdávelRESUMO
We have experimentally investigated the collisional dynamics in femtosecond-laser-induced plasmas and presented the evidence for electron-impact excitation through enhanced high-order harmonic (HH) generation. The measurements were carried out by using an elliptically polarized pump pulse to induce the underdense plasmas and by using a time-delayed linearly polarized probe pulse to drive the HH generation from the plasmas. We found that the rise time of this enhanced HH generation was insensitive to the ellipticity degree (ED) of pump pulse but sensitive to its laser intensity (LI). With further comparison between physical scenarios and qualitative analysis, we demonstrated that the atomic excitation causing the HH enhancement should be attributed to the electron-impact excitation, i.e., the excitation from the collision between neutral atoms and electrons during the lifetime of the underdense plasma.
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Compact passively Q-switched RbTiOPO4 cascaded Raman laser operation has been investigated for the first time, to our knowledge. A Nd:YAG/Cr4+:YAG composite crystal was adopted for passively Q-switched fundamental laser generation. 440 mW multi-Stokes laser output with X(ZZ)X configuration according to the Porto notations was achieved under the incident pump power of 10 W. The measured spectra contained three wavelengths of 1149, 1165, and 1185 nm based on the Raman shift of 271 and 687 cm-1. Different from actively Q-switch cascaded Raman laser with Stokes wave from low order to high order oscillating in sequence, three intensity lines were output for the whole experiment in this passively Q-switched multi-Stokes laser. The output spectra could be varied and optimized based on the output coupler coating design. Output spectra not sensitive to incident pump power for passively Q-switched cascaded Raman laser have advantages in multiwavelength laser applications.
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An intra-cavity optical parametric oscillator (OPO) emitting at 1.7 µm derived by Nd:YVO4 self-Raman laser is demonstrated in this Letter, with a KTiOAsO4 (KTA) crystal used as nonlinear optical crystal. A laser diode end-pumped acousto-optic Q-switched Nd:YVO4 self-Raman laser at 1176 nm was employed as the pump source. At an incident pump power of 12.1 W and a pulse repetition frequency of 60 kHz, average output power up to 1.2 W signal light at 1742 nm was obtained, with diode-to-signal conversion efficiency of 10%. The pulse width was about 11 ns and spectral line width was less than 0.5 nm for the signal light. The results show that compact intra-cavity KTA-OPO derived by Nd:YVO4 self-Raman laser is an efficient method for 1.7 µm waveband laser generation, with potential applications in biological imaging, laser therapy, special materials processing, etc.