Histone acetylation is one of the most common epigenetic modifications and plays a crucial role in tumorigenesis. However, the prognostic significance of histone acetylation-related lncRNAs (HARlncRNAs) in esophageal carcinoma (ESCA) is not well understood. A total of 653 differentially expressed lncRNAs (DElncRNAs) were identified between 162 ESCA tissues and 11 normal tissues in the TCGA database, and 7 of them were correlated with acetylation regulators. We employed univariate Cox regression analysis, combining it with clinical prognosis information, to select 3 prognostic-related HARlncRNAs for further analysis. Subsequently, we used LASSO regression analysis to construct a risk signature for ESCA and identified C21orf62-AS1 and SSTR5.AS1 as potential biomarkers for the prognosis of ESCA patients. Based on the risk score calculated using the risk signature, we categorized patients into high- and low-risk groups. We identified the risk score as an independent risk factor and validated it in the training, test, and GSE53624 datasets. Additionally, patients categorized by their risk scores exhibited distinct immune statuses, tumor mutation burdens, responses to immunotherapy, and drug sensitivities.
Carcinoma , Esophageal Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Tumor Microenvironment/genetics , Histones/genetics , Acetylation , Prognosis , Esophageal Neoplasms/genetics
Background: Long non-coding RNAs (lncRNAs) were demonstrated to be key to cancer progression and highly associated with the tumor immune microenvironment. Oxidative stress and immune may modulate the biological behaviors of tumors. Therefore, biomarkers that combined oxidative stress, immune, and lncRNA can be a promising candidate bioindicator in clinical therapy of cancers. Methods: Immune-related genes (IRGs) and oxidative stress-related genes (ORGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of lung adenocarcinoma (LUAD) patients were obtained from TCGA database. Lasso and Cox regression analyses were conducted to develop a prognostic model. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated, and predict the sensitivity of immunotherapy. Results: 2498 IRGs and 809 ORGs were extracted from previous studies, and 190 immune- and oxidative stress-related genes (IOGs) were acquired by overlapping the above genes. 658 immune- and oxidative stress-related lncRNAs (IOLs) were screened by Pearson correlation analysis. A total of 25 prognosis-related IOLs were screened by univariate regression analysis. Finally, LASSO Cox regression analysis was adopted for determining a 12-IOLs prognostic risk signature. The signature performance was confirmed in the training cohort and the testing cohort, and cases were classified into low- and high-risk groups by the risk score calculated from the signature. Patients in the high-risk group had poor prognoses and immunosuppression, while the risk score was significantly associated with tumor-infiltrating immune cells, immune checkpoint expression, and immunotherapy responses. In vitro experiments further confirmed the expression of key signature gene. Conclusion: Our new IOLs-related prognostic signature can be reliable prognostic tools and therapeutic targets for LUAD patients.
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.
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.
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.
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.
By development of ProPhenol/Ti(IV) catalysts, a catalytic enantioselective hydroxylative dearomatization of naphthols is achieved by using TBHP as a simple oxidative reagent. The side coordinative chain equipped on the C1-position of ß-naphthols plays an important role for initiating this asymmetric hydroxylative reaction, which might be a result of the proper cocoordination effects to the titanium center in the catalyst. A reasonable catalytic cycle is proposed, the catalytic system is applied to a reasonable range of this type of phenolic compound, and related concise transformations are carried out.
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.
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.
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%.
Cotton is the most important fiber crop and provides indispensable natural fibers for the textile industry. Micronaire (MIC) is determined by fiber fineness and maturity and is an important component of fiber quality. Gossypium barbadense L. possesses long, strong and fine fibers, while upland cotton (Gossypium hirsutum L.) is high yielding with high MIC and widely cultivated worldwide. To identify quantitative trait loci (QTLs) and candidate genes for MIC in G. barbadense, a population of 250 backcross inbred lines (BILs), developed from an interspecific cross of upland cotton CRI36 × Egyptian cotton (G. barbadense) Hai7124, was evaluated in 9 replicated field tests. Based on a high-density genetic map with 7709 genotyping-by-sequencing (GBS)-based single-nucleotide polymorphism (SNP) markers, 25 MIC QTLs were identified, including 12 previously described QTLs and 13 new QTLs. Importantly, two stable MIC QTLs (qMIC-D03-2 on D03 and qMIC-D08-1 on D08) were identified. Of a total of 338 genes identified within the two QTL regions, eight candidate genes with differential expression between TM-1 and Hai7124 were identified. Our research provides valuable information for improving MIC in cotton breeding.
For about a century, plant breeding has widely exploited the heterosis phenomenon-often considered as hybrid vigor-to increase agricultural productivity. The ensuing F1 hybrids can substantially outperform their progenitors due to heterozygous combinations that mitigate deleterious mutations occurring in each genome. However, only fragmented knowledge is available concerning the underlying genes and processes that foster heterosis. Although cotton is among the highly valued crops, its improvement programs that involve the exploitation of heterosis are still limited in terms of significant accomplishments to make it broadly applicable in different agro-ecological zones. Here, F1 hybrids were derived from mating a diverse Upland Cotton germplasm with commercially valuable cultivars in the Line × Tester fashion and evaluated across multiple environments for 10 measurable traits. These traits were dissected into five different heterosis types and specific combining ability (SCA). Subsequent genome-wide predictions along-with association analyses uncovered a set of 298 highly significant key single nucleotide polymorphisms (SNPs)/Quantitative Trait Nucleotides (QTNs) and 271 heterotic Quantitative Trait Nucleotides (hQTNs) related to agronomic and fiber quality traits. The integration of a genome wide association study with RNA-sequence analysis yielded 275 candidate genes in the vicinity of key SNPs/QTNs. Fiber micronaire (MIC) and lint percentage (LP) had the maximum number of associated genes, i.e., each with 45 related to QTNs/hQTNs. A total of 54 putative candidate genes were identified in association with HETEROSIS of quoted traits. The novel players in the heterosis mechanism highlighted in this study may prove to be scientifically and biologically important for cotton biologists, and for those breeders engaged in cotton fiber and yield improvement programs.
BACKGROUND: Esophageal cancer is one of the most common cancers across the globe; the 5-year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. METHODS: Through experiments in vivo and in vitro, we explored potential signaling pathways, miR-493/Wnt5A/c-JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. RESULTS: Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR-493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR-493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR-493 inhibits the activity of c-JUN and p-PI3K/p-AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c-JUN binds the promoter region of miR-493 and suppressed the expression of miR-493, forming a negative feedback loop. CONCLUSIONS: The miR-493/Wnt5A/c-JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.
B7-H1 Antigen/metabolism , Esophageal Neoplasms/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , MicroRNAs/metabolism , Wnt-5a Protein/metabolism , Cell Proliferation/physiology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Female , Humans , Male , MicroRNAs/genetics , Survival Analysis
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.
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.
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.
Gossypium , Plant Breeding , Chromosome Mapping , Cytoplasm , Gossypium/genetics , Humans , INDEL Mutation , Plant Infertility/genetics
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.
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.
Cotton Fiber , Gossypium/genetics , Polymorphism, Single Nucleotide , Chimera , Gene Expression Regulation, Plant , Genetic Pleiotropy , Genetics, Population , Genome, Plant , Genome-Wide Association Study , Gossypium/physiology , Haplotypes , Plant Breeding , Quantitative Trait Loci
OBJECTIVE: To explore the appropriate procedures for preparing extracellular microvesicles (MV) derived from human mesenchymal stem cells (MSC). METHODS: Human MSCs from umbilical cords were cultured in a serum-free medium and maintained in a basal medium for 72 hours after the cell confluence reached to 80%. The supernatants of cultured cells were collected and MVs were enriched. MVs were identified by flow cytometry and electron microscopy. The total protein amount in MVs was used as a parameter for the content of MVs. The supernatants were adjusted to different pH values, and the output of MVs was detected. The supernatants were also collected for enriching the MV and detecting the protein content of MV after the cells were maintained in the basic medium for different time. RESULTS: Flow cytometric analysis showed that the MVs expressed CD9, CD63 and CD81, morphologically presented round under an electron microscope and the diameter of MV was around 100 nm. After enrichment of MV, the protein content of MVs in the supernatants was 416.8±128.1, 255.4±77.9 and 142.8±46.4 µg per 107 MSCï¼respectively at pH of supernatant 3, 7 and 9 (Pï¼0.05). The protein content of the supernatants per 107 MSC was 173.6±44.5, 262.4±49.6 and 364.2±37.8 µg respectively after starvation culture for 48, 72 and 96 hrs (Pï¼0.05). CONCLUSION: MVs can be readily collected after MSCs were starved for 96 hours, and the pH of the supernatants is adjusted at 3.0.
Cell-Derived Microparticles , Mesenchymal Stem Cells , Cells, Cultured , Flow Cytometry , Humans , Umbilical Cord
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.
