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1.
Microb Pathog ; 136: 103715, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31491550

RESUMO

The rare minnow, Gobiocypris rarus, is small experimental fish proven to be sensitive to Grass Carp Reovirus (GCRV) infection. In present study we established a new cell (GrE) from eggs of G. rarus. GrE cells grew well at 28 °C in M199 medium containing 10% fetal bovine serum, and has been subcultured for over 70 passages. Chromosome analysis indicated that 40% of the cells were diploid 2n = 66 while the chromosome number of the fish is 2n = 50. Viral replication in GrE cells was confirmed by transmission electron microscopy, immunofluorescence assays and virus titration experiments. GrE cells and Cyenopharyngodon idellus kidney cells were infected with two GCRV genotypes while the virus copies of GCRV II in GrE peaked at 2.25 × 105 on 12th dpi. In vivo challenge experiments using GCRV I and II isolates at generations 1 and 20 indicated that GCRV II reproduce similar symptoms and histopathological changes of the disease in the rare minnow. These results indicated that GrE is permissive for GCRV genotype II propagation and can be used for pathogenesis studies and vaccine development of the predominant genotype of GCRV.

2.
Opt Express ; 27(17): 24847-24856, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510366

RESUMO

Dual-frequency microwave signals have potential applications in radar and communication systems to improve system integration and signal conversion convenience. Flexible frequency tunability and low phase noise are important factors for dual-frequency microwave signals. This research focuses on improving frequency tunability of dual-frequency microwave signals meanwhile maintaining low phase noise and high spectrum purity. The outputs of two optical injection-locked slave lasers as Brillouin pump signals are employed combining with an integrated polarization-multiplexing modulator to realize orthogonal polarization multiplexing. Stable dual-frequency microwave signals are obtained in an optoelectronic oscillation loop simultaneously. The obtained microwave signals inherit the flexible frequency tunability of Brillouin effect and low phase noise of the optoelectronic oscillator at the same time.

3.
Anal Chim Acta ; 1081: 184-192, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31446957

RESUMO

Hypochlorite (ClO-), one of reactive oxygen species (ROS), is closely related with many physiological and pathological processes. Especially as one of cellular reactive oxygen species in mitochondria, ClO- can induce mitochondrial permeability, which leads to apoptosis. Thus, developing an effective method which is able to sense ClO- in mitochondria is important. Although fluorescent probe has become a powerful tool for imaging ClO- in mitochondria, most of them suffered from phototoxicity to biosamples, autofluorescence, and photobleaching phenomenon due to their short-wavelength excitations and emissions. Based on advantages of two-photon fluorescent probe and far-red to NIR fluorescent probe, a mitochondria-targetable two-photon fluorescent probe with a turn-on signal in far-red to NIR region, Mito-TP-ClO, was developed for ClO- in this paper. Mito-TP-ClO is consisted of a triphenylphosphonium cations as a mitochondria-targetable unit and a structure of dibenzoylhydrazine as a response unit to ClO-. Mito-TP-ClO exhibited a high sensitivity and a high selectivity to ClO-, with a linear range from 6.0 × 10-8 to 1.0 × 10-5 M and a detection limit of 2.5 × 10-8 M. Due to its large two-photon cross section (267 GM) and far-red to NIR emission, Mito-TP-ClO exhibits excellent performances including low autofluorescence, photostable fluorescence signal, and deep tissue penetration (230 µM). Moreover, Mito-TP-ClO was successfully used to detect endogenous ClO- in bacteria-infected cells and inflammatory mouse model, which confirmed that Mito-TP-ClO is a powerful tool to monitor ClO- in mitochondria and study on effects of hypochlorite on mitochondria.

4.
Adv Mater ; : e1903125, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31402540

RESUMO

Hard carbon is regarded as a promising anode material for sodium-ion batteries (SIBs). However, it usually suffers from the issues of low initial Coulombic efficiency (ICE) and poor rate performance, severely hindering its practical application. Herein, a flexible, self-supporting, and scalable hard carbon paper (HCP) derived from scalable and renewable tissue is rationally designed and prepared as practical additive-free anode for room/low-temperature SIBs with high ICE. In ether electrolyte, such HCP achieves an ICE of up to 91.2% with superior high-rate capability, ultralong cycle life (e.g., 93% capacity retention over 1000 cycles at 200 mA g-1 ) and outstanding low-temperature performance. Working mechanism analyses reveal that the plateau region is the rate-determining step for HCP with a lower electrochemical reaction kinetics, which can be significantly improved in ether electrolyte.

5.
Phytother Res ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435973

RESUMO

Airway remodeling is one important feature of childhood asthma, which is one of the most common chronic childhood diseases. Phenotype switching of airway smooth muscle cells (ASMCs), defined as a reversible switching between contractile and proliferative phenotypes, plays an important role in the process of airway remodeling. Esculetin has shown antiinflammatory action in animal models of asthma; however, the effects of esculetin on ASMC phenotype switching have not been investigated. In the present study, platelet-derived growth factor (PDGF) was used to induce the phenotype modulation of ASMCs. The results demonstrated that esculetin pretreatment mitigated the PDGF-caused inhibitory effects on expressions of contractile phenotype protein markers, including calponin and SM22α. Esculetin also inhibited PDGF-induced migration and proliferation of ASMCs. Besides, the PDGF-induced expressions of extracellular matrix components, collagen I and fibronectin, were attenuated by esculetin pretreatment. Furthermore, PDGF-caused activation of PI3K/Akt pathway in ASMCs was inhibited by esculetin. These findings suggest that esculetin might exert its inhibitory effect on PDGF-induced ASMC phenotype switching through inhibition of PI3K/Akt pathway.

6.
PLoS One ; 14(8): e0221221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425521

RESUMO

In the study, a facile one-step method for synthesizing magnetic-TiO2-nanophotocatalysts was developed. With the same composing ratio of 0.5 and 0.35 (Fe:Ti, mole:mole), we prepared two types of magnetic-TiO2-nanocomposites as one-step synthesized FexOy-composed TiO2 (FexOy/TiO2-0.5 and FexOy/TiO2-0.35) and two-step synthesized core-shell FexOy@TiO2 (FexOy@TiO2-0.5 and FexOy@TiO2-0.35), and tested their performance in rhodamine 6G (R6G) photodegradation. X-ray diffraction (XRD) analysis showed that FexOy@TiO2-0.5 has the smallest crystallite size (16.8 nm), followed by FexOy@TiO2-0.5 (18.4 nm), FexOy/TiO2-0.35 (21.0 nm) and FexOy/TiO2-0.5 (19.0 nm), and X-ray photoelectron spectroscopy (XPS) suggested the decreasing percentage of Fe3O4 from 52.1% to 36.7%-47.2% after Ti-deposition treatment. The saturated magnetisms followed the order: FexOy@TiO2-0.5 > FexOy@TiO2-0.35 > FexOy/TiO2-0.5 > FexOy/TiO2-0.35. R6G photodegradation followed the first order kinetics and was slightly influenced by pH but significantly affected by initial photocatalyst concentration. FexOy/TiO2-0.35 achieved the highest removal efficiency for R6G (92.5%), followed by FexOy@TiO2-0.35 (88.97%), FexOy@TiO2-0.5 (60.49%) and FexOy/TiO2-0.5 (48.06%). Additionally, all these magnetic-TiO2-nanocomposites had satisfied magnetic recoverability and exhibited laudable reusability after 5-times reuse, even achieving higher R6G removal efficiencies from 97.30% to 98.47%. Our one-step method took only 75 min for nanocomposite synthesis, 90 min less than conventional two-step method, showing its feasibility as a practical method for magnetic-TiO2-nanocomposite synthesis in industrial application.

7.
Bull Math Biol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468263

RESUMO

Antibodies have been shown to hinder the movement of herpes simplex virus virions in cervicovaginal mucus, as well as other viruses in other mucus secretions. However, it has not been possible to directly observe the mechanisms underlying this phenomenon, so the nature of virion-antibody-mucin interactions remain poorly understood. In this work, we analyzed thousands of virion traces from single particle tracking experiments to explicate how antibodies must cooperate to immobilize virions for relatively long time periods. First, using a clustering analysis, we observed a clear separation between two classes of virion behavior: freely diffusing and immobilized. While the proportion of freely diffusing virions decreased with antibody concentration, the magnitude of their diffusivity did not, implying an all-or-nothing dichotomy in the pathwise effect of the antibodies. Proceeding under the assumption that all binding events are reversible, we used a novel switch-point detection method to conclude that there are very few, if any, state switches on the experimental timescale of 20 s. To understand this slow state switching, we analyzed a recently proposed continuous-time Markov chain model for binding kinetics and virion movement. Model analysis implied that virion immobilization requires cooperation by multiple antibodies that are simultaneously bound to the virion and mucin matrix and that there is an entanglement phenomenon that accelerates antibody-mucin binding when a virion is immobilized. In addition to developing a widely applicable framework for analyzing multistate particle behavior, this work substantially enhances our mechanistic understanding of how antibodies can reinforce a mucus barrier against passive invasive species.

8.
Water Res ; 165: 114979, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31445309

RESUMO

Microplastics have been found to be ubiquitous in freshwater ecosystems, providing a novel substrate for biofilm formation. Here, we incubated biofilm on microplastics and two natural substrates (rock and leaf) under a controlled environment to investigate the differences of microbial community structure, antibiotic resistance gene (ARG) profiles, and ARG microbial hosts between biofilms on three types of substrates. Results from high-throughput sequencing of 16S rRNA gene revealed that microplastic biofilm had a distinctive community structure. Network analyses suggested that microplastic biofilm possessed the highest node connected community, but with lower average path length, network diameter and modularity compared with biofilm on two natural particles. Metagenomic analyses further revealed microplastic biofilm with broad-spectrum and distinctive resistome. Specifically, according to taxonomic annotation of ARG microbial hosts, two opportunisitic human pathogens (Pseudomonas monteilii, Pseudomonas mendocina) and one plant pathogen (Pseudomonas syringae) were detected only in the microplastic biofilm, but not in biofilms formed on natural substrates. Our findings suggest that microplastic is a novel microbial niche and may serve as a vector for ARGs and pathogens to new environment in river water, generating freshwater environmental risk and exerting adverse impacts on human health.

9.
Opt Lett ; 44(16): 4048-4051, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415544

RESUMO

We demonstrate the first, to the best of our knowledge, photothermal carbon monoxide (CO) sensor using a hollow-core negative curvature fiber. The hollow-core fiber features a typical structure of one ring cladding containing eight nontouching capillaries to form a negative curvature core-surround. The photothermal effect in a 40-µm hollow core is induced by CO absorption at 2327 nm and detected by a Mach-Zehnder interferometer operating at 1533 nm. By using wavelength modulation spectroscopy, we achieve a normalized noise equivalent absorption coefficient of 4.4×10-8 cm-1 WHz-1/2. As CO has a very slow vibrational-translational relaxation process, we enhance the photothermal signal by enhancing the relaxation with the water vapor additive.

10.
Nanoscale ; 11(35): 16690, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31465062

RESUMO

Correction for 'Ionic-liquid-bifunctional wrapping of ultrafine SnO2 nanocrystals into N-doped graphene networks: high pseudocapacitive sodium storage and high-performance sodium-ion full cells' by Yan Yang et al., Nanoscale, 2019, 11, 14616-14624.

11.
Int J Mol Sci ; 20(16)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394718

RESUMO

Allelopathy is a central process in crop-weed interactions and is mediated by the release of allelochemicals that result in adverse growth effects on one or the other plant in the interaction. The genomic mechanism for the biosynthesis of many critical allelochemicals is unknown but may involve the clustering of non-homologous biosynthetic genes involved in their formation and regulatory gene modules involved in controlling the coordinated expression within these gene clusters. In this study, we used the transcriptomes from mono- or co-cultured rice and barnyardgrass to investigate the nature of the gene clusters and their regulatory gene modules involved in the allelopathic interactions of these two plants. In addition to the already known biosynthetic gene clusters in barnyardgrass we identified three potential new clusters including one for quercetin biosynthesis and potentially involved in allelopathic interaction with rice. Based on the construction of gene networks, we identified one gene regulatory module containing hub transcription factors, significantly positively co-regulated with both the momilactone A and phytocassane clusters in rice. In barnyardgrass, gene modules and hub genes co-expressed with the gene clusters responsible for 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) biosynthesis were also identified. In addition, we found three genes in barnyardgrass encoding indole-3-glycerolphosphate synthase that regulate the expression of the DIMBOA cluster. Our findings offer new insights into the regulatory mechanisms of biosynthetic gene clusters involved in allelopathic interactions between rice and barnyardgrass, and have potential implications in controlling weeds for crop protection.

12.
Artif Cells Nanomed Biotechnol ; 47(1): 3478-3484, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31432701

RESUMO

Circular antisense non-coding RNA in the INK4 locus (cANRIL) participated in inflammation of endothelial cells. However, whether cANRIL is associated with inflammatory injury of HK-2 cells, thereby affecting chronic kidney disease has not been investigated. We tested the hypothesis that cANRIL participated in inflammatory response in vitro. HK-2 cells were stimulated by lipopolysaccharides (LPS). RT-qPCR was executed for cANRIL expression assessment. After transfection, cell viability, apoptosis, inflammatory cytokines and ROS generation were appraised to evaluate the impact of silencing cANRIL on LPS-induced inflammatory injury. The regulatory relationship between cANRIL and microRNA-9 (miR-9) was verified. In addition, whether miR-9 affected LPS-induced inflammatory injury was measured after miR-9 inhibitor transfection. Western blot was utilized to detect NF-κB and JNK/p38 pathway-related proteins. The results showed that LPS promoted cANRIL expression and cell injuries in HK-2 cells. Furthermore, silencing cANRIL alleviated inflammatory injuries by promoting viability, suppressing apoptosis, inflammatory cytokines and ROS generation in HK-2 cells. In addition, miR-9 expression was accelerated by silencing cANRIL. Meanwhile, miR-9 down-regulation invalidated the effect of silencing cANRIL on inflammation and NF-κB and JNK/p38 pathways. The study clarified that silencing cANRIL hindered NF-κB and JNK/p38 pathways by positively regulating miR-9, thereby protecting HK-2 cells from LPS-induced injury.

13.
Nutrients ; 11(7)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315230

RESUMO

OBJECTIVE: Obesity and homocysteine (Hcy) are two important risk factors for cardiovascular disease (CVD). However, evidence on the association between obesity and Hcy concentration was conflicting. The aim of our study is to explore the associations of general and central obesity with hyperhomocysteinemia (HHcy) in middle-aged women. METHODS: The current analysis was based on data from 11,007 women aged 40-60 years. Height, weight, and waist circumference (WC) were measured and serum homocysteine was determined. Multiple logistic regression models were used to assess the associations of the risk of hyperhomocysteinemia (HHcy, Hcy > 15 µmol/L) with BMI and WC. RESULTS: 13.71% women had HHcy. The prevalences of BMI-based general obesity and WC-based central obesity were 11.17% and 22.88%, respectively. Compared with non-obese women, the mean serum Hcy concentration was significantly higher in WC-based central obese women (p = 0.002), but not in BMI-based general obese women (p > 0.05). In the multiple logistic regression models, central obesity was positively related to the risk of HHcy (OR = 1.30, 95% CI = 1.10 to 1.52), while general obesity was inversely related to the risk of HHcy (OR = 0.82, 95% CI = 0.72 to 0.93 and OR = 0.71, 95% CI = 0.57 to 0.89). CONCLUSIONS: Central obesity was positively related to the risk of HHcy, while general obesity was negatively related. Menopause showed no effect modification on these associations.

14.
Bioorg Med Chem Lett ; 29(16): 2168-2172, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31257080

RESUMO

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.

15.
Cell Cycle ; 18(18): 2215-2227, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286834

RESUMO

Various drug treatments including doxorubicin (DOX) have been proved efficient in the suppression of breast cancer. Nonetheless, drug resistance became an obstacle in the therapeutic process. According to recent literatures, breast cancer stem cells (BCSCs) were considered contributing to drug resistance, besides, microRNAs (miRNAs) could regulate proteins associated with drug resistance in human breast cancer. To further understand the inner mechanism of drug resistance in breast cancer and look for remedy methods, we referred to bioinformatic analysis and predicted that signal transducer and activator of transcription 3 (STAT3) and miR-124 was overexpressed in MCF7-R cells (MCF7 cells resistant to DOX) compared with MCF cells. Expression levels of RNA and protein were separately determined by qRT-PCR and western blot. Dual luciferase assay was performed to verify the targeting relationship between STAT3 and miR-124. Optical density (OD) values and apoptotic rates of cells were respectively determined via MTT assays and flow cytometric analysis. Cell invasion was detected to verify drug resistance. Results of above assays indicated that STAT3 was highly expressed in MCF7-R cells than in MCF7 cell lines and affected doxorubicin resistance of BCSCs, and miR-124 reversed the doxorubicin resistance of breast cancer stem cells through targeting STAT3 to control the HIF-1 signaling pathway. To conclude, this research may be valuable for the treatment of breast cancer as the restoration of miR-124 and inhibition of STAT3 could be applied to therapeutic strategy and help overcome drug resistance.

16.
Neuropsychologia ; 132: 107135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295449

RESUMO

Reactivation returns a consolidated memory to a plastic state, opening a window for the existing memory to be updated. For episodic memory, learning of competing information upon reactivation either integrates the new information into the reactivated memory or disrupts the reactivated memory directly, but the two effects were found in distinct experimental paradigms and their neural mechanisms are largely unknown. The current study explored the effects and neural mechanisms of episodic memory reactivation using behavioural and MEG techniques. Taking advantage of an independent-cue retrieval procedure, we revealed both the integration and the forgetting effects by a single post-reactivation interference paradigm. However, while the integration effect followed the reconsolidation window, the forgetting effect did not, suggesting only the integration effect being caused by memory reconsolidation. MEG measurements further revealed beta-band power decrease during reactivation and alpha-band power decrease during post-reactivation interference, both of which parametrically predicted the degree of memory integration. But neither the beta nor the alpha desynchronization was related to the forgetting of the original memory. Our results suggest original memory forgetting and new information integration happen in different time periods after memory reactivation, and beta and alpha desynchronizations underlie reconsolidation-mediated episodic memory updating.

17.
Apoptosis ; 24(9-10): 798-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321634

RESUMO

Sirtuins have emerged as a promising novel class of anti-cancer drug targets. Inhibition of SIRT1 and SIRT2 induces apoptosis in cancer cells and they play multifaceted roles in regulating autophagy. In the present study, we found that salermide, a SIRT1/2-specific inhibitor or small interfering RNAs (siRNAs) to block SIRT1/2 expression could induce autophagy in human NSCLC cells. Moreover, SIRT1/2 inhibition increased the expression levels of ATF4 and DDIT4 and downregulated p-RPS6KB1 and p-EIF4EBP1, two downstream molecules of mTORC1. Moreover, ATF4 or DDIT4 knockdown attenuated salermide-induced autophagy, suggesting that SIRT1/2 inhibition induced autophagy through the ATF4-DDIT4-mTORC1 axis. Mechanistically, SIRT1/2 inhibition led to HSPA5 acetylation and dissociation from EIF2AK3, leading to ER stress response and followed by upregulation of ATF4 and DDIT4, triggering autophagy. Silencing of the autophagic gene ATG5 in lung cancer cells resulted in increased apoptotic cell death induced by SIRT1/2 inhibition. Our data show that inhibition of SIRT1/2 induces pro-survival autophagy via acetylation of HSPA5 and subsequent activation of ATF4 and DDIT4 to inhibit the mTOR signaling pathway in NSCLC cells. These findings suggest that combinatorial treatment with SIRT1/2 inhibitors and pharmacological autophagy inhibitors is an effective therapeutic strategy for cancer therapy.

18.
Environ Int ; 131: 104998, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330365

RESUMO

The omnipresence of filterable bacteria that can pass through 0.22-µm membrane filters demands a change in the sterile filtration practice. In this study, we identified that filterable bacteria enriched from a surface water are members of the Bacteroidetes, Proteobacteria, Spirochaetae, Firmicutes, and Actinobacteria. Filterable bacteria displayed superior filterability during the entire bacterial growth phase, especially at the exponential phase. Maximal passage percentages were comparable at different cell densities, and achieved earlier at high cell density. Furthermore, filter retention for the investigated bacteria is independent of liquid temperature. However, cultivation temperature could affect the growth of some specific filterable bacteria and lead to variability in the passage percentage. Additionally, membrane materials, pore size and filtering flux greatly affected the passage of filterable bacteria. The majority of filterable Hylemonella and SAR324 could pass through 0.1-µm polyvinylidene fluoride and polyethersulfone filters but could not pass through 0.1-µm polycarbonate and mixed cellulose esters filters. Taken together, our results demonstrated that the ultra-small size of filterable bacteria, membrane characteristics and filtration operational conditions could challenge the validity of the 0.22/0.1-µm sterilizing grade filters in providing bio-safety barriers.

19.
Environ Sci Pollut Res Int ; 26(25): 25538-25549, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267391

RESUMO

Environmental waters cover a range of water quality characteristics which could greatly affect the behavior and fate of C60 in the aquatic environment. In this study, the dispersion and stability of C60 in several environmental water matrices during a 70-day extended mixing period were investigated to better understand its environmental behavior and fate in environmental waters. Relatively stable nanoscale aggregates in water (aqu/nC60) could be formed in wastewater influent, while unstable suspensions were obtained in river water, wastewater effluent, seawater, and estuarine water. During the extended mixing under sunlight, oxygen-containing moieties were produced on the surface of the C60 aggregates, independent of the kind of environmental water matrices. Once the mixed system went under quiescent condition, aggregation and sedimentation of aqu/nC60 occurred. However, an extremely short-time disturbance could easily resuspend the C60 aggregates deposited and increase the concentration of aqu/nC60 in the overlying water column. Therefore, the effects of resuspension should be considered when investigating the environmental behavior and fate of C60.

20.
Stem Cell Res Ther ; 10(1): 220, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358062

RESUMO

BACKGROUND: Human naïve pluripotency state cells can be derived from direct isolation of inner cell mass or primed-to-naïve resetting of human embryonic stem cells (hESCs) through different combinations of transcription factors, small molecular inhibitors, and growth factors. Long noncoding RNAs (lncRNAs) have been identified to be crucial in diverse biological processes, including pluripotency regulatory circuit of mouse pluripotent stem cells (PSCs), but few are involved in human PSCs' regulation of pluripotency and naïve pluripotency derivation. This study initially planned to discover more lncRNAs possibly playing significant roles in the regulation of human PSCs' pluripotency, but accidently identified a lncRNA whose knockdown in human PSCs induced naïve-like pluripotency conversion. METHODS: Candidate lncRNAs tightly correlated with human pluripotency were screened from 55 RNA-seq data containing human ESC, human induced pluripotent stem cell (iPSC), and somatic tissue samples. Then loss-of-function experiments in human PSCs were performed to investigate the function of these candidate lncRNAs. The naïve-like pluripotency conversion caused by CCDC144NL-AS1 knockdown (KD) was characterized by quantitative real-time PCR, immunofluorescence staining, western blotting, differentiation of hESCs in vitro and in vivo, RNA-seq, and chromatin immunoprecipitation. Finally, the signaling pathways in CCDC144NL-AS1-KD human PSCs were examined through western blotting and analysis of RNA-seq data. RESULTS: The results indicated that knockdown of CCDC144NL-AS1 induces naïve-like state conversion of human PSCs in the absence of additional transcription factors or small molecular inhibitors. CCDC144NL-AS1-KD human PSCs reveal naïve-like pluripotency features, such as elevated expression of naïve pluripotency-associated genes, increased developmental capacity, analogous transcriptional profiles to human naïve PSCs, and global reduction of repressive chromatin modification marks. Furthermore, CCDC144NL-AS1-KD human PSCs display inhibition of MAPK (ERK), accumulation of active ß-catenin, and upregulation of some LIF/STAT3 target genes, and all of these are concordant with previously reported traits of human naïve PSCs. CONCLUSIONS: Our study unveils an unexpected role of a lncRNA, CCDC144NL-AS1, in the naïve-like state conversion of human PSCs, providing a new perspective to further understand the regulation process of human early pluripotency states conversion. It is suggested that CCDC144NL-AS1 can be potentially valuable for future research on deriving higher quality naïve state human PSCs and promoting their therapeutic applications.

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