PICKLE-mediated nucleosome condensing drives H3K27me3 spreading for the inheritance of Polycomb memory during differentiation.

Spreading of H3K27me3 is crucial for the maintenance of mitotically inheritable Polycomb-mediated chromatin silencing in animals and plants. However, how Polycomb repressive complex 2 (PRC2) accesses unmodified nucleosomes in spreading regions for spreading H3K27me3 remains unclear. Here, we show in Arabidopsis thaliana that the chromatin remodeler PICKLE (PKL) plays a specialized role in H3K27me3 spreading to safeguard cell identity during differentiation. PKL specifically localizes to H3K27me3 spreading regions but not to nucleation sites and physically associates with PRC2. Loss of PKL disrupts the occupancy of the PRC2 catalytic subunit CLF in spreading regions and leads to aberrant dedifferentiation. Nucleosome density increase endowed by the ATPase function of PKL ensures that unmodified nucleosomes are accessible to PRC2 catalytic activity for H3K27me3 spreading. Our findings demonstrate that PKL-dependent nucleosome compaction is critical for PRC2-mediated H3K27me3 read-and-write function in H3K27me3 spreading, thus revealing a mechanism by which repressive chromatin domains are established and propagated.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Amelioration effects of the soybean lecithin-gallic acid complex on iron-overload-induced oxidative stress and liver damage in C57BL/6J mice.

CONTEXT: Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. OBJECTIVE: This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. MATERIALS AND METHODS: In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. RESULTS: In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 µg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). CONCLUSIONS: These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Oxidation Flow Reactor Results in a Chinese Megacity Emphasize the Important Contribution of S/IVOCs to Ambient SOA Formation.

Oxygenated volatile organic compounds (OVOCs) and secondary organic aerosol (SOA) formation potential of ambient air in Guangzhou, China was investigated using a field-deployed oxidation flow reactor (OFR). The OFR was used to mimic hours to weeks of atmospheric exposure to hydroxyl (OH) radicals within the 2-3 min residence time. A comprehensive investigation on the variation of VOCs and OVOCs as a function of OH exposure is shown. Substantial formation of organic acids and nitrogen-containing OVOC species were observed. Maximum SOA formation in the OFR was observed following 1-4 equiv days' OH exposure. SOA produced from known/measured VOC/IVOC precursors such as single-ring aromatics and long-chain alkanes can account for 52-75% of measured SOA under low NOx and 26-60% under high NOx conditions based on laboratory SOA yield parametrizations. To our knowledge, this is the first time that the contribution (8-20%) of long-chain (C8-C20) alkane oxidation to OFR SOA formation was quantified from direct measurement. By additionally estimating contribution from unmeasured semivolatile and intermediate volatility compounds (S/IVOCs) that are committed with C8-C20 alkanes, 64-100% of the SOA formation observed in the OFR can be explained, signifying the important contribution of S/IVOCs such as large cyclic alkanes to ambient SOA.

Chemical composition and sources of amines in PM2.5 in an urban site of PRD, China.

Atmospheric amines have attracted increasing attention due to their significant impact on new particle formation, particle hygroscopicity and particle optical properties. In this study, four low-molecule-weight amines were detected from PM2.5 filter samples collected at an urban site of Pearl River Delta (PRD) region of China in 2018 autumn. During the campaign, the mass concentrations of ambient particulate methylamine (MA, CH3NH2), dimethylamine (DMA, (CH3)2NH), trimethylamine (TMA, (CH3)3N), and diethylamine (DEA, (C2H5)2NH) were quantified at daily or 12-h resolution using an optimized Ion Chromatograph (IC) method. The total measured amine concentration was 297 ± 209 ng/m3, which can account for 0.76 ± 0.33% of PM2.5 mass concentrations. The particulate amines in PRD urban area were dominated by MA (243 ± 179 ng/m3), accounting for over 80% of total amines, then followed by DMA (49 ± 30 ng/m3, 16.5%), TMA (4 ± 2 ng/m3) and DEA (1 ± 1 ng/m3). Based on the correlation analysis, MA and DMA mainly presented as nitrate and sulfate salts. We speculate the amines tend to react with gas-phase HNO3 or particle-phase nitrate to form particulate amine salts via local process in Guangzhou. As the relative humidity (RH) increased, enhanced partitioning of amine towards the particle phase was observed. Using approach of multiple linear regression, 71% of the particulate amines in PRD urban site could be explained by acid-base process and the rest by primary emissions from combustion sources (29%).

A Novel L-Phenylalanine Dipeptide Inhibits the Growth and Metastasis of Prostate Cancer Cells via Targeting DUSP1 and TNFSF9.

Prostate cancer (PCa) is a common malignant cancer of the urinary system. Drug therapy, chemotherapy, and radical prostatectomy are the primary treatment methods, but drug resistance and postoperative recurrence often occur. Therefore, seeking novel anti-tumor compounds with high efficiency and low toxicity from natural products can produce a new tumor treatment method. Matijin-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] is a phenylalanine dipeptide monomer compound that is isolated from the Chinese ethnic medicine Matijin (Dichondra repens Forst.). Its derivatives exhibit various pharmacological activities, especially anti-tumor. Among them, the novel MTS derivative HXL131 has a significant inhibitory effect against prostate tumor growth and metastasis. This study is designed to investigate the effects of HXL131 on the growth and metastasis of human PCa cell lines PC3 and its molecular mechanism through in vitro experiments combined with proteomics, molecular docking, and gene silencing. The in vitro results showed that HXL131 concentration dependently inhibited PC3 cell proliferation, induced apoptosis, arrested cell cycle at the G2/M phase, and inhibited cell migration capacity. A proteomic analysis and a Western blot showed that HXL131 up-regulated the expression of proliferation, apoptosis, cell cycle, and migration-related proteins CYR61, TIMP1, SOD2, IL6, SERPINE2, DUSP1, TNFSF9, OSMR, TNFRSF10D, and TNFRSF12A. Molecular docking, a cellular thermal shift assay (CETSA), and gene silencing showed that HXL131 had a strong binding affinity with DUSP1 and TNFSF9, which are important target genes for inhibiting the growth and metastasis of PC3 cells. This study demonstrates that HXL131 exhibited excellent anti-prostate cancer activity and inhibited the growth and metastasis of prostate cancer cells by regulating the expression of DUSP1 and TNFSF9.

Inter-comparisons of VOC oxidation mechanisms based on box model: A focus on OH reactivity.

Volatile organic compounds (VOCs) oxidation processes play a very important role in atmospheric chemistry, and the chemical reactions are expressed in various manners in chemical mechanisms. To gain an improved understanding of VOCs evolution during oxidation processes and evaluate the discrepancies of VOCs oxidation schemes among different mechanisms, we used the total VOC reactivity as a diagnostic and evaluated tool to explore the differences for six widely used chemical mechanisms. We compared the total VOC reactivity evolution under high-NOx conditions for several sets of precursors, including n-pentane, toluene, ethene, isoprene and a mixture of 57 Photochemical Assessment Monitoring Stations (PAMS) species in a 0-D photochemical box model. Inter-comparison of total VOC reactivity of individual precursor simulations showed discrepancies to different extent of the oxidation schemes among the studied mechanisms, which are mainly attributed to the different lumping approaches for organic species. The PAMS simulation showed smaller discrepancy than individual precursor cases in terms of total VOC reactivity. SAPRC07 and RACM2 performances are found to better match the MCM for simulation of total VOC reactivity. Evidences suggest that the performance in simulating secondary organic products, OH concentrations and NOx concentrations are related to the OH reactivity discrepancies among various chemical mechanisms. Information in this study can be used in selection of chemical mechanisms to better model OH reactivity in different environments. The results in this study also provide directions to further improve the ability in modelling total VOC reactivity with the chemical mechanisms.

Volatile organic compounds in wintertime North China Plain: Insights from measurements of proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS).

The characteristics of wintertime volatile organic compounds (VOCs) in the North China Plain (NCP) region are complicated and remain obscure. VOC measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS) at a rural site in the NCP from November to December 2018. Uncalibrated ions measured by PTR-ToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector (GC-MS/FID). The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions, the secondary formation of oxygenated VOCs (OVOCs) is non-negligible in the wintertime, i.e., OVOCs accounts for 42% ± 7% in the total VOCs (151.3 ± 75.6 ppbV). We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of cycloalkanes. The chemical changes of organic carbon in a pollution accumulation period were investigated, which suggests an essential role of fragmentation reactions for large, chemically reduced compounds during the heavy-polluted stage in wintertime pollution. The changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of "coal to gas" strategies in curbing air pollutants. The high abundances of some key species (e.g. oxygenated aromatics) indicate the strong emissions of coal combustion in wintertime of NCP. The ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.

Freeze-thawing impairs the motility, plasma membrane integrity and mitochondria function of boar spermatozoa through generating excessive ROS.

BACKGROUND: Cryopreservation is an efficient way to store spermatozoa and is closely associated with the quality of sperm after the freeze-thaw process. During freeze-thaw cycling, excessive reactive oxygen species (ROS) are produced, and the effects of ROS on boar sperm during cryopreservation have not been identified. RESULTS: In this study, we evaluated the quality of boar spermatozoa in different steps of cryopreservation (extension, cooling, and thawing for 30 min and 240 min) with or without boar-sperm antioxidant (N-acetylcysteine (NAC)). The ROS levels, sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, ATP content, and sperm apoptosis were assayed. After thawing, the ROS level and sperm apoptosis were significantly increased, and the sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, and ATP content were significantly impaired compared with those at the extension period and cooling period. Moreover, the addition of N-acetyl L-cysteine (NAC) reversed these changes. CONCLUSION: The freeze-thawing of boar spermatozoa impaired their motility, plasma membrane, mitochondrial activity, sperm chromatin structure and apoptosis by producing excessive ROS. Thus, the downregulation of ROS level by antioxidants, especially the NAC, is important for manufacturing frozen pig sperm to increase reproductive cells and livestock propagation, as well as to improve the application of frozen semen in pigs worldwide.

Thirst Relief Effect of 0.75% Citric Acid Spray During the Anesthesia Recovery Period: A Randomized Controlled Trial.

PURPOSE: Postoperative thirst is a common clinical issue. The discomfort caused by thirst during the perioperative period is strong and significant. Postoperative thirst is associated with emotional changes, giving rise to a series of adverse psychological and physical problems to patients. This study aimed to explore the effect of 0.75% citric acid spray on thirst relief during the anesthesia recovery period in China. DESIGN: A randomized controlled trial was conducted on subjects immediately after the removal of the endotracheal tube in a postanesthesia care unit. METHODS: A total of 112 patients with TI scores ≥3 on 0-10 numeric rating scale were randomized to the intervention group (0.75% citric acid spray group; n = 56) or control group (cool water spray; n = 56) by computerized randomization. Thirst assessment was performed before and 5 minutes after the intervention. Five minutes after the intervention, if the TI score was still ≥3 points, the spray would be added and the thirst assessment would be performed again until the TI score was <3 points. The onset time, duration time, and the number of additional sprays within 20 minutes was recorded. FINDINGS: Five minutes after the intervention, the thirst intensity score of the 0.75% citric acid spray group decreased from 5.57 ± 1.35 to 3.09 ± 1.20. The onset and duration times were 0.77 ± 0.47 min and 4.41 ± 2.59 min, respectively, and the number of spray additions in 20 min was 1.09 ± 0.92. The thirst intensity score of the cool water spray group decreased from 5.29 ± 1.52 to 3.73 ± 1.54. The onset and duration time were 0.84 ± 0.42 min and 2.77 ± 1.80 min, respectively, and the number of spray additions was 1.91 ± 1.24. No incidence of adverse events, including choking, aspiration, and allergies occurred. CONCLUSION: For thirsty patients during the anesthesia recovery period, the spray method is safe and has fewer side effects, including choking, aspiration, and allergies. Thus, 0.75% citric acid spray and cool water spray are both safe and effective; however, the 0.75% citric acid spray has a better thirst relief effect that lasts longer than the cool water spray.

Photochemical Aqueous-Phase Reactions Induce Rapid Daytime Formation of Oxygenated Organic Aerosol on the North China Plain.

Secondary organic aerosol (SOA) constitutes a large fraction of organic aerosol worldwide, however, the formation mechanisms in polluted environments remain poorly understood. Here we observed fast daytime growth of oxygenated organic aerosol (OOA) (with formation rates up to 10 µg m-3 h-1) during low relative humidity (RH, daytime average 38 ± 19%), high RH (53 ± 19%), and fog periods (77 ± 13%, fog occurring during nighttime with RH reaching 100%). Evidence showed that photochemical aqueous-phase SOA (aqSOA) formation dominantly contributed to daytime OOA formation during the periods with nighttime fog, while both photochemical aqSOA and gas-phase SOA (gasSOA) formation were important during other periods with the former contributing more under high RH and the latter under low RH conditions, respectively. Compared to daytime photochemical aqSOA production, dark aqSOA formation was only observed during the fog period and contributed negligibly to the increase in OOA concentrations due to fog scavenging processes. The rapid daytime aging, as indicated by the rapid decrease in m,p-xylene/ethylbenzene ratios, promoted the daytime formation of precursors for aqSOA formation, e.g., carbonyls such as methylglyoxal. Photooxidants related to aqSOA formation such as OH radical and H2O2 also bear fast daytime growth features even under low solar radiative conditions. The simultaneous increases in ultraviolet radiation, photooxidant, and aqSOA precursor levels worked together to promote the daytime photochemical aqSOA formation. We also found that biomass burning emissions can promote photochemical aqSOA formation by adding to the levels of aqueous-phase photooxidants and aqSOA precursors. Therefore, future mitigation of air pollution in a polluted environment would benefit from stricter control on biomass burning especially under high RH conditions.

High Concentrations of Atmospheric Isocyanic Acid (HNCO) Produced from Secondary Sources in China.

Isocyanic acid (HNCO) is a potentially toxic atmospheric pollutant, whose atmospheric concentrations are hypothesized to be linked to adverse health effects. An earlier model study estimated that concentrations of isocyanic acid in China are highest around the world. However, measurements of isocyanic acid in ambient air have not been available in China. Two field campaigns were conducted to measure isocyanic acid in ambient air using a high-resolution time-of-flight chemical ionization mass spectrometer (ToF-CIMS) in two different environments in China. The ranges of mixing ratios of isocyanic acid are from below the detection limit (18 pptv) to 2.8 ppbv (5 min average) with the average value of 0.46 ppbv at an urban site of Guangzhou in the Pearl River Delta (PRD) region in fall and from 0.02 to 2.2 ppbv with the average value of 0.37 ppbv at a rural site in the North China Plain (NCP) during wintertime, respectively. These concentrations are significantly higher than previous measurements in North America. The diurnal variations of isocyanic acid are very similar to secondary pollutants (e.g., ozone, formic acid, and nitric acid) in PRD, indicating that isocyanic acid is mainly produced by secondary formation. Both primary emissions and secondary formation account for isocyanic acid in the NCP. The lifetime of isocyanic acid in a lower atmosphere was estimated to be less than 1 day due to the high apparent loss rate caused by deposition at night in PRD. Based on the steady state analysis of isocyanic acid during the daytime, we show that amides are unlikely enough to explain the formation of isocyanic acid in Guangzhou, calling for additional precursors for isocyanic acid. Our measurements of isocyanic acid in two environments of China provide important constraints on the concentrations, sources, and sinks of this pollutant in the atmosphere.

[Nasal endoscopy-assisted bulboprostatic anastomosis for posterior urethral stricture].

OBJECTIVE: To study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture. METHODS: Between January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills. RESULTS: Eight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured. CONCLUSION: Nasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.

The role of sodium alginate in improving floc size and strength and the subsequent effects on ultrafiltration membrane fouling.

BACKGROUND: Dosing environment-friendly polymer as coagulant aids is an encouraging method in water treatment to obtain desirable floc characteristics. Sodium alginate (SA) was used as the coagulant aid for synthetic humic acid (HA) water treatment to investigate the effect on flocs characteristics and ultrafiltration (UF) membrane fouling. RESULTS: When SA content was 0.3 mg L-1, the treatment of HA by polyaluminium chloride (PAC) plus SA (PAC/SA) yielded the maximum removal efficiency of 66.5%, which was higher than the maximum HA removal efficiency of PAC (58%). Moreover, the HA flocs size of PAC would grow from 269 to 367 Iim after SA was added. Strength factor and recovery factor of PAC/SA were larger than those of PAC. These resulted in the improvement in subsequent UF membrane performance. The membrane fouling decreased in the following order: the raw water > PAC coagulated water > PAC/SA coagulated water. CONCLUSION: The study showed that the application of SA as coagulant aids resulted in larger and stronger flocs, which would improve treatment efficiency of the coagulation process. And the flocs formed by PAC/SA contributed to the restriction of the fouling of UF membrane, which would decrease the cost of advanced water treatment.

Screening compounds of Chinese medicinal herbs anti-Marek's disease virus.

CONTEXT: Marek's disease (MD) seriously threatens the world poultry industry and has resulted in great economic losses. Chinese medicinal herbs are a rich source for lead compounds and drug candidates for antiviral treatments. OBJECTIVE: To investigate the anti-MDV activity and mechanism of 20 compounds extracted from Chinese medicinal herbs. MATERIALS AND METHODS: Antiviral assay, time of addition experiments, and virucidal assay were performed on chicken embryo fibroblast cells. The 50% cytotoxic concentration and 50% effective concentration were determined and, accordingly, selectivity index and inhibition ratio were calculated. RESULTS: Antiviral assay showed dipotassium glycyrrhizinate (DG) and sodium tanshinone IIA sulfonate (STS) exhibited significantly inhibitory activity against MDV in a dose-dependent manner. EC50 of DG and STS were 893.5 ± 36.99 µg/mL and 54.82 ± 2.99 µg/mL, and selective index (SI) were >3.36 and >9.12, respectively. Time of addition experiment and virucidal assay demonstrated DG inhibited viral replication in the full replication cycle and inactivated MDV particles in non-time-dependent manner, but STS interfered with the early stage of MDV replication and inactivated MDV particles in a time-dependent manner. Moreover, both DG and STS promoted apoptosis of cells infected by MDV. DISCUSSION AND CONCLUSION: DG and STS have great potential for developing new anti-MDV drugs for clinic application.

The impact of social participation on Subjective Wellbeing in the older adult: the mediating role of anxiety and the moderating role of education.

Introduction: The study aims to examine the mediating role of anxiety in the relationship between social participation and Subjective Wellbeing among Chinese older adults. Additionally, it investigates the moderating ed of education in this relationship. Methods: The data came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) published by peking University, with a sample size of 10,626 individuals aged 60 years and above. SPSS 21.0 was used for the statistical analysis of the data, and Mplus 8.0 was used for the statistical processing of the mediating and moderating effects analysis. Results: (1) The social participation significantly and positively predicated Subjective Wellbeing; (2) Anxiety partially mediated the eect between social participation and Subjective Wellbeing. The mediating eect value was 0.103; (3) Education plays a moderating role in the impact of social participation on subjective Wellbeing. Discussion: In summary, social participation can reduce the anxiety and enhance their Subjective Wellbeing. Meanwhile, the eet of social participation on Subjective Wellbeing was the greatest for the older adult with high education. The findings suggest that community-led activities can be initiated to improve social participation in the older adult. Furthermore, educational courses could be to support the healthy aging of older adults in China.

Clinical significance of lncRNA XIST expression in cholangiocarcinoma and its effect on cell migration and invasion.

BACKGROUND: Cholangiocarcinoma is a malignant tumor that occurs in the bile duct system, and the prognosis of patients is poor. Currently, research suggests that long non-coding RNAs (lncRNAs) in the treatment and prevention of cholangiocarcinoma. This study primarily focuses on the regulation and potential mechanism of the lncRNA XIST (XIST) in cholangiocarcinoma. METHODS: The levels of XIST and miR-126-3p in cholangiocarcinoma tissues and cells were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell transfection status, including migration and invasion, was examined via the Transwell method. The relationship between XIST and miR-126-3p was observed by dual-luciferase gene reporter assay and verified by rescue assays. Additionally, the prognostic significance of XIST in cholangiocarcinoma was determined using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: XIST expression was increased in cholangiocarcinoma, while miR-126-3p was decreased, in both tissues and cells. The successful construction of silencing XIST was found to inhibit the count of cell migration and invasion. XIST directly targeted miR-126-3p to regulate the progression of cholangiocarcinoma. CONCLUSION: XIST sponging miR-126-3p inhibited the progression of cholangiocarcinoma and improved the prognosis for patients. This finding provides new insights and opportunities for future studies on cholangiocarcinoma prognostic biomarkers.

Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = - 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = - 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.

Erratum: [Corrigendum] Macleaya cordata extracts exert antiviral effects in newborn mice with rotavirus­induced diarrhea via inhibiting the JAK2/STAT3 signaling pathway.

[This corrects the article DOI: 10.3892/etm.2020.8766.].

Deacetylation of HnRNP U mediated by sirtuin1 ameliorates aged rat with liver fibrosis via inhibiting p53-related senescence and NLRP3-related inflammation.

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1ß secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.