A review of chloride ions removal from high chloride industrial wastewater: Sources, hazards, and mechanisms.

To reduce metal pipe corrosion, improve product quality, and meet zero liquid discharge (ZLD) criteria, managing chloride ion concentrations in industrial wastewaters from metallurgical and chemical sectors has become increasingly important. This review provides detailed information on the sources, concentration levels, and deleterious effects of chloride ions in representative industrial wastewaters, and also summarizes and discusses various chloride ion removal techniques, including precipitation, ion exchange, physical separation, and advanced oxidation (AOPs). Among these, AOPs are particularly promising due to their ability to couple with other technologies and the diversity of their auxiliary technologies. The development of dechlorination electrode materials by electro-adsorption (CDI) can be inspired by the electrode materials used in chloride ion battery (CIB). This review also provides insights into exploring the effective combination of multiple chloride removal mechanisms, as well as the development of environmentally friendly composite materials. This review provides a theoretical basis and development direction for the effective treatment and secondary utilization of chlorine-containing industrial wastewater in the future.

SHMT2 reduces fatty liver but is necessary for liver inflammation and fibrosis in mice.

Non-alcoholic fatty liver disease is associated with an irregular serine metabolism. Serine hydroxymethyltransferase 2 (SHMT2) is a liver enzyme that breaks down serine into glycine and one-carbon (1C) units critical for liver methylation reactions and overall health. However, the contribution of SHMT2 to hepatic 1C homeostasis and biological functions has yet to be defined in genetically modified animal models. We created a mouse strain with targeted SHMT2 knockout in hepatocytes to investigate this. The absence of SHMT2 increased serine and glycine levels in circulation, decreased liver methylation potential, and increased susceptibility to fatty liver disease. Interestingly, SHMT2-deficient mice developed simultaneous fatty liver, but when fed a diet high in fat, fructose, and cholesterol, they had significantly less inflammation and fibrosis. This study highlights the critical role of SHMT2 in maintaining hepatic 1C homeostasis and its stage-specific functions in the pathogenesis of NAFLD.

Comparative alternative polyadenylation profiles in differentiated adipocytes of subcutaneous and intramuscular fat tissue in cattle.

Alternative polyadenylation (APA) is a key molecular mechanism involved in the post-transcriptional regulation of gene expression, which has been proven to play a critical role in cell differentiation. In the present study, we performed IVT-SAPAS sequencing to profile the dynamic changes of APA sites in bovine subcutaneous preadipocytes and intramuscular preadipocytes during adipogenesis. A total of 52621 high quality APA sites were identified in preadipocytes and adipocytes. Compared with preadipocytes, the increased usage of canonical AATAAA was observed in the cell-biased APA sites of adipocytes. Furthermore, 1933 and 2140 differentially expressed APA (DE-APA) sites, as well as 341 and 337 untranslated region-APA (UTR-APA) switching genes were identified in subcutaneous preadipocytes and intramuscular preadipocytes during adipogenesis, respectively. The UTR-APA switching genes showed divergent trends in preadipocytes, among which UTR-APA switching genes in intramuscular preadipocytes tended to use shorter 3'UTR for differentiation into mature adipocytes. APA events mediated by UTR-APA switching in intramuscular adipocytes were enriched in lipid synthesis and adipocyte differentiation. TRIB3, WWTR1, and INSIG1 played important roles in the differentiation of intramuscular preadipocytes. Briefly, our results provided new insights into understanding the mechanisms of bovine adipocyte differentiation.

Alternative Polyadenylation of Malic Enzyme 1 Is Essential for Accelerated Adipogenesis.

Understanding the mechanism of adipogenesis is an important basis for improving meat quality traits of livestock. Alternative polyadenylation (APA) is a vital mechanism to regulate the expression of eukaryotic genes. However, how the individual APA functions in adipogenesis remains elusive. This study was intended to investigate the effect of malic enzyme 1 (ME1) APA on adipogenesis. Here, intracellular lipid droplets were stained using Oil red O. 3' RACE was used to verify APA events of the ME1 gene. Interactions between ME1 3' untranslated region (3' UTR)-APA isoforms and miRNAs, as well as differential expression of isoforms, were examined using dual-luciferase reporter and molecular experiments. The mechanism of ME1 APA on adipogenesis was explored by gain and loss of function assays. In this study, two ME1 isoforms with different 3' UTR lengths were detected during adipogenesis. Moreover, the ME1 isoform with a short 3' UTR was significantly upregulated compared with the one with a long 3' UTR. Mechanistically, only the long ME1 isoform was targeted by miR-153-3p to attenuate adipogenesis, while the short one escaped the regulation of miR-153-3p to accelerate adipogenesis. Our results reveal a novel mechanism of ME1 APA in regulating adipogenesis.

Bovine C-X-C Motif Chemokine Ligand 14 Expression Is Regulated by Alternative Polyadenylation and MicroRNAs.

Alternative polyadenylation (APA), including APA that occurs only in the 3' UTR (3' UTR-APA), is an important post-transcriptional regulatory mechanism that leads to distinct 3' UTRs for some genes, increasing the complexity of the transcriptome. The post-transcriptional events regulating the expression of bovine, the C-X-C motif chemokine ligand 14 (CXCL14) gene, remains largely unknown. Here, we find that the bovine CXCL14 gene produces two different lengths of mRNA isoforms due to 3' UTR-APA, and the short and long 3' UTR is 126 bp and 1155 bp, respectively. We found that the expression level of the short isoform was significantly higher than that of the long isoform by luciferase assays and overexpression of different CXCL14 3' UTR-APA isoforms. Moreover, using luciferase assay and site-directed mutagenesis experiments, the results showed that the long CXCL14 3' UTR-APA isoform is downregulated by miR-17-5p, miR-150, and miR-217. However, because the short isoform lacks the true target of miR-17-5p, miR-150, and miR-217 in its 3' UTR and thus escapes the inhibitory effect of these microRNAs, its expression level is significantly higher than that of the long isoform. Finally, we demonstrate that the short CXCL14 3' UTR-APA isoform promotes preadipocyte proliferation by cell counting kit 8 (CCK8) assays. Collectively, our results show that the CXCL14 gene is post-transcriptionally regulated through APA and microRNAs.

Comparison of the Mg2+-Li+ Separation of Different Nanofiltration Membranes.

Nanofiltration application for the separation of Mg2+-Li+ from salt-lake brines was attempted in the present work. Four different nanofiltration membranes identified in the manuscript as DL, DK, NF-270, and NF-90 were used to treat salt brine with a magnesium to lithium ratio (MLR) of 61, additionally contaminated by the other ions such as Na+, K+, Ca2+, etc. The effect of the dilution factor, operating pressure, circulation rate, and feed pH were assessed to identify the optimal operating conditions for each membrane based on the retention efficiency of each ion. The results showed an insignificant effect of Ca2+ on the retention performance of Mg2+-Li+. Na+ and K+ had a smaller hydration radius and larger diffusion coefficient, which competed with Li+ and altered the separation of Mg2+-Li+. Under the optimal conditions (dilution factor: 40; operating pressure: 1.2 MPa; circulation flow rate: 500 L/h; pH: 7), the retention efficiency of lithium was as low as 5.17%, separation factor (SF) was as low as 0.074, and the MLR in the permeate reduced to 0.088.

The psc-CVM assessment system: A three-stage type system for CVM assessment based on deep learning.

BACKGROUND: Many scholars have proven cervical vertebral maturation (CVM) method can predict the growth and development and assist in choosing the best time for treatment. However, assessing CVM is a complex process. The experience and seniority of the clinicians have an enormous impact on judgment. This study aims to establish a fully automated, high-accuracy CVM assessment system called the psc-CVM assessment system, based on deep learning, to provide valuable reference information for the growth period determination. METHODS: This study used 10,200 lateral cephalograms as the data set (7111 in train set, 1544 in validation set and 1545 in test set) to train the system. The psc-CVM assessment system is designed as three parts with different roles, each operating in a specific order. 1) Position Network for locating the position of cervical vertebrae; 2) Shape Recognition Network for recognizing and extracting the shapes of cervical vertebrae; and 3) CVM Assessment Network for assessing CVM according to the shapes of cervical vertebrae. Statistical analysis was conducted to detect the performance of the system and the agreement of CVM assessment between the system and the expert panel. Heat maps were analyzed to understand better what the system had learned. The area of the third (C3), fourth (C4) cervical vertebrae and the lower edge of second (C2) cervical vertebrae were activated when the system was assessing the images. RESULTS: The system has achieved good performance for CVM assessment with an average AUC (the area under the curve) of 0.94 and total accuracy of 70.42%, as evaluated on the test set. The Cohen's Kappa between the system and the expert panel is 0.645. The weighted Kappa between the system and the expert panel is 0.844. The overall ICC between the psc-CVM assessment system and the expert panel was 0.946. The F1 score rank for the psc-CVM assessment system was: CVS (cervical vertebral maturation stage) 6 > CVS1 > CVS4 > CVS5 > CVS3 > CVS2. CONCLUSIONS: The results showed that the psc-CVM assessment system achieved high accuracy in CVM assessment. The system in this study was significantly consistent with expert panels in CVM assessment, indicating that the system can be used as an efficient, accurate, and stable diagnostic aid to provide a clinical aid for determining growth and developmental stages by CVM.

Treatment of skeletal class III malocclusion using a combined clear aligner and surgery-early approach : Assessment based on the American Board of Orthodontics Objective Grading System.

PURPOSE: To evaluate whether clear aligner therapy (CAT) combined with a surgery-early approach can achieve good therapeutic effects in patients with skeletal class III malocclusion. METHODS: Thirty consecutive skeletal class III malocclusion cases treated with clear aligners combined with early surgery were selected. Treatment time, lateral cephalograms and American Board of Orthodontics Objective Grading System (ABO-OGS) scores of the treatment models were measured to evaluate the treatment efficiency, facial profile, and occlusion. RESULTS: The results showed that early surgery was achieved after 7.71 months of presurgical orthodontics, on average. ANB decreased by 5.57° (P < 0.001), and STissue N Vert to Pog' decreased by 7.29 mm (P = 0.001), both reaching normal values. The posttreatment ABO-OGS scores were 26.600 on average, meeting its standards. CONCLUSIONS: With the assistance of CAT, early surgery can be accomplished in patients with skeletal class III malocclusion, improving their facial profile and achieving functional occlusion.

Calcination-Induced Oxygen Vacancies Enhancing the Photocatalytic Performance of a Recycled Bi2O3/BiOCl Heterojunction Nanosheet.

With the rapid development of industry, bismuth-based semiconductors have been widely used for the photocatalytic degradation of organic contaminants discharged into wastewater. Herein, a Bi2O3/BiOCl (BBOC) heterojunction was constructed with high photocatalytic activity toward Rhodamine B (RhB) in the first cycle of the photocatalysis test, while the photocatalytic performance was drastically reduced after repeated testing. The adsorbed RhB molecules occupying the facial active sites of BBOC contributed to the decline of photocatalytic activity. The spent BBOC can be reactivated by the decomposition of the adsorbed RhB and the introduction of oxygen vacancies during calcination under an air atmosphere. The BBOC thus recovered exhibited a superior apparent rate constant of 0.08087 min-1 compared with 0.05228 min-1 of pristine BBOC. This study provided an effective strategy to investigate the deactivation/activation mechanism of bismuth-based heterojunction photocatalysts.

Co-alterations of circadian clock gene transcripts in human placenta in preeclampsia.

Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs. non-PE (a mixture of pregnant women with term, preterm, small-for-gestational-age, or chorioamnionitis) using two independent gene expression datasets: GSE75010-157 (80 PE vs. 77 non-PE) and GSE75010-173 (77 PE and 96 non-PE). We found a robust difference in circadian gene expression between PE and non-PE across the two datasets, where CRY1 mRNA increases and NR1D2 and PER3 transcripts decrease in PE placenta. Gene set variation analysis revealed an interplay between co-alterations of circadian clock genes and PE with altered hypoxia, cell migration/invasion, autophagy, and membrane trafficking pathways. Using human placental trophoblast HTR-8 cells, we show that CRY1/2 and NR1D1/2 regulate trophoblast migration. A subgroup study including only term samples demonstrated that CLOCK, NR1D2, and PER3 transcripts were simultaneously decreased in PE placenta, a finding supported by CLOCK protein downregulation in an independent cohort of human term PE placenta samples. These findings provide novel insights into the roles of the molecular clock in the pathogenesis of PE.

Detection of Cardiac Functions of Fetus with Diabetic Metabolic Disease through PEG-PCLNano Micelle and Ultrasound Technique.

The study was to probe into the application of ultrasound technique in gestational diabetes mellitus (GDM) and research the progress of PEG-PCL nano micelle and ultrasound technique. METHOD: 210 patients with a singleton pregnancy fetus, who received the fetal echocardiography in Yuhang District First People's Hospital from March 2019 to March 2020, were selected as the subjects, including 101 fetuses who were confirmed as gestational diabetes mellitus(GDM), and 109 normal fetuses (control group). The ultrasound cardiogram technique was employed to detect the thickness of the fetus ventricle septum, mitral/tricuspid annular displacement, left/right TEI indexes, and so on. The mean value of three cardiac cycles was taken as the test results. Finally, SPSS17.0 software was applied to the analysis of data. The nano micelle was made from the amphiphilic block copolymers (PEG-PCL) using the dialysis method/solvent evaporation method. The nanoscale ultrasound contrast agent was prepared from Decafluoropentane which was imaging gas. The characterizations were studied using the optical microscope, and transmission electron microscopy (TEM). The temperature sensitivity and ultrasound sensitivity of the nano-ultrasound contrast agent were analyzed with the particle size as the evaluation index. The in-vitro ultrasound contrast experiment was conducted to study the contrast-enhanced effect. RESULTS: The fetal Tei index of the case group was higher than that of the control group, of which P<0.05 had statistical significance. However, the thickness of the fetus ventricle septum, Em, Am, and Em/Am of mitral/tricuspid annular were not significantly different from those of the control group (P>0.05). The nano ultrasonic contrast agent prepared through the ultrasonic injection method had a uniform particle size and a hollow shell-core structure under an electron projection microscope. The particle size of the nano-ultrasound contrast agent varied with temperature, and its microbubbles were generated under ultrasonic conditions. As compared with the blank degassed water group, a real linear echo appeared inside the contrast agent group, with small and even echo spots. The back echo remained with no obvious attenuation and lasted for a longer period. However, the blank degassed group had no distinct echo intensity and spot. CONCLUSION: PEG-PCL nano-ultrasound contrast agent achieved an excellent imaging effect; there was no obvious change to heart function and structure of the fetus, when gestational diabetes pregnant had blood sugar perfectly controlled, however, the fetus's heart function may change in the last trimester.

Identification of Bamboo Species Based on Extreme Gradient Boosting (XGBoost) Using Zhuhai-1 Orbita Hyperspectral Remote Sensing Imagery.

Mapping the distribution of bamboo species is vital for the sustainable management of bamboo and for assessing its ecological and socioeconomic value. However, the spectral similarity between bamboo species makes this work extremely challenging through remote sensing technology. Existing related studies rarely integrate multiple feature variables and consider how to quantify the main factors affecting classification. Therefore, feature variables, such as spectra, topography, texture, and vegetation indices, were used to construct the XGBoost model to identify bamboo species using the Zhuhai-1 Orbita hyperspectral (OHS) imagery in the Southern Sichuan Bamboo Sea and its surrounding areas in Sichuan Province, China. The random forest and Spearman's rank correlation analysis were used to sort the main variables that affect classification accuracy and minimize the effects of multicollinearity among variables. The main findings were: (1) The XGBoost model achieved accurate and reliable classification results. The XGBoost model had a higher overall accuracy (80.6%), kappa coefficient (0.708), and mean F1-score (0.805) than the spectral angle mapper (SAM) method; (2) The optimal feature variables that were important and uncorrelated for classification accuracy included the blue band (B1, 464-468 nm), near-infrared band (B27, 861-871 nm), green band (B5, 534-539 nm), elevation, texture feature mean, green band (B4, 517-523 nm), and red edge band (B17, 711-720 nm); and (3) the XGBoost model based on the optimal feature variable selection showed good adaptability to land classification and had better classification performance. Moreover, the mean F1-score indicated that the model could well balance the user's and producer's accuracy. Additionally, our study demonstrated that OHS imagery has great potential for land cover classification and that combining multiple features to enhance classification is an approach worth exploring. Our study provides a methodological reference for the application of OHS images for plant species identification.

Spatial-Temporal Evolution and Driving Forces of Drying Trends on the Qinghai-Tibet Plateau Based on Geomorphological Division.

The Qinghai-Tibet Plateau (QTP) is a sensor of global climate change and regional human activities, and drought monitoring will help to achieve its ecological protection and sustainable development. In order to effectively control the geospatial scale effect, we divided the study area into eight geomorphological sub-regions, and calculated the Temperature-Vegetation Drought Index (TVDI) of each geomorphological sub-region based on MODIS Normalized Difference Vegetation Index (NDVI) and Land Surface Temperature (LST) data, and synthesized the TVDI of the whole region. We employed partial and multiple correlation analyses to identify the relationship between TVDI and temperature and precipitation. The random forest model was further used to study the driving mechanism of TVDI in each geomorphological division. The results of the study were as follows: (1) From 2000 to 2019, the QTP showed a drought trend, with the most significant drought trend in the central region. The spatial pattern of TVDI changes of QTP was consistent with the gradient changes of precipitation and temperature, both showing a gradual trend from southeast to northwest. (2) There was a risk of drought in the four seasons of the QTP, and the seasonal variation of TVDI was significant, which was characterized by being relatively dry in spring and summer and relatively humid in autumn and winter. (3) Drought in the QTP was mainly driven by natural factors, supplemented by human factors. The driving effect of temperature and precipitation factors on TVDI was stable and significant, which mainly determined the spatial distribution and variation of TVDI of the QTP. Geomorphological factors led to regional intensification and local differentiation effects of drought, especially in high mountains, flat slopes, sunny slopes and other places, which had a more significant impact on TVDI. Human activities had local point-like and linear impacts, and grass-land and cultivated land that were closely related to the relatively high impacts on TVDI of human grazing and farming activities. In view of the spatial-temporal patterns of change in TVDI in the study area, it is important to strengthen the monitoring and early warning of changes in natural factors, optimize the spatial distribution of human activities, and scientifically promote ecological protection and restoration.

Susceptibility Analysis of Geohazards in the Longmen Mountain Region after the Wenchuan Earthquake.

Multitemporal geohazard susceptibility analysis can not only provide reliable results but can also help identify the differences in the mechanisms of different elements under different temporal and spatial backgrounds, so as to better accurately prevent and control geohazards. Here, we studied the 12 counties (cities) that were severely affected by the Wenchuan earthquake of 12 May 2008. Our study was divided into four time periods: 2008, 2009-2012, 2013, and 2014-2017. Common geohazards in the study area, such as landslides, collapses and debris flows, were taken into account. We constructed a geohazard susceptibility index evaluation system that included topography, geology, land cover, meteorology, hydrology, and human activities. Then we used a random forest model to study the changes in geohazard susceptibility during the Wenchuan earthquake, the following ten years, and its driving mechanisms. We had four main findings. (1) The susceptibility of geohazards from 2008 to 2017 gradually increased and their spatial distribution was significantly correlated with the main faults and rivers. (2) The Yingxiu-Beichuan Fault, the western section of the Jiangyou-Dujiangyan Fault, and the Minjiang and Fujiang rivers were highly susceptible to geohazards, and changes in geohazard susceptibility mainly occurred along the Pingwu-Qingchuan Fault, the eastern section of the Jiangyou-Dujiangyan Fault, and the riparian areas of the Mianyuan River, Zagunao River, Tongkou River, Baicao River, and other secondary rivers. (3) The relative contribution of topographic factors to geohazards in the four different periods was stable, geological factors slowly decreased, and meteorological and hydrological factors increased. In addition, the impact of land cover in 2008 was more significant than during other periods, and the impact of human activities had an upward trend from 2008 to 2017. (4) Elevation and slope had significant topographical effects, coupled with the geological environmental effects of engineering rock groups and faults, and river-derived effects, which resulted in a spatial aggregation of geohazard susceptibility. We attributed the dynamic changes in the areas that were highly susceptible to geohazards around the faults and rivers to the changes in the intensity of earthquakes and precipitation in different periods.

The Performance and Mechanism of a Mg-Al Double-Layer Oxide in Chloride ion Removal from an Aqueous Solution.

The increasing threat of chloride ions (Cl-) has led researchers to explore efficient removal technologies. Sewage treatment with a double-layer hydroxide/oxide (LDH/LDO) is receiving increasing attention. In this work, Mg-Al LDO adsorbents were produced by the calcination of the Mg-Al LDH precursor, which was constituted by improved coprecipitation. The influence of calcination temperature, calcination time, adsorbent dosage, Cl- initial concentration, contact time, and adsorption temperature on Cl- elimination was investigated systematically. The experimental results showed that a better porous structure endowed the Mg-Al LDO with outstanding adsorption properties for Cl-. The adsorption process was well matched to the pseudo-second-order kinetics model and the Freundlich model. Under optimal conditions, more than 97% of the Cl- could be eliminated. Moreover, the removal efficiency was greater than 90% even after 11 adsorption-desorption cycles. It was found that the electrostatic interaction between Cl- and the positively charged Mg-Al LDO laminate, coupled with the reconstruction of the layer structure, was what dominated the Cl- removal process.

Maternal blood EBF1-based microRNA transcripts as biomarkers for detecting risk of spontaneous preterm birth: a nested case-control study.

OBJECTIVE: Both genetic variants and maternal blood mRNA levels of EBF1 gene have been linked to sPTB. Animal and human studies suggest that specific EBF1-based miRNAs are involved in various physiological and pathophysiological processes. However, to date, we did not find any reports of EBF1-based miRNAs or miRNA transcripts in relation to sPTB. We therefore aimed to examine whether maternal blood early B cell factor 1 (EBF1) gene-based microRNA (miRNA) transcripts can be used for detecting risk of spontaneous preterm birth (sPTB). METHODS: We conducted a nested case-control study within a Canadian cohort consisting of 1878 singleton pregnancies enrolled from May 2008 to December 2010 in Calgary, Alberta, Canada. We used a public gene expression dataset (GSE59491) derived from maternal blood in trimesters 2-3 that included women with sPTB (n = 51) and term births (n = 106) matched for maternal age, race/ethnicity, pre-pregnancy body mass index, smoking during pregnancy, and parity within the Canadian cohort. Two bioinformatics tools, miRWalk and STarMirDB, with different algorithms were applied to retrieve miRNA transcripts that putatively target the EBF1 gene (i.e. EBF1-based). Limma moderated t-tests were used to examine differentially expressed (DE) miRNA transcripts (sPTB vs term) within trimesters. Logistic regression models with miRNA transcript tertiles were applied to assess threshold associations between candidate miRNA transcripts' levels and sPTB. Receiver operating characteristic (ROC) analyses were used to identify the maximum Youden Index and its corresponding optimal sensitivity/specificity cut-point of EBF1-based miRNA transcripts for classifying sPTB, and to compare the classification performance of a linear combination (score) of miRNA transcripts with that of individual miRNA transcripts. A five-fold cross-validation was applied to examine the possible overfitting problem of the final ROC model. RESULTS: Four maternal blood EBF1-based miRNA transcripts (MIR4266, MIR1251, MIR601, MIR3612) in the 3rd trimester were significantly associated with sPTB. The odds ratios (95%CIs) for highest versus lowest tertile of the four miRNA transcripts were 3.01-5.25(1.21-13.14, p ≤ .018). The combined 4-miRNA transcripts' score significantly improved the classification of sPTB compared to individual miRNA transcripts (AUC increased from 0.65-0.69 to 0.82, p ≤ .0034) and showed a sensitivity for sPTB of 0.81 and a specificity of 0.72. The final ROC model of the EBF1-based 4 miRNA transcripts' score in cases and controls had no significant overfitting issue. CONCLUSIONS: Maternal blood EBF1-based miRNA transcripts may, along with other biomarkers, be useful in screening for sPTB risk in 3rd trimester. Our results also provide clues for further study of potential molecular mechanisms underlying the relationship between EBF1 gene and sPTB, e.g. connecting genetic variants, mRNA expression, and miRNA regulation.

Placental circadian lincRNAs and spontaneous preterm birth.

Long non-coding RNAs (lncRNAs) have a much higher cell- and/or tissue-specificity compared to mRNAs in most cases, making them excellent candidates for therapeutic applications to reduce off-target effects. Placental long non-coding RNAs have been investigated in the pathogenesis of preeclampsia (often causing preterm birth (PTB)), but less is known about their role in preterm birth. Preterm birth occurs in 11% of pregnancies and is the most common cause of death among infants in the world. We recently identified that genes that drive circadian rhythms in cells, termed molecular clock genes, are deregulated in maternal blood of women with spontaneous PTB (sPTB) and in the placenta of women with preeclampsia. Next, we focused on circadian genes-correlated long intergenic non-coding RNAs (lincRNAs, making up most of the long non-coding RNAs), designated as circadian lincRNAs, associated with sPTB. We compared the co-altered circadian transcripts-correlated lincRNAs expressed in placentas of sPTB and term births using two published independent RNAseq datasets (GSE73712 and GSE174415). Nine core clock genes were up- or downregulated in sPTB versus term birth, where the RORA transcript was the only gene downregulated in sPTB across both independent datasets. We found that five circadian lincRNAs (LINC00893, LINC00265, LINC01089, LINC00482, and LINC00649) were decreased in sPTB vs term births across both datasets (p ≤ .0222, FDR≤.1973) and were negatively correlated with the dataset-specific clock genes-based risk scores (correlation coefficient r = -.65 ∼ -.43, p ≤ .0365, FDR≤.0601). Gene set variation analysis revealed that 65 pathways were significantly enriched by these same five differentially expressed lincRNAs, of which over 85% of the pathways could be linked to immune/inflammation/oxidative stress and cell cycle/apoptosis/autophagy/cellular senescence. These findings may improve our understanding of the pathogenesis of spontaneous preterm birth and provide novel insights into the development of potentially more effective and specific therapeutic targets against sPTB.

Inhibition of HMGB1/RAGE axis suppressed the lipopolysaccharide (LPS)-induced vicious transformation of cervical epithelial cells.

The chronic inflammation operates as one of the critical causes of cervical cancer. Activation of HMGB1/RAGE axis could induce the inflammation and lead to multiple types of cancer. However, whether the HMGB1/RAGE axis could affect the development of cervical cancer by regulating the inflammation is unclear. Here, we stimulated normal cervical epithelial cells with lipopolysaccharide (LPS). Next, the expression of RAGE in these cells was suppressed by the RAGE inhibitor. CCK-8 and wound healing assays were performed to detect the proliferation and invasion. To determine how inflammatory factors (IL-1ß, IL-6 and TNF-α) expressed in supernatant of these cells, ELISA was conducted. Western blotting was used for the detection of the expression of pyroptosis-related proteins (NLRP3 and caspase4). It was found that stimulation of LPS enhanced the proliferation and invasion of normal cervical epithelial cells. The expression of inflammatory factors (IL-1ß, IL-6 and TNF-α) in these cells was promoted as well. Application of RAGE inhibitor abolished the efficacy of LPS on these cells. Furthermore, LPS promoted the expression of NLRP3 and caspase4 in these cells while RAGE inhibitor exerted suppressive effects on the expression of these proteins. In summary, LPS-induced inflammation of normal cervical epithelial cells resulted in the malignant transformation of these cells by activating HMGB1/RAGE axis.

Shortening of HO1 3'UTRs by Alternative Polyadenylation Suppresses Adipogenesis in 3T3-L1.

Appropriately increasing intramuscular fat content can help improve meat quality, so it is necessary to explore the internal molecular mechanism of preadipocyte differentiation. The role of heme oxygenase 1 (HO1) in cell oxidative stress, energy metabolism, cell proliferation, and differentiation has gradually been revealed. Here, we used 3'RACE to identify the full-length 3' untranslated region (3'UTR) of HO1 and found that a very short 3'UTR variant was produced by alternative polyadenylation (APA). HO1 with a long 3'UTR variant was identified as a direct target of miR155-5P and miR377-3P. Our experimental results verified the inhibitory effect of HO1 on preadipocyte differentiation. In addition, our research confirms that by escaping microRNA inhibitory effects, the HO1 3'UTR short variant produced by APA has a higher level of expression. Thus, the HO1 3'UTR short variant has a stronger inhibitory effect on the preadipocyte differentiation than the HO1 3'UTR long variants in 3T3-L1.

Low CLOCK and CRY2 in 2nd trimester human maternal blood and risk of preterm birth: a nested case-control study†.

Previous studies have observed an association between maternal circadian rhythm disruption and preterm birth (PTB). However, the underlying molecular mechanisms and the potential of circadian clock genes to serve as predictors of PTB remain unexplored. We examined the association of 10 core circadian transcripts in maternal blood with spontaneous PTB (sPTB) vs term births using a nested case-control study design. We used a public gene expression dataset (GSE59491), which was nested within the All Our Babies (AOB) study cohort in Canada. Maternal blood was sampled in Trimesters 2-3 from women with sPTB (n = 51) and term births (n = 106), matched for five demographic variables. In 2nd trimester maternal blood, only CLOCK and CRY2 transcripts were significantly lower in sPTB vs term (P = 0.02-0.03, false discovery rate (FDR) < 0.20). A change of PER3 mRNA from trimesters 2-3 was significantly associated with sPTB (decline in sPTB, P = 0.02, FDR < 0.20). When CLOCK and CRY2 were modeled together in 2nd trimester blood, the odds of being in the low level of both circadian gene transcripts was greater in sPTB vs term (OR = 4.86, 95%CI = (1.75,13.51), P < 0.01). Using GSVA and Pearson correlation, we identified 98 common pathways that were negatively or positively correlated with CLOCK and CRY2 expression (all P < 0.05, FDR < 0.10). The top three identified pathways were amyotrophic lateral sclerosis, degradation of extracellular matrix, and inwardly rectifying potassium channels. These three processes have previously been shown to be involved in neuron death, parturition, and uterine excitability during pregnancy, respectively.