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.

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.

ABHD5 suppresses cancer cell anabolism through lipolysis-dependent activation of the AMPK/mTORC1 pathway.

ABHD5 is an essential coactivator of ATGL, the rate-limiting triglyceride (TG) lipase in many cell types. Importantly, ABHD5 also functions as a tumor suppressor, and ABHD5 mRNA expression levels correlate with patient survival for several cancers. Nevertheless, the mechanisms involved in ABHD5-dependent tumor suppression are not known. We found that overexpression of ABHD5 induces cell cycle arrest at the G1 phase and causes growth retardation in a panel of prostate cancer cells. Transcriptomic profiling and biochemical analysis revealed that genetic or pharmacological activation of lipolysis by ABHD5 potently inhibits mTORC1 signaling, leading to a significant downregulation of protein synthesis. Mechanistically, we found that ABHD5 elevates intracellular AMP content, which activates AMPK, leading to inhibition of mTORC1. Interestingly, ABHD5-dependent suppression of mTORC1 was abrogated by pharmacological inhibition of DGAT1 or DGAT2, isoenzymes that re-esterify fatty acids in a process that consumes ATP. Collectively, this study maps out a novel molecular pathway crucial for limiting cancer cell proliferation, in which ABHD5-mediated lipolysis creates an energy-consuming futile cycle between TG hydrolysis and resynthesis, leading to inhibition of mTORC1 and cancer cell growth arrest.

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.

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.

The apheresis platelet donation was increased after a nationwide ban on family/replacement donation in China.

BACKGROUND: A nationwide ban on family/replacement donation (FRD) went into effect on April 1, 2018 in China. To date, no reports relevant to the trend of plateletpheresis donations before and after a nationwide ban on FRD were found. METHODS: We used two independent full samples, consisting of 135,851 and 82,129 plateletpheresis donors from Guangzhou and Chengdu between October 2012 and September 2019, respectively. A pseudo-panel data approach was applied by grouping three time-invariant covariates - gender, blood donation history, and birth year across 14 cross-sections (a 6-month interval each) to form a total of 24 cohort groups (14 × 24 = 336 cohorts, i.e., cells) with each having common covariates. The outcome was average apheresis platelet units per donor in each cell. We performed a two-piecewise linear mixed model with the cross-section (i.e., time) just right before the ban as a time breakpoint (i.e., 11th cross-section) to examine the trend of outcome with the adjustment of three time-invariant covariates. We removed the FRDs in each of the first 11 cross-sections to detect its possible influence on the trend. RESULTS: The final model for the samples from Guangzhou presented a two-piecewise linear trend of the outcome over time with a horizontal line to the left of the breakpoint (ßtimeBefore11 = 0.0111, p = 0.0976) and a significantly positive linear trend to the right (ßtimeAfter11 = 0.0404, p < 0.0001). The male donors and the donors with plateletpheresis donation history had an increased baseline outcome and a significant outcome change over time after the ban. Such a two-piecewise linear trend pattern can be replicated using the samples from Chengdu with some minor variations. Removing the FRD before the ban can change the pattern. CONCLUSION: The significant increase of the average apheresis platelet units per donor over time after the FRD ban may be related to the implement of the FRD ban and the improved donation behavior of male donors and/or donors with platelet donation history after the ban. Our findings may potentially motivate the policymakers in other countries where the FRD for plateletpheresis donation is still legitimate to phase out their FRD strategy and ultimately achieve 100% voluntary plateletpheresis donation.

Suppression of NSDHL attenuates adipogenesis with a downregulation of LXR-SREBP1 pathway in 3T3-L1 cells.

Previous RNA-Seq analyses revealed that NAD(P)H steroid dehydrogenase-like (NSDHL) has a different expression during 3T3-L1 differentiation; however, its roles in adipogenesis are unknown. In the present study, using quantitative real-time PCR, we confirmed that NSDHL knockdown increased the proliferation of 3T3-L1 preadipocytes, but attenuated the differentiation of 3T3-L1 preadipocytes, as evidenced by reduced lipid accumulation and down-regulation of PPARγ gene expression. Further analyses showed that the expression peak of NSDHL was at the early stage of 3T3-L1 preadipocytes differentiation and LXR-SREBP1 signaling pathway was downregulated in NSDHL-knockdown 3T3-L1 cells. Collectively, our findings indicate that NSDHL is a novel modulator of adipogenesis. Moreover, our data provide insight into the complex relationships between sterol sensing, LXR-SREBP1 signaling pathway, and PPARγ in 3T3-L1 cells.

Effects of puerarin on the AKT signaling pathway in bovine preadipocyte differentiation.

OBJECTIVE: Puerarin has the potential of regulating the differentiation of preadipocytes, but its mechanism of action has not yet been elucidated. Adipocytes found in adipose tissue, the main endocrine organ, are the main sites of lipid deposition, and are widely used as a cell model in the study of in vitro fat deposition. This study aimed to investigate the effects of puerarin on adipogenesis in vitro. METHODS: Puerarin was added to the culture medium during the process of adipogenesis. The proliferation and differentiation of bovine preadipocytes was measured through cell viability and staining with Oil Red O. The content of triacylglycerol (TG) was measured using a triglyceride assay kit. The mRNA and protein expression levels of adipogenic genes, peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: The addition of puerarin significantly increased adipogenesis of bovine preadipocytes and enhanced the mRNA and protein level expression of PPARγ (p&lt;0.01). The expression of P-Akt increased after adipogenic hormonal induction, whereas puerarin significantly increased PPARγ expression by promoting the Akt signaling component, P-Akt. The mechanism of adipogenesis was found to be related to the phosphorylation level of Ser473, which may activate the downstream signaling of the Akt pathway. CONCLUSION: Puerarin was able to promote the differentiation of preadipocytes and improve fat deposition in cattle. The mechanism of adipogenesis was found to be related to the phosphorylation level of Ser473.

RNA-Seq analysis reveals a negative role of MSMO1 with a synergized NSDHL expression during adipogenesis of 3T3-L1.

To investigate a comprehensive transcriptome information of adipogenesis, we assessed global changes in the transcriptional events during 3T3-L1 adipogenesis by RNA-Seq. Compared to the preadipocyte stage (day 0), gene expression profiling demonstrated that 2013 genes were up-regulated, and 2430 genes were down-regulated at the differentiated adipocyte stage (day 13). Among these differentially expressed genes, we found the expression of MSMO1 was down-regulated at day 13, but whether it impacts adipogenesis has not been characterized. Thus, we investigated its role in adipogenesis. Results showed that overexpression of MSMO1 inhibited the differentiation of 3T3-L1, and led to the down-regulated expression of adipogenic marker genes, while knockdown of MSMO1 had totally opposite effects. Furthermore, interaction network model allowed us to validate an unexpected role between MSMO1 and its partner, NSDHL, in regulating adipogenesis, which plays a synergized expression pattern with MSMO1. Our findings indicate that MSMO1 and NSDHL are novel modulators of adipogenesis.

Density Functional Theory plus Hubbard U Study of the Segregation of Pt to the CeO2- x Grain Boundary.

Grain boundaries (GBs) can be used as traps for solute atoms and defects, and the interaction between segregants and GBs is crucial for understanding the properties of nanocrystalline materials. In this study, we have systematically investigated the Pt segregation and Pt-oxygen vacancies interaction at the ∑3 (111) GB in ceria (CeO2). The Pt atom has a stronger tendency to segregate to the ∑3 (111) GB than to the (111) and (110) free surfaces, but the tendency is weaker than to (112) and (100). Lattice distortion plays a dominant role in Pt segregation. At the Pt-segregated-GB (Pt@GB), oxygen vacancies prefer to form spontaneously near Pt in the GB region. However, at the pristine GB, oxygen vacancies can only form under O-poor conditions. Thus, Pt segregation to the GB promotes the formation of oxygen vacancies, and their strong interactions enhance the interfacial cohesion. We propose that GBs fabricated close to the surfaces of nanocrystalline ceria can trap Pt from inside the grains or other types of surface, resulting in the suppression of the accumulation of Pt on the surface under redox reactions, especially under O-poor conditions.

DNA-binding activity of STAT3 increased in hypothalamus of DIO mice; the reduction of STAT3 phosphorylation may facilitate leptin signaling.

Leptin-mediated DNA-binding activity of STAT3 in hypothalamus plays crucial roles in the maintenance of energy homeostasis in lean mice; however its effects still remains unclear in case of leptin resistance in mice with diet induced obesity (DIO). In this study significant elevation of both basal and exogenously leptin-treated DNA-binding activity of STAT3 was detected using EMSA in the hypothalamus of male C57BL/6J mice fed high-fat diet for 10 wks, in concomitant with hyperleptinemia, high body weight, high fat mass, and hyperphagia as well as decreased POMC expression. The studies in vitro showed that both DNA binding activity and the proximal SBE of POMC promoter was essential to leptin-mediated POMC expression. However, the diminution of STAT3 phosphorylation, achieved by S3I-201 or a FoxO1 mutant, facilitated leptin-mediated POMC expression. The findings here demonstrated excess STAT3 activity negatively regulated POMC expression in hypothalamus of DIO mice, and suggested the limitation of STAT3 activity may promote leptin signaling.

Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study.

OBJECTIVE: We aimed to study the association of urine fluoride with intelligence quotient (IQ) in children with a careful consideration of up to 30 potential confounding factors as well as possible heterogeneity of the relation between urine fluoride levels and IQ scores across children with different dopamine receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT). METHODS: A school-based cross-sectional study design was applied. A total of 323 children (2014-2015, 7-12 years old) were enrolled from four schools in both historical endemic and non-endemic areas of fluorosis in Tianjin of China using a cluster sampling method. Urine fluoride levels and age-specific IQ scores in children were measured at the enrollment. Polymerase chain reaction-restriction fragment length polymorphism methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated from whole blood collected at the enrollment. Multiple linear regression models were applied to evaluate the relationship between urine fluoride levels and IQ scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques. A safety threshold of urine fluoride levels for IQ impairment was determined in the subgroup TT. RESULTS: In overall participants, the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels and IQ scores in children were unrelated (adjusted ß (95% confidence interval (CI)) = - 1.59 (- 4.24, 1.05), p = 0.236). Among the participants carrying the TT genotype, there was a strong and robust negative linear relationship between log-urine fluoride and IQ scores in children (adjusted ß (95% CI) = - 12.31 (- 18.69, - 5.94), p < 0.001). Urine fluoride levels had a stronger association with IQ in children carrying the TT genotype (adjusted ß = - 12.31, bootstrapped standard error (SE) = 1.28), compared to that in overall participants (adjusted ß = - 2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007). The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L (95% CI = (1.51, 1.97) (mg/L)). CONCLUSIONS: There is heterogeneity in the relation between urine fluoride and IQ across children carrying different DRD2 Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our findings.

[In vivo anti-tumor effect and in vitro anti-angiogenic effect of alcohol extract from Euphorbia prostrata].

The study was designed to investigate the anti-tumor and anti-angiogenic effects of alcohol extract from Euphorbia prostrata. The alcohol extract of E. prostrata was prepared, and the tolerated dosage was determined in mice by the test for acute toxicity. Then, MTT method was used to study the anti-proliferation effect of E. prostrata on normal cells and tumor cells. The rat aortic endothelial cells(RAECs) were primarily cultured. Subsequently, in vitro cell proliferation, migration and tubule formation assays were performed to detect the effect of alcohol extract of E. prostrata on proliferation, migration and angiogenesis. Western blot analysis was performed to detect the protein expressions of Akt, p-Akt, eNOS, p-eNOS, TGF-ß1 and Smad3 in RAECs treated with E. prostrata. In addition, an in vivo transplanted hepatocellular carcinoma model in nude mice was established to detect nude mass, tumor volume and tumor weight. The contents of vascular endothelial growth factor(VEGF) and the platelet-derived growth factor-BB(PDGF-BB) in blood serum were detected by using ELISA kits. HE staining was performed to study the morphology of tumor tissues. The tolerated dosage of alcohol extract of E. prostrata in mice was 94.29 g•kg⁻¹. Alcohol extract of E. prostrata showed no inhibitory effect on L6 cells, but significantly inhibited the proliferations of HepG-2, PC12, A549, and Hela cells with the following order： HepG-2>Hela>PC12>A549. Meanwhile, alcohol extract of E. prostrata markedly inhibited the proliferation, migration and tube formation of RAECs, and enhanced the expressions of phosphorylated Akt and eNOS and increased the expressions of TGF-ß1 and Smad3. In addition, E. prostrata notably inhibited the tumor growth in mice, and decreased the amount of VEGF, but increased the amount of PDGF-BB factor in serum of nude mice. The alcohol extract of E. prostrata may show an inhibitory effect on tumor growth and angiogenesis, which may contribute to its anti-tumor effect.

Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti.

Wolbachia are maternally transmitted symbiotic bacteria that can spread within insect populations because of their unique ability to manipulate host reproduction. When introduced to nonnative mosquito hosts, Wolbachia induce resistance to a number of human pathogens, including dengue virus (DENV), Plasmodium, and filarial nematodes, but the molecular mechanism involved is unclear. In this study, we have deciphered how Wolbachia infection affects the Aedes aegypti host in inducing resistance to DENV. The microarray assay indicates that transcripts of genes with functions related to immunity and reduction-oxidation (redox) reactions are up-regulated in Ae. aegypti infected with Wolbachia. Infection with this bacterium leads to induction of oxidative stress and an increased level of reactive oxygen species in its mosquito host. Reactive oxygen species elevation is linked to the activation of the Toll pathway, which is essential in mediating the expression of antioxidants to counterbalance oxidative stress. This immune pathway also is responsible for activation of antimicrobial peptides-defensins and cecropins. We provide evidence that these antimicrobial peptides are involved in inhibition of DENV proliferation in Wolbachia-infected mosquitoes. Utilization of transgenic Ae. aegypti and the RNAi depletion approach has been instrumental in proving the role of defensins and cecropins in the resistance of Wolbachia-infected Ae. aegypti to DENV. These results indicate that a symbiotic bacterium can manipulate the host defense system to facilitate its own persistent infection, resulting in a compromise of the mosquito's ability to host human pathogens. Our discoveries will aid in the development of control strategies for mosquito-transmitted diseases.

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.

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.

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.

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.