Cumulative ecological risk and cyberbullying among college students: a chain mediation model.

Introduction: Cyberbullying among college students has been receiving increased research attention. Previous studies have focused primarily on the impact of a single risk factor on cyberbullying among college students. However, individual behavior is influenced by multiple ecosystems simultaneously, including family, school, and peers. To explore the effects of a single risk factor alone is not in line with the reality of everyday life, and the effect of the single risk factor can often be overestimated. Therefore, this study aimed to explore the impact of multiple risk factors, namely cumulative ecological risk, on cyberbullying, while analyzing the mediating roles of belief in a just world and moral disengagement. Methods: A survey was conducted among 805 college students from two universities in Hebei Province, China, using the cumulative ecological risk questionnaire, the cyberbullying scale, the belief in a just world scale, and the moral disengagement scale. Results: The results showed that: (a) Cumulative ecological risk was positively correlated with moral disengagement and cyberbullying, and negatively correlated with belief in a just world. Belief in a just world was negatively correlated with moral disengagement and cyberbullying. Moral disengagement was positively correlated with cyberbullying; (b) Belief in a just world partially mediated the relationship between cumulative ecological risk and cyberbullying; (c) Moral disengagement partially mediated the relationship between cumulative ecological risk and cyberbullying; (d) Belief in a just world and moral disengagement played a chain mediating role between cumulative ecological risk and college students' cyberbullying. Discussion: This study provides valuable insight for the reduction of cyberbullying behavior among college students, and offers suggestions on how to create a more favorable online environment.

Induction of immortal-like and functional CAR T cells by defined factors.

Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects. Following the elimination of target cells, CARTIF cells enter a metabolically dormant state, persisting in vivo with a saturable niche and providing memory protection. TIF represents a novel state of T cells with unprecedented stemness, which confers long-term functional persistence of CAR T cells in vivo and holds broad potential in T cell therapies.

Recapitulation of the Powassan virus life cycle in cell culture.

Powassan virus (POWV) is a tick-borne flavivirus known for causing fatal neuroinvasive diseases in humans. Recently, there has been a noticeable increase in POWV infections, emphasizing the urgency of understanding viral replication, pathogenesis, and developing interventions. Notably, there are no approved vaccines or therapeutics for POWV, and its classification as a biosafety level-3 (BSL-3) agent hampers research. To overcome these obstacles, we developed a replicon system, a self-replicating RNA lacking structural proteins, making it safe to operate in a BSL-2 environment. We constructed a POWV replicon carrying the Gaussia luciferase (Gluc) reporter gene and blasticidin (BSD) selectable marker. Continuous BSD selection led to obtain a stable POWV replicon-carrying Huh7 cell lines. We identified cell culture adaptive mutations G4079A, G4944T and G6256A, resulting in NS2AR195K, NS3G122G, and NS3V560M, enhancing RNA replication. We demonstrated the utility of the POWV replicon system for high-throughput screening (HTS) assay to identify promising antivirals against POWV replication. We further explored the applications of the POWV replicon system, generating single-round infectious particles (SRIPs) by transfecting Huh7-POWV replicon cells with plasmids encoding viral capsid (C), premembrane (prM), and envelope (E) proteins, and revealed the distinct antigenic profiles of POWV with ZIKV. In summary, the POWV replicon and SRIP systems represent crucial platforms for genetic and functional analysis of the POWV life cycle and facilitating the discovery of antiviral drugs.IMPORTANCEIn light of the recent surge in human infections caused by POWV, a biosafety level-3 (BSL-3) classified virus, there is a pressing need to understand the viral life cycle and the development of effective countermeasures. To address this, we have pioneered the establishment of a POWV RNA replicon system and a replicon-based POWV SRIP system. Importantly, these systems are operable in BSL-2 laboratories, enabling comprehensive investigations into the viral life cycle and facilitating antiviral screening. In summary, these useful tools are poised to advance our understanding of the POWV life cycle and expedite the development of antiviral interventions.

Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells.

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells (HUCMSCs). Utilizing dual-nozzle and cell electrospinning techniques, the system encapsulates L-ascorbic acid-2-phosphate magnesium (ASP), ß-glycerophosphate sodium and dexamethasone (DEX) within the fibers, ensuring sustained osteogenic differentiation. The scaffold's morphology, characterization, hydrophilicity, mechanical properties and cellular behavior were examined. Immediate subcutaneous implantation in rabbits was conducted to observe its ectopic osteogenic induction effect. Successfully fabricated P34HB ultrafine fiber slow-release system. Characterization confirmed the uniform distribution of HUCMSCs and inducing components within the scaffold, with no chemical reactions affecting the active components. In vitro tests showcased a prolonged release of DEX and ASP, while biocompatibility assays highlighted the scaffold's suitability for cellular growth. Alizarin Red, type I collagen, and osteopontin (OPN) staining verified the scaffold's potent osteogenic induction effect on HUCMSCs. Notably, immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks. These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction, marking a promising advancement in bone tissue engineering.

A rationally designed 3DTiO2@CdZnS heterojunction photocatalyst for effectively enhanced visible-light-driven hydrogen evolution.

Hydrogen production with higher efficiency and lower cost is of great significance for the sustainable development of energy. Zinc cadmium sulfide (CZS) is gaining more attention owing to its excellent photocatalytic properties. However, its development is greatly limited due to photogenerated charge recombination. In this work, an innovative design with a unique 3D morphology was introduced by integrating 3DTiO2 into CZS to form a novel 3DTiO2/CZS heterojunction photocatalyst. As a result, the optimized composite achieved a very high hydrogen production rate of 75.38 mmol h-1 g-1 under visible light, which is 2.4 times higher than that of the original CZS. It can also be greatly demonstrated through photoelectrochemical tests that this unique 3D morphology contributes to the effective separation of electrons and holes, thus dramatically improving the photocatalytic activity of 3DTiO2/CZS composites. The 3DTiO2/CZS composite has a rational energy band structure, which makes it more favorable for the hydrogen precipitation reaction. It is believed that such a modification strategy based on 3DTiO2 can be applied to other similar photocatalysts as well for boosting hydrogen evolution.

Dietary Potassium and Magnesium Intake with Risk of Type 2 Diabetes Mellitus Among Rural China: the Henan Rural Cohort Study.

Previous studies exploring the relationship between dietary potassium and magnesium intake and the risk of type 2 diabetes mellitus (T2DM) have yielded inconsistent results and the lack evidence from rural China. Therefore, we aimed to investigate the association between dietary potassium and magnesium intake and the risk of T2DM in rural China. Data was collected from the Henan Rural Cohort Study in 2017. A validated semi-quantitative food frequency questionnaire assessed dietary potassium and magnesium intake. Logistic regression models were used to calculate odds ratio (ORs) and 95% confidence intervals (CIs) to evaluate the effect of dietary potassium, magnesium and the potassium-magnesium ratio on the risk of T2DM. A total of 38384 individuals were included in the study, and 3616 participants developed T2DM. Logistic regression analysis revealed that the OR (95% CI) of the highest versus dietary potassium and magnesium and potassium-magnesium ratio intakes were 0.67 (0.59, 0.75), 0.76 (0.67, 0.88), and 0.57 (0.50, 0.66), respectively, compared to the subjects with the lowest quartile of intakes. In addition, gender partially influences the relationship between dietary magnesium and T2DM prevalence (P-interaction = 0.042). The group with the highest dietary potassium and dietary magnesium intake had the lowest risk of T2DM, with an OR (95% CI) of 0.63 (0.51-0.77). Dietary potassium and magnesium intake are important modifiable risk factors for T2DM in rural China. Dietary potassium intake > 1.8g/day, dietary magnesium intake > 358.6mg/day and < 414.7mg/day and potassium-magnesium ratio >5.1 should be encouraged to prevent better and manage T2DM.

Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia.

Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

Cadmium-tolerant Bacillus cereus 2-7 alleviates the phytotoxicity of cadmium exposure in banana plantlets.

Bananas are the world's important fruit and staple crop in the developing countries. Cadmium (Cd) contamination in soils results in the decrease of crop yield and food safety. Bioremediation is an environmental-friendly and effective measure using Cd-tolerant plant growth promoting rhizobacteria (PGPR). In our study, a Cd-resistant PGPR Bacillus cereus 2-7 was isolated and identified from a discarded gold mine. It could produce multiple plant growth promoting biomolecules such as siderophores, indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC)-deaminase and phosphatase. The extracellular accumulation was a main manner of Cd removal. Surplus Cd induced the expression of Cd resistance/transport genes of B. cereus 2-7 to maintain the intracellular Cd homeostasis. The pot experiment showed that Cd contents decreased by 50.31 % in soil, 45.43 % in roots, 56.42 % in stems and 79.69 % in leaves after the strain 2-7 inoculation for 40 d. Bacterial inoculation alleviated the Cd-induced oxidative stress to banana plantlets, supporting by the increase of chlorophyll contents, plant height and total protein contents. The Cd remediation mechanism revealed that B. cereus 2-7 could remodel the rhizosphere bacterial community structure and improve soil enzyme activities to enhance the immobilization of Cd. Our study provides a Cd-bioremediation strategy using Cd-resistant PGPR in tropical and subtropical area.

Strigolactones promote plant freezing tolerance by releasing the WRKY41-mediated inhibition of CBF/DREB1 expression.

Cold stress is a major abiotic stress that adversely affects plant growth and crop productivity. The C-REPEAT BINDING FACTOR/DRE BINDING FACTOR 1 (CBF/DREB1) transcriptional regulatory cascade plays a key role in regulating cold acclimation and freezing tolerance in Arabidopsis (Arabidopsis thaliana). Here, we show that max (more axillary growth) mutants deficient in strigolactone biosynthesis and signaling display hypersensitivity to freezing stress. Exogenous application of GR245DS , a strigolactone analog, enhances freezing tolerance in wild-type plants and strigolactone-deficient mutants and promotes the cold-induced expression of CBF genes. Biochemical analysis showed that the transcription factor WRKY41 serves as a substrate for the F-box E3 ligase MAX2. WRKY41 directly binds to the W-box in the promoters of CBF genes and represses their expression, negatively regulating cold acclimation and freezing tolerance. MAX2 ubiquitinates WRKY41, thus marking it for cold-induced degradation and thereby alleviating the repression of CBF expression. In addition, SL-mediated degradation of SMXLs also contributes to enhanced plant freezing tolerance by promoting anthocyanin biosynthesis. Taken together, our study reveals the molecular mechanism underlying strigolactones promote the cold stress response in Arabidopsis.

Epidemiological characteristics and transmissibility of HPV infection: A long-term retrospective study in Hokkien Golden Triangle, China, 2013-2021.

OBJECTIVE: Multiple human papillomavirus (HPV)-associated diseases have put a significant disease burden on the world. Therefore, we conducted a study to explore the epidemiological characteristics of HPV and the transmissibility of its genotypes. METHODS: HPV testing data was collected from Hospital. A transmission dynamics model of HPV was constructed to simulate and compare the transmissibility of different HPV genotypes, which was quantitatively described by the basic reproduction number (R0). RESULTS: The collected HPV subjects were mainly from Xiamen City, Zhangzhou City and Quanzhou City, together, they are known as the Hokkien golden triangle. There were variations in the distribution of HPV infections by age groups. Among all HPV genotypes, 13 of them had R0 > 1, with 10 of them being high-risk types. The top five were HPV56, 18, 58, 52 and 53, among which, HPV56, 18, 58 and 42 were of high risk, whereas HPV53 was not, and the R0 values for the five were 3.35 (CI: 0.00-9.99), 3.20 (CI: 0.00-6.46), 3.19 (CI: 1.27-6.94), 3.19 (CI: 1.01-8.42) and 2.99 (CI: 0.00-9.39), respectively. In addition, HPV52 had R0 > 1 for about 51 months, which had the longest duration. CONCLUSION: Most high-risk HPV types in the Hokkien golden triangle could transmit among the population. Therefore, there is a need of further optimization for developing HPV vaccines and better detection methods in the region.

Response of nitrite accumulation to elevated C/NO- 3-N ratio during partial denitrification process: Insights of extracellular polymeric substance, microbial community and metabolic function.

This study investigated the response of nitrite accumulation to elevated COD/NO3--N ratio (C/N) during partial denitrification (PD). Results indicated nitrite was gradually accumulated and remained stable (C/N = 1.5 âˆ¼ 3.0), while that rapidly declined after reaching the peak (C/N = 4.0 âˆ¼ 5.0). The polysaccharide (PS) and protein (PN) content of tightly-bound extracellular polymeric substances (TB-EPS) reached the maximum at C/N of 2.5 âˆ¼ 3.0, which might be stimulated by high level of nitrite. Illumina MiSeq sequencing showed Thauera and OLB8 were dominated denitrifying genera at C/N of 1.5 âˆ¼ 3.0, while Thauera was further enriched with fading OLB8 at C/N of 4.0 âˆ¼ 5.0. Meanwhile, the highly-enriched Thauera might enhance the activity of nitrite reductase (nirK) promoting further nitrite reduction. Redundancy analysis (RDA) showed positive correlations between nitrite production and PN content of TB-EPS, denitrifying bacteria (Thauera and OLB8) and nitrate reductases (narG/H/I) in low C/N. Finally, their synergistic effects for driving nitrite accumulation were comprehensively elucidated.

Association between preoperative concurrent fibular pseudarthrosis and risk of postoperative ankle valgus in patients with congenital pseudarthrosis of the tibia.

BACKGROUND: This study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical treatment. METHOD: The children with CPT who were treated at our institution between 1 January 2013 and 31 December 2020 were retrospectively reviewed. The independent variable was preoperative concurrent fibular pseudarthrosis, and the dependent variable was postoperative ankle valgus. Multivariable logistic regression analysis was performed after adjusting for variables that might affect the risk of ankle valgus. Subgroup analyses with stratified multivariable logistic regression models were used to assess this association. RESULTS: Of the 319 children who underwent successful surgical treatment, 140 (43.89%) developed ankle valgus deformity. Moreover, 104 (50.24%) of 207 patients with preoperative concurrent fibular pseudarthrosis developed an ankle valgus deformity compared with 36 (32.14%) of 112 patients without preoperative concurrent fibular pseudarthrosis (p=0.002). After adjusting for sex, body mass index, fracture age, age of patient undergoing surgery, surgery method, type 1 neurofibromatosis (NF-1), limb-length discrepancy (LLD), CPT location and fibular cystic change, patients with concurrent fibular pseudarthrosis presented a higher risk of ankle valgus than those without concurrent fibular pseudarthrosis (OR 2.326, 95% CI 1.345 to 4.022). This risk further increased with CPT location at the distal one-third of the tibia (OR 2.195, 95% CI 1.154 to 4.175), age <3 years of patient undergoing surgery (OR 2.485, 95% CI 1.188 to 5.200), LLD <2 cm (OR 2.478, 95% CI 1.225 to 5.015) and occurrence of NF-1 disorder (OR 2.836, 95% CI 1.517 to 5.303). CONCLUSION: Our results indicate that patients with CPT and preoperative concurrent fibular pseudarthrosis have a significantly increased risk of ankle valgus compared with those without preoperative concurrent fibular pseudarthrosis, particularly in those with CPT location at the distal third, age <3 years at surgery, LLD <2 cm and NF-1 disorder.

Model-based risk assessment of dengue fever transmission in Xiamen City, China.

Background: Quantitative assessment of the risk of local transmission from imported dengue cases makes a great challenge to the development of public health in China. The purpose of this study is to observe the risk of mosquito-borne transmission in Xiamen City through ecological and insecticide resistance monitoring. Quantitative evaluation of mosquito insecticide resistance, community population and the number of imported cases affecting the transmission of dengue fever (DF) in Xiamen was carried out based on transmission dynamics model, so as to reveal the correlation between key risk factors and DF transmission. Methods: Based on the dynamics model and combined with the epidemiological characteristics of DF in Xiamen City, a transmission dynamics model was built to simulate the secondary cases caused by imported cases to evaluate the transmission risk of DF, and to explore the influence of mosquito insecticide resistance, community population and imported cases on the epidemic situation of DF in Xiamen City. Results: For the transmission model of DF, when the community population is between 10,000 and 25,000, changing the number of imported DF cases and the mortality rate of mosquitoes will have an impact on the spread of indigenous DF cases, however, changing the birth rate of mosquitoes did not gain more effect on the spread of local DF transmission. Conclusions: Through the quantitative evaluation of the model, this study determined that the mosquito resistance index has an important influence on the local transmission of dengue fever caused by imported cases in Xiamen, and the Brayton index can also affect the local transmission of the disease.

[Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes].

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION: Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Pregnancy associated cancer, timing of birth and clinical decision making-a NSW data linkage study.

BACKGROUND: The incidence of pregnancy-associated cancer (PAC), comprising cancer diagnosed during pregnancy or within one year postpartum, is increasing. We investigated the obstetric management and outcomes of women with PAC and their babies. METHODS: A population-based observational study of all women who gave birth between 1994 and 2013 in New South Wales, Australia. Women were stratified into three groups: those diagnosed during pregnancy (gestational cancer group), those diagnosed within one year of giving birth (postpartum cancer group), and a no-PAC group. Generalized estimating equations were used to examine the association between PAC and adverse maternal and neonatal outcomes. RESULTS: One million seven hundred eighty-eight thousand four hundred fifty-onepregnancies were included-601 women (614 babies) were in the gestational cancer group, 1772 women (1816 babies) in the postpartum cancer group, and 1,786,078 women (1,813,292 babies) in the no-PAC group. The overall crude incidence of PAC was 132.7/100,000 women giving birth. The incidence of PAC increased significantly over the twenty-year study period from 93.5/100,000 in 1994 to 162.5/100,000 in 2013 (2.7% increase per year, 95% CI 1.9 - 3.4%, p-value < 0.001). This increase was independent of maternal age. The odds of serious maternal complications (such as acute abdomen, acute renal failure, and hysterectomy) were significantly higher in the gestational cancer group (adjusted odds ratio (AOR) 5.07, 95% CI 3.72 - 6.90) and the postpartum cancer group (AOR 1.55, 95% CI 1.16 - 2.09). There was no increased risk of perinatal mortality in babies born to women with PAC. However, babies of women with gestational cancer (AOR 8.96, 95% CI 6.96 - 11.53) or postpartum cancer (AOR 1.36, 95% CI 1.05 - 1.81) were more likely to be planned preterm birth. Furthermore, babies of women with gestational cancer had increased odds of a severe neonatal adverse outcome (AOR 3.13, 95% CI 2.52 - 4.35). CONCLUSION: Women with PAC are more likely to have serious maternal complications. While their babies are not at increased risk of perinatal mortality, they are more likely to experience poorer perinatal outcomes associated with preterm birth. The higher rate of birth intervention among women with gestational cancers reflects the complexity of clinical decision-making in this context.

Physical Activity among Rural Residents in Eastern, Central, and Western Provinces of China: A Cross-Sectional Survey.

Physical activity (PA) in which physical exercise (PE) is an important component is probably the most important intervention for preventing noncommunicable diseases (NCDs). However, few studies on PA and PE of rural residents in China were reported. This study conducted the first population-based cross-sectional survey in three provinces of China in 2021 that examined both PA and PE as well as the associated factors of rural residents. The International Physical Activity Questionnaire Short Form (IPAQ-S) was used, and a total of 3780 rural residents were surveyed. The result showed that 22.2% of the rural residents were physical inactivity and rural residents reporting practice of PE was 54.4%. Binary logistic regression analyses showed that being female, people aged between 15 to 34 years or 60 years old and above, employees of governmental departments/retirees, school students, the unemployed, and people with NCDs were risk factors of PA while ethnic minority groups, smoking, and alcohol consumption were risk factors of PE. Health promotion programme aiming at increasing people's PA in rural China is urgently needed, and it should focus on the population groups of the female, people aged 60 years and above, school students, the unemployed, and people with NCDs.

Adipocyte Thyroid Hormone ß Receptor-Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis.

Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis; however, whether TH regulates systemic metabolic homeostasis through its action on adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor (TR) α or TRß, we show that TRß is the major TR isoform that mediates T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and use, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that glucose-responsive lipogenic transcription factor in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Mice with adipocyte TRß deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRß in adipocytes may be a potential target for metabolic diseases. ARTICLE HIGHLIGHTS: How thyroid hormone (TH) achieves its diverse biological activities in the regulation of metabolism is not fully understood. Whether TH regulates systemic metabolic homeostasis via its action on white adipose tissue is unclear. Adipocyte TH receptor (TR) ß mediates the triiodothyronine effect on multiple metabolic pathways by targeting glucose-responsive lipogenic transcription factor in white adipose tissue; mice lacking adipocyte TRß are susceptible to high-fat diet-induced metabolic abnormalities. TRß in white adipocytes controls intracellular and systemic metabolism and may be a potential target for metabolic diseases.

Differential expression and effect analysis of lncRNA-mRNA in congenital pseudarthrosis of the tibia.

Background: To analyze the lncRNA-mRNA differential expression and co-expression network of periosteal stem cells (PSCs) from congenital pseudarthrosis of the tibia (CPT) and normal patients, and to explore the role of key lncRNAs. Methods: Differentially expressed lncRNAs and mRNAs in PSCs were obtained by sequencing, and biological functions of differentially expressed mRNAs were detected by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein -protein interaction (PPI) analysis. The co-expression network of lncRNA-mRNA was constructed by correlation analysis of differentially expressed lncRNAs and mRNAs, and the key lncRNAs were screened according to the connectivity degree. After that, the cis-regulated target genes of differential expressed lncRNAs and mRNAs were predicted. Results: A total of 194 differentially expressed lncRNAs were identified, including 73 upregulated and 121 downregulated genes. A total of 822 differentially expressed mRNAs were identified, including 311 upregulated and 511 downregulated genes. GO, KEGG and PPI enrichment analysis showed that the regulatory function of differentially expressed mRNAs were mainly gathered in skeletal system development and tissue morphogenesis. The co-expression network with 226 nodes and 3,390 edges was constructed based on correlation analysis. A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147 and AC103702, were screened according to connectivity degree. Prediction of target genes indicated that FAM227B-FGF7 and AC103702-HOXB4/5/6 may play an important role in the pathogenesis of CPT. Conclusion: A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147, and AC103702, occupy the core position in the co-expression network, suggesting that these lncRNAs and their target genes may play an important role in the pathogenesis of CPT.

Multidimensional analysis of the essential elements in pregnant women's whole blood and characterization of maternal status by elemental pattern.

BACKGROUND: During pregnancy, the fetus needs to obtain a lot of nutrients from the mother, but the micronutrient deficiencies in pregnancy are not clear at present, and there is no reliable basis for nutrient intake and supplement. The purpose of this study was to understand the levels of essential elements in whole blood of pregnant women during various pregnancy stages at different ages and in different regions, to evaluate the deficiency of essential elements in Chinese pregnant women, and to explore the feasibility of using the elemental pattern to characterize maternal status. METHODS: Whole blood samples of 11222 healthy pregnant women enrolled in different areas of China from Jan-Dec 2019, were analyzed for concentrations of six essential elements including Mn, Cu, Zn, Ca, Mg, and Fe, using the inductively coupled plasma mass spectrometer. A retrospective comparative study during different pregnancy periods at different ages and in different regions in whole blood essential elements content from non-pregnant normal women and pregnant normal women was developed using multivariate statistical analysis. Principal component analysis evaluation elemental pattern was used to characterize pregnancy status of pregnant women. RESULTS: In general, the levels of six essential elements in whole blood of pregnant women can satisfy the needs of normal physiological activities. With the development of pregnancy, the contents of Cu and Mn increased, while the contents of Fe and Mg decreased, and the contents of Zn and Ca have no noteworthy change. At the same gestation stage, the Cu content in whole blood of elderly pregnant women was higher. There were some differences in whole blood essential elements content of pregnant women in different regions. Principal component analysis and heat map analysis showed the feasibility of using bioinformatics research strategies to identify different pregnancies. CONCLUSIONS: There are differences in the content of whole blood essential elements of women at different stages of pregnancy in different regions. It was found that there was no obvious deficiency in whole blood essential elements levels of pregnant women in recent years. The pattern of essential elements has a certain application potential in the evaluation of pregnancy and pregnant women's health status.

Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs.

Previous studies have indicated an association of fat mass and obesity-associated (FTO) with nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. This study aimed to decipher the complex role of FTO in hepatic lipid metabolism. We found that a decrease in N6-methyladenosine (m6A) RNA methylation in the liver of mice fed with a high-fat diet (HFD) was accompanied by an increase in FTO expression. Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes. Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1 (SREBF1) and carbohydrate responsive element binding protein (ChREBP), two master lipogenic transcription factors, by demethylating m6A sites. Knockdown of either SREBF1 or ChREBP attenuated the lipogenic effect of FTO, suggesting that they are bona fide effectors for FTO in regulating lipogenesis. Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta, while knockdown of FTO abrogated the lipogenic effect of insulin. Inhibition of FTO by entacapone decreased the expression of SREBF1, ChREBP, and downstream lipogenic genes, ameliorating liver steatosis in HFD-fed mice. Thus, our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategy for treating NAFLD.