Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and interleukin-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reductions in CD8+ T cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence, and tumor-infiltrating lymphocytes thus provides a rational approach for improving immunotherapy in CRC.

Magnetic propelled hydrogel microrobots for actively enhancing the efficiency of lycorine hydrochloride to suppress colorectal cancer.

Research and development in the field of micro/nano-robots have made significant progress in the past, especially in the field of clinical medicine, where further research may lead to many revolutionary achievements. Through the research and experiment of microrobots, a controllable drug delivery system will be realized, which will solve many problems in drug treatment. In this work, we design and study the ability of magnetic-driven hydrogel microrobots to carry Lycorine hydrochloride (LH) to inhibit colorectal cancer (CRC) cells. We have successfully designed a magnetic field driven, biocompatible drug carrying hydrogel microsphere robot with Fe3O4 particles inside, which can achieve magnetic field response, and confirmed that it can transport drug through fluorescence microscope. We have successfully demonstrated the motion mode of hydrogel microrobots driven by a rotating external magnetic field. This driving method allows the microrobots to move in a precise and controllable manner, providing tremendous potential for their use in various applications. Finally, we selected drug LH and loaded it into the hydrogel microrobot for a series of experiments. LH significantly inhibited CRC cells proliferation in a dose- and time-dependent manner. LH inhibited the proliferation, mobility of CRC cells and induced apoptosis. This delivery system can significantly improve the therapeutic effect of drugs on tumors.

Deciphering Immune-Related Gene Signatures in Diabetic Retinopathy: Insights from In Silico Analysis and In vitro Experiment.

BACKGROUND: Diabetes retinopathy (DR) is one of the most common microvascular consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting DR. Provide a basis for the treatment and prevention of DR. METHOD: The immune infiltration enrichment score of DR patients was evaluated from the single- cell RNA sequencing dataset, and the samples were divided into low immune subgroups and high immune subgroups based on this result. Through weighted gene correlation network analysis, differentially expressed genes (DEGs) between two subgroups were identified and crossed with genes with the strongest immune association, resulting in significant key genes. Then divide the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to further explore their functions. A protein-protein interaction (PPI) network of IDEG was established to further identify central genes associated with DR. Use the discovered central genes to predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified hub gene in the pathogenesis of DR was further studied through in vitro experiments. RESULT: We found that the immune scores of DR and control groups were different, and 27 IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly enriched. GSEA indicates that these genes are associated with T cell activation, regulation of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of these hub genes were ultimately constructed. The discovery and identification of these genes will provide biomarkers for targeted prediction and treatment of DR. CONCLUSION: By integrating bioinformatics analysis and in vitro experiments, we have identified a set of central genes, indicating that these genes can serve as potential biomarkers for DR, which may be promising targets for future DR immunotherapy interventions.

Development of a prognostic model to predict BLCA based on anoikis-related gene signature: preliminary findings.

BACKGROUND: The prevalence of bladder urothelial carcinoma (BLCA) is significant on a global scale. Anoikis is a type of procedural cell death that has an important role in tumor invasion and metastasis. The advent of single-cell RNA sequencing (scRNA-seq) approaches has revolutionized the genomics field by providing unprecedented opportunities for elucidating cellular heterogeneity. Understanding the mechanisms associated with anoikis in BLCA is essential to improve its survival rate. METHODS: Data on BLCA and clinical information were acquired from the databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ARGs were obtained from Genecards and Harmonizome databases. According to univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to select the ARGs associated with the overall rate (OS). A multivariate Cox regression analysis was carried out to identify eight prognostic ARGs, leading to the establishment of a risk model. The OS rate of BLCA patients was evaluated using Kaplan-Meier survival analysis. To explore the molecular mechanism in low- and high-risk groups, we employed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSVA). Immune infiltration landscape estimation was performed using ESTIMATE, CIBERSOT, and single sample gene set enrichment analysis (ssGSEA) algorithms. Patients were categorized into different subgroups through consensus clustering analysis. We employed biological functional enrichment analysis and conducted immune infiltration analysis to examine the disparities in potential biological functions, infiltration of immune cells, immune activities, and responses to immunotherapy. RESULTS: We identified 647 ARGs and 37 survival-related genes. We further developed a risk scoring model to quantitatively assess the predictive capacity of ARGs. The high-risk score group exhibited an unfavorable prognosis, whereas the low-risk score group demonstrated a converse effect. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CONCLUSION: The nomogram with 8 ARGs may help guide treatment of BLCA. The systematic assessment of risk scores can help to design more individualized and precise treatment strategies for BLCA patients.

Lonicerin alleviates ovalbumin-induced asthma of mice via inhibiting EZH2/NF-κB signaling pathway.

Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 µg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18-20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16-P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-ĸB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.

The aging of polyethylene mulch films in the presence of cadmium.

To determine the fates of the persistent pollutants cadmium (Cd) and micro-plastics in agricultural soils, an in-depth understanding of the interactions between Cd and mulching film is required. In the present work, pot experiments are conducted under natural conditions to study the influence of various Cd concentrations on the aging process of polyethylene mulching film in soil collected from Changzhi, Shanxi Province. The results indicate that during 150 days, the aging degree of the mulch film increases gradually as the increased Cd concentration in the soil. Further, the results of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectrometry and X-ray photoelectron spectroscopy (XPS) demonstrate that the average vinyl index (VI) of the aging mulch film increases from 1.29 to 1.82, while the oxygen-to-carbon (O/C) ratio of the mulch film decreases significantly from 0.344 to 0.045, as the Cd concentration is increased from 0 to 10 mg kg-1. When the aging time exceeds 90 days, the oxygen-containing functional groups (C-O and CO) generated consumed by the adsorbed Cd. In addition, electron paramagnetic resonance (EPR) measurements indicate that Cd both enhances the formation of hydroxyl radical (·OH) on the surface of the mulch film and prevents the combination of ·OH and electrons, thereby accelerating the aging of the mulch. Hence, the present study indicates that the presence of Cd will hasten the decomposition of mulch, which will inevitably result in the faster release of micro-plastics from the mulch into the soil environment.

The application of nanomedicine in clinical settings.

As nanotechnology develops in the fields of mechanical engineering, electrical engineering, information and communication, and medical care, it has shown great promises. In recent years, medical nanorobots have made significant progress in terms of the selection of materials, fabrication methods, driving force sources, and clinical applications, such as nanomedicine. It involves bypassing biological tissues and delivering drugs directly to lesions and target cells using nanorobots, thus increasing concentration. It has also proved useful for monitoring disease progression, complementary diagnosis, and minimally invasive surgery. Also, we examine the development of nanomedicine and its applications in medicine, focusing on the use of nanomedicine in the treatment of various major diseases, including how they are generalized and how they are modified. The purpose of this review is to provide a summary and discussion of current research for the future development in nanomedicine.

Natural variation of GmRj2/Rfg1 determines symbiont differentiation in soybean.

Symbiotic nitrogen fixation (SNF) provides much of the N utilized by leguminous plants throughout growth and development. Legumes may simultaneously establish symbiosis with different taxa of microbial symbionts. Yet, the mechanisms used to steer associations toward symbionts that are most propitious across variations in soil types remain mysterious. Here, we demonstrate that GmRj2/Rfg1 is responsible for regulating symbiosis with multiple taxa of soybean symbionts. In our experiments, the GmRj2/Rfg1SC haplotype favored association with Bradyrhizobia, which is mostly distributed in acid soils, whereas the GmRj2/Rfg1HH haplotype and knockout mutants of GmRj2/Rfg1SC associated equally with Bradyrhizobia and Sinorhizobium. Association between GmRj2/Rfg1 and NopP, furthermore, appeared to be involved in symbiont selection. Furthermore, geographic distribution analysis of 1,821 soybean accessions showed that GmRj2/Rfg1SC haplotypes were enriched in acidic soils where Bradyrhizobia were the dominant symbionts, whereas GmRj2/Rfg1HH haplotypes were most prevalent in alkaline soils dominated by Sinorhizobium, and neutral soils harbored no apparent predilections toward either haplotype. Taken together, our results suggest that GmRj2/Rfg1 regulates symbiosis with different symbionts and is a strong determinant of soybean adaptability across soil regions. As a consequence, the manipulation of the GmRj2/Rfg1 genotype or application of suitable symbionts according to the haplotype at the GmRj2/Rfg1 locus might be suitable strategies to explore for increasing soybean yield through the management of SNF.

Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis.

PR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy individuals were collected as experimental samples. Then, macrophages were induced from monocytes using phorbol myristate acetate (PMA). The expression patterns of PRDM1, sirtuin 2 (SIRT2), and NLR family, pyrin domain-containing 3 (NLRP3) were characterized by RT-qPCR and Western blot assay. PMA-induced macrophages were stimulated by monosodium urate (MSU) for in vitro experimentation. Meanwhile, a murine model of MSU-induced acute gouty arthritis was established for in vivo validation. PRDM1 was highly expressed while SIRT2 poorly expressed in patients with acute gouty arthritis. Loss of PRDM1 could reduce NLRP3 inflammasome and mature IL-1ß levels and downregulate inflammatory cytokines in macrophages, which contributed to protection against acute gouty arthritis. Furthermore, results showed that PRDM1 could inhibit SIRT2 expression via binding to the deacetylase SIRT2 promoter. Finally, the in vivo experiments demonstrated that PRDM1 increased NLRP3 inflammasome and mature IL-1ß through transcriptional inhibition of SIRT2, whereby aggravating MSU-induced acute gouty arthritis. To sum up, PRDM1 increased NLRP3 inflammasome through inhibiting SIRT2, consequently aggravating MSU-induced acute gouty arthritis.

IL­37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway.

IL-37 is a newly discovered inflammatory factor. However, the protective effect and underlying mechanisms of IL-37 on atherosclerosis remain unclear. In the present study, IL-37 was used for intraperitoneal injection in diabetic ApoE-/- mice caused by streptozotocin. High glucose (HG)/ox-LDL was used to stimulate THP-1 original macrophage followed by IL-37 pretreatment in vitro. The atheromatous plaque area, oxidative stress and inflammation levels in ApoE-/- mice were evaluated, and the level of macrophage ferroptosis was detected in vivo and in vitro. It was identified that IL-37 treatment significantly decreased plaque area in diabetic ApoE-/- mice. IL-37 not only improved blood lipid levels in mice, but also reduced serum levels of inflammatory factors including IL-1ß and IL-18. Furthermore, IL-37 increased GPX4 and nuclear factor erythroid 2-related factor 2 (NRF2) in the aorta of diabetic mice. In vitro experiment revealed that IL-37 inhibited HG/ox-LDL-induced ferroptosis in macrophages, as evidenced by improved cell membrane oxidation, reduced malondialdehyde production and increased GPX4 expression. Moreover, it was also found that IL-37 enhanced the nuclear translocation of NRF2 in macrophages, while ML385, a specific NRF2 inhibitor, significantly attenuated the protective effect of IL-37 on macrophage ferroptosis caused by HG/ox-LDL. In conclusion, IL-37 suppressed macrophage ferroptosis to attenuate atherosclerosis progression via activating the NRF2 pathway.

Intramolecular-Catalyzed Vitrimers with White-Light Emission for Light-Emitting Diode Encapsulation.

Currently available encapsulating materials for white light-emitting diodes (WLEDs) have certain limitations, such as the toxicity of phosphors and the non-recyclable nature of the encapsulating materials. In this study, relatively promising encapsulating materials with two significant advantages are developed. First, the chips can be directly encapsulated without phosphors using luminescent encapsulating materials. Second, the encapsulating materials can be reprocessed for recycling via intramolecular catalysis. To this end, blue-light-emitting vitrimers (BEVs) are prepared by the reaction of epoxy resin with amines and are found to exhibit strong blue emission and fast stress relaxation via internal catalysis. To obtain white-light emission, a well-designed yellow component, perylenetetracarboxylic dianhydride, is grafted into the BEVs to generate white-light-emitting vitrimers (WEVs). A rare synergy of blue- and yellow-light emission affords white-light emission. When the WEV is used as an encapsulating adhesive for 365 nm LED chips without inorganic phosphors, stable white light with CIE coordinates (0.30, 0.32) is successfully achieved, indicating a promising future for WLED encapsulation.

Comparison of labor analgesia efficacy between single-orifice and multiorifice wire-reinforced catheters during programmed intermittent epidural boluses: a randomized controlled clinical trial.

AIMS: We compared analgesic outcomes between single-orifice and multiorifice wire-reinforced catheters under 480 mL/hour delivery rate with programmed intermittent epidural bolus administration. METHODS: Between August and November 2021, 182 nulliparous and healthy women with singleton pregnancy, 2-5 cm cervical dilation, and requesting neuraxial analgesia were randomized to receive either single-orifice or multiorifice catheters. Epidural analgesia was initiated and maintained with 0.1% ropivacaine and 0.3 µg/mL sufentanil. Programmed intermittent epidural bolus volume of 10 mL was administered every 45 min at 480 mL/hour beginning immediately after the test dose. Primary outcome was the percentage of parturients in the two groups with adequate analgesia 20 min after the initial bolus. RESULTS: Compared with multiorifice catheters, single-orifice catheters were associated with a higher proportion of parturients with adequate analgesia (71.8% vs 56.0%, respectively; 95% CI 1.3% to 29%, p=0.03) and more frequent S2 sensory blockade (37.6% vs 22.6%, respectively; 95% CI -30% to 1%, p=0.03) 20 min after block initiation. Median time (IQR) to adequate analgesia was 12 (8-30) min and 20 (10-47) min with single-orifice and multiorifice catheters, respectively (95% CI 0.1 to 0.7 min, p<0.01). The median (IQR) ropivacaine consumption per hour was higher in parturients receiving multiorifice catheters than those with single-orifice catheters (15.3 (13.3-17.0) mg/hour vs 13.3 (13.3-15.4) mg/hour, respectively; 95% CI 0.2 to 0.8 mg/hour, p<0.001). CONCLUSION: Single-orifice catheters used for programmed intermittent epidural bolus at 480 mL/hour for epidural labor analgesia had improved analgesic efficacy than multiorifice catheters. TRIAL REGISTRATION NUMBER: ChiCTR2100049872.

Overexpression of GmPHR1 Promotes Soybean Yield through Global Regulation of Nutrient Acquisition and Root Development.

MYB-CC transcription factors (TFs) are essential for plant growth and development. Members of the MYB-CC subfamily with long N terminal domains, such as phosphate starvation response 1 (PHR1) or PHR1-like TFs, have well documented functions, while those with short N terminal domains remain less understood. In this study, we identified a nodule specific MYB-CC transcription factor 1 (GmPHR1) in soybean that is different from other canonical PHR family genes in that GmPHR1 harbors a short N terminal ahead of its MYB-CC domain and was highly induced by rhizobium infection. The overexpression of GmPHR1 dramatically increased the ratio of deformed root hairs, enhanced subsequent soybean nodulation, and promoted soybean growth in pot experiments. The growth promotion effects of GmPHR1 overexpression were further demonstrated in field trails in which two GmPHR1-OE lines yielded 10.78% and 8.19% more than the wild type line. Transcriptome analysis suggested that GmPHR1 overexpression led to global reprogramming, with 749 genes upregulated and 279 genes downregulated, especially for genes involved in MYB transcription factor activities, root growth, and nutrient acquisition. Taken together, we conclude that GmPHR1 is a key gene involved in the global regulation of nodulation, root growth, and nutrient acquisition in soybeans, and is thus a promising candidate gene to target for soybean yield enhancement.

Security Performance Analysis of LEO Satellite Constellation Networks under DDoS Attack.

Low Earth orbit satellite constellation networks (LSCNs) have attracted significant attention around the world due to their great advantages of low latency and wide coverage, but they also bring new challenges to network security. Distributed denial of service (DDoS) attacks are considered one of the most threatening attack methods in the field of Internet security. In this paper, a space-time graph model is built to identify the key nodes in LSCNs, and a DDoS attack is adopted as the main means to attack the key nodes. The scenarios of two-satellite-key-node and multi-satellite-key-node attacks are considered, and their security performance against DDoS attacks is also analyzed. The simulation results show that the transmission path of key satellite nodes will change rapidly after being attacked, and the average end-to-end delay and packet loss are linearly related to the number of key-node attacks. This work provides a comprehensive analysis of the security performance of LSCNs under a DDoS attack and theoretical support for future research on anti-DDoS attack strategies for LSCNs.

Exogenous calcium promotes growth of adzuki bean (Vigna angularis Willd.) seedlings under nitrogen limitation through the regulation of nitrogen metabolism.

Plants exhibit lower nitrogen use efficiency (NUE) under N-limitation conditions. Although the function of calcium (Ca) has been widely studied in plants, it remains to be explored whether regulation of nitrate uptake and reduction is needed. A hydroponics experiment on adzuki beans (Vigna angularis Willd.) was used as a test material to determine the interactions between Ca and three levels of nitrogen supply. The height of the plant, the leaf area per plant, the biomass of the plant, the morphology of the roots, the hydraulic conductivity of the roots, the level of gas exchange, and the level of N metabolism of the adzuki beans were evaluated. Furthermore, RT-qPCR was conducted to explore the expression of genes related to nitrate transporter responses to Ca under N-limitation stress conditions. The rate of accumulation of N in plant tissue increased with the application of Ca. However, plant biomass, photosynthetic parameters, and root activity peaked for Ca2+ supply under N-marginal conditions. Further investigation revealed that the activities of nitrate reductase and glutamine synthetase were relatively high. The transcription of the nitrate transporter (VaNRT1.1; VaNRT2.5) was up-regulated in the roots of the Ca-treated plants. Both N-marginal conditions and N deficiency inhibit N absorption and utilization. The favorable effects of Ca on seedling growth and N metabolism under N-marginal conditions were more significant than those under N-deficiency conditions. The supply of Ca2+ is optimal, as it increases NUE by enhancing photosynthesis, N-metabolizing enzyme activities, and NO3 uptake and transport under N-marginal conditions.

Identification of Candidate Genes and Genomic Selection for Seed Protein in Soybean Breeding Pipeline.

Soybean is a primary meal protein for human consumption, poultry, and livestock feed. In this study, quantitative trait locus (QTL) controlling protein content was explored via genome-wide association studies (GWAS) and linkage mapping approaches based on 284 soybean accessions and 180 recombinant inbred lines (RILs), respectively, which were evaluated for protein content for 4 years. A total of 22 single nucleotide polymorphisms (SNPs) associated with protein content were detected using mixed linear model (MLM) and general linear model (GLM) methods in Tassel and 5 QTLs using Bayesian interval mapping (IM), single-trait multiple interval mapping (SMIM), single-trait composite interval mapping maximum likelihood estimation (SMLE), and single marker regression (SMR) models in Q-Gene and IciMapping. Major QTLs were detected on chromosomes 6 and 20 in both populations. The new QTL genomic region on chromosome 6 (Chr6_18844283-19315351) included 7 candidate genes and the Hap.X AA at the Chr6_19172961 position was associated with high protein content. Genomic selection (GS) of protein content was performed using Bayesian Lasso (BL) and ridge regression best linear unbiased prediction (rrBULP) based on all the SNPs and the SNPs significantly associated with protein content resulted from GWAS. The results showed that BL and rrBLUP performed similarly; GS accuracy was dependent on the SNP set and training population size. GS efficiency was higher for the SNPs derived from GWAS than random SNPs and reached a plateau when the number of markers was >2,000. The SNP markers identified in this study and other information were essential in establishing an efficient marker-assisted selection (MAS) and GS pipelines for improving soybean protein content.

Twin Growth Discordance and Risk of Postpartum Hemorrhage: A Retrospective Cohort Study.

Background: In recent years, the incidence of postpartum hemorrhage has increased globally. Multiple pregnancies and cesarean sections are well-known risk factors for postpartum hemorrhage. No studies have evaluated the associations between fetal growth anomalies and postpartum hemorrhage in women with twin pregnancies undergoing cesarean section. This study aimed to identify the relationship between fetal growth anomalies and postpartum hemorrhage in women with twin pregnancies undergoing cesarean section. Methods: This retrospective single-center study included 3,180 women with twin pregnancies at a tertiary hospital between August 2013 and July 2020. Singleton reference charts were used to assess fetal growth restriction at birth. Discordant growth was defined as an intertwin birth weight difference of ≥20%. Logistic regression analyses were used to evaluate the association between fetal growth anomalies and postpartum hemorrhage. Additionally, sensitivity analysis of abnormal placenta and stratification by twin chorionicity were conducted. Results: The overall incidence of postpartum hemorrhage was 4.3%. Twin growth discordance, especially with fetal growth restriction, was associated with an increased risk of postpartum hemorrhage (adjusted odds ratio [AOR] = 1.62, 95% confidence interval [CI], 1.05-2.51, P = 0.031; AOR = 1.71; 95% CI, 1.08-2.70, P = 0.022; AOR = 1.98, 95% CI, 1.21-3.25, P = 0.006, respectively). After stratification, this relationship persisted in dichorionic twins (OR = 1.71, 95% CI, 1.04-2.82, P = 0.036; OR = 1.90, 95% CI, 1.13-3.21, P = 0.016; OR = 2.48, 95% CI, 1.41-4.38, P = 0.002, respectively). However, no significant association was observed in monochorionic twin pregnancies. Conclusion: Growth discordance, especially complicated by fetal growth restriction, was associated with an increased risk of postpartum hemorrhage in women with twin pregnancies undergoing cesarean section, and was more evident in patients with dichorionic twins.

Regulation of the Proliferation of Diabetic Vascular Endothelial Cells by Degrading Endothelial Cell Functional Genes with QKI-7.

Background: Diabetes has emerged as one of the most serious and common chronic diseases of our times, causing life-threatening, disabling and costly complications, and reducing life expectancy. Studies have shown that cardiovascular morbidity is 1-3 times higher in diabetic patients than in normal people. There are many clinical and experimental data that prove that most of the complications of diabetes are related to atherosclerosis, which suggests that chronic hyperglycemia may induce an imbalance in the proliferation of vascular endothelial cells. Purpose: This study aims to explore the relationship between QKI-7 and vascular endothelial cell dysfunction and lay a foundation for further clarifying the molecular mechanism of endothelial cell damage in the process of diabetes with atherosclerosis. Methods: We chose blood samples and pluripotent stem cells and vascular endothelial cells of hospitalized patients with diabetes and diabetes atherosclerosis as research subjects. The expression levels of endothelial cell proliferation and genes related to endothelial cell proliferation were analyzed by RT-qPCR and Western blot, to study the influence of QKi-7 on the physiological state of endothelial cells. Through gene knockdown experiment, the effects of QKi-7 knockdown on functional genes and physiological functions of endothelial cells were analyzed. Finally, RNA immunoprecipitation was used to test the mutual effect among QKI-7 and the transcription level of functional genes, and the mRNA attenuation experiment proved that QKI-7 participated in the degradation process of functional genes. Results: The findings of the RT-qPCR and Western blot tests revealed that QKI-7 was highly expressed in blood samples of diabetic patients and atherosclerosis as well as in endothelial cells induced by human pluripotent stem cells and human vascular endothelial cells after high-glucose treatment. Overexpression and high glucose of QKI-7 resulted in inhibiting expressed function genes CD144, NLGN1, and TSG6 and upregulation of inflammatory factors TNF-α, IL-1ß, and IFN-γ, leading to excessive proliferation of endothelial cells. After QKI-7 gene knockdown, the expression levels of CD144, NLGN1, and TSG6, inflammatory factors TNF-α, IL-1ß, and IFN-γ, and the cell proliferation rate all returned to normal levels. RNA immunoprecipitation showed that QKi-7 interacted with CD144, NLGN1, and TSG6 mRNAs and was involved in the transcriptional degradation of functional genes through their interactions. Conclusion: This research initially revealed the relevant molecular mechanism of QKI-7 leading to the excessive proliferation of endothelial cells in diabetic and atherosclerotic patients. In view of the role of QKI-7 in diabetic vascular complications, we provided a potential target for clinical diabetes treatment strategies in the future.

Expression of colorectal neoplasia differentially expressed in anaplastic thyroid carcinoma and its effect on cancer cell proliferation.

Background: The incidence of anaplastic thyroid cancer (ATC) is high among human cancers. Colorectal neoplasia differentially expressed (CRNDE) is highly expressed in common tumors, and is therefore a potential molecular target for anti-tumor therapy. However, the function of CRNDE in ATC remains elusive. Methods: The Gene Expression Omnibus (GEO) database was used to screen the differential expression of long-noncoding RNA (lncRNA) in ATC tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CRNDE in thyroid cancer (THCA) tissues and its impact on patient prognosis. Quantitative real-time PCR (qRT-PCR) was used to determine the expression level of CRNDE in tumor and control tissues. The biological function of CRNDE in THCA was explored using TCGA RNA sequencing (RNA-seq) data analysis. ATC cell lines with low and high CRNDE expression were selected for CRNDE siRNA transfection, and the proliferation of cells was detected in each group. Results: The GEO and TCGA databases analysis results showed that CRNDE was highly expressed in ATC tissues, which is related to the poor prognosis of THCA patients. Also, the expression of CRNDE in the ATC cell line, ARO (human thyroid cancer cell line), was relatively high, while the expression in sw579 is relatively low. Therefore, ARO and sw579 were chosen for CRNDE small interfering RNA (siRNA) transfection. Compared with negative control (si-NC), the expression of CRNDE in si-CRNDE-1, si-CRNDE-2, and si-CRNDE-3 was reduced, indicating that the inhibitory effect was significantly enhanced and the cell proliferation ability was reduced, and the cell cycle is arrested in the G0/G1 phase. Finally, it was found that the wnt3a, ß-catenin, and cyclinD1 protein expressions of si-CRNDE-1 and si-CRNDE-2 were significantly reduced. Conclusions: The high expression of CRNDE in ATC tissues may promote the proliferation of ATC cells by regulating the Wnt/ß-catenin signaling pathway. CRNDE may be a potential molecular target for the treatment of ATC.