The Roles of Microprobe in Localized Electrodeposition: Electrolyte Localized Transport and Force-Displacement Sensitivity.

Facing the rapid development of 6G communication, long-wave infrared metasurface and biomimetic microfluidics, the performance requirements for microsystems based on metal tiny structures are gradually increasing. As one of powerful methods for fabrication metal complex microstructures, localized electrochemical deposition microadditive manufacturing technology can fabricate copper metal micro overhanging structures without masks and supporting materials. In this study, the role of the microprobe cantilever (MC) in localized electrodeposition was studied. The MC can be used for precise deposition with electrolyte localized transport function and high accuracy force-displacement sensitivity. To prove this, the electrolyte flow was simulated when the MC was in bending or normal state. The simulation results can indicate the influence of turbulent flow on the electrolyte flow velocity and the pressure at the end of the pyramid. The results show that the internal flow velocity increased by 8.9% in the bending probe as compared with normal. Besides, this study analyzed the force-potential sensitivity characteristics of the MC. Using the deformation of the MC as an intermediate variable, the model of the probe tip displacement caused by the growth of the deposit and the voltage value displayed by the photodetector was mathematically established. In addition, the deposition of a single voxel was simulated by simulation process with the simulated height of 520 nm for one voxel, and the coincidence of simulation and experimental results was 93.1%. In conclusion, this method provides a new way for localized electrodeposition of complex microstructures.

Mutation of negative regulatory gene CEHC1 encoding an FBXO3 protein results in normoxic expression of HYDA genes in Chlamydomonas reinhardtii.

Oxygen is known to prevent hydrogen production in Chlamydomonas, both by inhibiting the hydrogenase enzyme and by preventing the accumulation of HYDA-encoding transcripts. We developed a screen for mutants showing constitutive accumulation of HYDA1 transcripts in the presence of oxygen. A reporter gene required for ciliary motility, placed under the control of the HYDA1 promoter, conferred motility only in hypoxic conditions. By selecting for mutants able to swim even in the presence of oxygen we obtained strains that express the reporter gene constitutively. One mutant identified a gene encoding an F-box only protein 3 (FBXO3), known to participate in ubiquitylation and proteasomal degradation pathways in other eukaryotes. Transcriptome profiles revealed that the mutation, termed cehc1-1 , leads to constitutive expression of HYDA1 and other genes regulated by hypoxia, and of many genes known to be targets of CRR1, a transcription factor in the nutritional copper signaling pathway. CRR1 was required for the constitutive expression of the HYDA1 reporter gene in cehc1-1 mutants. The CRR1 protein, which is normally degraded in Cu-supplemented cells, was stabilized in cehc1-1 cells, supporting the conclusion that CEHC1 acts to facilitate the degradation of CRR1. Our results reveal a novel negative regulator in the CRR1 pathway and possibly other pathways leading to complex metabolic changes associated with response to hypoxia.

Pro-endothelialization of nitinol alloy cardiovascular stents enhanced by the programmed assembly of exosomes and endothelial affinity peptide.

Stent implantation is one of the most effective methods for the treatment of atherosclerosis. Nitinol stent is a type of stent with good biocompatibility and relatively mature development; however, it cannot effectively achieve long-term anticoagulation and early endothelialization. In this study, nitinol surfaces with the programmed assembly of heparin, exosomes from endothelial cells, and endothelial affinity peptide (REDV) were fabricated through layer-by-layer assembly technology and click-chemistry, and then exosomes/REDV-modified nitinol interface (ACC-Exo-REDV) was prepared. ACC-Exo-REDV could promote the rapid proliferation and adhesion of endothelial cells and achieve anticoagulant function in the blood. Besides, ACC-Exo-REDV had excellent anti-inflammatory properties and played a positive role in the transformation of macrophage from the pro-inflammatory to anti-inflammatory phenotype. Ex vivo and in vivo experiments demonstrated the effectiveness of ACC-Exo-REDV in preventing thrombosis and hyperplasia formation. Hence, the programmed assembly of exosome interface could contribute to endothelialization and have potential application on the cardiovascular surface modification to prevent stent thrombosis and restenosis.

Characterization of novel PHEX variants in X-linked hypophosphatemic rickets and genotype-PHEX activity correlation.

BACKGROUND: X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. At present, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully understood. METHODS: In this study, we summarized clinical features in a new cohort of 49 HR patients and detected 16 novel PHEX and 5 novel non-PHEX variants. Subsequently, we studied the pathogenesis of new variants by protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. RESULTS: The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering protein length and localization, whereas truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein in cells. Interestingly, no evident correlation was observed between mutation types and clinical phenotypes. However, when we analyzed the relationship between PHEX activity and serum phosphorus level, we found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Following this observation, we established two new knock-in XLHR mouse models with two novel Phex variants (c.T1349C and c.C426G, respectively) using CRISPR/Cas9 technology. Both mouse models demonstrated clinical manifestations of XLHR seen in patients and PhexC426G mice showed more severe phenotype than PhexT1349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. CONCLUSION: Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study facilitates a better understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation, which is of crucial importance for future diagnosis and treatment of XLHR.

Effect of eHealth interventions on perinatal depression: A meta-analysis.

BACKGROUND: Perinatal depression (PND) is a common mental health problem, and eHealth interventions may provide a strategy for alleviating PND. AIM: This meta-analysis aimed to determine the effect of eHealth interventions on PND. METHODS: Six databases were searched to retrieve published randomized controlled trials (RCTs) on the effect of eHealth interventions on PND. A meta-analysis was performed on the data of these studies using a random effects model. RESULTS: A total of 21 RCTs were included in the meta-analysis, which revealed that eHealth interventions significantly reduced antenatal depression (WMD = -1.64, 95 % CI [-2.92, -0.35], P = .013), postpartum depression (SMD = -0.41, 95 % CI [-0.52, -0.29], P < .001), anxiety (SMD = -0.39, 95 % CI [-0.51, -0.28], P < .001), stress (WMD = -2.93, 95 % CI [-4.58, -1.27], P = .001), and improved self-efficacy (SMD = 0.42, 95 % CI [0.21, 0.63], P < .001) compared with the control group. However, eHealth interventions did not significantly improve social support (SMD = 0.27, 95 % CI [-0.01, 0.56], P = .058). For antenatal depression, significant subgroup differences were observed in the digital platform and material presentation format. In addition, for postpartum depression, significant subgroup differences were found in the type of therapy. CONCLUSIONS: The meta-analysis results suggest that eHealth interventions can relieve depression, anxiety, and stress symptoms and improve self-efficacy in perinatal women. However, these interventions did not improve social support. Additional high-quality studies on eHealth interventions in PND are needed to validate these results.

DNA Methylation and Chromatin Accessibility Impact Subgenome Expression Dominance in the Common Carp (Cyprinus carpio).

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.

Inorganic Phosphate as "Bioenergetic Messenger" Triggers M2-Type Macrophage Polarization.

The effects of calcium phosphate (CaP) materials on macrophage polarization state vary with their physicochemical properties. The study aims to elucidate the impact of phosphate ion-mediated energy metabolism on M2 macrophage polarization and the corresponding regulatory mechanism. The phosphate ions released from CaP ceramic as bioenergetic factor is identified; its concentration is closely associated with the polarized state. After being taken up by the sodium-dependent phosphate transporter 1, extracellular phosphate ions produce energy via oxidative phosphorylation by facilitating tricarboxylic acid flux, thereby contributing to M2 macrophage polarization. Further mechanistic analysis reveals that the elevation of the bioenergetic basis can drive macrophage M2 polarization via the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) axis. Another regulatory effect is that of the adenosine triphosphate (ATP), a signaling molecule. Intracellular ATP is released into the extracellular space and degraded to adenosine, which serves as a signaling molecule through the A2b adenosine receptor to activate the cyclic adenosine monophosphate (cAMP) pathway, thereby promoting M2 macrophage polarization. Overall, these findings may transform the existing knowledge on cell metabolism and energy homeostasis from bystanders to pivotal factors guiding M2 macrophage polarization and have implications for the future design of biomimetic CaP scaffolds.

The effects of thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens on TGF-ß signaling pathway and Th17 cells differentiation in Jurkat cells by transcriptomics.

Thioredoxin peroxidase (TPx) protein from the excretory-secretory antigens (ESAs) of Cysticercus cellulosae (C. cellulosae) has been shown to regulate the differentiation of host Treg and Th17 cells, resulting in an immunosuppressive response dominated by Treg cells. However, the molecular mechanism by which TPx protein from the ESAs of C. cellulosae regulates the imbalance of host Treg/Th17 cell differentiation has not been reported. TPx protein from porcine C. cellulosae ESAs was used to stimulate Jurkat cells activated with PMA and ionomycin at 0, 24, 48, and 72 h. Transcriptomic analysis was performed to investigate the signaling pathways associated with Jurkat cells differentiation regulated by TPx protein from C. cellulosae ESAs. Gene Set Enrichment Analysis (GSEA) revealed that TPx protein from porcine C. cellulosae ESAs could induce upregulation of the TGF-ß signaling pathway and downregulation of Th17 cell differentiation in Jurkat cells. TPx protein from porcine C. cellulosae ESAs can activate the TGF-ß signaling pathway in Jurkat cells, thereby regulating the differentiation of Treg/Th17 cells and leading to an immunosuppressive response dominated by Treg cells, enabling evasion of the host immune attack. This study provides a foundation for further validation of these pathways and further elucidates the molecular mechanisms underlying immune evasion caused by porcine C. cellulosae.

Differential Expression of miRNAs, lncRNAs, and circRNAs between Ovaries and Testes in Common Carp (Cyprinus carpio).

Female common carp grow faster than male individuals, implying that rearing females could be more profitable in aquaculture. Non-coding RNAs (ncRNAs) serve as versatile regulators with multiple functions in diverse biological processes. However, the roles of ncRNAs in the sex differentiation of common carp are less studied. In this study, we investigated the expression profiles of ncRNAs, including miRNAs, lncRNAs, and circRNAs, in the gonads to comprehend the roles of ncRNAs in sex differentiation in common carp. A substantial number of differentially expressed (DE) ncRNAs in ovaries and testes were identified. Some miRNAs, notably miR-205, miR-214, and miR-460-5p, might modulate hormone synthesis and thus maintain sex. A novel miRNA, novel_158, was predicted to suppress the expression of foxl3. DE lncRNAs were associated with oocyte meiosis, GnRH signaling pathways, and steroid biosynthesis, while DE circRNA target genes were enriched in the WNT signaling pathway and MAPK signaling pathway. We also analyzed ncRNA-mRNA interactions to shed light on the crosstalk between competing endogenous RNAs (ceRNAs), which is the critical mechanism by which lncRNAs and circRNAs function. Some lncRNAs and circRNAs may be able to competitively bind novel_313, a new miRNA, and thus regulate hsd17ß3. Our research will provide a valuable resource for understanding the genetic basis of gonadal differentiation and development in common carp.

Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial.

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition. METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls. FINDINGS: In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome. INTERPRETATION: Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment. FUNDING: Bill & Melinda Gates Foundation; Médecins sans Frontières Operational Center Paris; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Edward Mallinckrodt Jr Foundation; Doris Duke Foundation.

[Risk Analysis and Study of Post-marketing Adverse Events for Absorbable Sutures].

Objective To investigate, analyze, and evaluate the risk data associated with the clinical use of absorbable sutures by retrieving and summarizing information from the databases of the US FDA and CNKI, as well as the adverse event reports related to absorbable sutures from January 2019 to October 2022 within Zhejiang province. The adverse event reports are obtained from both incident locations and monitoring organizations affiliated with the registrant. The aim is to identify the main risk factors associated with the clinical use of absorbable sutures. The key risk factors are potential product quality defects, product design and material selection, clinical selection and application, and postoperative recovery care including patient's self-care. Risk control strategies are further proposed to reduce or minimize the risk of adverse events caused by this product.

Rapid and Non-Invasive Assessment of Texture Profile Analysis of Common Carp (Cyprinus carpio L.) Using Hyperspectral Imaging and Machine Learning.

Hyperspectral imaging (HSI) has been applied to assess the texture profile analysis (TPA) of processed meat. However, whether the texture profiles of live fish muscle could be assessed using HSI has not been determined. In this study, we evaluated the texture profile of four muscle regions of live common carp by scanning the corresponding skin regions using HSI. We collected skin hyperspectral information from four regions of 387 scaled and live common carp. Eight texture indicators of the muscle corresponding to each skin region were measured. With the skin HSI of live common carp, six machine learning (ML) models were used to predict the muscle texture indicators. Backpropagation artificial neural network (BP-ANN), partial least-square regression (PLSR), and least-square support vector machine (LS-SVM) were identified as the optimal models for predicting the texture parameters of the dorsal (coefficients of determination for prediction (rp) ranged from 0.9191 to 0.9847, and the root-mean-square error for prediction ranged from 0.1070 to 0.3165), pectoral (rp ranged from 0.9033 to 0.9574, and RMSEP ranged from 0.2285 to 0.3930), abdominal (rp ranged from 0.9070 to 0.9776, and RMSEP ranged from 0.1649 to 0.3601), and gluteal (rp ranged from 0.8726 to 0.9768, and RMSEP ranged from 0.1804 to 0.3938) regions. The optimal ML models and skin HSI data were employed to generate visual prediction maps of TPA values in common carp muscles. These results demonstrated that skin HSI and the optimal models can be used to rapidly and accurately determine the texture qualities of different muscle regions in common carp.

Effect of psychological interventions on mental health, personal relationships and quality of life of women who have subjectively experienced traumatic childbirth.

BACKGROUND: No targeted review has assessed the effect of psychological interventions on the mental health, personal relationships, and the quality of life of women who have subjectively experienced traumatic childbirth. METHODS: Eight databases were searched from inception to January 2023. Study selection, data extraction, quality appraisal, and data analysis were conducted by two researchers independently. RESULTS: In total, eight studies were included. The results indicated that psychological interventions could effectively alleviate post-traumatic stress disorder (PTSD) symptoms, depression, and anxiety in women who have subjectively experienced traumatic childbirth. The interventions were more effective in alleviating PTSD symptoms than depression or anxiety. The subgroup analysis results showed that the effect of multiple sessions might be better than that of a single session. There was insufficient evidence supporting the effect of psychological interventions to improve personal relationships and the quality of life. LIMITATIONS: Study limitations included the small number of studies included for meta-analysis, substantial heterogeneity, and the retrieval of only studies written in English or Chinese. CONCLUSIONS: Psychological intervention is a promising method for the mental health of women who have subjectively experienced traumatic childbirth, but more studies are needed to confirm the effects. More studies are also required to explore the impact of psychological interventions on personal relationships and the quality of life. Future studies should focus on comparing which specific type of psychological intervention is most effective. Additional investigations should include the potential adverse effects and long-term effects of psychological interventions and details, such as content, process, and timing.

Fads2b Plays a Dominant Role in ∆6/∆5 Desaturation Activities Compared with Fads2a in Common Carp (Cyprinus carpio).

Highly unsaturated fatty acids (HUFAs) are essential for mammalian health, development and growth. However, most mammals, including humans, are incapable of synthesizing n-6 and n-3 HUFAs. Fish can convert C18 unsaturated fatty acids into n-6 and n-3 HUFAs via fatty acid desaturase (Fads), in which Fads2 is a key enzyme in HUFA biosynthesis. The allo-tetraploid common carp theoretically encode two duplicated fads2 genes. The expression patterns and desaturase functions of these two homologous genes are still unknown. In this study, the full length of the fads2a and fads2b were identified in common carp (Cyprinus carpio). Expression analyses indicate that both genes were mainly expressed in the liver and the expression of fads2b is higher than fads2a at different developmental stages in carp embryos. Heterogenous expression and 3D docking analyses suggested that Fads2b demonstrated stronger ∆6 and ∆5 desaturase activities than Fads2a. The core promotor regions of fads2a and fads2b were characterized and found to have different potential transcriptional binding sites. These results revealed the same desaturase functions, but different activities of two homologues of fasd2 genes in common carp. The data showed that fads2b played a more important role in HUFA synthesis through both expression and functional analyses.

Identifying interactions of linked irrigated lake-groundwater system by combining hydrodynamic and hydrochemical method.

During the irrigation period, the interactions between the linked lake-groundwater systems are complicated and change. This is because natural and human activities are happening at the same time, which makes it harder to identify the interactions. This study uses data on water level, hydrochemistry, and hydrogen-oxygen stable isotopes to analyze the hydrodynamics, electrical conductivity (EC), isotopic characteristics, and spatial distribution of lake water and groundwater to reveal lake-groundwater interactions. The results indicate that the hydrochemical type of Chagan Lake and groundwater is dominated by the HCO3-Na type. The key hydrochemical indicator EC obtained by principal component analysis (PCA) can be used to reveal the lake-groundwater interaction, and the interaction should be identified by location according to the significant correlation between hierarchical clustering results and regional distribution. The lake body's geographic coefficient of variation for EC and δ18O is small, and irrigation return flow is one factor in the region's surface water's significant spatial variation for EC and δ18O. The three study methods indicate that the groundwater supplies the lake in the vicinity of the Huoling River-Hongzi Pool, while in other sections, the lake water leaks and replenishes the groundwater, exhibiting geographic inconsistency. The isotope method was employed as a support tool to determine that groundwater might recharge the lake at Xinmiao Pool. According to the calculations of the Mix SIAR model, the groundwater recharge contribution rate in the Xinmiao Pool section is approximately 51%, while in the remaining sections, the contribution rate of lake water to groundwater ranges from approximately 25% to 52%. Therefore, the identification of the interaction is crucial for the linked irrigated lake-groundwater system where water sources are scarce and threatened by agricultural pollution.

Hydrochemistry and strontium isotope fingerprints of solute sources and CO2 consumption in Changbai Mountain area, Northeast China.

As one of the most representative forms of groundwater, mineral water provides a critical understanding of regional hydrogeochemical features and rock weathering processes. However, current studies have mostly focused on the quality of mineral water and have rarely addressed the weathering process during its formation. Therefore, a multi-tracer approach combines chemical parameters, major ions, selected trace elements, and 87Sr/86Sr ratios for mineral water samples in Changbai Mountain during 2020-2021. First, we determined the hydrogeochemical characteristics of different types of mineral water. Secondly, the water-rock interaction processes governing the water mineralization were described to fix the hydrogeochemical background. Thirdly, the chemical weathering rate was calculated. The total dissolved load generated by rock weathering was around 6.76 tons/km2/year in the mineral water catchment area; 44.6% and 36.9% of the dissolved load were derived from silicate and carbonate weathering, respectively. The trace carbonates also played an important role in the overall rock weathering. Finally, after fully considering various influencing factors, we concluded that lithological characteristics and the soil environment rich in organic acids were the most important factors affecting rock weathering in the Changbai Mountain area. Overall, this study highlights the mineral water's role in the fluxes of CO2 in local area and reveals possible influence of the unique ecological and geological environment on rock weathering in Changbai Mountain. It can provide a reference for the subsequent assessment of environmental stability for basalt areas and the possibility of sustainable water resources development.

Spontaneous behaviors during breast crawling and factors influencing self-locating mothers' breasts in newborns: A cross-sectional study.

Breast crawling in newborns to propel themselves to their mothers' breasts normally occurs upon skin-to-skin contact with mothers immediately after birth but is often missed by the neglect of hospital staff and insufficient evidence support. Hence, this study described the behavioral characteristics of 135 newborns from China during breast crawling and further explored the factors influencing newborns' self-locating mothers' breasts (measured by whether fail to experience the familiarization stage, initial time and duration of the familiarization stage) using multivariable analysis. The findings supported and extended previous studies that newborns could emerge in nine instinctive stages and corresponding spontaneous behaviors early in life. Moreover, abnormal fetal heart rate during labor appeared to interfere with newborns experiencing the familiarization stage (aOR = 9.27, 95% CI: 1.41 to 61.07, P = 0.021), while using synthetic oxytocin (ß = 5.94, 95% CI: 0.35 to 11.54, P = 0.037), using antibiotics (ß = 11.09, 95% CI: 4.11 to 18.07, P = 0.002), and newborns' gender (ß = -5.69, 95% CI: 11.26 to -0.12, P = 0.045) would alter the initial time of the familiarization stage. Finally, this study proposes evidence-based strategies to prevent abnormal fetal heart rates and improve medication use.

Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205.

Breast cancer (BC) is the most common cancer and the top cause of female mortality worldwide. The prognosis for patients with breast cancer liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated with the progression of BC. Exploration of circRNAs presents a promising avenue for identifying metastasis-targeting agents and improving the prognosis of patients with BCLM. Microarray and bioinformatic analyses were used to analyze differentially expressed circRNAs between three pairs of BCLM and primary BC. The roles of hsa_circ_0060467 (circMYBL2) and its target gene E2F1 in BC cells were explored by multiple functional experiments. And xenograft mouse models and hepatic metastases of BC hemi-spleen models were used to illustrate the function of circMYBL2 in vivo. The intrinsic molecular mechanism involving circMYBL2 was confirmed by bioinformatics analyses, RIP assays, CHIRP assays, luciferase reporter assays, and rescue experiments. CircMYBL2 was overexpressed in BCLM tissues and BC cells. Functionally, circMYBL2 can facilitate the proliferation and liver metastasis of BC. Mechanistically, circMYBL2 upregulated the transcription factor E2F1 by sponging miR-1205 and complexing with eukaryotic translation initiation factor 4A3 (eIF4A3) and then facilitated the epithelial-mesenchymal transition (EMT) process in BC cells. Our findings showed that circMYBL2 promoted the tumorigenesis and aggressiveness of BC through the circMYBL2/miR-1205/E2F1 and circMYBL2/eIF4A3/E2F1 axes, which may provide a novel targeted therapy for patients with BCLM.

The Promoter SNPs Were Associated with Both the Contents of Poly-Unsaturated Fatty Acids (PUFAs) and the Expressions of PUFA-Related Genes in Common Carp.

The allo-tetraploid common carp encodes two duplicated fads2 genes (fads2a and fads2b) and two duplicated elovl5 genes (elovl5a and elovl5b). The coding SNPs (cSNPs) of these genes were reported to be significantly associated with the PUFA contents. Whether the promoter SNPs (pSNPs) were associated with the PUFA contents has not been reported yet. In this study, after sequencing the promoters of these four genes, we identified six pSNPs associated with the contents of PUFAs in common carp, including one elovl5a pSNP, one elovl5b pSNP, and four fads2b pSNPs. The pSNPs were predicted in the locations of transcriptional factor binding sites. Together with previously identified cSNPs in fads2b and elovl5b, the pSNPs and cSNPs of these two genes had the joint effects on the PUFA contents with higher explained percentage of phenotypic variation of the PUFA contents than single gene. The expression levels of both fads2a and fads2b were significantly positively correlated with the contents of six PUFAs. The fads2b pSNPs corresponding to higher fads2b expression levels were associated with higher PUFA contents. The pSNPs and cSNPs will be useful for the future selection breeding of common carp with higher PUFA contents.

Pretreatment soluble Siglec-5 protein predicts early progression and R-CHOP efficacy in diffuse large B-cell lymphoma.

Aims: To explore the clinical association between soluble Siglec-5/CD163 and clinical feature and prognosis in peripheral blood samples of patients with diffuse large B-cell lymphoma. Method: Significantly elevated cytokines in peripheral blood were characterized by cytokines array and validated by ELISA. Results: Compared with CD163, Siglec-5 exhibited superiority in discriminating patients into low- and high-risk subgroups based on overall survival and progression-free survival. In addition, Siglec-5 was an indicator of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment efficacy. Conclusion: Siglec-5 may be applied as a reliable independent immune indicator for overall survival and progression-free survival. It may also predict R-CHOP efficacy in diffuse large B-cell lymphoma.