Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease.

Design Strategy for Improving Detection Sensitivity in a Bromoplumbate Photochromic Semiconductor.

Reducing the dark current of photodetectors is an important strategy for enhancing the detection sensitivity, but hampered by the manufacturing cost due to the need for controlling the complex material composition and processing intricate interface. This study reports a new single-component photochromic semiconductor, [(HDMA)4(Pb3Br10)(PhSQ)2]n (1, HDMA = dimethylamine cation, PhSQ = 1-(4-sulfophenyl)-4,4'-bipyridinium), by introducing a redox-active monosubstituted viologen zwitterion into inorganic semiconducting skeleton. It features yellow to green coloration after UV irradiation with the sharply dropping intrinsic conductivity of 14.6-fold, and the photodetection detection sensitivity gain successfully doubles. The reason of decreasing conductivity originates from the increasing the band gap of the inorganic semiconducting component and formation of Frenkel excitons with strong Coulomb interactions, thereby decreasing the concentration of thermally excited intrinsic carriers.

Metabolomics reveals arbuscular mycorrhizal fungi-mediated tolerance of walnut to soil drought.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) have a positive effect on drought tolerance of plants after establishing reciprocal resymbiosis with roots, while the underlying mechanism is not deciphered. Metabolomics can explain the mechanism of plant response to environmental stress by analyzing the changes of all small molecular weight metabolites. The purpose of this study was to use Ultra High Performance Liquid Chromatography Q Exactive Mass Spectrometer to analyze changes in root metabolites of walnut (Juglans regia) after inoculation with an arbuscular mycorrhizal fungus Diversispora spurca under well-watered (WW) and drought stress (DS). RESULTS: Sixty days of soil drought significantly inhibited root mycorrhizal colonization rate, shoot and root biomass production, and leaf water potential in walnut, while AMF inoculation significantly increased biomass production and leaf water potential, accompanied by a higher increase magnitude under DS versus under WW. A total of 3278 metabolites were identified. Under WW, AMF inoculation up-regulated 172 metabolites and down-regulated 61 metabolites, along with no changes in 1104 metabolites. However, under DS, AMF inoculation up-regulated 49 metabolites and down-regulated 116 metabolites, coupled with no changes in 1172 metabolites. Among them, juglone (a quinone found in walnuts) as the first ranked differential metabolite was up-regulated by AMF under WW but not under DS; 2,3,5-trihydroxy-5-7-dimethoxyflavanone as the first ranked differential metabolite was increased by AMF under DS but not under WW. The KEGG annotation showed a large number of metabolic pathways triggered by AMF, accompanied by different metabolic pathways under WW and DS. Among them, oxidative phosphorylation and phenylalanine metabolism and biosynthesis were triggered by AMF in response to WW and DS, where N-acetyl-L-phenylalanine was induced by AMF to increase under DS, while decreasing under WW. CONCLUSION: This study provides new insights into the metabolic mechanisms of mycorrhiza-enhanced drought tolerance in walnuts.

6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy.

Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.

miR-451-3p alleviates myocardial ischemia/reperfusion injury by inhibiting MAP1LC3B-mediated autophagy.

OBJECTIVE AND DESIGN: We aim to explore the molecular mechanism of myocardial ischemia-reperfusion injury (MIRI). METHODS: The H9C2 cells were cultured under hypoxia/reoxygenation (H/R) condition to induce myocardial injury in vitro. The expression of miR-451-3p and MAP1LC3B was detected by RT-qPCR. Dual-luciferase reporter assay and RNA pull-down assay were performed to examine the relationship between microRNA (miR)-451-3p and MAP1LC3B. CCK8 was used to test cell viability. The level of LDH and CK was evaluated via ELISA. Immunofluorescence assay and flow cytometry were applied to detect autophagy and apoptosis, respectively. Autophagy-related protein expressions were determined by western blotting. Furthermore, an in vivo rat model of MIRI was established by subjection to 30 min ischemia and subsequently 24 h reperfusion for validation of the role of miR-451-3p in regulating MIRI in vivo. RESULTS: miR-451-3p was down-regulated in MIRI, and miR-451-3p mimics transfection alleviated autophagy and apoptosis induced by MIRI. miR-451-3p could target MAP1LC3B directly. Co-transfection miR-451-3p mimics and pcDNA 3.1 MAP1LC3B curbed the protected effects of miR-451-3p mimics on MIRI. CONCLUSIONS: miR-451-3p played a protective role in MIRI via inhibiting MAP1LC3B-mediated autophagy, which may provide new molecular targets for the treatment of MIRI and further improves the clinical outcomes of heart diseases.

[6-Gingerol Pretreatment Alleviates Hypoxia/Reoxygenation-induced H9C2 Cardiomyocyte Injury by Inhibiting Oxidative Stress and Inflammation].

OBJETIVE: To observe the effect of 6-gingerol (6-G) pretreatment on hypoxia/reoxygenation (H/R) induced injury in H9C2 myocardial cell and investigate its related mechanism. METHODS: The H/R in vitro model of cardiomyocytes was prepared by conventional methods. In detail, H9C2 cells were added with the nitrogen-saturated hypoxic liquid, and placed in an incubator, mixed with gas (1% O 2, 5% CO 2, 94% N 2) applying for 15 min. After culturing for 3 h, the cells were taken out and placed in an incubator (37℃, 5% CO 2) for 1 h. Before establishing the cell model, the cells were pretreated with 6-G, and the cell viability was measured by MTT method to observe the protective effect of different concentrations of 6-G on H/R-induced cell damage. The 6-G mass concentration for pretreatment that led to the highest cell viability was used for follow-up experiments. DCFH-DA fluorescent probe was used to detect the effect of 6-G pretreatment on H9C2 oxidative stress level, and the intracellular oxidative stress was observed with fluorescence microscope and flow cytometry. Western blot method was used to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in H/R-induced cell inflammatory responses. RESULTS: Compared with the H/R group, the cell viability of the 6-G+H/R group began to increase when the concentration of 6-G promoted to50 µg/mL. The cell viability was the highest after pretreated with 200 µg/mL 6-G. Therefore, 200 µg/mL was considered as the best 6-G intervention concentration for subsequent experiment. The content of reactive oxygen species (ROS) in the 200 µg/mL 6-G group had no significant changes compared with the control group (P>0.05), and the ROS fluorescence peak did not migrate significantly. However the ROS content in the H/R group increased significantly compared with the control (P<0.05), and the ROS fluorescence peak shifted to the right. Compared with the H/R group, the ROS content of the 6-G+H/R group decreased (P<0.05), and the ROS fluorescence peak shifted to the left. Compared with the control group, the expressions of TNF-α, IL-6, IL-1ß in the 6-G group had no significant changes (P>0.05); the expressions of TNF-α, IL-6, IL-1ß in the H/R group increased (P<0.05). Compared with H/R group, the expressions of TNF-α, IL-6 and IL-1ß in 6-G+H/R group decreased (P<0.05). CONCLUSION: 6-G pretreatment can alleviate H/R-induced H9C2 myocardial injury, which may be related to the inhibition of oxidative stress and inflammatory responses.

Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves' Disease but Not with Hashimoto's Thyroiditis.

BACKGROUND/AIMS: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves' disease (GD) and Hashimoto's thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. METHODS: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. RESULTS: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. CONCLUSION: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by Inhibiting the ß-Catenin Signaling Pathway.

Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese Herbal medicine "Blood Circulation Promoting Recipe" could retard retinopathy development. This study investigated whether EBR-84 protects retinas by inhibiting the ß-catenin pathway using a rat model of retinopathy and a retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the ß-catenin pathway). After the corresponding treatment with EBR-84, RGC death and the protein expression levels of ß-catenin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in rat retinas were examined. ß-Catenin accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84 (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss accompanying the reduction of ß-catenin expression. Moreover, the expression levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the expression levels of ß-catenin, COX-2, and VEGF. In vitro, EBR-84 increased the viability of NMDA-treated RGC-5 while decreased ß-catenin expression. In conclusion, EBR-84 retarded ratretinopathy, and the ß-catenin signaling pathway played an important role during this protective process.

Differential cytokine expression detected by protein microarray screening in peripheral blood of patients with refractory Graves' disease.

OBJECTIVE: The prognosis of Graves' disease (GD) varies among patients. However, the immune pathogenesis of refractory GD is still unknown. The aim of this study was to explore the cytokine expression profile associated with refractory GD. METHODS: Preliminary cytokine protein microarray screening was performed to detect differentially expressed cytokines in the plasma of four patients with refractory GD and four patients with stable GD. Some differentially expressed cytokines were then validated in plasma by enzyme-linked immunosorbent assay (ELISA) and in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction (qRT-PCR) on another independent set of samples. RESULTS: We found that 21 cytokines were differentially expressed between patients with intractable GD and those in remission, including 18 upregulated and 3 downregulated cytokines with a fold change >1·30 and <0·77, respectively. Intractability-related elevation of three cytokines (IL-4, IL-6 and IL-10) was validated by ELISA in plasma on another GD cohort with 30 patients in recurrence and 14 in remission (t-test, P = 0·035, 0·033 and 0·041, respectively). Furthermore, mRNA expression of IL-4, IL-6 and IL-10 in PBMCs, detected by qRT-PCR, was significantly elevated in patients with refractory GD compared with those in remission (P = 0·039, 0·047 and 0·042, respectively). CONCLUSION: The severity of GD is associated with the aberrant expression and secretion of several cytokines that may serve as potential biomarkers and predictors for disease prognosis. Targeting these cytokines or their receptors may also lead to a novel therapeutic intervention for GD.

Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease.

The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

Genome-wide DNA methylation analysis in Graves' disease.

As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathogenesis of GD. Here, we for the first time reported the DNA methylation pattern in GD through a high-throughput analysis. In order to investigate genome-wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and Nimblegen human DNA methylation 3 × 720 K promoter plus CpG island microarrays were used to identify differentially methylated regions (DMRs) from blood samples in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation state of candidate genes. Transcription level of each gene was estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in GD patients and normal controls was significantly different (p<0.05). In the female group, significantly decreased methylation was observed in GD patients compared with normal controls (p<0.05). The transcription of ICAM1 at the mRNA level was significantly higher in GD patients compared with normal controls (p<0.05). Besides, the transcription of DNMT1 and MECP2 at the mRNA level was significantly decreased in GD patients compared with normal controls (p<0.05). Our findings revealed that the DNA methylation pattern in GD was distinct from that of controls. These results provided new molecular insights into the pathogenesis of GD.

Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves' disease.

BACKGROUND AND AIMS: Abnormal microRNA (miRNA) expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. METHODS: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls) were also collected for further validation by quantitative real-time PCR ( qRT-PCR ). RESULTS: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC ≥ 1.3 or ≤ 0.77 and p<0.05). In addition, the transcription of 1271 mRNAs was up-regulated, while the expression of 777 mRNAs transcripts was down-regulated (FC ≥ 2.0 or ≤ 0.5 and p<0.05). Furthermore, integrated analysis of differentially expressed miRNA and their target mRNAs demonstrated that 2 miRNA (miR-22 and miR-183) were increased while their potential target mRNAs were decreased. 3 miRNA (miR-101, miR-197 and miR-660) were decreased while their potential target mRNAs were increased. The above findings from microarray screening were confirmed by qRT-PCR in more samples. The results were consistent with those observed in the microarray assays. CONCLUSION: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.

RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population.

BACKGROUND: Polymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population. METHODS: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Three CCR6 single nucleotides polymorphisms (SNPs) (rs3093023/rs3093024/rs6902119) and one tagging SNP (rs9355610) within RNASET2 gene were selected for genotyping by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). RESULTS: The frequency of rs9355610 genotypes in the patients with GD differed significantly from that in the controls (p = 0.017). The frequency of the minor G allele of rs9355610 was significantly higher in the GD patients than in the healthy controls (p = 0.005, OR = 1.225, 95% CI:1.063-1.412). However, we could not find significant differences in the genotype or allele frequencies of HT patients compared with healthy controls. After gender stratification, the frequency of the minor G allele in both male and female GD patients was significantly higher than that in the healthy controls (p = 0.036, OR = 1.308, 95% CI:1.017-1.684 ; p = 0.048, OR = 1.19, 95% CI:1.001-1.413; respectively);. Furthermore, the frequency of haplotype AT in GD patients was significantly lower than that in their control groups (p = 0.003) and showed a protective effect against GD (OR = 0.806, 95% CI: 0.699-0.929). The frequency of haplotype GT in GD patients was significantly higher than that in their control groups (p = 0.048), indicating that GT was the risk haplotype to GD (OR = 1.267, 95% CI: 1.001-1.603). There were no significant differences in the allele or genotype frequencies of three SNPs of CCR6 (rs3093023/rs3093024/ rs6902119) gene between GD patients, HT patients and controls. CONCLUSIONS: Our results suggest that the rs9355610 tag SNP of RNASET2 gene is positively associated with susceptibility to GD in the Chinese Han population. No association was found for the tested CCR6 SNPs.

Transcriptome differences in the hypopharyngeal gland between Western Honeybees (Apis mellifera) and Eastern Honeybees (Apis cerana).

BACKGROUND: Apis mellifera and Apis cerana are two sibling species of Apidae. Apis cerana is adept at collecting sporadic nectar in mountain and forest region and exhibits stiffer hardiness and acarid resistance as a result of natural selection, whereas Apis mellifera has the advantage of producing royal jelly. To identify differentially expressed genes (DEGs) that affect the development of hypopharyngeal gland (HG) and/or the secretion of royal jelly between these two honeybee species, we performed a digital gene expression (DGE) analysis of the HGs of these two species at three developmental stages (newly emerged worker, nurse and forager). RESULTS: Twelve DGE-tag libraries were constructed and sequenced using the total RNA extracted from the HGs of newly emerged workers, nurses, and foragers of Apis mellifera and Apis cerana. Finally, a total of 1482 genes in Apis mellifera and 1313 in Apis cerana were found to exhibit an expression difference among the three developmental stages. A total of 1417 DEGs were identified between these two species. Of these, 623, 1072, and 462 genes showed an expression difference at the newly emerged worker, nurse, and forager stages, respectively. The nurse stage exhibited the highest number of DEGs between these two species and most of these were found to be up-regulated in Apis mellifera. These results suggest that the higher yield of royal jelly in Apis mellifera may be due to the higher expression level of these DEGs. CONCLUSIONS: In this study, we investigated the DEGs between the HGs of two sibling honeybee species (Apis mellifera and Apis cerana). Our results indicated that the gene expression difference was associated with the difference in the royal jelly yield between these two species. These results provide an important clue for clarifying the mechanisms underlying hypopharyngeal gland development and the production of royal jelly.

Increased interleukin-9 and Th9 cells in patients with refractory Graves' disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases.

Introduction: Autoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited. Methods: We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs. Results: We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08). Discussion: Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.

Visible-light-driven photoelectrochemical sensor based on conjugated microporous polymer-grafted graphene for o-aminophenol detection.

The pollutant o-aminophenol (o-AP) presents considerable risk to environmental safety, and its detection is therefore critical. Although various optical and electrochemical methods have been proposed for the detection of o-AP, there are a limited number of detection methods based on photoelectrochemical (PEC) sensors. In this study, a sensitive visible-light-driven PEC sensor was developed for o-AP detection in water. A conjugated microporous polymer (CMP)-coated graphene heterostructure (CMP-rGO) was synthesized and used to develop a PEC sensor. Under optimal conditions, the proposed sensor exhibited a high sensitivity of 0.03 µM with a wide linear range of 0.0034-37.6 µM. The PEC sensor also displayed acceptable repeatability and reproducibility, good long-term stability, and excellent recovery (98-102%). In addition, the binding patterns of CMP to o-AP and o-AP analog molecules were analyzed by molecular docking. Therefore, this study provides a new and feasible PEC sensor-based detection scheme for o-AP detection.

Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey.

Objective: Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. Methods: A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. Results: The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion: The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.

A Polysaccharide from Ficus carica L. Exerts Immunomodulatory Activity in Both In Vitro and In Vivo Experimental Models.

Polysaccharides from Ficus carica L. (FCP) exert multiple biological activities. As a biological macromolecule, the available knowledge about the specific structures and mechanisms of the biological activity of purified 'Brunswick' fig polysaccharides is currently limited. In the present study, chemical purification and characteristics were identified via chemical and instrumental analysis, and then the impact of FCP on immunomodulation activity in vitro and in vivo was examined. Structural characteristics showed that the molecular weight of the FCP sample was determined to be 127.5 kDa; the primary monosaccharides present in the FCP sample were galacturonic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), and xylose (Xyl) at a ratio of 0.321:0.287:0.269:0.091:0.013:0.011. Based on the investigation of in vitro immunomodulatory activity, FCP was found to stimulate the production of NO, TNF-α, and IL-6, and increased the pinocytic activity of macrophages. Further analysis revealed that FCP activated macrophages by interacting with Toll-like receptor 4 (TLR4). Moreover, the in vivo test results indicate that FCP showed a significant increase in serum pro-inflammatory factors in immunosuppressed mice. Overall, this study suggests that FCP has the potential to be utilized as a novel immunomodulator in the pharmaceutical and functional food industries.

Gene expression analysis following olfactory learning in Apis mellifera.

The honeybee has a strong learning and memory ability, and is recognized as the best model organism for studying the neurobiological basis of learning and memory. In this study, we analyzed the gene expression difference following proboscis extension response-based olfactory learning in the A. mellifera using a tag-based digital gene expression (DGE) method. We obtained about 5.71 and 5.65 million clean tags from the trained group and untrained group, respectively. A total of 259 differentially expressed genes were detected between these two samples, with 30 genes up-regulated and 229 genes down-regulated in trained group compared to the untrained group. These results suggest that bees tend to actively suppress some genes instead of activating previously silent genes after olfactory learning. Our DGE data provide comprehensive gene expression information for olfactory learning, which will facilitate our understanding of the molecular mechanism of honey bee learning and memory.