Imaging the Magnetic Anisotropy in Ultrathin Fe4GeTe2 with a Nitrogen-Vacancy Magnetometer.

Two-dimensional (2D) FenGeTe2, with n = 3, 4, and 5, has been realized in experiments, showing strong magnetic anisotropy with enhanced critical temperature (Tc). The understanding of its magnetic anisotropy is crucial for the exploration of more stable 2D magnets and its spintronic applications. Here, we report a quantitative reconstruction of the magnetization magnitude and its direction in ultrathin Fe4GeTe2 using nitrogen vacancy centers. Through imaging stray magnetic fields, we identified the spin-flop transition at approximately 80 K, resulting in a change of the easy axis from the out-of-plane direction to the in-plane direction. Moreover, by analyzing the thermally activated escape behavior of the magnetization near Tc in terms of the Ginzburg-Landau model, we observed the in-plane magnetic anisotropy effect and the formation capability of magnetic domains at ∼0.4 µm2 µT-1. Our findings contribute to the quantitative understanding of the magnetic anisotropy effect in a vast range of 2D van der Waals magnets.

Improving tumor sensitivity by the introduction of an ester chain to triaryl derivatives targeting PD-1/PD-L1.

PD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC50 of 1.21 nM in HTRF assay, and a KD value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function. 22 showed significant in vivo antitumor activity in a 4T1 mouse model without obvious toxicity, with a TGI rate of 67.8 % (20 mg/kg, ip). Immunohistochemistry data indicated that 22 activates the immune activity in tumors. These results suggest that 22 is a promising compound for further development of PD-1/PD-L1 inhibitor for cancer therapy.

Regioselective Olefination and Arylation of Arene-Tethered Diols Using the Easily Foldable Directing Groups.

Arene-tethered diols constitute a valuable class of structural motifs of drug and bioactive natural product molecules. In this study, a regioselective protocol for olefination and arylation of arene-tethered 1,2-diols and 1,3-diols has been developed using easily foldable acetal structures for attaching pyridine and nitrile directing groups. The method overcomes the steric hindrance effect of the short-chain diols and affords products in high yield and regioselectivity. This efficient cascaded catalysis has been successfully utilized in the syntheses of natural products such as peucedanol, decursinol, and marmesin.

Dual target PARP1/EZH2 inhibitors inducing excessive autophagy and producing synthetic lethality for triple-negative breast cancer therapy.

Currently available PARP inhibitors are mainly used for the treatment of BRCA-mutated triple-negative breast cancer (TNBC), with a narrow application range of approximately 15% of patients. Recent studies have shown that EZH2 inhibitors have an obvious effect on breast cancer xenograft models and can promote the sensitivity of ovarian cancer cells to PARP inhibitors. Here, a series of new dual-target PARP1/EZH2 inhibitors for wild-BRCA type TNBC were designed and synthesized. SAR studies helped us identify compound 12e, encoded KWLX-12e, with good inhibitory activity against PARP1 (IC50 = 6.89 nM) and EZH2 (IC50 = 27.34 nM). Meanwhile, KWLX-12e showed an optimal cytotoxicity against MDA-MB-231 cells (IC50 = 2.84 µM) and BT-549 cells (IC50 = 0.91 µM), with no toxicity on normal breast cell lines. KWLX-12e also exhibited good antitumor activity with the TGI value of 75.94%, more effective than Niraparib plus GSK126 (TGI = 57.24%). Mechanistic studies showed that KWLX-12e achieved synthetic lethality indirectly by inhibiting EZH2 to increase the sensitivity to PARP1, and induced cell death by regulating excessive autophagy. KWLX-12e is expected to be a potential candidate for the treatment of TNBC.

Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis.

Background: Hashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT. Method: Using the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR. Results: The DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δß| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4. Conclusion: This investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT.

SPACEL: deep learning-based characterization of spatial transcriptome architectures.

Spatial transcriptomics (ST) technologies detect mRNA expression in single cells/spots while preserving their two-dimensional (2D) spatial coordinates, allowing researchers to study the spatial distribution of the transcriptome in tissues; however, joint analysis of multiple ST slices and aligning them to construct a three-dimensional (3D) stack of the tissue still remain a challenge. Here, we introduce spatial architecture characterization by deep learning (SPACEL) for ST data analysis. SPACEL comprises three modules: Spoint embeds a multiple-layer perceptron with a probabilistic model to deconvolute cell type composition for each spot in a single ST slice; Splane employs a graph convolutional network approach and an adversarial learning algorithm to identify spatial domains that are transcriptomically and spatially coherent across multiple ST slices; and Scube automatically transforms the spatial coordinate systems of consecutive slices and stacks them together to construct a 3D architecture of the tissue. Comparisons against 19 state-of-the-art methods using both simulated and real ST datasets from various tissues and ST technologies demonstrate that SPACEL outperforms the others for cell type deconvolution, for spatial domain identification, and for 3D alignment, thus showcasing SPACEL as a valuable integrated toolkit for ST data processing and analysis.

Indirubin derivatives as bifunctional molecules inducing DNA damage and targeting PARP for the treatment of cancer.

Based on the facts that significant synergistic effect existed between PARP inhibitors and DNA damage agents and the DNA damage caused by indirubin's derivatives, we herein adopted the strategy to combine the pharmacophores of PARP inhibitors and the unique scaffold of indirubin to design a series of bifunctional molecules inducing DNA damage and targeting PARP. After SAR studies, the most potent compound 12a, encoded as KWWS-12a, exhibited improved inhibitory effect against PARP1 compared with PARP1 inhibitor Olaparib (IC50 = 1.89 nM vs 7.48 nM) and enhanced antiproliferative activities than the combination of Olaparib and indirubin-3'-monoxime towards HCT-116 cells (IC50 = 0.31 µM vs 1.37 µM). In the normal NCM-460 cells, 12a showed low toxicity (IC50 > 60 µM). The mechanism research indicated that 12a could increase the levels of γH2AX concentration dependently, arrest the cell cycle in S phase and induce apoptosis in HCT-116 cells. In vivo experiments showed that 12a displayed more significant antitumor potential than that of the positive controls. Our studies demonstrated that 12a could be a promising candidate for cancer therapy.

Laser irradiation induced structural transformation in layered transition metal trichalcogenide nanoflakes.

Laser irradiation is a powerful tool in inducing changes in lattice structures and properties of two-dimensional (2D) materials through processes such as heating, bleaching, catalysis, etc. However, the underlying mechanisms of such transformations vary dramatically in different 2D materials. Here, we report the structural transformation of layered titanium trisulfide (TiS3) to titanium disulfide (TiS2) after irradiation. We systematically characterized the dependence of the transformation on laser power, flake thickness, irradiation time, and vacuum conditions using microscopic and spectroscopic methods. The underlying mechanism is confirmed as the heat-induced materials decomposition, a process that also occurs in many other transition metal trichalcogenide materials. Furthermore, we demonstrate that this spatial-resolved method also enables the creation of in-plane TiS3-TiS2 heterostructures. Our study identifies a new family of 2D materials that undergo a structural transformation after laser irradiation and enriches the methods available for developing new prototypes of low-dimensional devices in the future.

Salidroside ameliorates memory impairment following long-term ethanol intake in rats by modulating the altered intestinal microbiota content and hippocampal gene expression.

Background: Salidroside (Sal), the main component of a famous herb Rhodiola rosea L, enhances memory performance and reduces fatigue. Therefore, this study assessed the effect of Sal on memory impairment induced by a long-term intake of ethanol (EtOH) in rats and investigated its relevant mechanisms using gut microbiota metagenomic analysis and hippocampal transcriptomic analysis. Methods: Eighteen male SD rats were divided into the normal control group (CON group), EtOH model group (Model group), and Sal treatment group (Sal group). The rats in the Model and Sal groups intragastrically (i.g.) received 2 g/kg EtOH for 30 consecutive days, whereas the CON group was given an equal volume of distilled water. Meanwhile, the rats in the Sal group were administered i.g. 30 mg/kg Sal 60 min after EtOH intake. All rats were tested in the eight-arm maze for their memory function every 3 days. On the 30th day, metagenomic analyses of gut microbiota and transcriptomic analyses of the hippocampus were performed. Results: Compared with the Model group, Sal treatment reduced the total time to complete the eight-arm maze task, decreased the number of arm entries, and abated the working memory error that was significant from the 9th day. Additionally, Sal intervention improved the gut microbiota composition, such as the increased abundance of Actinobacteria and Bifidobacterium, which was related to the metabolism of amino acids and terpenoid carbohydrate, endocrine function, and signal transduction by neurotransmitters. In the hippocampus, the EtOH intake differentially expressed 68 genes (54 genes increased, whereas 14 genes decreased), compared with the CON group, whereas Sal intervention affected these changes: 15 genes increased whereas 11 genes decreased. And, enrichment analyses revealed these genes were related to the structural components of the ribosome, mRNA splicing process, protein translation, mitochondria function, and immunological reaction. Finally, a correlation analysis found the memory impairment was positively correlated with the abnormal upregulation of Tomm7 but negatively correlated with decreased abundance of gut Alistipes_indistinctus, Lactobacillus_taiwanensis, Lactobacillus_paragasseri, and Lactobacillus johnsonii. Conclusion: Sal improved memory impairment caused by long-term EtOH intake in rats, which may be related to its regulation of gut dysbiosis and hippocampal dysfunction.

Oxazole-4-carboxamide/butylated hydroxytoluene hybrids with GSK-3ß inhibitory and neuroprotective activities against Alzheimer's disease.

Neuronal cells overexpressing phosphorylated Tau proteins can increase the susceptibility to oxidative stress. Regulation of glycogen synthase-3ß (GSK-3ß) and reduction of Tau protein hyperphosphorylation, along with alleviation of oxidative stress, may be an effective way to prevent or treat Alzheimer's disease (AD). For this purpose, a series of Oxazole-4-carboxamide/butylated hydroxytoluene hybrids were designed and synthesized to achieve multifunctional effects on AD. The biological evaluation showed that the optimized compound KWLZ-9e displayed potential GSK-3ß (IC50 = 0.25 µM) inhibitory activity and neuroprotective capacity. Tau protein inhibition assays showed that KWLZ-9e reduced the expression of GSK-3ß and downstream p-Tau in HEK GSK-3ß 293T cells. Meanwhile, KWLZ-9e could alleviate H2O2-induced ROS damage, mitochondrial membrane potential imbalance, Ca2+ influx and apoptosis. Mechanistic studies suggest that KWLZ-9e activates the Keap1-Nrf2-ARE signaling pathway and enhances the expression of downstream oxidative stress proteins including TrxR1, HO-1, NQO1, GCLM to exert cytoprotective effects. We also confirmed that KWLZ-9e could ameliorate learning and memory impairments in vivo model of AD. The multifunctional properties of KWLZ-9e suggest that it is a promising lead for the treatment of AD.

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene-environment interactions in patients with autoimmune thyroiditis.

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

Relationship between mild iodine deficiency in pregnant women and thyroid function: A meta-analysis.

BACKGROUND: Pregnant women are among the key groups in iodine nutrition evaluation. The purpose of the present study was to summarize the evidence supporting the relationship between mild iodine deficiency (UIC: 100-150 µg/L) in pregnant women and levels of thyroid function tests. METHODS: This review follows the guidelines for systematic reviews (PRISMA 2020). Three electronic databases (PubMed, Medline, and Embase) were searched for relevant publications in English on the association between mild iodine deficiency in pregnant women and thyroid function. Articles published in Chinese were searched in China's electronic databases (CNKI, WanFang, CBM, and WeiPu). Pooled effects were presented as standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) using fixed or random effect models, respectively. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120. RESULTS: We summarized the results from 7 articles with 8261 participants. The overall pooled results showed that the levels of FT3, FT4, and abnormal TgAb (the antibody levels exceeded the upper limit of the reference range) were significantly increased in pregnant women with mild iodine deficiency compared to pregnant women with adequate iodine status (FT3: SMD=0.854, 95% CI: 0.188, 1.520; FT4: SMD=0.550, 95% CI: 0.050, 1.051; TgAb: OR=1.292, 95% CI: 1.095; 1.524). Subgroup analysis was carried out on the sample size, ethnicity, country, and gestation of FT3, FT4, and TSH, but no plausible factor was found. Egger's tests indicated no publication bias.The increase in FT3 and FT4, as well as TgAb levels, in pregnant women is associated with mild iodine deficiency. CONCLUSION: Mild iodine deficiency is associated with an increase in FT3，FT4 and TgAb levels in pregnant women. Mild iodine deficiency may increase the risk of thyroid dysfunction in pregnant women.

A descriptive analysis of the coverage of newborn care services among women who delivered in health facilities in 17 sub-Saharan African countries.

BACKGROUND: Sub-Saharan Africa (SSA) has seen an increase in facility-based births over the years. However, the region has the world's highest newborn mortality rate (42% in 2019). Quality care around the time of birth can avert these deaths. This study examined the newborn care interventions given to women who gave birth in health facilities in 17 countries in SSA. METHODS: A cross-sectional population-based study was conducted. We used data from the most recent Demographic and Health Surveys (DHS) conducted in 17 sub-Saharan African countries. We analysed a weighted sample of 226,706 women aged 15-49 years who gave birth in the five years preceding the surveys. We described the coverage of nine newborn care services, namely weighing at birth, breastfeeding initiation within 1 h after birth, skin-to-skin contact, temperature measurement, cord examination, counselling on newborn danger signs, counselling on breastfeeding, breastfeeding observation, and child health assessment before discharge. RESULTS: Overall, 72.0% (95% CI: 71.1, 72.8) of births occurred in health facilities, ranging from 40.0% (95% CI: 38.0, 42.1) in Nigeria to 96.3% (95% CI: 95.4, 97.1) in South Africa. Weighing at birth was the most common intervention (91.4%), followed by health checks before discharge (81%). The other interventions, including those given immediately at birth (breastfeeding and skin-to-skin contact), had suboptimal coverage. For instance, 66% of newborns were breastfed within 1 h after birth, and 56% had immediate skin-to-skin contact. Service coverage varied considerably by country and healthcare provider type. CONCLUSIONS: The majority of the examined services, namely early breastfeeding, skin-to-skin contact, cord examination, temperature measurement, counselling on newborn danger signs, breastfeeding observation, and counselling on breastfeeding, were found to have suboptimal coverage. Even though many pregnant women in SSA give birth in healthcare facilities, some newborns do not always get the care they need to be healthy and live. This is a missed chance to improve newborn health and survival around the time of birth.

Alteration of Lipid Profile Between Subclinical Hypothyroidism and Well-Matched Controls: A Meta-Analysis.

In previous studies, subclinical hypothyroidism (SCH) has been associated with altered lipid profiles. However, since the discrepancy between these study results may reside in the great heterogeneity of the populations studied, this relationship is controversial. This study aimed to explore the changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) between subclinical hypothyroidism (SCH) and well-matched euthyroid (EU) groups. Multiple databases were searched for publications before December 1, 2021, including cross-sectional studies on the association between SCH and lipid profile matched by age, gender, and BMI. Twenty-five articles with 3347 participants were included for meta-analysis. The results showed that the TC, TG, and LDL-c levels of the SCH groups were higher than the EU groups (TC, SMD=0.49, 95% CI 0.27, 0.71, p<0.001) (TG, SMD=0.43, 95% CI 0.21, 0.64, p<0.05 ) (LDL-c, SMD=0.75, 95% CI 0.46, 1.03, p<0.001 ). The HDL-c levels of the SCH group were lower than the control group (SMD=-0.53, 95% CI -0.81, -0.25, p<0.05). SCH has a larger impact on LDL-c than the other three indicators. After subgroup analyses, there was a larger impact on lipid alteration in the subgroup of TSH>10 µIU/ml, especially on LDL-c. This study found that SCH was associated with altered lipid profiles. Appropriate clinical treatment may be needed to prevent dyslipidemia and related diseases.

Quasi-One-Dimensional ZrS3 Nanoflakes for Broadband and Polarized Photodetection with High Tuning Flexibility.

Two-dimensional (2D) layered materials with low crystal symmetries have exhibited unique anisotropic physical properties. Here, we report systematic studies on the photoresponse of field effect transistors (FETs) fabricated using quasi-one-dimensional ZrS3 nanoflakes. The as-fabricated phototransistors exhibit a broadband photocurrent response from ultraviolet to visible regions, where the responsivity and detectivity can be enhanced via additional gate voltages. Furthermore, benefiting from the strong in-plane anisotropy of ZrS3, we observe a gate-voltage and illumination wavelength-dependent polarized photocurrent response, while its sub-millisecond-time response speed is also polarization-dependent. Our results demonstrate the flexible tunability of photodetectors based on anisotropic layered semiconductors, which substantially broadens the application of low symmetry layered materials in polarization-sensitive optoelectronic devices.

Discovery of Sibiriline derivatives as novel receptor-interacting protein kinase 1 inhibitors.

Receptor-interacting protein kinase 1 (RIPK1), a vital protein of the necroptosis pathway, plays a pivotal role in various inflammatory diseases. Sibiriline has been reported to be a potent ATP-competitive RIPK1 inhibitor, but its anti-necroptotic effects are limited. A series of structural analogues of Sibiriline were synthesized and evaluated for their anti-necroptotic activity. Comprehensive structure-activity relationship (SAR) was performed to left azaindole and right substituents of benzene of Sibiriline, respectively. The optimal compound KWCN-41, specifically inhibiting cell necroptosis but not apoptosis, protects cell survival by blocking the necroptotic pathway, which inhibits the phosphorylation of essential proteins of the necroptosis. It also prevented the development of inflammation and reduced the level of inflammatory factors in mice. KWCN-41 is expected to be a lead compound for further studies in inflammatory diseases.

Effect of different iodine levels on the DNA methylation of PRKAA2, ITGA6, THEM4 and PRL genes in PI3K-AKT signaling pathway and population-based validation from autoimmune thyroiditis patients.

PURPOSE: Autoimmune thyroiditis (AIT) is one of the most common autoimmune endocrine diseases. The currently recognized causes are genetic susceptibility, environmental factors and immune disorders. It is important to clarify the pathogenesis for the prevention, diagnosis, treatment of AIT and scientific iodine supplementation. This study analyzed the DNA methylation levels of PRKAA2, ITGA6, PRL and THEM4 genes related to PI3K-AKT signaling pathway, compared the DNA methylation levels between cases and controls from different water iodine levels in Shandong Province of China, and evaluated the contribution of PI3K-AKT signaling pathway-related genes in AIT. METHODS: A total of 176 adult AIT patients were included from three different water iodine areas, and 176 healthy controls were included according to gender, age and BMI. According to the results of the Illumina Methylation 850 K BeadChip in our previous research, the significant methylation differences of genes on the PI3K-AKT signaling pathway related to AIT were determined. The MethylTarget™ assay was used to detect the methylation levels of the target genes, and real-time PCR experiments were used to verify the mRNA expression levels. RESULTS: Compared with the control group, PRKAA2_3 and 15 CpG sites were hyper-methylated. ITGA6 gene and 2 CpG sites were hypo-methylated in AIT cases. The mRNA expression of ITGA6 gene was negatively correlated with the DNA methylation levels of ITGA6 gene and 2 CpG sites. Compared with cases and controls in areas with different water iodine levels, methylation differences were mainly in PRKAA2 and ITGA6 genes. The methylation levels of PRKAA2_1 and PRKAA2_3 were positively correlated with age. The methylation levels of PRL and THEM4 genes were negatively correlated with age. The methylation level of PRKAA2_3 was positively correlated with FT4. CONCLUSION: In summary, we identified aberrant DNA methylation levels of PRKAA2 and ITGA6 genes related to PI3K-AKT signaling pathway in the blood of AIT patients. Both iodine supplementation after long-term iodine deficiency and iodine excess can affect the DNA methylation levels of PRKAA2 and ITGA6 genes, and the former affects more obviously. In ITGA6 gene, this aberrant epigenetic modification is associated with the increased mRNA expression.

Nonvolatile Ferroelectric Memory with Lateral ß/α/ß In2Se3 Heterojunctions.

The electric dipole locking effect observed in van der Waals (vdW) ferroelectric α-In2Se3 has resulted in a surge of applied research in electronics with nonvolatile functionality. However, ferroelectric tunnel junctions with advantages of lower power consumption and faster writing/reading operations have not been realized in α-In2Se3. Here, we demonstrate the tunneling electroresistance effect in a lateral ß/α/ß In2Se3 heterojunction built by local laser irradiation. Switchable in-plane polarizations of the vdW ferroelectric control the tunneling conductance of the heterojunction device by 4000% of magnitude. The electronic logic bit can be represented and stored with different orientations of electric dipoles. This prototype enables a new approach to rewritable nonvolatile memory with in-plane ferroelectricity in vdW 2D materials.

The Whole Blood DNA Methylation Patterns of Extrinsic Apoptotic Signaling Pathway Related Genes in Autoimmune Thyroiditis among Areas with Different Iodine Levels.

Autoimmune thyroiditis (AIT) has a complex etiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signaling pathway related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas (IFA), iodine-adequate areas (IAA) and water-based iodine-excess areas (IEA) from Shandong Province of China as survey sites. Totally 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes' DNA methylation levels and mRNA expression levels, respectively. We found that DAPK1 DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t=2.7715, P=0.0059; t=2.4638, P=0.0143 in female). There were differences in DAPK1(t=2.5384, P=0.0121), TNFSF8(t=2.1667, P=0.0334) and TNFAIP8(t=2.5672, P=0.0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1(t=4.329, P<0.001) and TNFAIP8(t=3.775, P<0.001) in the cases were increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signaling pathway related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent.

The Relationship between PTPN22 R620W Polymorphisms and the Susceptibility to Autoimmune Thyroid Diseases: An Updated Meta-analysis.

The protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W polymorphism has been related to susceptibility to autoimmune thyroid disease (AITD) with inconsistent results. Therefore, this meta-analysis was designed to assess a more accurate association between the PTPN22 R620W polymorphism and AITD susceptibility. A systematic search of the EMBASE, PubMed, Web of Science, CBM, CNKI, and WanFang databases was performed to determine relevant publications. Statistical analyses of the odds ratios (ORs), 95% confidence intervals (CIs), and p values were performed using STATA software. Our meta-analysis included 18 separate studies comprised of 4,726 cases and 4,220 controls. In the allele and all genetic models, PTPN22 R620W polymorphism and Graves' disease (GD) (allele model TvsC: OR = 1.573; 95% CI = 1.378-1.795; P < .001) and Hashimoto's thyroiditis (HT) (allele model TvsC: OR = 1.737; 95% CI = 1.230-2.454; P = .002) susceptibility was positively associated. A racial subgroup analysis showed that the T allele significantly increased AITD susceptibility in all genetic models involving Caucasians, but not in Asians. This meta-analysis showed that the PTPN22 R620W polymorphism is associated with the risk of GD and HT in the overall study population. In addition, the PTPN22 R620W polymorphism is associated with elevated AITD risk in Caucasians, but not in Asians.