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Autoimmune thyroiditis (AIT) is increasingly common, and serological markers include thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). To determine if selected metals influence thyroiditis antibody positivity, this cross-sectional study investigated associations between metals and thyroiditis antibody status. Healthy individuals (n = 1104) completed a questionnaire and underwent checkups of anthropometric parameters, thyroid function status, and levels of seven metals in blood (magnesium, iron, calcium, copper, zinc, manganese, and lead). Associated profiles of glyco- and lipid metabolism were also established. Logistic regression and restricted cubic spline (RCS) regression analysis were applied to adjudge associations between metals and TPOAb and TgAb status. It was found that, after adjusting for likely cofounding factors, participants with antibody positivity had significantly lower serum concentrations of magnesium and iron. When serum magnesium levels were analyzed in quartiles, the odds ratios of quartile 4 were 0.329–fold (95% confidence interval (CI): 0.167–0647) and 0.259-fold (95% CI 0.177–0.574) that of quartile 1 regarding TPOAb and TgAb positivity (P = 0.004, 0.003). After adjustment, the RCS analysis detected nonlinear associations between iron and TPOAb and TgAb positivity (P

Background Long non-coding RNAs (lncRNAs) play an essential role in biological processes. However, the expression patterns of lncRNAs that regulate the non-Mendelian inheritance feather phenotypes remain unknown. Objective This study aimed to compare the expression profiles of lncRNAs in the follicles of the late-feathering cocks (LC) and late-feathering hens (LH) that followed genetic rules and the early-feathering hen (EH) and early-feathering cock (EC) that did not conform to the genetic laws. Methods We performed RNA sequencing and investigated the differentially expressed lncRNAs (DElncRNAs) between the early- and late-feathering chickens, which function by cis-acting or participate in the competing endogenous RNA (ceRNA) network. Results A total of 53 upregulated and 43 downregulated lncRNAs were identified in EC vs. LC, and 58 upregulated and 109 downregulated lncRNAs were identified in EH vs. LH. The target mRNAs regulated by lncRNAs in cis were enriched in the pentose phosphate pathway, TGF-β signaling pathway and Jak-STAT signaling pathway in EC vs. LC and were associated with the TGF-β signaling pathway, Wnt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway in EH vs. LH. In addition, the lncRNA-mediated ceRNA regulatory pathways of hair follicle formation were mainly enriched in the TGF-β signaling pathway, Wnt signaling pathway, melanogenesis, and calcium signaling pathways. The levels of ENSGALG00000047626 were significantly higher in the late-feathering chickens than in the early-feathering chickens, which regulated the expression of SSTR2 by gga-miR-1649-5p. Conclusion This study provides a novel molecular mechanism of lncRNA’s response to the feather rate that does not conform to the genetic laws in chickens.

Due to the rise of 5G, IoT, AI, and high-performance computing applications, datacenter traffic has grown at a compound annual growth rate of nearly 30%. Furthermore, nearly three-fourths of the datacenter traffic resides within datacenters. The conventional pluggable optics increases at a much slower rate than that of datacenter traffic. The gap between application requirements and the capability of conventional pluggable optics keeps increasing, a trend that is unsustainable. Co-packaged optics (CPO) is a disruptive approach to increasing the interconnecting bandwidth density and energy efficiency by dramatically shortening the electrical link length through advanced packaging and co-optimization of electronics and photonics. CPO is widely regarded as a promising solution for future datacenter interconnections, and silicon platform is the most promising platform for large-scale integration. Leading international companies (e.g., Intel, Broadcom and IBM) have heavily investigated in CPO technology, an inter-disciplinary research field that involves photonic devices, integrated circuits design, packaging, photonic device modeling, electronic-photonic co-simulation, applications, and standardization. This review aims to provide the readers a comprehensive overview of the state-of-the-art progress of CPO in silicon platform, identify the key challenges, and point out the potential solutions, hoping to encourage collaboration between different research fields to accelerate the development of CPO technology. Graphical Abstract

Background Spinal cord injury (SCI) brings a heavy burden to individuals and society, and there is no effective treatment at present. Exosomes (EX) are cell secreted vesicles containing molecules such as nucleic acids and proteins, which hold promise for the treatment of SCI. Netrin-1 is an axon guidance factor that regulates neuronal growth. We investigated the effects of engineered EX enriched in netrin-1 chemically synthetic modified message RNA (modRNA) in treating SCI in an attempt to find a novel therapeutic approach for SCI. Methods Netrin-1 modRNA was transfected into bone marrow mesenchymal stem cells to obtain EX enriched with netrin-1 (EX-netrin1). We built an inflammatory model in vitro with lipopolysaccharide (LPS) in vitro to study the therapeutic effect of EX-netrin1 on SCI. For experiments in vitro, ELISA, CCK-8 assay, immunofluorescence staining, lactate dehydrogenase release experiments test, real-time quantitative polymerase chain reaction, and western blot were conducted. At the same time, we constructed a rat model of SCI. MRI, hematoxylin-eosin and Nissl staining were used to assess the extent of SCI in rats. Results In vitro experiments showed that EX had no effect on the viability of oligodendrocytes and PC12 cells. EX-netrin1 could attenuate LPS-induced inflammation and pyroptosis and accelerate axonal/dentritic growth in PC12 cells/oligodendrocytes. In addition, netrin-1 could activate the PI3K/AKT/mTOR signalling pathway upon binding to its receptor unc5b. When Unc5b and PI3K were inhibited, the effect of EX-netrin1 was weakened, which could be reversed by PI3K or mTOR activator. Our in vivo experiments indicated that EX-netrin1 could promote recovery in rats with SCI. Conclusion We found that EX-netrin1 regulated inflammation, pyroptosis and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway, which provides a new strategy for the treatment of SCI.

Background The quantity and quality of the paraspinal muscles are important factors that lead to spinal diseases. However, the role of paraspinal muscles in the pathogenesis of adjacent segment disease (ASD) after lumbar fusion surgery is rarely studied. The purpose of the research is to investigate the relationship between paraspinal muscles and ASD. Methods Thirty-three patients with ASD were included, and 33 controls without ASD were matched according to the basic demographic information. Cross-sectional images of the paraspinal muscles at each intervertebral disk level (L1–S1) before the first operation were analyzed, and the cross-sectional area (CSA) and degree of fat infiltration (FI) of the multifidus (MF) muscle and the erector spinae muscle were compared. Results There was no significant difference in demographic characteristics (P > 0.05) except for the bone mineral density (BMD) (P = 0.037) between the two groups. There were significant differences in the CSA and FI of the lower lumbar multifidus (P P Conclusions The CSA, FI and BMD of the lower lumbar MF muscle were closely related to the occurrence of ASD. The CSA of the MF muscle at L3–L4, the degree of FI of the MF muscle at L4–L5 and L5–S1 and BMD were important risk factors for ASD. The number of fusion segments in the first operation has a certain impact on the above-mentioned conclusions.

We fine-mapped QBp.caas-3BL for black point resistance in an interval of 1.7 Mb containing five high-confidence annotated genes and developed a KASP marker suitable for selection of QBp.caas-3BL. Wheat black point, which occurs in most wheat-growing regions of the world, is detrimental to grain appearance, processing and nutrient quality. Mining and characterization of genetic loci for black point resistance are helpful for breeding resistant wheat cultivars. We previously identified a major QTL QBp.caas-3BL in a recombinant inbred line (RIL) population of Linmai 2/Zhong 892 across five environments. Here we confirmed the QTL in two additional environments. The genetic region of QBp.caas-3BL was enriched with newly developed markers. Using four sets of near isogenic lines, QBp.caas-3BL was narrowed down to a physical interval of approximately 1.7 Mb, including five annotated genes according to IWGSC reference genome. TraesCS3B02G404300, TraesCS3B02G404600 and TraesCS3B02G404700 were predicted as candidate genes based on the analyses of sequence polymorphisms and differential expression. We also converted a SNP of TraesCS3B02G404700 into a breeding-applicable KASP marker and verified its efficacy for marker-assisted breeding in a panel of germplasm. The findings not only lay a foundation for map-based cloning of QBp.caas-3BL but also provide a useful marker for selection of resistant cultivars genotypes in wheat breeding.

Cell-free fetal DNA fraction (FF) in maternal plasma is a key parameter affecting the performance of noninvasive prenatal testing (NIPT). Accurate quantitation of FF plays a pivotal role in these tests. However, there are few methods that could determine FF with high accuracy using shallow‐depth whole‐genome sequencing data. In this study, we hypothesized that the actual FF in maternal plasma should be proportional to the discrepancy rate between the observed genotypes and inferred genotypes based on the linkage disequilibrium rule in certain polymorphism sites. Based on this hypothesis, we developed a method named Linkage Disequilibrium information-based cell-free Fetal DNA Fraction (LDFF) to accurately quantify FF in maternal plasma. This method achieves a high performance and outperforms existing methods in the fetal DNA fraction estimation. As LDFF is a gender-independent method and developed on shallow-depth samples, it can be easily incorporated into routine NIPT test and may enhance the current NIPT performance.

Intestinal Paneth cells are professional exocrine cells that play crucial roles in maintenance of homeostatic microbiome, modulation of mucosal immunity, and support for stem cell self-renewal. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Cdk5 activator binding protein Cdk5rap3 (also known as C53 and LZAP) was originally identified as a binding protein of Cdk5 activator p35. Although previous studies have indicated its involvement in a wide range of signaling pathways, the physiological function of Cdk5rap3 remains largely undefined. In this study, we found that Cdk5rap3 deficiency resulted in very early embryonic lethality, indicating its indispensable role in embryogenesis. To further investigate its function in the adult tissues and organs, we generated intestinal epithelial cell (IEC)-specific knockout mouse model to examine its role in intestinal development and tissue homeostasis. IEC-specific deletion of Cdk5rap3 led to nearly complete loss of Paneth cells and increased susceptibility to experimentally induced colitis. Interestingly, Cdk5rap3 deficiency resulted in downregulation of key transcription factors Gfi1 and Sox9, indicating its crucial role in Paneth cell fate specification. Furthermore, Cdk5rap3 is highly expressed in mature Paneth cells. Paneth cell-specific knockout of Cdk5rap3 caused partial loss of Paneth cells, while inducible acute deletion of Cdk5rap3 resulted in disassembly of the rough endoplasmic reticulum (RER) and abnormal zymogen granules in the mature Paneth cells, as well as loss of Paneth cells. Together, our results provide definitive evidence for the essential role of Cdk5rap3 in Paneth cell development and maintenance.

Highlights A novel N-doped strategy of C2N3− in situ trimerization between the 2D MXene interlayers was first proposed. The ultra-fast pseudocapacitive behavior of Ti3C2Tx/Na3TCM anode was managed and verified. The as-fabricated sodium-ion capacitor delivers excellent electrochemical performance by anode/cathode mass matching. Electronic supplementary material The online version of this article (10.1007/s40820-020-00473-7) contains supplementary material, which is available to authorized users., 2D MXenes are attractive for energy storage applications because of their high electronic conductivity. However, it is still highly challenging for improving the sluggish sodium (Na)-ion transport kinetics within the MXenes interlayers. Herein, a novel nitrogen-doped Ti3C2Tx MXene was synthesized by introducing the in situ polymeric sodium dicyanamide (Na-dca) to tune the complex terminations and then utilized as intercalation-type pseudocapacitive anode of Na-ion capacitors (NICs). The Na-dca can intercalate into the interlayers of Ti3C2Tx nanosheets and simultaneously form sodium tricyanomelaminate (Na3TCM) by the catalyst-free trimerization. The as-prepared Ti3C2Tx/Na3TCM exhibits a high N-doping of 5.6 at.% in the form of strong Ti–N bonding and stabilized triazine ring structure. Consequently, coupling Ti3C2Tx/Na3TCM anode with different mass of activated carbon cathodes, the asymmetric MXene//carbon NICs are assembled. It is able to deliver high energy density (97.6 Wh kg−1), high power output (16.5 kW kg−1), and excellent cycling stability (≈ 82.6% capacitance retention after 8000 cycles). Electronic supplementary material The online version of this article (10.1007/s40820-020-00473-7) contains supplementary material, which is available to authorized users.

Genotype estimates from short-read sequencing data are typically based on the alignment of reads to a linear reference, but reads originating from more complex variants (for example, structural variants) often align poorly, resulting in biased genotype estimates. This bias can be mitigated by first collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a 'variation-prior' database containing already known variants significantly improves sensitivity.

The IRE1α/XBP1 branch of unfolded protein response (UPR) pathway has a critical function in endoplasmic reticulum (ER) expansion in plasma cells via unknown mechanisms; interestingly, another UPR branch, PERK, is suppressed during plasma cell development. Here we show that Ufbp1, a target and cofactor of the ufmylation pathway, promotes plasma cell development by suppressing the activation of PERK. By contrast, the IRE1α/XBP1 axis upregulates the expression of Ufbp1 and ufmylation pathway genes in plasma cells, while Ufbp1 deficiency impairs ER expansion in plasma cells and retards immunoglobulin production. Structure and function analysis suggests that lysine 267 of Ufbp1, the main lysine in Ufbp1 that undergoes ufmylation, is dispensable for the development of plasmablasts, but is required for immunoglobulin production and stimulation of ER expansion in IRE1α-deficient plasmablasts. Thus, Ufbp1 distinctly regulates different branches of UPR pathway to promote plasma cell development and function., IRE1 and PERK, both important mediators of the unfold protein response pathway, are differentially regulated during plasma cell differentiation. Here the authors show that an ufmylation target, Ufbp1, suppresses PERK to stimulate plasma cell development and is induced by the IRE1/XBP1 pathway to promote ER expansion .

Electrically-triggered micro-explosions in a metal-insulator-semiconductor (MIS) structure can fragment/atomize analytes placed on it, offering an interesting application potential for chip-scale implementation of atomic emission spectroscopy (AES). We have investigated the mechanisms of micro-explosions occurring in a graphene/SiO2/Si (GOS) structure under a high-field pulsed voltage drive. Micro-explosions are found to occur more readily in inversion bias than in accumulation bias. Explosion damages in inversion-biased GOS differ significantly between n-Si and p-Si substrate cases: a highly localized, circular, protruding cone-shape melt of Si for the n-Si GOS case, whereas shallow, irregular, laterally-propagating trenches in SiO2/Si for the p-Si GOS case. These differing damage morphologies are explained by different carrier-multiplication processes: in the n-Si case, impact ionization propagates from SiO2 to Si, causing highly-localized melt explosions of Si in the depletion region, whereas in the p-Si case, from SiO2 towards graphene electrode, resulting in laterally wide-spread micro-explosions. These findings are expected to help optimize the GOS-based atomizer structure for low voltage, small-volume analyte, high sensitivity chip-scale emission spectroscopy.

The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

The present study was conducted to assess genetic associations for type 1 diabetes (T1D) reported in previous genome-wide association studies (GWAS). A total of 21 previously reported single-nucleotide polymorphisms (SNPs) were genotyped by TaqMan assays in 1434 Caucasian T1D patients and 1864 normal controls from Georgia. Analysis of the samples identified 18 SNPs (PTPN22, INS, IFIH1, SH2B3, ERBB3, CTLA4, C14orf181, CTSH, CLEC16A, CD69, ITPR3, C6orf173, SKAP2, PRKCQ, RNLS, IL27, SIRPG and CTRB2) with putative association.

In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Han Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction (PCR-LDR). In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJ11 was strongly associated with type 2 diabetes in Han Chinese in Hubei China. There were significant differences in the TT genotype frequency (OR=1.6, 95%CI 1.1-2.3, p=0.01) and T allele frequency (OR=1.3, 95%CI 1.1-1.6, p=0.03) of SNP rs5219 between cases and controls. The other nine SNP loci did not show significant association with type 2 diabetes in Han Chinese in Hubei. The result suggests that KCNJ11 gene is a susceptibility gene of type 2 diabetes among this population.

Background In this study, the prevalence of HIV-1 CRF01_AE intrasubtype recombinants in China is estimated and their contributions to the epidemic are explored. Methods Available HIV-1 complete genomes of CRF01_AE were retrieved from the HIV database. The two alignments were evaluated with RDP3. Recombinants were defined as cases in which the recombination signal was supported by at least 3 methods with P-values of ≤0.05 after Bonferroni correction for multiple comparisons implemented in RDP3. Phylogenetic analysis was performed to further investigate the role of intrasubtype recombinants in epidemics. Results Here, 124 out of the 339 sequences from around the world (36.6 %) showed significant evidence of recombination. Here, 84 of these recombinants were from China, accounting for 54.9 % of local total sequences (84 out of 153). The results indicated non-negligible levels of intrasubtype recombination. Subsequent phylogenetic analysis indicated that a considerable proportion of CRF01_AE strains in China originated from circulating intrasubtype recombinant forms. Three large, well-supported intrasubtype recombinants clusters were identified here. Through a survey of risk factors and sampling cities and provinces, cluster I and cluster II were found to be prevalent primarily among men who have sex with men in major northern cities. Cluster III was prevalent among heterosexuals and intravenous drug users in southern and southwestern provinces. Conclusions The current work highlighted the remarkable prevalence of intrasubtype recombination within the CRF01_AE epidemic and emphasized the value of intrasubtype recombinants, which came to circulate in the same manner as intersubtype recombinants. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1273-5) contains supplementary material, which is available to authorized users.

Background DNA methylation plays an essential role in regulating gene expression under a variety of conditions and it has therefore been hypothesized to underlie the transitions between life cycle stages in parasitic nematodes. So far, however, 5'-cytosine methylation has not been detected during any developmental stage of the nematode Caenorhabditis elegans. Given the new availability of high-resolution methylation detection methods, an investigation of life cycle methylation in a parasitic nematode can now be carried out. Results Here, using MethylC-seq, we present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis, and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages. Conclusions Our data contribute to the understanding of the developmental changes that occur in an important human parasite, and raises the possibility that targeting DNA methylation processes may be a useful strategy in developing therapeutics to impede infection. In addition, our conclusion that DNA methylation is a mechanism for life cycle transition in T. spiralis prompts the question of whether this may also be the case in any other metazoans. Finally, our work constitutes the first report, to our knowledge, of DNA methylation in a nematode, prompting a re-evaluation of phyla in which this epigenetic mark was thought to be absent.