Atomistic structure of the SARS-CoV-2 pseudoknot in solution from SAXS-driven molecular dynamics.

SARS-CoV-2 depends on -1 programmed ribosomal frameshifting (-1 PRF) to express proteins essential for its replication. The RNA pseudoknot stimulating -1 PRF is thus an attractive drug target. However, the structural models of this pseudoknot obtained from cryo-EM and crystallography differ in some important features, leaving the pseudoknot structure unclear. We measured the solution structure of the pseudoknot using small-angle X-ray scattering (SAXS). The measured profile did not agree with profiles computed from the previously solved structures. Beginning with each of these solved structures, we used the SAXS data to direct all atom molecular dynamics (MD) simulations to improve the agreement in profiles. In all cases, this refinement resulted in a bent conformation that more closely resembled the cryo-EM structures than the crystal structure. Applying the same approach to a point mutant abolishing -1 PRF revealed a notably more bent structure with reoriented helices. This work clarifies the dynamic structures of the SARS-CoV-2 pseudoknot in solution.

Nipped-A regulates the Drosophila circadian clock via histone deubiquitination.

Psychiatric diseases are often accompanied by circadian disruptions, but the molecular underpinnings remain largely unclear. To address this, we screened genes that have been previously reported to be associated with psychiatric diseases and found that TRRAP, a gene associated with schizophrenia, is involved in circadian rhythm regulation. Knocking down Nipped-A, the Drosophila homolog of human TRRAP, leads to lengthened period of locomotor rhythms in flies. Molecular analysis demonstrates that NIPPED-A sets the pace of the clock by increasing the mRNA and protein levels of core clock genes timeless (tim) and Par domain protein 1ε (Pdp1ε). Furthermore, we found that NIPPED-A promotes the transcription of tim and Pdp1ε possibly by facilitating deubiquitination of histone H2B via the deubiquitination module of the transcription co-activator Spt-Ada-Gcn5 acetyltransferase complex. Taken together, these findings reveal a novel role for NIPPED-A in epigenetic regulation of the clock.

Abundance of Modifications in Mature miRNAs Revealed by LC-MS/MS Method Coupled with a Two-Step Hybridization Purification Strategy.

Accurate detection of endogenous miRNA modifications, such as N6-methyladenosine (m6A), 7-methylguanosine (m7G), and 5-methylcytidine (m5C), poses significant challenges, resulting in considerable uncertainty regarding their presence in mature miRNAs. In this study, we demonstrate for the first time that liquid chromatography coupled with a tandem mass spectrometry (LC-MS/MS) nucleoside analysis method is a practical tool for quantitatively analyzing human miRNA modifications. The newly designed liquid-solid two-step hybridization (LSTH) strategy enhances specificity for miRNA purification, while LC-MS/MS offers robust capability in recognizing modifications and sufficient sensitivity with detection limits ranging from attomoles to low femtomoles. Therefore, it provides a more reliable approach compared to existing techniques for revealing modifications in endogenous miRNAs. With this approach, we characterized m6A, m7G, and m5C modifications in miR-21-5p, Let-7a/e-5p, and miR-10a-5p isolated from cultured cells and observed unexpectedly low abundance (<1% at each site) of these modifications.

2D Memory Selectors with Giant Nonlinearity Enabled by Van der Waals Heterostructures.

The integration of one-selector-one-resistor crossbar arrays requires the selectors featured with high nonlinearity and bipolarity to prevent leakage currents and any crosstalk among distinct cells. However, a selector with sufficient nonlinearity especially in the frame of device miniaturization remains scarce, restricting the advance of high-density storage devices. Herein, a high-performance memory selector is reported by constructing a graphene/hBN/WSe2 heterostructure. Within the temperature range of 300-80 K, the nonlinearity of this selector varies from ≈103 - ≈104 under forward bias, and increases from ≈300 - ≈105 under reverse bias, the highest reported nonlinearity among 2D selectors. This improvement is ascribed to direct tunneling at low bias and Fowler-Nordheim tunneling at high bias. The tunneling current versus voltage curves exhibit excellent bipolarity behavior because of the comparable hole and electron tunneling barriers, and the charge transport polarity can be effectively tuned from N-type or P-type to bipolar by simply changing source-drain bias. In addition, the conceptual memory selector exhibits no sign of deterioration after 70 000 switching cycles, paving the way for assembling 2D selectors into modern memory devices.

The effect of in vitro simulated colonic pH gradients on microbial activity and metabolite production using common prebiotics as substrates.

BACKGROUND: The interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon. RESULTS: Here we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates. CONCLUSIONS: Together, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research.

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Drivers and suppressors of triple-negative breast cancer.

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor ß (ERß) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERß. ERß is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERß+ TNBC patient-derived xenografts in mice and found that the ERß agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERß is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERß functionless on genes involved in proliferation and inflammation.

CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.

Through dominant mutations, aminoacyl-tRNA synthetases constitute the largest protein family linked to Charcot-Marie-Tooth disease (CMT). An example is CMT subtype 2N (CMT2N), caused by individual mutations spread out in AlaRS, including three in the aminoacylation domain, thereby suggesting a role for a tRNA-charging defect. However, here we found that two are aminoacylation defective but that the most widely distributed R329H is normal as a purified protein in vitro and in unfractionated patient cell samples. Remarkably, in contrast to wild-type (WT) AlaRS, all three mutant proteins gained the ability to interact with neuropilin 1 (Nrp1), the receptor previously linked to CMT pathogenesis in GlyRS. The aberrant AlaRS-Nrp1 interaction is further confirmed in patient samples carrying the R329H mutation. However, CMT2N mutations outside the aminoacylation domain do not induce the Nrp1 interaction. Detailed biochemical and biophysical investigations, including X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange (HDX), switchSENSE hydrodynamic diameter determinations, and protease digestions reveal a mutation-induced structural loosening of the aminoacylation domain that correlates with the Nrp1 interaction. The b1b2 domains of Nrp1 are responsible for the interaction with R329H AlaRS. The results suggest Nrp1 is more broadly associated with CMT-associated members of the tRNA synthetase family. Moreover, we revealed a distinct structural loosening effect induced by a mutation in the editing domain and a lack of conformational impact with C-Ala domain mutations, indicating mutations in the same protein may cause neuropathy through different mechanisms. Our results show that, as with other CMT-associated tRNA synthetases, aminoacylation per se is not relevant to the pathology.

Worm Generator: A System for High-Throughput in Vivo Screening.

Large-scale screening of molecules in organisms requires high-throughput and cost-effective evaluating tools during preclinical development. Here, a novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nanogenerators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. Unlike the traditional methods for behavioral monitoring of the animals, which are laborious and costly, HB-TENGs with micropillars are designed to efficiently convert animals' behaviors into friction deformation and result in a contact-separation motion between two triboelectric layers to generate electrical outputs. The triboelectric signals are recorded and extracted to various bioinformation for each screened compound. Moreover, the information-rich electrical readouts are successfully demonstrated to be sufficient to predict a drug's identity by multiple-Gaussian-kernels-based machine learning methods. This proposed strategy can be readily applied to various fields and is especially useful in in vivo explorations to accelerate the identification of novel therapeutics.

Giant Magnetocaloric Effect in Magnets Down to the Monolayer Limit.

2D magnets can potentially revolutionize information technology, but their potential application to cooling technology and magnetocaloric effect (MCE) in a material down to the monolayer limit remain unexplored. Herein, it is revealed through multiscale calculations the existence of giant MCE and its strain tunability in monolayer magnets such as CrX3 (X = F, Cl, Br, I), CrAX (A = O, S, Se; X = F, Cl, Br, I), and Fe3 GeTe2 . The maximum adiabatic temperature change ( Δ T ad max $\Delta T_{{\rm{ad}}}^{\max }$ ), maximum isothermal magnetic entropy change, and specific cooling power in monolayer CrF3 are found as high as 11 K, 35 µJ m-2  K-1 , and 3.5 nW cm-2 under a magnetic field of 5 T, respectively. A 2% biaxial and 5% a-axis uniaxial compressive strain can remarkably increase Δ T ad max $\Delta T_{{\rm{ad}}}^{\max }$ of CrCl3 and CrOF by 230% and 37% (up to 15.3 and 6.0 K), respectively. It is found that large net magnetic moment per unit area favors improved MCE. These findings advocate the giant-MCE monolayer magnets, opening new opportunities for magnetic cooling at nanoscale.

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages.

BACKGROUND: There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. METHODS: To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. RESULTS: The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-ß signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. CONCLUSION: Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

A new Einstein coefficient method for mesopause-lower thermosphere atmosphere temperature retrieval under a non-local thermal equilibrium situation.

The mesopause-lower thermosphere (MLT) region is an important spatial region in the Earth's atmosphere, making it a valuable area to investigate the temperature variations. Kirchhoff's law fails with the altitude increase due to the non-local thermal equilibrium effect, resulting in an increase in the error of the method to retrieve the atmospheric temperature in the MLT region using the A-band spectral line intensity. In the non-LTE state, the temperature retrieval method based on the Einstein coefficients is proposed to retrieve atmospheric temperature in the 92-140 km height range using the airglow radiation intensity images obtained from the Michelson Interferometer for global high-resolution thermospheric imaging (MIGHTI) measurements. Results show that the temperature deviation of the two-channel combinations does not exceed 15 K in the altitude range of 92-120 km. This deviation increases up to 45 K when the altitude is in the range of 120-140 km due to the influence of the N2 airglow spectrum. The two-channel combinations self-consistency is increased by 85 K compared with the temperature obtained using the spectral line intensity retrieval. Additionally, the comparison of the retrieval results with the spectral line intensity method and the comparison with the atmospheric chemistry experiment Fourier transform spectrometer (ACE-FTS) temperature measurement data shows that the Einstein coefficient method is significantly more rational and accurate than the spectral line intensity method.

Functional connectivity of the language area in migraine: a preliminary classification model.

BACKGROUND: Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment. METHODS: Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI(rfMRI), and diffusion weighted scans were obtained from 31 patients with migraine, and 17 controls. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into diagnostic groups based on functional connectivity (FC) and derive networks and parcels contributing to the model. PageRank centrality analysis was also performed on the structural connectome to identify changes in hubness. RESULTS: Our model attained an area under the receiver operating characteristic curve (AUC-ROC) of 0.68, which rose to 0.86 following hyperparameter tuning. FC of the language network was most predictive of the model's classification, though patients with migraine also demonstrated differences in the accessory language, visual and medial temporal regions. Several analogous regions in the right hemisphere demonstrated changes in PageRank centrality, suggesting possible compensation. CONCLUSIONS: Although our small sample size demands caution, our preliminary findings demonstrate the utility of our method in providing a network-based perspective to diagnosis and treatment of migraine.

The correlation between triiodothyronine and the severity of liver fibrosis.

BACKGROUND: The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS: We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS: Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION: The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.

Dual nuclear magnetic resonance for probing intrinsic bone structure and a potential gut-bone axis in ovariectomized rats.

Currently, the existence of a gut-bone axis receives massive attention, and while sound premises and indirect proofs exist for the gut-bone axis concept, few studies have provided actual data linking the gut and bone physically. This study aimed to exploit the versatile nature of nuclear magnetic resonance (NMR) to link NMR relaxometry data on bone mineralization with NMR spectroscopic profiling of gut metabolites. For this purpose, sample material was obtained from a 6-week intervention study with ovariectomized (OVX) rats (n = 49) fed with seven different diets varying in calcium content (0.2-6.0 mg/kg) and prebiotic fiber content (0-5.0% w/w). This design ensured a span in (i) calcium available for bone mineralization and (ii) metabolic activity in the gut. After termination of the intervention, longitudinal (T1 ), transverse (T2 ) relaxation, and mechanical bone strength were measured on the excised femur bones. A PLS model with high predictability (Q2 = 0.86, R2 = 0.997) was demonstrated between T2 decay curves and femur mechanical strength. Correlations were established between bone T2 populations and gut short-chain fatty acids. In conclusion, the present dual NMR approach showed strong correlation between T2 relaxation and mechanical strength of the bone, and when metabolic activity in the gut was modulated by inulin, the potential existence of a gut-bone axis was demonstrated.

Cathepsin L Contributes to Reproductive Diapause by Regulating Lipid Storage and Survival of Coccinella septempunctata (Linnaeus).

Cathepsin L protease, which belongs to the papain-like cysteine proteases family, is an important player in many physiological and pathological processes. However, little was known about the role of cathepsin L in ladybird beetles (Coccinella septempuctata Linnaeus) during diapause. Here, we analyzed the characteristics of cathepsin L (CsCatL) in the females of C. septempunctata and its role during the diapause of the ladybeetle. CsCatL was cloned and identified from beetle specimens by rapid amplification of cDNA-ends (RACE). The cDNA sequence of CsCatL was 971 bp in length, including an 843 bp open reading frame encoding a protein of 280 amino acids. It was identified as the cathepsin L group by phylogenetic analysis. Knockdown of CsCatL by RNA interference led to decreased expression levels of fatty acid synthase 2 (fas 2) genes and suppressed lipid accumulation. Furthermore, silencing the CsCatL gene distinctly reduced diapause-related features and the survival of female C. spetempunctata under diapause-inducing conditions. The results suggested that the CsCatL gene was involved in fatty acid biosynthesis and played a crucial role in the survival of adult C. septempunctata during the diapause preparation stage.

Highly Stretchable Composite Foams via Sustainable Utilization of Waste Tire Rubbers for Temperature-Dependent Electromagnetic Wave Absorption.

Recently, the sustainable utilization of waste resources has become a low-cost and effective strategy to design high-performance functional materials to solve the increasingly serious environmental pollution problem. Herein, the flexible and highly stretchable polyurethane (PU) composite foams assisted by one-dimensional carbon nanotubes (CNTs) and zero-dimensional Fe3O4 were fabricated using waste tire rubbers (WTRs) as reinforcements during a simple self-foaming process. The collaborative introduction of conductive CNTs, magnetic Fe3O4, and WTRs with three-dimensional cross-linked structures enabled the construction of an efficient electronic transmission path and heterointerfaces inside the composite foam. The resulting composite foam possessed a desired minimum reflection loss (RLmin) of −47.43 dB, and also exhibited superior mechanical properties with a tensile strength of >3 MPa and multiple tensile deformation recovery abilities. In addition, increasing the temperature could significantly improve the electromagnetic wave absorption performance of the composite foam. This comprehensive composite foam derived from WTRs has shown a promising development potential for using waste materials to relieve electromagnetic pollution.

Environment-friendly Cu-based thin film solar cells: materials, devices and charge carrier dynamics.

Cu-based thin films are ideal absorbing layer materials for new-generation thin-film solar cells, which have many advantages, such as environment-friendly components, abundant raw materials, low cost, simple manufacturing process, strong anti-interference, radiation resistance, high light absorption coefficient and suitable band gap. Copper indium gallium selenide (CIGS) thin-film solar cells, which have the highest photoelectric conversion efficiency (23.35%) among the various Cu-based materials, have been intensively investigated and exploited. To promote the progress of Cu-based thin-film solar cells, the rational design of efficient materials and devices and the in-depth understanding of their photophysical mechanisms are not only urgently required, but also have plenty of room for research. Accordingly, herein, we firstly define the concept of "Cu-based materials", and further present a comprehensive review on the materials (design and fabrication), devices (assembly and performances), and charge carrier dynamics of Cu-based thin-film semiconductor materials, including perovskites, oxides, chalcogenides (binary, ternary, quaternary and quinary) and perovskite-like iodides. In addition, the current challenges and prospects in this topic are critically concluded. Particularly, this review may help researchers focused on investigating thin-film solar cells.

Associations between CD160 polymorphisms and autoimmune thyroid disease: a case-control study.

BACKGROUND: Recent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD. METHODS: A total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. RESULTS: There was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66-0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64-0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65-0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63-0.93, P = 0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR = 0.84, 95%CI 0.71-0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60-0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58-0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis. CONCLUSION: This is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.

Using real-world data to estimate the changing trends in the prevalence and incidence of type 2 diabetes mellitus in Xiamen of China from 2014 to 2019.

BACKGROUND: The prevalence of diabetes is increasing worldwide. Our study aimed to estimate the changing trends in the prevalence and incidence of diagnosed type 2 diabetes mellitus (T2DM) among Xiamen residents and the floating population using real-world data. METHOD: We used real-world data from the System of Xiamen Citizens Health Information from 2014 to 2019 to estimate the changing trends in the prevalence and incidence of diagnosed T2DM. The System included the diagnosis of diabetes and the prescription of hypoglycemic drugs. Prevalent cases of T2DM were individuals who were diagnosed with T2DM and/or using hypoglycemic drugs. Incident cases were individuals with diagnosed T2DM and/or using hypoglycemic drugs in 2014 or 2019 who had not been diagnosed and/or did not use hypoglycemic drugs in the past. RESULTS: In 2014 and 2019, the prevalence of T2DM in Xiamen was 4.04 and 4.84%, respectively. In 2014 and 2019, the incidence rate of T2DM in Xiamen was 14.1 per 1000 person-year and 15.0 per 1000 person-year, respectively. There was a significant increase in both the prevalence (Prevalence difference: 0.80, 95%CI 0.76-0.83%, P < 0.001) and the incidence of T2DM (Incidence difference: 0.9, 95%CI 0.7-1.1, P < 0.001). in Xiamen. The prevalence and incidence of T2DM in people aged 18-39 increased significantly (P < 0.001), while the prevalence and incidence of T2DM in people aged 40-69 reduced significantly (P < 0.001). CONCLUSIONS: There was a significant increase in the prevalence and incidence of T2DM in Xiamen from 2014 to 2019 especially among those with younger age.