Cross-species scRNA-seq reveals the cellular landscape of retina and early alterations in type 2 diabetes mice.

Single-cell RNA sequencing (scRNA-seq) analysis have provided an unprecedented resolution for the studies on diabetic retinopathy (DR). However, the early changes in the retina in diabetes remain unclear. A total of 8 human and mouse scRNA-seq datasets, containing 276,402 cells were analyzed individually to comprehensively delineate the retinal cell atlas. The neural retinas were isolated from the type 2 diabetes (T2D) and control mice, and scRNA-seq analysis was conducted to evaluate the early effects of diabetes on the retina. Bipolar cell (BC) heterogeneity were identified. We found some stable BCs across multiple datasets, and explored their biological functions. A new RBC subtype (Car8_RBC) in the mouse retina was validated using the multi-color immunohistochemistry. AC149090.1 was significantly upregulated in the rod cells, ON cone BCs (CBCs), OFF CBCs, and RBCs in T2D mice. Additionally, the interneurons, especially BCs, were the most vulnerable cells to diabetes by integrating scRNA-seq and genome-wide association studies (GWAS) analyses. In conclusion, this study delineated a cross-species retinal cell atlas and uncovered the early pathological alterations in the retina of T2D mice.

Efficacy of anti-osteoporosis treatment for men with osteoporosis: a meta-analysis.

INTRODUCTION: Osteoporosis and fracture are important healthcare problems for men worldwide, which are relevant to severe disability and mortality. This meta-analysis aimed to assess the effectiveness of pharmacological therapy in men with osteoporosis, and to provide evidence-based hints for clinical practice. MATERIALS AND METHODS: PubMed, Embase, Web of Science were searched from inception to July 31, 2022. Pooled standardized mean difference (SMD) and relative risk (RR) were calculated. Heterogeneity between included studies and publication bias were detected. RESULTS: Twenty clinical studies were enrolled in this meta-analysis. The pooled SMD for mean percentage differences of change from baseline in lumbar spine BMD between the treatment group and the control group was 4.95 (95% CI 2.48, 7.42, I2 = 99%, p < 0.0001). For mean percentage differences of change in femoral neck BMD, the overall SMD was 3.08 (95% CI 0.95, 5.20, I2 = 99%, p = 0.0045). For a change in total hip BMD, the overall SMD was 1.06 (95% CI 0.50, 1.63, I2 = 82%, p = 0.0002). The overall RR for incident vertebral fractures was 0.50 (95% CI 0.37, 0.68, I2 = 5%, p = 0.3971). The pooled RR for nonvertebral fractures and clinical fracture were 0.74 (95% CI 0.41, 1.33, I2 = 28%, p = 0.3139) and 0.81 (95% CI 0.54, 1.21, I2 = 0%, p = 0.2992). CONCLUSION: Findings in this meta-analysis indicate that pharmacological treatment increases lumbar spine, femoral neck, total hip BMD, and decreases incident vertebral fractures in men with osteoporosis.

Effects of calorie intake and sampling time on thyroid stimulating hormone concentration.

BACKGROUND: This study aimed to investigate the effects of blood sampling after calorie intake on thyroid stimulating hormone (TSH) level, compared with blood sampling in fasting state. METHODS: This was a prospective, randomized, controlled study. Subjects from the outpatients in the department of endocrinology without evidence of thyroid diseases were included and then randomized into the fasting group, diet intake group, and glucose intake group, respectively. Fasting blood was collected from all subjects at 7:00 am for the measurement of TSH and free thyroxine (FT4) concentrations. Afterwards, the subjects were maintained at fasting state (fasting group), had an intake of the mixed diet with 400 kcal calories (diet intake group), and had an intake of 75 g glucose (glucose intake group), respectively, and blood was collected again 2 h later (9:00 am on the same day) for TSH and FT4 level measurement and comparison. RESULTS: A total of 150 subjects were enrolled, of whom 146 met the inclusion criteria, with 48, 48, and 50 in the diet intake group, glucose intake group, and fasting group, respectively. The TSH in the diet intake group was significantly lower at 9:00 am (TSH9am) than the level at 7:00 am (TSH7am) (P < 0.001), with a median variation of -0.71 mU/L, and a median variation rate of -32.4%. In the glucose intake group, TSH9am was also significantly lower than TSH7am (P < 0.001), with a median variation of -0.73 mU/L, and a median variation rate of -31.5%. For the fasting group, TSH9am decreased slightly but was significantly lower than TSH7am (P < 0.001), with a median variation of -0.1 mU/L, and a median variation rate of -5.2%. According to TSH7am measurements, 9 subjects (3 subjects in each group) met the diagnostic criteria of subclinical hypothyroidism. However, according toTSH9am measurements, only 2 patients in the fasting group met the diagnostic criteria of subclinical hypothyroidism. CONCLUSION: Compared with the fasting state, the TSH level at 2 h after the calorie intake was decreased by about 30%, which might influence the diagnosis of subclinical hypothyroidism. TRIAL REGISTRATION: ChiCTR2100047454 (18/06/2021).

Analytical and clinical evaluation of the light-initiated chemiluminescent assays for measurement of human thyroid hormones.

BACKGROUND: Light-initiated chemiluminescent assay (LiCA) is a new homogeneous immunoassay. The aim of this study was to evaluate the analytical and clinical performance of the assays for the detection of thyroid hormones based on the fully automated LiCA 800 analyzer. METHODS: Analytical validations of the LiCA thyroid assays (TSH, FT3, FT4, T3, and T4) included precision, linearity, analytical sensitivity, interference, and method comparison applying the protocols of the Clinical and Laboratory Standards Institute (CLSI). The diagnostic performance was assessed by the receiver operating characteristic (ROC) curve analysis with different assay schemes for the diagnosis of hyperthyroidism and hypothyroidism. RESULTS: Within-run and within-lab precisions (%CV) of the five assays ranged from 1.06 to 6.40% at all concentrations evaluated. A satisfactory linearity was verified over the entire measuring range for TSH, T3, and T4 (R > 0.99, change in recovery <10%, p = 0.000 all). Paired-comparison measurements presented a comparable assay for each of the five assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. The diagnostic accuracy of the LiCA assays for hyperthyroidism or hypothyroidism was quantified by the areas under curves (AUC) as 0.925 or 0.832 with the five-assay panel (TSH, FT3, FT4, T3, and T4) and as 0.921 or 0.811 with the three-assay panel (TSH, FT3, and FT4), respectively. No significant difference was found between the AUC of LiCA and that of DxI, Cobas, or Centaur (p > 0.3 all). CONCLUSION: LiCA 800 provides a precise and high-throughput immunoassay platform for detection of thyroid hormones. It is acceptable for clinical use.

Vertical Graphene Growth on SiO Microparticles for Stable Lithium Ion Battery Anodes.

Silicon-based materials are considered as strong candidates to next-generation lithium ion battery anodes because of their ultrahigh specific capacities. However, the pulverization and delamination of electrochemical active materials originated from the huge volume expansion (>300%) of silicon during the lithiation process results in rapid capacity fade, especially in high mass loading electrodes. Here we demonstrate that direct chemical vapor deposition (CVD) growth of vertical graphene nanosheets on commercial SiO microparticles can provide a stable conducting network via interconnected vertical graphene encapsulation during lithiation, thus remarkably improving the cycling stability in high mass loading SiO anodes. The vertical graphene encapsulated SiO (d-SiO@vG) anode exhibits a high capacity of 1600 mA h/g and a retention up to 93% after 100 cycles at a high areal mass loading of 1.5 mg/cm2. Furthermore, 5 wt % d-SiO@vG as additives increased the energy density of traditional graphite/NCA 18650 cell by ∼15%. We believe that the results strongly imply the important role of CVD-grown vertical graphene encapsulation in promoting the commercial application of silicon-based anodes.

Scalable Seashell-Based Chemical Vapor Deposition Growth of Three-Dimensional Graphene Foams for Oil-Water Separation.

A seashell-based CVD technique for preparing three-dimensional (3D) graphene foams is reported. The graphene sheets in thus-obtained foams are seamlessly interconnected into a 3D flexible network, forming highly porous materials with negligible non-carbon impurities, ultralow density, and outstanding mechanical flexibility and electrical conductivity. These 3D graphene foams demonstrate a fast adsorption performance toward various oils and organic solvents, with adsorption capacity up to 250-fold weight gain. The present approach offers a practical route for scalable construction of 3D graphene foams for versatile applications such as energy storage and water remediation.

[Establishment of reference ranges for thyroid-related indicators in normal pregnant women].

OBJECTIVE: To establish the gestational age-specific reference ranges for thyroid-related indicators of pregnant women in our hospital, especially for serum thyroid stimulating hormone (TSH) in the first trimester. METHODS: A total of 548 pregnant women in the first trimester were collected in Peking University First Hospital from June 2013 to April 2014. Among them, 254 pregnant women with single fetus who conformed to the National Academy of Clinical Biochemistry criteria, without adverse pregnancy outcomes and obstetric complications, were enrolled in the current study. To establish their own self-sequential longitudinal reference intervals, serum TSH, total thyroxine (TT4) and free thyroxine (FT4) levels were measured using Siemens detection kits during three different trimesters. Urine iodine (UI) was measured using digestion instrument in some of the pregnant women. RESULTS: The gestational age-specific reference ranges for thyroid-related indicators of pregnant women in our hospital were as follows: in the first trimester: TSH 0.23-4.08 mU/L, TT4 92.59-186.25 nmol/L, FT4 13.36-20.81 pmol/L; in the second trimester: TSH 0.78-4.25 mU/L, TT4 103.20-180.95 nmol/L, FT4 11.57-16.62 pmol/L; in the third trimester: TSH 0.65-4.52 mU/L, TT4 78.20-174.70 nmol/L, FT4 10.01-20.57 pmol/L. The median level of TSH during 7 to 12 weeks of gestational age was lower than that of 4 to 6 weeks, but with no significant statistical difference (P=0.063). The medians of UI during three trimesters of pregnancy were 211.60 µg/L, 195.55 µg/L and 198.65 µg/L, respectively, which were all classified as adequate iodine status. CONCLUSIONS: The gestational age-specific reference ranges for thyroid-related indicators are different from the kits' reference ranges, which are also different among the three trimesters. It may be more reasonable to establish different reference ranges for thyroid-related indicators at 4 to 6 weeks and 7 to 12 weeks in the first trimester separately.

The expression of Fcγ receptors in Hashimoto's thyroiditis.

The pathophysiological mechanism underlying Hashimoto's thyroiditis (HT) is still unclear. Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) are diagnostic hallmarks of HT. These IgG antibodies regulate the balance of immunologic tolerance and autoimmunity via Fcγ receptors (FcγRs). The aim of our study was to investigate the role of FcγRs in the pathogenesis of HT. The percentage of peripheral blood mononuclear cells (PBMCs) from HT patients bearing FcγRII was significantly lower than that seen in healthy donors, and the mean fluorescence intensity (MFI) value of FcγRII on PBMCs from HT patients was significantly higher. The percentage of PBMCs positive for FcγRIII also was significantly higher in HT patients, and the percentage of B cells bearing FcγRIIB in HT patients was significantly lower than that seen in healthy donors. Our study therefore provides evidence for FcγRs, especially FcγRIIB, being involved in the pathogenesis of HT.

[Distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease, Graves' disease plus Hashimoto's thyroiditis and Hashimoto's thyrotoxicosis].

OBJECTIVE: To evaluate the distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease (GD), Graves' disease plus Hashimoto's thyroiditis (GH) and Hashimoto's thyrotoxicosis. METHODS: Patients with GD (n = 33), GH (n = 31) or Hashimoto's thyrotoxicosis (n = 18) diagnosed by fine needle aspiration cytology at Department of Endocrinology of Peking University First Hospital, Beijing Haidian Hospital, China-Japan Friendship Hospital and Civil Aviation General Hospital during the period from January 2010 to May 2013 were enrolled. All of them had TgAb and TPOAb. The total serum IgG and IgG subclasses of TgAb and TPOAb were detected by antigen-specific enzyme-linked immunosorbent assay (ELISA). The prevalence and relative amount of IgG subclasses were calculated and compared among three groups. RESULTS: The levels of TRAb in GD group (21.80(7.53, 40) U/L) were significantly higher than those in GH (7.30(3.10, 25.40) U/L) (P = 0.000) and Hashimoto's thyrotoxicosis groups (4.90(1.69, 16.43) U/L) (P = 0.003). And no significant differences were found in the levels of TgAb and TPOAb. The prevalence of TgAb IgG3 subclass in Hashimoto's thyrotoxicosis group (66.7%) was higher than GD group (35.5%) and GH group (36.4%) and the difference was close to significance (P = 0.066). There were significant differences of relative amount of TgAb IgG2 and TgAb IgG4 among three groups (P = 0.039 and 0.013), and GD patients had higher relative amounts of TgAb IgG2 (0.59(0.34, 0.94)) and TgAb IgG4 (0.57(0.28, 0.97)) than GH patients (TgAb IgG2, 0.31(0.23, 0.34); TgAb IgG4, 0.26(0.09, 0.48)) or patients with Hashimoto's thyrotoxicosis (TgAb IgG2, 0.32(0.24, 0.83); TgAb IgG4, 0.33(0.10, 0.65)) (for TgAb IgG2, P = 0.009 and 0.167; for TgAb IgG4, P = 0.005 and 0.041 respectively). No significant difference was found in the prevalence of each TPOAb IgG subclass. The difference of relative amount of TPOAb IgG2 among three groups was close to significance (P = 0.069). And the relative amount was higher in sera from GD patients (0.39 ± 0.04) than that in GH patients (0.29 ± 0.13) or patients with Hashimoto's thyrotoxicosis (0.26 ± 0.02) (P = 0.104 and 0.002 respectively). CONCLUSION: The patients with high levels of TgAb IgG2, TgAb IgG4 and TPOAb IgG2 subclasses have a greater risk of GD. The IgG subclass distribution of TgAb and TPOAb might help to differentiate the causes of thyrotoxicosis in autoimmune thyroid diseases.

Consistency Between Thyrotropin Receptor Antibody (TRAb) and Thyroid-Stimulating Antibody (TSAb) Levels in Patients with Graves Disease.

OBJECTIVE: To investigate the consistency between thyrotropin receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) levels in patients with Graves disease (GD). METHODS: We performed a cross-sectional observational study to recruit eligible patients with GD who visited the outpatient endocrinology clinic for the purpose of evaluating the consistency between their TRAb and TSAb levels. Our cohort included 28 men and 99 women. RESULTS: The median levels of TRAb and TSAb were 5.65 IU/L and 3.76 IU/L, respectively, in the enrolled patients with GD. The levels of TRAb (5.03 vs 8.42 IU/L; P = .008) and TSAb (2.69 vs 5.37 IU/L; P = .008) in patients with adequate thyroid regulation were all lower than those in patients with inadequate thyroid regulation. CONCLUSIONS: Although TRAb is closely related to TSAb, we observed high heterogeneity of TRAb due to relatively low consistency between the levels of the 2 antibodies.

Single-cell RNA-seq transcriptomic landscape of human and mouse islets and pathological alterations of diabetes.

Single-cell RNA sequencing has paved the way for delineating the pancreatic islet cell atlas and identifying hallmarks of diabetes. However, pathological alterations of type 2 diabetes (T2D) remain unclear. We isolated pancreatic islets from control and T2D mice for single-cell RNA sequencing (scRNA-seq) and retrieved multiple datasets from the open databases. The complete islet cell landscape and robust marker genes and transcription factors of each endocrine cell type were identified. GLRA1 was restricted to beta cells, and beta cells exhibited obvious heterogeneity. The beta subcluster in the T2D mice remarkably decreased the expression of Slc2a2, G6pc2, Mafa, Nkx6-1, Pdx1, and Ucn3 and had higher unfolded protein response (UPR) scores than in the control mice. Moreover, we developed a Web-based interactive tool, creating new opportunities for the data mining of pancreatic islet scRNA-seq datasets. In conclusion, our work provides a valuable resource for a deeper understanding of the pathological mechanism underlying diabetes.

Analytical validation of the LiCA® high-sensitivity human thyroid stimulating hormone assay.

BACKGROUND: We aimed to assess the analytical characteristics of a new high-sensitivity human thyroid stimulating hormone (hTSH) assay on a light-initiated chemiluminescent immunoassay system (LiCA Smart) and examine the utility of this assay in the context of profoundly low TSH levels (<0.01 mIU/L). METHODS: Analytical validations included precision, linearity, reportable range, analytical sensitivity, interference, reagent lot-to-lot and between-instrument variability, and method comparisons. Additionally, a cross-sectional study was performed to evaluate the assay for the detection of profoundly low TSH levels in comparison to those of two other ultrasensitive hTSH assays. RESULTS: Within-run and within-lab imprecisions (%CV) were < 5% at all concentrations studied. A satisfactory linearity (R = 0.998, change in recovery < 5%) was verified over the entire measuring range. Method comparisons demonstrated a reasonable agreement (R > 0.99, median bias < 5%) between LiCA and Cobas, ADVIA, UniCel or Architect. The limit of quantitation was 0.0019 mIU/L. Comparative measurements of 236 patient samples with profoundly low TSH levels (<0.01 mIU/L) by LiCA, Cobas, and Architect revealed that the detection rate observed with LiCA (67.8%) was significantly higher than that with Cobas (28.0%) or Architect (21.7%). In a further comparative follow-up of patients with overt hyperthyroidism who were receiving treatment, an earlier recovery response of TSH was observed in LiCA. CONCLUSIONS: The LiCA Smart hTSH is a precise and highly sensitive fourth-generation assay. The assay demonstrated superior detection sensitivity for profoundly low TSH levels and was acceptable for clinical use.

Hydrogen Sulfide Promotes Thyroid Hormone Synthesis and Secretion by Upregulating Sirtuin-1.

Objective: One mechanism of hypothyroidism involves the disruption of thyroid hormone synthesis and secretion by thyrocytes. Hydrogen sulfide (H2S), as a gas signaling molecule, participates in many physiopathologic processes by upregulating sirtuin-1 (SIRT1). The aim of the current study was to explore whether H2S promotes the synthesis and secretion of thyroid hormones by upregulating SIRT1. Methods: Real-time PCR and immunohistochemistry were used to detect the mRNA and protein expression of H2S-generating enzymes in normal human thyroid tissues. Serum H2S concentrations from hypothyroid patients (n = 32) and euthyroid participants (n = 41) were detected by H2S-selective sensors. Thirty-one Sprague-Dawley rats were divided into control group (n = 10), hypothyroid group (induced by MMI, n = 10) and hypothyroid + NaHS group (n = 11), and the FT4, TT4 and TSH levels were assayed. Human primary thyrocytes were incubated with H2S donor sodium hydrosulfide (NaHS) or NaHS plus SIRT1 inhibitor (EX527) in vitro. Thyroid hormone synthesis- and secretion-related proteins [thyroid peroxidase (TPO), sodium iodide transporter (NIS), Pendrin, monocarboxylic acid transporter 8 (MCT8)] were analyzed by real-time PCR and Western blot. Results: H2S levels in serum from hypothyroid patients were decreased compared to those from euthyroid participants (p < .05), and serum H2S levels were positively correlated with FT3, FT4, TT3, and TT4 levels in all subjects (all p < .0001). In vivo, NaHS promoted thyroid function in hypothyroid rats (p < .05). In vitro, H2S was detected in supernatant, and CBS mRNA was higher than CSE and 3-MPST in human primary thyrocytes (p < .05). The protein levels of TPO, NIS, Pendrin and MCT8 were upregulated in a concentration-dependent manner for NaHS in thyrocytes. After blocking SIRT1 with EX527, we found that the increasing levels of TPO, NIS, Pendrin, and MCT8 and TPO activity were downregulated in thyrocytes incubated with NaHS, and FT4 levels in the cell supernatant were also decreased significantly (all p < .05). Conclusion: H2S is mainly generated in thyrocytes by CBS. Serum H2S levels are decreased with hypothyroidism. H2S promotes the synthesis and secretion of thyroid hormones and the expression of related molecules by upregulating SIRT1.

CD11c+ B Cells Participate in the Pathogenesis of Graves' Disease by Secreting Thyroid Autoantibodies and Cytokines.

Graves' disease (GD) is a common autoimmune disorder with an elevation in pathogenic autoantibodies, specifically anti-thyrotropin receptor antibodies (TRAbs), which are secreted by autoreactive B cells. To date, there has been little research on self-reactive B cells in GD. In the current study, we reported that a unique B-cell subset, CD11c+ B cells, was expanded in the peripheral blood (PB) of GD patients, as detected by flow cytometry. The frequency of CD11c+ B cells was positively correlated with serum TRAb levels. The flow cytometry data showed that CD11c expression was higher in a variety of B-cell subsets and that CD11c+ B cells presented a distinct immunophenotype compared to paired CD11c- B cells. Immunohistochemical and immunofluorescence staining indicated the presence of CD11c+CD19+ B cells in lymphocyte infiltration areas of the GD thyroid. Flow cytometric analysis of PB and fine-needle aspiration (FNA) samples showed that compared to PB CD11c+ B cells, CD11c+ B cells in the thyroid accumulated and further differentiated. We found that CD11c+ B cells from the PB of GD patients were induced to differentiate into autoreactive antibody-secreting cells (ASCs) capable of secreting TRAbs in vitro. Luminex liquid suspension chip detection data showed that CD11c+ B cells also secreted a variety of cytokines, including proinflammatory cytokines, anti-inflammatory cytokines, and chemokines, which might play roles in regulating the local inflammatory response and infiltration of lymphocytes in the thyroid. In addition, we performed a chemotaxis assay in a Transwell chamber to verify that CD11c+ B cells were recruited by thyroid follicular cells (TFCs) via the CXCR3-CXCL10 axis. In conclusion, our study determined that CD11c+ B cells were involved in the pathogenesis of GD in multiple ways and might represent a promising immunotherapeutic target in the future.

Rational Design of Effective Binders for LiFePO4 Cathodes.

Polymer binders are critical auxiliary additives to Li-ion batteries that provide adhesion and cohesion for electrodes to maintain conductive networks upon charge/discharge processes. Therefore, polymer binders become interconnected electrode structures affecting electrochemical performances, especially in LiFePO4 cathodes with one-dimensional Li+ channels. In this paper, recent improvements in the polymer binders used in the LiFePO4 cathodes of Li-ion batteries are reviewed in terms of structural design, synthetic methods, and working mechanisms. The polymer binders were classified into three types depending on their effects on the performances of LiFePO4 cathodes. The first consisted of PVDF and related composites, and the second relied on waterborne and conductive binders. Profound insights into the ability of binder structures to enhance cathode performance were discovered. Overcoming the bottleneck shortage originating from olivine structure LiFePO4 using efficient polymer structures is discussed. We forecast design principles for the polymer binders used in the high-performance LiFePO4 cathodes of Li-ion batteries. Finally, perspectives on the application of future binder designs for electrodes with poor conductivity are presented to provide possible design directions for chemical structures.

Glycosylation of Anti-Thyroglobulin IgG1 and IgG4 Subclasses in Thyroid Diseases.

OBJECTIVE: Thyroglobulin antibodies (TgAb), principally comprising immunoglobulin G (IgG), are frequently found in healthy individuals. Previously, we showed that the glycosylation levels of TgAb IgG differed across various thyroid diseases, suggesting an important role of glycosylation on antibodies in the pathogenesis of thyroid diseases. Since IgG1 and IgG4 are the primary TgAb IgG subclasses, this study aimed to investigate the glycosylation of TgAb IgG1 and IgG4 subclasses in thyroid diseases. METHODS: TgAb IgG was purified by affinity chromatography from the serum of patients with Hashimoto's thyroiditis (HT) (n = 16), Graves' disease (GD) (n = 8), papillary thyroid carcinoma (PTC) (n = 6), and PTC with histological lymphocytic thyroiditis (PTC-T) (n = 9) as well as healthy donors (n = 10). TgAb IgG1 and IgG4 concentrations were determined by enzyme-linked immunosorbent assay, and a lectin microassay was used to assess TgAb IgG1 and IgG4 glycosylation. RESULTS: Significantly elevated mannose, sialic acid, and galactose levels on TgAb IgG1 were found in HT and PTC patients compared to GD patients and healthy controls (all p < 0.05). The mannose, sialic acid, and core fucose levels on TgAb IgG1 in PTC-T patients were higher than in healthy controls (all p < 0.05). Additionally, TgAb IgG1 from PTC-T patients exhibited lower sialylation than that from patients with PTC and higher fucosylation than that from patients with HT (both p < 0.05). However, TgAb IgG4 glycosylation did not differ among the five groups (p < 0.05). CONCLUSION: Our study describes different distributions of TgAb IgG1 glycosylation in various thyroid diseases. The aberrantly increased glycosylation levels of TgAb IgG1 observed in HT, PTC, and PTC-T might be indicative of immune disorders and participate in the pathogenesis of these diseases.

Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.

Background: Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs). The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs. However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood. Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells. Methods: First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs). Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation. Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray. The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS). Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting. Results: We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns. Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05). The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of ß-1,4-galactosyltransferase 1. Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of ß-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A. Conclusion: Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.

The Impact of Thyroid Function and TPOAb in the First Trimester on Pregnancy Outcomes: A Retrospective Study in Peking.

CONTEXT: The impact of mild TSH elevation (2.5-4.08 mIU/L) on pregnancy outcomes is unclear. The treatment strategy for mild TSH elevation is dependent on thyroid peroxidase antibody (TPOAb) status according to the guidelines. OBJECTIVE: To assess the effects of mild thyroid dysfunction combined with TPOAb status in the first trimester on pregnancy outcomes and the impact of levothyroxine (L-T4) treatment on pregnancy outcomes. DESIGN: The study retrospectively evaluated 3562 pregnant women. A total of 3296 untreated women were divided into 4 subgroups: group A: 4.08 < TSH <10 mIU/L, TPOAb+/-; group B: 2.5 < TSH ≤ 4.08 mIU/L, TPOAb+; group C: 2.5 < TSH ≤ 4.08 mIU/L, TPOAb-; and group D: 0.23 ≤ TSH ≤ 2.5 mIU/L, TPOAb+/-. The other 266 women with L-T4 treatment were divided into TSH 4.08 to 10 mIU/L and 2.5 to 4.08 mIU/L subgroups. SETTING: The study was conducted at Peking University First Hospital in China. PATIENTS: A total of 3562 pregnant women were evaluated. MAIN OUTCOME MEASURES: The incidence of pregnancy outcomes in the untreated subgroups (groups A-D) and treated subgroups were measured. RESULTS: Miscarriage and maternal composite outcome risks were 3.53 (1.85-6.75) and 2.19 (1.26-3.81) times greater in group A; 1.58 (1.17-2.13) and 1.27 (1.04-1.54) times greater in group C than in group D. L-T4 improved the miscarriage risk in the TSH 4.08 to 10 and 2.5 to 4.08 mIU/L groups but doubled the risk of gestational diabetes mellitus in the TSH 2.5 to 4.08 mIU/L treated group compared with the untreated group. CONCLUSIONS: TSH 2.5 to 4.08 mIU/L combined with TPOAb- during early pregnancy was associated with miscarriages and maternal composite outcomes. The advantages and disadvantages of L-T4 administration in TSH 2.5 to 4.08 mIU/L pregnant women remain uncertain.

Thyroid function of twin-pregnant women in early pregnancy.

BACKGROUND: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies. METHODS: Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018; 160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies. RESULTS: First-trimester reference ranges (4-12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01-3.35) mIU/L and FT4 16.38 (12.45-23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P = 0.000) in twin pregnancies in the first trimester. CONCLUSIONS: Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Walnut-structure Si-G/C materials with high coulombic efficiency for long-life lithium ion batteries.

Nano-sized silicon is a potential high energy density anode material for lithium ion batteries. However, the practical use of a nano-Si anode is still challenging due to its low coulombic efficiency, poor scalability and cycling stability. Herein, a Si/graphite/carbon (Si-G/C) composite with a core-shell structure was fabricated by a facile two-step chemical process, stirring-evaporating followed by heat treatment. The composite structure consists of a graphite core, coated first by silicon and then amorphous carbon, which was decomposed by pitch. The as-prepared Si-G/C composite anode demonstrates a first cycle capacity of about 650 mA h g-1, over 90% coulombic efficiency, and high capacity retention of 96.7% after 50 cycles. When paired with a commercial NCA cathode, superior cycling stability with more than 81% capacity retention was achieved for 1200 cycles. These results demonstrate that such a core-shell Si-G/C composite is a promising anode material for high energy Li-ion batteries.