IgG glycosylation profile and the glycan score are associated with type 2 diabetes in independent Chinese populations: A case-control study

Background. The relationship between the IgG glycan panel and type 2 diabetes remains unclear in Chinese population. We aimed to investigate the association of the IgG glycan profile and glycan score with type 2 diabetes. Methods. In the discovery population, 162 individuals diagnosed with type 2 diabetes and 162 matched controls from Beijing health management cohort were included. We analyzed the IgG glycan profile and composed a glycan score for type 2 diabetes. Findings were validated in the replication population from Beijing Xuanwu community cohort (280 cases and 508 controls). Area under curve (AUC) using 10-fold and bootstrap validation, net reclassification index (NRI), and integrated discrimination index (IDI) were calculated for the glycan score. Results. In the discovery population, 5 initial IgG glycans and 7 derived traits were significantly associated with type 2 diabetes after Bonferroni correction and Lasso selection, which were validated in the replication population subsequently. The glycan score composed of these IgG glycans and traits showed a strong association with type 2 diabetes (combined odds ratio (OR): 3.78) and its risk factors. In the replication population, AUC of the model involving clinical traits improved from 0.74 to above 0.90, and the values of NRI and IDI were 0.35 and 0.42, respectively, with the glycan score added. Conclusions. IgG glycosylation profiles were associated with type 2 diabetes and the glycan score may be a novel indicator for diabetes which reflected a proinflammatory status

The cessation and detoxification effect of tea filters on cigarette smoke

To treat tobacco addiction, a tea filter was developed and studied for smoking cessation. This work reports the smoking cessation effect of tea when it was used as a component of cigarette filters. In one trial it was found that after using the tea filters for 2 months, the volunteer smokers decreased their cigarette consumption by 56.5%, and 31.7% of them stopped smoking. This work identified a new method and material, tea filter and theanine, which inhibit tobacco and nicotine addiction and provide an effective strategy for treating tobacco addiction

IgG Glycosylation Profile and the Glycan Score Are Associated with Type 2 Diabetes in Independent Chinese Populations: A Case-Control Study

Background. The relationship between the IgG glycan panel and type 2 diabetes remains unclear in Chinese population. We aimed to investigate the association of the IgG glycan profile and glycan score with type 2 diabetes. Methods. In the discovery population, 162 individuals diagnosed with type 2 diabetes and 162 matched controls from Beijing health management cohort were included. We analyzed the IgG glycan profile and composed a glycan score for type 2 diabetes. Findings were validated in the replication population from Beijing Xuanwu community cohort (280 cases and 508 controls). Area under curve (AUC) using 10-fold and bootstrap validation, net reclassification index (NRI), and integrated discrimination index (IDI) were calculated for the glycan score. Results. In the discovery population, 5 initial IgG glycans and 7 derived traits were significantly associated with type 2 diabetes after Bonferroni correction and Lasso selection, which were validated in the replication population subsequently. The glycan score composed of these IgG glycans and traits showed a strong association with type 2 diabetes (combined odds ratio (OR): 3.78) and its risk factors. In the replication population, AUC of the model involving clinical traits improved from 0.74 to above 0.90, and the values of NRI and IDI were 0.35 and 0.42, respectively, with the glycan score added. Conclusions. IgG glycosylation profiles were associated with type 2 diabetes and the glycan score may be a novel indicator for diabetes which reflected a proinflammatory status

MORC2B is essential for meiotic progression and fertility

<div><p>The microrchidia (MORC) family proteins are chromatin-remodelling factors and function in diverse biological processes such as DNA damage response and transposon silencing. Here, we report that mouse <i>Morc2b</i> encodes a functional germ cell-specific member of the MORC protein family. <i>Morc2b</i> arose specifically in the rodent lineage through retrotransposition of <i>Morc2a</i> during evolution. Inactivation of <i>Morc2b</i> leads to meiotic arrest and sterility in both sexes. <i>Morc2b</i>-deficient spermatocytes and oocytes exhibit failures in chromosomal synapsis, blockades in meiotic recombination, and increased apoptosis. Loss of MORC2B causes mis-regulated expression of meiosis-specific genes. Furthermore, we find that MORC2B interacts with MORC2A, its sequence paralogue. Our results demonstrate that <i>Morc2b</i>, a relatively recent gene, has evolved an essential role in meiosis and fertility.</p></div

Persistence of γH2AX in <i>Morc2b</i>^-/- spermatocytes.

<p>(A, B) Spread nuclei of spermatocytes from wild type (A) and <i>Morc2b</i>^-/- (B) males at PND25 were immunostained with anti-SYCP2 and anti-γH2AX antibodies. Representative images of wild type spermatocytes at the leptotene through diplotene stages are shown. In <i>Morc2b</i>^-/- males, zygotene-like spermatocytes formed lateral elements and contained a high level of γH2AX, whereas pachytene-like spermatocytes showed more prominent lateral elements, alignment of lateral elements, and a low level of γH2AX. (C) Percentage of spermatocytes at meiotic stages (leptotene through diplotene). The number of spermatocytes analysed: wild type, 460; <i>Morc2b</i>^-/-, 480. Scale bars, 10 μm.</p

MORC2B is essential for male meiosis.

<p>(A) Targeted inactivation of the <i>Morc2b</i> gene. Deletion of exon 2 removes the entire coding region and thus results in a null allele. The neomycin selection marker PGKNeo is flanked by loxP sites. HyTK provides negative selection by ganciclovir. (B) Dramatic reduction in testis size in 3-month-old <i>Morc2b</i>^-/- males. (C) Western blot analysis of postnatal day 20 (PND20) <i>Morc2b</i>^+/- and <i>Morc2b</i>^-/- testes. ACTB serves as a loading control. (D) Histological analysis of 8-week-old <i>Morc2b</i>^+/- and <i>Morc2b</i>^-/- testes. Abbreviations: Pa, pachytene spermatocytes; RS, round spermatids; ES, elongated spermatids. Scale bars, 25 μm. (E) TUNEL analysis of seminiferous tubules from the testes of 8-week-old wild-type and <i>Morc2b</i>^-/- males. TUNEL-positive cells are shown in green. DNA was counterstained with DAPI. Scale bars, 25 μm. The graph on the left shows quantification of TUNEL-positive cells. Only tubule cross-sections with at least one TUNEL-positive cell (3 wild type testes and 3 <i>Morc2b</i>^-/- testes) were analyzed. 18 to 24 tubules per testis were counted. Statistical analysis was performed with Student’s <i>t</i>-test.</p

<i>Morc2b</i> is a retrotransposed germ cell-specific derivative of <i>Morc2a</i>.

<p>(A) Gene structure of <i>Morc2a</i> and <i>Morc2b</i>. Coding regions are shown in black. Percent identities of nucleotide (nt) and amino acid (aa) sequences in the coding region are shown. 5’ and 3’ untranslated regions (UTRs) lack significant nt identity and are represented as open boxes. (B) Timing of the <i>Morc2b</i> retrotransposition. mya, million years ago. (C) Western blot analysis of MORC2A and MORC2B in lysates from adult mouse tissues. ACTB served as a loading control. (D, E) Expression and subcellular localization of MORC2B in adult testes. Immunofluorescence analysis of MORC2B was performed on frozen sections from wild type (D) and <i>Morc2b</i>^-/- (E) testes. DNA was stained with DAPI. Insets show enlarged view of boxed regions. Abbreviations: Pa, pachytene spermatocytes; Spc, spermatocytes; RS, round spermatids; ES, elongated spermatids; Sertoli, Sertoli cells. Scale bars, 25 μm. (F) RT-PCR expression analysis of <i>Morc2b</i> in juvenile testes. <i>Actb</i> serves as a control. (G) Quantification of <i>Morc2b</i> expression in juvenile testes by real-time PCR. The expression level of <i>Morc2b</i> was normalized to <i>Actb</i>. The relative expression level at postnatal day 20 was set at 1.0.</p

Transcript profiling analysis of wild type and <i>Morc2b</i>^-/- testes.

<p>(A) Volcano plot of transcript levels between wild type and <i>Morc2b</i>^-/- testes at postnatal day 12. The expression cut-off is at least 1 FPKM in either wild type or <i>Morc2b</i>^-/- testes. The differentially expressed genes (FDR < 0.05) are highlighted in red (upregulated in <i>Morc2b</i>^-/-) and green (downregulated in <i>Morc2b</i>^-/-). (B) Validation of differentially expressed genes by real-time PCR analysis. Statistics was performed with Student’s <i>t</i>-test: *, p<0.05; **, p<0.01; ***, p<0.001. (C) GO term enrichment in differentially expressed genes.</p

MORC2B is required for chromosomal synapsis in meiosis in both sexes.

<p>(A) Surface spread nuclei of spermatocytes from the testes of juvenile wild type and <i>Morc2b</i>^-/- males were immunostained for synaptonemal complex proteins (SYCP1 and SYCP2). The sex chromosomes in wild type pachytene spermatocyte (left) are labelled. Three paired chromosomes in <i>Morc2b</i>^-/- spermatocytes are indicated by arrowheads. (B) Surface spread nuclei of oocytes from wild type and <i>Morc2b</i>^-/- embryonic day 17.5 (E17.5) embryos were immunostained for SYCP1 and SYCP2. Note the apparent pairing and alignment of presumably homologous chromosomes judged by the equal length of SC axial elements in the <i>Morc2b-</i>deficient oocyte. (C) Surface spread nuclei of spermatocytes from wild type and <i>Morc2b</i>^-/- postnatal day 18 testes were immunostained for SYCP3 and HORMAD1. Arrows indicate synapsed regions. Scale bars, 10 μm.</p