Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization

Background Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. Methods A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. Results The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47–2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74–36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85–2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19–1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34–1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204–3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001–1.009, p = 0.014). Conclusions Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention

Water-Soluble and Clickable Segmented Hyperbranched Polymers for Multifunctionalization and Novel Architecture Construction

A series of novel and narrowly polydispersed regular chain-segmented hyperbranched poly­(tertiary amino methacrylate)­s (HPTAM)­s with hydrophilic core and hydrophobic shell were synthesized via the combination of self-condensing vinyl copolymerization (SCVCP) and reversible addition–fragmentation chain transfer (RAFT) methodology. 2-(Dimethylamino)­ethyl methacrylate (DMAEMA) and 2-((2-(((dodecylthio)­carbonothioyl)­thio)-2-methylpropanoyl)­oxy)­ethyl acrylate (ACDT) at various molar feed ratios (γ, [DMAEMA]:[ACDT]) were chosen as monomers for linear segment formation of the structure. The copolymerization kinetics revealed that during the polymerization the real-time γ value kept almost constant and was consistent with the initial feed ratio. So HPTAMs possesses regular linear chains between every two neighboring branching units, which closely resemble HyperMacs in structure. Fast click-like Menschutkin reaction (i.e., quaternarization) of the segmented hyperbranched polymers with propargyl bromide and 2-azidoethyl 2-bromoacetate readily afforded water-soluble and clickable poly­(propargyl quaternary ammonium methacrylate) (HPPrAM) and poly­(azide quaternary ammonium methacrylate) (HPAzAM), respectively. Through Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAC), the HPPrAMs were functionalized with 1-azidododecane and 2-azidoethyl 2-bromoisobutyrate, giving birth to amphiphilic hyperbranched polyelectrolytes (or hyperbranched surfactants) and hyperbranched ATRP macroinitiators, respectively. The HPAzAMs were efficiently decorated with monoalkynyl poly­(ethylene glycol) (PEG-Alk) via CuAAC, generating dendritic polymer brushes, a novel architecture reported for the first time. In addition, core-functionazlied star-shaped HPPrAM-<i>star-</i>poly­(<i>tert-</i>butyl acrylate) was synthesized by RAFT copolymerization and Menschutkin reaction

Water soluble octa-functionalized POSS: all-click chemistry synthesis and efficient host guest encapsulation

A series of water soluble octa-functionalized POSSs were facilely synthesized via thiol-ene and Menschutkin click chemistry. Among them, octa-alkynyl POSS further reacted with azide-terminal alkyl long chains, resulting in a well-defined, amphiphilic octopus-like POSS. For the first time it was used for host-guest encapsulation and it exhibited an ultrahigh loading capability

Effects of Genetic Variation of the Sorting Nexin 29 (<i>SNX29</i>) Gene on Growth Traits of Xiangdong Black Goat

Previous studies have found that the copy number variation (CNV) and insertion/deletion (indels) located in the sorting nexin 29 (SNX29) gene, which is an important candidate gene related to meat production and quality, are associated with growth traits of African goats and Shaanbei white cashmere goats. However, the genetic effects of SNX29 genetic variation on growth traits of Xiangdong black (XDB) goat (a representative meat goat breed in China) are still unclear. The purpose of this study was to detect the mRNA expression level of SNX29 and to explore the genetic effects of CNV and indel within SNX29 on growth traits and gene expression in XDB goat. The SNX29 mRNA expression profile showed that the SNX29 was highly expressed in adipose tissues, indicating that the SNX29 gene could play a key role in subcutaneous adipose deposition of XDB goat. 17 bp indel (g.10559298-10559314), 21 bp indel (g.10918982-10919002) and CNV were detected in 516 individuals of XDB goat by PCR or qPCR. The association analysis of SNX29 CNV with growth traits in XDB goats showed that SNX29 CNV was significantly correlated with chest circumference and abdominal circumference (p SNX29 CNV goat individuals were more advantageous. For the mRNA expression of SNX29 gene, individuals with SNX29 copy number normal type had a higher trend than that of SNX29 gene with copy number gain type in longissimus dorsi muscle (p = 0.07), whereas individuals with SNX29 copy number gain type had a higher trend in abdominal adipose (p = 0.09). Overall, these results suggested that the SNX29 gene could play an important role in growth and development of XDB goats and could be used for marker-assisted selection (MAS) in XDB goats

Inositol 1,4,5-trisphosphate receptor type 2 is associated with the bone–vessel axis in chronic kidney disease–mineral bone disorder

AbstractObjective: The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone–vessel axis in chronic kidney disease–mineral bone disorder (CKD–MBD). However, the mechanism of the bone–vessel axis in CKD–MBD remains unclear.Methods: We established a CKD–MBD rat model to observe the pathophysiological phenotype of the bone–vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone–vessel axis in CKD–MBD.Results: The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD–MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD–MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD–MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD–MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD–MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion: These findings provide preliminary insights into the role of ITPR2 in the bone–vessel axis in CKD–MBD. Thus, ITPR2 may be a potential target of the bone–vessel axis in CKD–MBD