Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications

A Simple Temporal Information Matching Mechanism for Entity Alignment Between Temporal Knowledge Graphs

Entity alignment (EA) aims to find entities in different knowledge graphs (KGs) that refer to the same object in the real world. Recent studies incorporate temporal information to augment the representations of KGs. The existing methods for EA between temporal KGs (TKGs) utilize a time-aware attention mechanism to incorporate relational and temporal information into entity embeddings. The approaches outperform the previous methods by using temporal information. However, we believe that it is not necessary to learn the embeddings of temporal information in KGs since most TKGs have uniform temporal representations. Therefore, we propose a simple graph neural network (GNN) model combined with a temporal information matching mechanism, which achieves better performance with less time and fewer parameters. Furthermore, since alignment seeds are difficult to label in real-world applications, we also propose a method to generate unsupervised alignment seeds via the temporal information of TKG. Extensive experiments on public datasets indicate that our supervised method significantly outperforms the previous methods and the unsupervised one has competitive performance.Comment: Accepted by COLING 202

Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized Caenorhabditis elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. We find that amino termini of human TMEM131 contain bacterial PapD chaperone-like domains, which recruit premature collagen monomers for proper assembly and secretion. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila, and humans

Hazard and vulnerability in urban inundated underground space: Hydrodynamic analysis of human instability for stairway evacuation

Underground flooding events are being exacerbated due to the rapid expanding of underground space in urban and the extreme precipitation events by climate change. It is increasingly necessary to study hydrodynamics and instabilities of human on staircases in the flood-prone underground space for risk identification and disaster reduction. However, the turbulent complexity and complicated fluid-human interaction still challenge the study of flow structure and the calibration of human instability model. In this work, a hydrodynamic model coupled with the mechanics-based method was proposed to study fluid-human interactions and hazard risks on flooding stairways. Numerical validations show that the model can obtain reliable solutions of flow characteristics on staircases. It is found that there exists a jet flow downstream the rest platform and the critical region after the 3rd step downstream the platform is identified as a high risk area to cause sliding instability. The risk of sliding instability for a child is higher than that for an adult in jet flow region. In addition, results show that the downstream vortical flow structure and turbulent effect are obviously enhanced because of the interdict of jet flow by the human obstacle

Prenatal exposure and transplacental transfer of perfluoroalkyl substance isomers in participants from the upper and lower reaches of the Yangtze River

Data on gestational exposure characteristics and transplacental transfer are quite limited for perfluoroalkyl substance (PFAS) isomers, especially those from large-scale comparative studies. To fill this gap, we examined isomers of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) in matched maternal and cord serum from Mianyang and Hangzhou, which are located in the upper and lower reaches of the Yangtze River, China, respectively. These data were compared with those from our previous study on Wuhan in the middle reach. The average ΣPFAS concentration increased from upstream to downstream (Mianyang (4.44 ng/mL) < Wuhan (9.88 ng/mL) < Hangzhou (19.72 ng/mL)) and may be related to the per capita consumption expenditure of each city. The ln-transformed PFAS concentrations showed significant differences between Mianyang and Hangzhou after adjusting confounding factors (p < 0.05). The percentages of linear PFOS and PFOA in maternal and cord serum from these cities all exceeded those in electrochemical fluorination products. The isomer profiles of PFASs in maternal and cord serum might be greatly influenced by local production processes of PFASs and residents’ dietary habits. The transplacental transfer efficiencies decreased significantly with increasing concentrations in maternal serum for ΣPFAS, ΣPFOS, ΣPFOA, ΣPFHxS, n-PFOS, iso-PFOS, 4m-PFOS, 1m-PFOS, n-PFOA, n-PFHxS, and br-PFHxS (Spearman rank correlation coefficients (r) = 0.373–0.687, p < 0.01). These findings support an understanding of the regional characteristics in maternal exposure to PFASs along the Yangtze River, isomeric profiles of PFASs in these regions, and the transplacental transfer processes of PFAS isomers

Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protects dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF's cytoprotection

A Significantly High Abundance of “Candidatus Liberibacter asiaticus” in Citrus Fruit Pith: in planta Transcriptome and Anatomical Analyses

Huanglongbing, a highly destructive disease of citrus, is associated with the non-culturable phloem-limited α-proteobacterium “Candidatus Liberibacter asiaticus” (CLas). The distribution patterns of CLas in infected plant are variable and not consistent, which make the CLas detection and characterization more challenging. Here, we performed a systemic analysis of CLas distribution in citrus branches and fruits of 14 cultivars. A significantly high concentration of CLas was detected in fruit pith (dorsal vascular bundle) of 14 citrus cultivars collected at fruit maturity season. A 2-year monitoring assay of CLas population in citrus branches of “Shatangju” mandarin (Citrus reticulata Blanco “Shatangju”) revealed that CLas population already exhibited a high level even before the appearance of visual symptoms in the fruit rind. Quantitative analyses of CLas in serial 1.5-cm segments of fruit piths showed the CLas was unevenly distributed within fruit pith and tended to colonize in the middle or distal (stylar end) regions of pith. The use of CLas-abundant fruit pith for dual RNA-seq generated higher-resolution CLas transcriptome data compared with the leaf samples. CLas genes involved in transport system, flagellar assembly, lipopolysaccharide biosynthesis, virulence, stress response, and cell surface structure, as well as host genes involved in biosynthesis of antimicrobial-associated secondary metabolites, was up-regulated in leaf midribs compared with fruit pith. In addition, CLas infection caused the severe collapse in phloem and callose deposition in the plasmodesmata of fruit pith. The ability of fruit pith to support multiplication of CLas to high levels makes it an ideal host tissue for morphological studies and in planta transcriptome analyses of CLas–host interactions

Repetitive transcranial magnetic stimulation for treatment of limb spasticity following multiple sclerosis: a systematic review and meta-analysis

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials