Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response.

The innate RNA sensor RIG-I is critical in the initiation of antiviral type I interferons (IFNs) production upon recognition of "non-self" viral RNAs. Here, we identify a host-derived, IFN-inducible long noncoding RNA, lnc-Lsm3b, that can compete with viral RNAs in the binding of RIG-I monomers and feedback inactivate the RIG-I innate function at late stage of innate response. Mechanistically, binding of lnc-Lsm3b restricts RIG-I protein's conformational shift and prevents downstream signaling, thereby terminating type I IFNs production. Multivalent structural motifs and long-stem structure are critical features of lnc-Lsm3b for RIG-I binding and inhibition. These data reveal a non-canonical self-recognition mode in the regulation of immune response and demonstrate an important role of an inducible "self" lncRNA acting as a potent molecular decoy actively saturating RIG-I binding sites to restrict the duration of "non-self" RNA-induced innate immune response and maintaining immune homeostasis, with potential utility in inflammatory disease management.

Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA.

Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.

GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas.

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

TLR9 triggers MyD88-independent anti-inflammatory signaling in lupus.

Activation of Toll-like receptor 7 (TLR7) can induce lupus in mice, whereas activation of TLR9 can prevent it, even though both receptors interact with myeloid differentiation primary response gene 88 (MyD88) for downstream signaling. How TLR9 triggers anti-inflammatory responses in autoimmunity is unclear. Leibler et al. recently reported that TLR9 initiates anti-inflammatory signaling and inhibits lupus pathogenesis in a MyD88-independent but ligand-dependent manner.

Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

Associations between socioeconomic status and risk of obesity and overweight among Chinese children and adolescents.

BACKGROUND: In China, the threat of obesity and overweight in children and adolescents is developing quickly. It may be possible to lower the risk of obesity and overweight in children and adolescents by understanding the factors that drive these conditions. Therefore, this study aimed to investigate the association between SES and risk of obesity and overweight among children and adolesecnts in China's provinces of Jiangsu, Anhui, Zhejiang, and Shanghai. METHODS: Chinese children and adolescents (n = 2,746; 46.3% boys) were recruited using multistage sampling. SES was measured using self-reported questionnaires, the specific indicators were parental education, perceived family wealth, and Family Affluence Scale II. Height and weight were measured and used to calculate body mass index (BMI, categorized into obesity or overweight). The definition of obesity or overweight was based on the Chinese standard "Screening for obesity and overweight among school-age children and adolescents". Descriptive statistics, independent sample t-tests, and a Chi-square test were used to report the sample characteristics and analyse BMI differences across different sociodemographic groups. A binary logistic regression was then applied to analyse the association of SES indicators with BMI in children and adolescents. RESULTS: Overall, 22.5% of children and adolescents were obese or overweight. Participants with medium and high maternal education levels were 1.48 [95% CI 1.15-1.91] and 1.47 [95% CI 1.03-2.11] times more likely to be obese/overweight. Girls with medium maternal education levels were 1.70[95% CI 1.21-2.40] times more likely to be obese/overweight. For boys, no association was observed. Junior middle school students with medium maternal education levels were 1.51[95% CI 1.10-2.07] times more likely to be obese/overweight. Participants with medium or high FAS, perceived family wealth, or paternal education levels were not associated with obesity/overweight. CONCLUSIONS: The findings of this study indicated a positive association between SES and risk of overweight/obesity in girls, suggesting that maternal education level may have a substantial impact on future prevention efforts for these conditions in girls. To increase the effectiveness of interventions, longitudinal studies are necessary to better understand the causal association between SES and obesity/overweight.

Fertility intentions to have a second or third child under China's three-child policy: a national cross-sectional study.

STUDY QUESTION: What proportion of people want to have a second or third child after the enactment of the three-child policy in China? SUMMARY ANSWER: Under the three-child policy, fertility intention to have a second child was ∼60% (56% of women vs 65% of men), and fertility intention to have a third child was 13% (10% of women vs 17% of men) among the Chinese population. WHAT IS KNOWN ALREADY: The Chinese government announced the three-child policy on 31 May 2021, allowing all couples to have up to three children. At present, there is a lack of national surveys on the fertility intentions of women and men to have a second or third child under the three-child policy in China. STUDY DESIGN, SIZE, DURATION: In June 2021, a national cross-sectional survey including 9243 respondents aged 18-49 years was conducted online from 31 provinces in China's mainland using a random sampling method. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on the intention to have a second or third child were collected by anonymous questionnaire. Descriptive statistics were performed to assess fertility intentions. Multivariate and multinomial logistic regression analyses were used to assess the association between fertility intentions and the investigated factors. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately 60% (5493/9243) of the investigated people (55.6% women vs 64.7% men) intended to have a second child, and 13.0% (1203/9243) of them (10.0% women vs 17.1% men) intended to have a third child under China's three-child policy. For non-child respondents, 46.8% of women and 60.4% of men intended to have a second child. For one-child respondents, 47.8% of women and 53.8% of men intended to have a second child. For two-child respondents, 14.4% of women and 25.9% of men intended to have a third child. The mean desired family size was 1.58 children per woman, which was lower than the 1.76 children per man. Notably, the age-specified fertility intentions of men were always higher than those of women. Women with a college or higher degree (adjusted odds ratio [aOR] 0.60, 95% CI 0.42-0.88) and a high-middle (aOR 0.71, 95% CI 0.53-0.95) or high (aOR 0.64, 95% CI 0.48-0.85) household income, as well as men living in urban areas (aOR 0.71, 95% CI 0.58-0.87) and having a high-middle household income (aOR 0.68, 95% CI 0.52-0.90), were associated with a lower intention to have a third child (all P < 0.05). In contrast, men of public service personnel had a higher intention to have a third child than factory workers (aOR 1.44, 95% CI 1.02-2.04, P < 0.05). Meanwhile, approximately one out of five two-child respondents intended to have a third child, while one out of four two-girl respondents (aOR 2.09, 95% CI 1.44-3.04) were willing to have a third child with a strong preference for boys (12.7% for boys vs 2.7% for girls). Economic and childrearing barriers were the leading barriers to having one more child. LIMITATIONS, REASONS FOR CAUTION: The online survey might limit the representativeness of the present study's sample. A large sample size was enrolled and a random sampling method was used to increase the sample diversity and representativeness. WIDER IMPLICATIONS OF THE FINDINGS: This study will assist in estimating the impact on population demographic of the three-child policy in China. Multiple efforts are needed to create a fertility-friendly environment for couples, thereby increasing fertility intentions to have one more child and increasing fertility rates. STUDY FUNDING/COMPETING INTEREST(S): No funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The "Matrisome" reveals the characterization of skin keloid microenvironment.

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

Efficacy and evaluation of therapeutic exercises on adults with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Exercises are an effective treatment in Parkinson's disease (PD), but there is still controversy over which types should be used. We aimed to compare and rank the types of exercise that improve PD symptoms by quantifying information from randomised controlled trials. METHODS: We performed a systematic review and network meta-analysis and searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and China National Knowledge Infrastructure (CNKI) from their inception date to June 30, 2022. We included randomized controlled trials of 24 types of exercise for the interventional treatment of adults (≥ 50 years old) with PD. Effect size measures were standardized mean differences (SMDs) with 95% credible intervals (CrIs). The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). RESULTS: We identified 10 474 citations and included 250 studies involving 13 011 participants. Results of NMA showed that power training (PT) had the best benefits for motor symptoms compared with the control group (CON), with SMDs (95% CrI) (-1.46, [-2.18 to -0.74]). Body weight support treadmill training (BWS_TT) showed the best improvement in balance (1.55, [0.72 to 2.37]), gait velocity (1.15 [0.57 to 1.31]) and walking distance (1.96, [1.18 to 2.73]), and robotic assisted gait training (RA_GT) had the most benefits for freezing of gait (-1.09, [-1.80 to -0.38]). For non-motor symptoms, Dance showed the best benefits for depression (-1.71, [-2.79 to -0.73]). Only Yoga significantly reduced anxiety symptom compared with CON (-0.53, [0.96 to -0.11]). Only resistance training (RT) significantly enhanced sleep quality and cognition (-1.42, [-2.60 to -0.23]; 0.51, [0.09 to 0.94]). For muscle strength, PT showed the best advance (1.04, [0.64 to 1.44]). For concern of falling, five types of exercise were more effective than CON. CONCLUSIONS: There is low quality evidence that PT, Yoga, BWS_TT, Dance, and RT are the most effective treatments, pending outcome of interest, for adults with PD. TRIAL REGISTRATION: PROSPERO (CRD42021220052).

The prevalence of barriers to rearing children aged 0-3 years following China's new three-child policy: a national cross-sectional study.

BACKGROUND: To further optimize birth policy, China implemented a new three-child policy to allow per couple to have up to three children on May 31, 2021. METHODS: A national cross-sectional survey was conducted among 18 to 49-year-old Chinese parents who had at least one child in June 2021. We calculated the prevalence of self-reported childrearing barriers and used univariate logistic regression and multivariate logistic regression to analyze associated factors. RESULTS: 94.7% of the respondents self-reported barriers to rearing children aged 0-3 years, and the biggest barrier included high time cost (39.3%), high parenting cost (36.5%) and high education cost (13.5%). Women (aOR 1.49, 95%CI 1.13,1.96) and people with college degree or above (aOR 3.46, 95%CI 2.08, 5.75) were associated with higher prevalence of childrearing barriers, and people who intended to have a second child (aOR 0.58, 95%CI 0.40, 0.83) and people who intended to have a third child (aOR 0.51,95%CI 0.37, 0.71) were less likely to report childrearing barriers. The biggest barrier was more likely to be high time cost for parents one of whom is only child (aOR1.21, 95%CI 1.03, 1.42) and physical factors for parents both of whom are only child (aOR 1.56,95%CI 1.08, 2.26). CONCLUSIONS: The prevalence of barriers to rearing children aged 0-3 years was high among Chinese people of childbearing age who had children. Full consideration should be given to the barriers of people with different sociodemographic characteristics and people with fertility intention, thus making targeted childrearing policies and supporting measures to reduce the burden on people of childbearing age, encourage suitable couples to have a second or third child and then cope with China's aging population.

Antimicrobial peptide AR-23 derivatives with high endosomal disrupting ability enhance poly(l-lysine)-mediated gene transfer.

BACKGROUND: pH-sensitive peptides are a relatively new strategy for conquering the poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improves its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection. METHODS: In the present study, we investigated the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 with respect to enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in the AR-23 sequence with Glu one-by-one. RESULTS: The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking, the transfection efficiency and the cytotoxicity of the polyplexes were determined. Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in the AR-23 sequence greatly improved poly(l-lysine)-mediated gene transfection efficiency at the same time as maintaining low cytotoxicity. CONCLUSIONS: The results indicate that replacement of positively-charged residues with sufficient Glu residues may be considered as a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images.

Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.

RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs to mediate RIG-I degradation.

The activation of retinoic acid-inducible gene 1 (RIG-I), a cytoplasmic innate sensor for viral RNA, is tightly regulated to maintain immune homeostasis properly and prevent excessive inflammatory reactions other than initiation of antiviral innate response to eliminate RNA virus effectively. Posttranslational modifications, particularly ubiquitination, are crucial for regulation of RIG-I activity. Increasing evidence suggests that E3 ligases play important roles in various cellular processes, including cell proliferation and antiviral innate signaling. Here we identify that E3 ubiquitin ligase RING finger protein 122 (RNF122) directly interacts with mouse RIG-I through MS screening of RIG-I-interacting proteins in RNA virus-infected cells. The transmembrane domain of RNF122 associates with the caspase activation and recruitment domains (CARDs) of RIG-I; this interaction effectively triggers RING finger domain of RNF122 to deliver the Lys-48-linked ubiquitin to the Lys115 and Lys146 residues of RIG-I CARDs and promotes RIG-I degradation, resulting in a marked inhibition of RIG-I downstream signaling. RNF122 is widely expressed in various immune cells, with preferential expression in macrophages. Deficiency of RNF122 selectively increases RIG-I-triggered production of type I IFNs and proinflammatory cytokines in macrophages. RNF122-deficient mice exhibit more resistance against lethal RNA virus infection, with increased production of type I IFNs. Thus, we demonstrate that RNF122 acts as a selective negative regulator of RIG-I-triggered antiviral innate response by targeting CARDs of RIG-I and mediating proteasomal degradation of RIG-I. Our study outlines a way for E3 ligase to regulate innate sensor RIG-I for the control of antiviral innate immunity.

Computer-Aided Diagnosis (CAD) of Pulmonary Nodule of Thoracic CT Image Using Transfer Learning.

Computer-aided diagnosis (CAD) has already been widely used in medical image processing. We recently make another trial to implement convolutional neural network (CNN) on the classification of pulmonary nodules of thoracic CT images. The biggest challenge in medical image classification with the help of CNN is the difficulty of acquiring enough samples, and overfitting is a common problem when there are not enough images for training. Transfer learning has been verified as reasonable in dealing with such problems with an acceptable loss value. We use the classic LeNet-5 model to classify pulmonary nodules of thoracic CT images, including benign and malignant pulmonary nodules, and different malignancies of the malignant nodules. The CT images are obtained from Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) where both pulmonary nodule scanning and nodule annotations are available. These images are labeled and stored in a medical images knowledge base (KB), which is designed and implemented in our previous work. We implement the 10-folder cross validation (CV) to testify the robustness of the classification model we trained. The result demonstrates that the transfer learning of the LeNet-5 is good for classifying pulmonary nodules of thoracic CT images, and the average values of Top-1 accuracy are 97.041% and 96.685% respectively. We believe that our work is beneficial and has potential for practical diagnosis of lung nodules.

GRGDS-functionalized chitosan nanoparticles as a potential intravenous hemostat for traumatic hemorrhage control in an animal model.

Hemostats, which are used for immediate intervention during internal hemorrhage in order to reduce resulting mortality and morbidity, are relatively rare. Here, we describe novel intravenous nanoparticles (CPG-NPs-2000) with chitosan succinate (CSS) as cores, polyethylene glycol (PEG-2000) as spacers and a glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide as targeted, active hemostatic motifs. CPG-NPs-2000 displayed significant hemostatic efficacy, compared to the saline control, CSS nanoparticles, and tranexamic acid in liver trauma rat models. Further studies have demonstrated that CPG-NPs-2000 are effectively cleared from organs and blood, within 2 and 48 h, respectively. In addition, administration of CPG-NPs-2000 does not affect clotting function under normal physiological conditions, indicating their potential safety in vivo. CPG-NPs-2000 exhibit excellent thermal stability, good solubility, and redistribution ability, in addition to being low cost. These characteristics indicate that CPG-NPs-2000 may have strong potential as effective intravenous hemostats for treating severe internal bleeding.

Seroepidemiological map of Toxoplasma gondii infection and associated risk factors in preconception period in China: A nationwide cross-sectional study.

AIM: The aims of this study were to investigate the regional differences in seroepidemiology of toxoplasmosis in preconception period among Chinese women of reproductive age and to evaluate associated risk factors. METHODS: This national, population-based, cross-sectional serosurvey covered all 31 provinces and province-level municipalities in Mainland China. Married women intending to get pregnant within 6 months between 2010 and 2012 were recruited. Information on demographic characteristics (age, place of residence, occupation, dietary habits and exposure to cat) was obtained using interviews, and venous blood samples were collected to screen for Toxoplasma gondii infection. RESULTS: Of 2 008 561 women recruited to the study, 45 405 (2.3%) were Toxoplasma gondii IgG positive, and 6884 (0.3%) were IgM positive. Geographical variation for seropositivity ranged from 0.2% in Heilongjiang to 11.2% in Tianjing for IgG and from 0% in Tibet to 0.9% in Anhui for IgM. Advanced maternal age, occupation of a farmer, vegetarian diet and exposure to cat was significantly associated with Toxoplasma gondii IgM seropositivity, and its association with occupation of farmer and exposure to cat was significant after adjusting for province of residence (P < 0.05). CONCLUSION: There were significant regional variations in Toxoplasma gondii seropositivity and associated risk factors among Chinese women of reproductive age during preconception period. This calls for a targeted primary prevention strategy. Screening and treatment before conception and preconception health education may have potential for reducing congenital Toxoplasmosis in China.

Design of pH-sensitive peptides from natural antimicrobial peptides for enhancing polyethylenimine-mediated gene transfection.

BACKGROUND: Poor endosomal release is a major barrier of polyplex-mediated gene transfection. Antimicrobial peptides (AMPs) are commonly used to improve polyethylenimine (PEI)-mediated gene transfection by increasing endosomal release. In the present study, we designed novel pH-sensitive peptides that highly enhance transfection efficiency compared to their parent peptides. METHODS: Two analogues of melittin (Mel) and RV-23 (RV) were synthesized by replacing the positively-charged residues in their sequences with glutamic acid residues. The pH-sensitive lysis ability of the peptides, the effect of the peptides on physicochemical characteristics, the intracellular trafficking, the transfection efficiency, and the cytotoxicity of the polyplexes were determined. RESULTS: The acidic peptides showed pH-sensitive lytic activity. The hemolytic activity of acidic peptides at pH 5.0 was higher than that at pH 7.4. The incorporation of acidic peptides did not affect the DNA binding ability of PEI but affected the physicochemical characteristics of the PEI/DNA polyplexes, which may be beneficial for endosomal release and gene transfection. The incorporation of acidic peptides into PEI/DNA polyplexes enhanced the PEI-mediated transfection efficiency corresponding to up to 42-fold higher luciferase activity compared to that of PEI alone. CONCLUSIONS: The results of the present study indicate that replacement of positively-charged residues with glutamic acid residues in the AMP sequence yields pH-sensitive peptides, which enhance the transfection efficiency of PEI/DNA polyplexes in various cell lines.

Preconception TSH and pregnancy outcomes: a population-based cohort study in 184 611 women.

BACKGROUND: Whether subclinical hypothyroidism adversely impacts pregnancy outcomes is inconclusive, and limited data are available on the optimal TSH range in women planning pregnancy. OBJECTIVE: To investigate the association between maternal preconception TSH levels and pregnancy outcomes. DESIGN: Population-based cohort study. METHODS: From 2010 to 2012, the free National Pre-pregnancy Checkups Project recruited 248 501 pairs of volunteer couples across China, of which 184 611 women, who subsequently became pregnant, were studied. Maternal TSH was measured within 6 months prior to conception. Participants were grouped according to TSH: 0·48-2·49 mIU/l (n = 133 232, 72%), 2·50-4·28 mIU/l (n = 44 239, 24%) and 4·29-10·0 mIU/l (n = 7140, 4%). Multivariable logistic regression models were used to study the association between TSH and pregnancy outcomes. MAIN OUTCOMES: Pregnancy loss, gestational age (GA), delivery modes and birthweight. RESULTS: The overall incidence of adverse pregnancy outcomes was 28·6%. Compared with TSH 0·48-2·50 mIU/l, TSH 2·50-4·29 mIU/l was associated with spontaneous abortion [aOR: 1·10, 95% confidence interval (CI): 1·03-1·18], preterm birth (aOR: 1·09, 95% CI: 1·04-1·15) and operative vaginal delivery (aOR: 1·15, 95% CI: 1·09-1·21), while TSH 4·29-10 mIU/l was correlated with spontaneous abortion (aOR: 1·15, 95% CI: 1·10-1·22), stillbirth (aOR: 1·58, 95% CI: 1·10-2·28), preterm birth (aOR: 1·20, 95% CI: 1·08-1·34), caesarean section (aOR: 1·15, 95% CI: 1·10-1·22) and large for gestational age (LGA) infants (aOR: 1·12, 95% CI: 1·04-1·21). CONCLUSION: Preconception TSH elevation was associated with increased risk of adverse pregnancy outcomes, even within the normal nonpregnant range.

Hepatitis B Virus Infection in Preconception Period Among Women of Reproductive Age in Rural China - A Nationwide Study.

BACKGROUND: Hepatitis B virus (HBV) infection during pregnancy is associated with perinatal complications and poor maternal and fetal outcomes. There is a lack of reports on HBV infection screening, prophylaxis, and/or treatment in preconception period among women planning a pregnancy. This study is to investigate the prevalence and demographic characteristics of HBV infection among rural women of reproductive age planning pregnancy within 6 months, in different geographical regions of China. METHODS: A population-based, cross-sectional, sero-survey of HBV infection among women intending to get pregnant within 6 months was carried out as a part of the National Free Preconception Health Examination Project covering 31 provinces in mainland China between 2010-12. General information (age, residence status, race, education, and occupation), HBV infection and vaccination history was collected. Results of HBV serological test panel were recorded for analysis. RESULTS: Of 2 120 131 women, 2 028 361 (95.7%) samples of HBV serology were available for analysis. Participating women were of young age (median 28.1 years), mostly engaged in agricultural activities (78.1%), and had high school education or lower (89.6%). The overall prevalence of HBsAg sero-positivity was 4.9%, which corresponds to an intermediate epidemic, with a wide geographical variation that ranged from 1.1% in Shanxi to 13.0% in Tibet. 90.1% women were susceptible to HBV with a 24.5% self-reported HBV vaccination rate. CONCLUSIONS: Significant regional differences in HBV prevalence, and a vast majority of women of childbearing age being susceptible to HBV, calls for a targeted HBV screening and vaccination strategy for women and their offspring in rural China.