Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α-Helical Polypeptides to Optimize Antibacterial Therapy.

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.

Associations between maternal syphilis infection during pregnancy and low birth weight and preterm birth: a prospective cohort study.

BACKGROUND: In recent years, syphilis is still the most common sexually transmitted disease worldwide. Pregnant women infected with syphilis can transmit it to the fetus in utero through mother-to-child transmission, which can directly lead to adverse pregnancy outcomes. The aim of this study was to investigate the associations between maternal syphilis infection and low birth weight and preterm birth in offspring. METHODS: Multinomial logistic regression model was used to analyze the associations between maternal syphilis infection and low birth weight and preterm birth, and to explore its stability through subgroup analysis. RESULTS: A total of 34,074 subjects were included in the study. After adjusting for potential confounders, maternal syphilis infection during pregnancy was associated with a 2.60-fold (95% CI 1.83-3.69) increased risk of low birth weight and a 1.91-fold (95% CI 1.35-2.69) increased risk of preterm birth. Subgroup analysis showed that the association was stable. CONCLUSION: We found that maternal syphilis infection during pregnancy was significantly associated with an increased risk of low birth weight and preterm birth. The implementation of reasonable syphilis screening and standardized treatment and follow-up of pregnant syphilis may have important practical significance in reducing the low birth weight and preterm birth rate in offspring.

The risk of attention-deficit hyperactivity disorder among children with congenital heart disease: A systematic review and meta-analysis.

BACKGROUND: Although current treatments are effective in dealing with congenital heart disease (CHD), non-cardiac comorbidities such as attention-deficit hyperactivity disorder (ADHD) have received widespread attention. The purpose of this systematic review and meta-analysis is to assess the risk of ADHD associated with CHD. METHODS: The literature search was carried out systematically through eight different databases by the end of September 2022. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. The heterogeneity of the studies was assessed by the Cochran Q test and the I2 statistic. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity. RESULTS: Eleven studies were included in this study, which involved a total of 296 741 participants. Our study showed that the children with CHD were at a significantly increased risk of ADHD compared with the reference group (OR = 2.98, 95% CI: 2.18-4.08). The results were moderately heterogeneous. These factors including study design, geographic region and study quality were identified as the first three of the most relevant heterogeneity moderators by subgroup analyses. Sensitivity analysis yielded consistent results. There was no evidence of publication bias. CONCLUSIONS: The present study suggests that CHD children have a significantly higher risk of ADHD when compared with those without CHD. Early identification and intervention of ADHD is important to reduce its symptoms and adverse effects; therefore, clinicians should increase screening for ADHD in children with CHD and intervene promptly to reduce its effects whenever possible.

[Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects]. / 母亲MTRåŸºå› å¤šæ€æ€§åŠå ¶ä¸Žå›´å­•æœŸå¶é ¸è¡¥å çš„äº¤äº’ä½œç”¨ä¸Žå­ä»£å®¤é—´éš”ç¼ºæŸçš„å ³è”ç ”ç©¶.

OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Injectable Thermo-Responsive Peptide Hydrogels and Its Enzyme Triggered Dynamic Self-Assembly.

Endogenous stimuli-responsive injectable hydrogels hold significant promise for practical applications due to their spatio-temporal controllable drug delivery. Herein, we report a facile strategy to construct a series of in situ formation polypeptide hydrogels with thermal responsiveness and enzyme-triggered dynamic self-assembly. The thermo-responsive hydrogels are from the diblock random copolymer mPEG-b-P(Glu-co-Tyr). The L-glutamic acid (Glu) segments with different γ-alkyl groups, including methyl, ethyl, and n-butyl, offer specific secondary structure, facilitating the formation of hydrogel. The L-tyrosine (Tyr) residues not only provide hydrogen-bond interactions and thus adjust the sol-gel transition temperatures, but also endow polypeptide enzyme-responsive properties. The PTyr segments could be phosphorylated, and the phosphotyrosine copolymers were amphiphilies, which could readily self-assemble into spherical aggregates and transform into sheet-like structures upon dephosphorylation by alkaline phosphatase (ALP). P(MGlu-co-Tyr/P) and P(MGlu-co-Tyr) copolymers showed good compatibility with both MC3T3-E1 and Hela cells, with cell viability above 80% at concentrations up to 1000 µg/mL. The prepared injectable polypeptide hydrogel and its enzyme-triggered self-assemblies show particular potential for biomedical applications.

Impact of multiple obesity metrics on hypertensive disorders of pregnancy: a meta-analysis and Mendelian randomisation study.

BACKGROUND: The relationships between various obesity measures and hypertensive disorders of pregnancy (HDP) remain inadequately explored, and their causal links are not well understood. This study aims to clarify these associations and investigate the mediating role of triglycerides. METHODS: We conducted a comprehensive meta-analysis of observational studies alongside Mendelian randomisation (MR) analysis to assess the impact of 10 obesity measures on HDP risk. Additionally, we evaluated the mediating effect of triglycerides. RESULTS: Our meta-analysis revealed significant associations between maternal prepregnancy overweight/obesity and increased risks of gestational hypertension (GH) (overweight: OR=1.98, 95% CI 1.83 to 2.15; obesity: OR=3.77, 95% CI 3.45 to 4.13) and pre-eclampsia (overweight: OR=1.78, 95% CI 1.67 to 1.90; obesity: OR=3.46, 95% CI 3.16 to 3.79). Higher maternal waist circumference (WC) was also linked to increased pre-eclampsia risk (OR=1.45, 95% CI 1.14 to 1.83). MR analyses indicated that each 1-SD increase in genetically predicted obesity measures (whole body fat mass, body fat percentage, trunk fat mass, trunk fat percentage, body mass index, WC, hip circumference) was associated with higher risks of GH and pre-eclampsia. Triglycerides mediated 4.3%-14.1% of the total genetic effect of these obesity measures on GH and pre-eclampsia risks. CONCLUSIONS: This study demonstrates that various obesity measures are causally linked to increased HDP risk and highlights the mediating role of triglycerides. These findings could inform clinical practices and public health strategies aimed at reducing HDP through targeted obesity and triglyceride management.

Associated factors of undernutrition in children with congenital heart disease: a cross-sectional study.

Objective: To evaluate the prevalence and associated factors of undernutrition among children with congenital heart disease (CHD) who have not undergone surgeries in China. Methods: This cross-sectional study included 734 CHD children along with their parents. The outcome of interest was undernutrition, including underweight, wasting, and stunting, defined as Z-scores (i.e., weight-for-age, weight-for-height, and height-for-age) ≤-2, according to the World Health Organization (WHO) growth standard. Exposures of interest, containing demographics, obstetric factors, maternal dietary factors, parents' life behaviors and habits, birth-related factors, cardiac-related factors, and preoperative factors, were analyzed using a multivariate logistic regression model to test their associations with undernutrition in CHD children. Results: Overall, 36.1%, 29.7%, and 21.3% of cases were underweight, wasted, and stunted, respectively. Multivariate logistic regression indicated that underweight was associated with demographic factors (including parents' occupational status, family income, and maternal body mass index pre-pregnancy), low birth weight (OR = 4.60, 2.76-7.70), pulmonary hypertension (OR = 4.46, 3.09-6.43), and pneumonia (OR = 1.88, 1.28-2.76). Artificially-fed children were 2.34 (1.36-4.01) times more likely to be underweight. Occupied mothers (OR = 0.62, 0.44-0.88) and fathers (OR = 0.49, 0.26-0.92) served as protective factors, while mothers having gestational complications (OR = 1.56, 1.11-2.18) and exposed to noisy environment (OR = 1.64, 1.11-2.42) during this pregnancy, and pulmonary hypertension (OR = 3.21, 2.30-4.49) increased the chance of wasting in offspring. The odds of being stunted were greater in families with >2 children (OR = 1.88, 1.13-3.14), placental abruption during this pregnancy (OR = 25.15, 2.55-247.89), preterm births (OR = 1.84, 1.02-3.31), low birth weight (OR = 3.78, 2.16-6.62), pulmonary hypertension (OR = 2.35, 1.56-3.53) and pneumonia (OR = 1.93, 1.28-2.90). In subgroup analyses, the associations differed between patients with different feeding patterns (breastfeeding vs. non-breastfeeding), CHD classifications (cyanotic vs. acyanotic), and prematurity (preterm vs. non-preterm). Conclusion: Undernutrition is common in preoperative CHD children. Familial demographics, maternal factors (including having gestational complications and exposure to noisy environment during pregnancy), and patient-related factors (encompassing preterm births, low birth weight, pulmonary hypertension, pneumonia, and feeding pattern) were found to contribute to undernutrition in CHD cases. However, associated factors among the three subgroups of distinct feeding patterns, CHD categorization, and prematurity exhibited varied outcomes, suggesting the necessity for targeted interventions.