Associations between mixed exposure to phthalates and latent tuberculosis infection among the general U.S. population from NHANES 2011-2012.

Background: People are constantly exposed to phthalates, but few reliable studies have focused on the connection between phthalate exposure and latent tuberculosis infection (LTBI). Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (2011-2012). The LTBI was assessed by QuantiFERON®-TB Gold-In-Tube (QFT) or tuberculin skin testing (TST). The odds ratios (ORs) and 95% confidence intervals (CIs) per log10 unit change in the concentration of phthalate metabolites were calculated using crude and adjusted logistic regression models. The relationships between mixed phthalate concentrations and LTBI were assessed using Bayesian kernel machine regression (BKMR) models. Results: According to the results of the multivariable logistic regression, in a fully adjusted model, only monobenzyl phthalate (MBZP) was negatively associated with LTBI in Q3 (OR (95% CI): 0.485 (0.286,0.823), P = 0.007). According to the restricted cubic spline (RCS) model, there was a linear dose‒response association between all 11 phthalate metabolites and LTBI (p for nonlinearity >0.05). We found a significant positive correlation between mixed phthalate metabolites and LTBI by using fully adjusted BKMR model. Conclusions: Our analysis demonstrated that LTBI in the general U.S. population is linearly linked with exposure to single or combined phthalates.

Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study.

OBJECTIVES: Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results. METHODS: The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis. RESULTS: In the B-cell panel, B-cell activating factor receptor (BAFF-R) on CD20- and CD20 on IgD-CD38bright (OR (95% CI): 0.93 (0.88, 0.99) and 0.97 (0.95, 0.98), respectively) were discovered to be protective. In the cDC panel, CD62L- plasmacytoid DC AC, CD80 on monocytes and CD11c on myeloid DCs (OR (95% CI): 0.94 (0.92, 0.97), 0.97 (0.94, 0.99) and (0.97 (0.95, 0.98), respectively) exerted protective effects. However, unswitched memory AC (OR (95%CI): 1.08 (1.01,1.15)) and CD 19 on IgD- CD 27- (OR (95%CI): 1.06 (1.02,1.10)) were hazardous in the B-cell panel. However, among the 731 immune cell phenotypes, no causal relationship was found for COPD on immune cells. CONCLUSION: This study found a potential causal relationship between immune cells in COPD, ruling out reverse causation. This study provides new avenues for studying the mechanisms of COPD.

GSK-3ß inhibitor TWS119 promotes neuronal differentiation after hypoxic-ischemic brain damage in neonatal rats.

Brain injury in preterm infants is a major cause of disability and mortality in children. GSK-3ß is a common pathogenic factor for cognitive dysfunction and involves in neuronal proliferation and differentiation. However, GSK-3ß affected neuronal differentiation and its molecular pathogenesis after hypoxic-ischemic brain damage in neonatal rats remains unclear. This study investigated the effects of GSK-3ß inhibitor (TWS119) on cell cycle regulatory proteins, a neuronal differentiation factor (CEND1), maturation neurons, T-box brain transcription factor 1 (TBR1)-positive neurons to clarify the mechanisms of hypoxic-ischemic brain damage in neonatal rats. We used hypoxic-ischemic Sprague-Dawley neonatal rats with brain damage as models. These rats were used for investigating the effect of GSK-3ß on cell cycle regulatory proteins, neuronal differentiation factor (CEND1), maturation neurons, TBR1-positive neurons by western blot and immunofluorescence. Cyclin D1 (a positive cell cycle regulator) expression decreased, and p21 (a negative cell cycle regulator) expression increased in the TWS119 group compared to the hypoxia-ischemia (HI) group 7 days after HI. Additionally, compared to the HI group, TWS119 treatment up-regulated CEND1 expression and promoted neuronal differentiation and cortex development based on NeuN and TBR1 expression. Our study suggests that the GSK-3ß inhibitor TWS119 promotes neuronal differentiation after hypoxic-ischemic brain damage in neonatal rats by inhibiting cell cycle pathway.

Cohort differences between preschool development of in vitro fertilization and naturally conceived infants.

To explore the differential cohort situation between preschool development of in vitro fertilization (IVF) and naturally conceived infants. From April 2014 to June 2022, 60 preschool IVFs were selected as the research subjects for follow-up at the pediatric health clinic of hospital's prevention and health department. They were set as the experimental group (Group S), and 60 naturally conceived infants of the same age were selected as the control group (Group Z). Data from both groups were collected through telephone follow-up and other methods. No significant difference showed between the 2 groups in age specific height, age specific weight, Gesell developmental score, Denver developmental screening test screening results, intellectual development index, and motor development index (P > .05). The influence of birth environment factors such as family background and maternal education level on children's height and weight was not significant (P > .05), while maternal education level had a significant impact on children's intellectual development index (P < .05). No significant difference showed in the development of preschool children in IVF compared to naturally conceived children, and the level of parental education has a significant impact on children's mental and motor development.

Constructing a Built-In Electric Field To Accelerate Water Dissociation for Efficient Alkaline Hydrogen Evolution.

The alkaline hydrogen evolution reaction (HER) is intricately linked to the water dissociation kinetics. The quest for new strategies to accelerate this step is a pivotal aspect of enhancing the HER performance. Herein, we designed and synthesized a heterogeneous nickel phosphide/cobalt phosphide nanowire array grown on nickel foam (Ni2P/CoP/NF) to form a p-n junction structure. The built-in electric field (BEF) in the p-n junction optimizes the binding ability of hydrogen and hydroxyl intermediates, efficiently promoting water dissociation for the alkaline HER. Consequently, Ni2P/CoP/NF exhibits a lower overpotential of 58 and 118 mV at 30 and 100 mA cm-2, respectively, and high stability over 40 h at 300 mA cm-2 for the HER in 1 M KOH. Computational calculations combined with experiment results testify that the BEF presence in the p-n junction of Ni2P/CoP/NF effectively promotes water dissociation, regulates intermediate adsorption/desorption, and boosts electron transport. This study presents a rational design approach for high-performance heterogeneous electrocatalysts.

NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis.

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.

The luciferase reporter system of the MMP12 endogenous promoter for investigating transcriptional regulation of the human MMP12 gene

Background: Matrix metalloproteinase 12 (MMP12), a member of MMPs, can take lots of roles including extracellular matrix component degradation, viral infection, inflammation, tissue remodeling and tumorigenesis. To explore the transcriptional regulation of MMP12 gene, a sensitive luciferase reporter HEK293 cell line for endogenous MMP12 promoter was generated by CRISPR/Cas9 technology. Results: The HEK293-MMP12-T2A-luciferase-KI cell line was successfully established by CRISPR/Cas9 technology. The sequencing results indicated that one allele of the genome was proven to have a site-directed insertion of luciferase gene and another allele of the genome was confirmed to have additional 48 bp insertion in this cell line. The cell line was further demonstrated to be a sensitive reporter of the endogenous MMP12 promoter by applying transcription factors STAT3, AP-1 and SP-1 to the cell line. The reporter cell line was then screened with bioactive small molecule library, and a small molecule Tanshinone I was found to significantly inhibit the transcriptional activity of MMP12 gene in HEK293-MMP12-T2A-luciferase-KI cell line by luciferase activity assay, which was further confirmed to inhibit the expression of MMP12 mRNA in wild-type HEK293 cells. Conclusions: This novel luciferase knock-in reporter system will be helpful for investigating the transcriptional regulation of MMP12 gene and screening the drugs targeting MMP12 gene.